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Sample records for adults starting antiretroviral

  1. Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

    PubMed Central

    Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias

    2012-01-01

    Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24 months after the start of treatment. Results Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6 months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings. PMID:23172344

  2. Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies

    PubMed Central

    Johnson, Leigh F.; Mossong, Joel; Dorrington, Rob E.; Schomaker, Michael; Hoffmann, Christopher J.; Keiser, Olivia; Fox, Matthew P.; Wood, Robin; Prozesky, Hans; Giddy, Janet; Garone, Daniela Belen; Cornell, Morna; Egger, Matthias; Boulle, Andrew

    2013-01-01

    Background Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. Methods and Findings Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. Conclusions South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later

  3. Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis

    PubMed Central

    Blanc, François-Xavier; Sok, Thim; Laureillard, Didier; Borand, Laurence; Rekacewicz, Claire; Nerrienet, Eric; Madec, Yoann; Marcy, Olivier; Chan, Sarin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeurn; Dim, Bunnet; Sin, Chhun Im; Sun, Sath; Guillard, Bertrand; Sar, Borann; Vong, Sirenda; Fernandez, Marcelo; Fox, Lawrence; Delfraissy, Jean-François; Goldfeld, Anne E.

    2016-01-01

    Background Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. Methods We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. Results A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log10 copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P = 0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. Conclusions Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of

  4. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

    PubMed

    Blanc, François-Xavier; Sok, Thim; Laureillard, Didier; Borand, Laurence; Rekacewicz, Claire; Nerrienet, Eric; Madec, Yoann; Marcy, Olivier; Chan, Sarin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeurn; Dim, Bunnet; Sin, Chhun Im; Sun, Sath; Guillard, Bertrand; Sar, Borann; Vong, Sirenda; Fernandez, Marcelo; Fox, Lawrence; Delfraissy, Jean-François; Goldfeld, Anne E

    2011-10-20

    Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number

  5. When to Start Antiretroviral Therapy

    MedlinePlus

    ... away. What conditions increase the urgency to start ART? The following conditions increase the urgency to start ... risk of HIV transmission. Once a person starts ART, why is medication adherence important? ART is a ...

  6. Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada

    PubMed Central

    Jenkins, Cathy A.; Lau, Bryan; Shepherd, Bryan E.; Justice, Amy C.; Tate, Janet P.; Buchacz, Kate; Napravnik, Sonia; Mayor, Angel M.; Horberg, Michael A.; Blashill, Aaron J.; Willig, Amanda; Wester, C. William; Silverberg, Michael J.; Gill, John; Thorne, Jennifer E.; Klein, Marina; Eron, Joseph J.; Kitahata, Mari M.; Sterling, Timothy R.; Moore, Richard D.

    2016-01-01

    Abstract The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4+ count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m2 between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ≥30 kg/m2) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5–24.9 kg/m2) at baseline had become overweight (BMI 25.0–29.9 kg/m2), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future. PMID:26352511

  7. Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada.

    PubMed

    Koethe, John R; Jenkins, Cathy A; Lau, Bryan; Shepherd, Bryan E; Justice, Amy C; Tate, Janet P; Buchacz, Kate; Napravnik, Sonia; Mayor, Angel M; Horberg, Michael A; Blashill, Aaron J; Willig, Amanda; Wester, C William; Silverberg, Michael J; Gill, John; Thorne, Jennifer E; Klein, Marina; Eron, Joseph J; Kitahata, Mari M; Sterling, Timothy R; Moore, Richard D

    2016-01-01

    The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m(2) between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ≥30 kg/m(2)) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9 kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future.

  8. Impact of malnutrition and social determinants on survival of HIV-infected adults starting antiretroviral therapy in resource-limited settings.

    PubMed

    Argemi, Xavier; Dara, Som; You, Seng; Mattei, Jean F; Courpotin, Christian; Simon, Bernard; Hansmann, Yves; Christmann, Daniel; Lefebvre, Nicolas

    2012-06-01

    Determining the impact of malnutrition, anaemia and social determinants on survival once starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in a rural HIV care centre in Sihanoukville, Cambodia. Retrospective and descriptive cohort study of adults starting ART between December 2004 and July 2009. We used the Kaplan-Meier and Cox regression survival analyses to identify predictors of death. Out of 1002 patients, 49.7% were men; median age was 40; median time of follow-up was 2.4 years and 10.4% died during the follow-up. At baseline, median CD4 cell count was 83 cells/μl, 79.9% were at WHO stage III or IV. In multivariate analysis, malnutrition appeared to be a strong and independent risk factor of death; 11.2% had a BMI less than 16 kg/m and hazard ratio was 6.97 [95% confidence interval (CI), 3.51-13.89], 21.5% had a BMI between 16 and 18 kg/m and hazard ratio was 2.88 (95% CI, 1.42-5.82), 30.8% had a BMI between 18 and 20 kg/m and hazard ratio was 2.18 (95% CI, 1.09-4.36). Severe anaemia (haemoglobin≤8.4 g/dl) and CD4 cell count below 100 cells/μl also predicted mortality, hazard ratio were 2.25 (95% CI, 1.02-4.34) and 2.29 (95% CI, 1.01-2.97), respectively. Social determinants were not significantly associated with death in univariate analysis. Malnutrition and anaemia are strong and independent prognostic factors at the time of starting ART. Nutritional cares are essential for the clinical success of HIV programs started in developing countries.

  9. Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting

    PubMed Central

    2014-01-01

    Background Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. Methods We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m2), moderate (16.00-16.99 kg/m2), and mild (17.00-18.49 kg/m2) malnutrition categories. Results 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m2 category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m2 patients. Among BMI 17.00-18.49 kg/m2 patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. Conclusions Low BMI adults starting ART in

  10. [Evolution of epidemiological and clinical characteristics of adults patients belonging to the national program at start of antiretroviral therapy in the Chilean AIDS Cohort, 2001-2015].

    PubMed

    Beltrán, Carlos; Zitko, Pedro; Wolff, Marcelo; Bernal, Fernando; Asenjo, Alicia; Fernández, Ana M; Miles, Ana; Barthel, Elizabeth; Wilson, Gonzalo

    2016-10-01

    Chilean AIDS Cohort is the oldest and extensive in Latin America and one of most numerous and with longer follow up time to international level. Records information from 14,873 patients out of approximately 22,000 in antiretroviral therapy in the public system and its results have allowed to know the national reality and have contributed to the adoption of public policies. To describe the demographic, clinical and immunological characteristics of patients who have started ART in Chile and its evolution over the past 15 years. The cases were stratified by five-year periods: 2001-2005, 2006-2010 and 2011-2015. The data analysis included calculating proportions, their respective confidence intervals 95% and X² test for significance analysis was applied. 17.4% of patients starting ART are women and the proportion has remained relatively constant. The highest proportion of new HIV cases are 30 and 39 years old, nevertheless the layer of 15-29 years demonstrates a significant increase from 21.7 to 36.4% in 2011-2015 especially in men. 12.1% of new cases are older than 50 years old with a stable trend over time; however, women over 50 have increased from 11.0 to 15.6%. Antiretroviral therapy initiation with CD4+ T lymphocytes less than 200 cells/mm³ has decreased from 79.7 to 42.4% and in stage C from 45.4 to 22.6%. Late presentation to antiretroviral therapy is higher in men but this gap has narrowed in the last five years. Pneumocystis jiroveci, wasting syndrome, tuberculosis, Kaposi's sarcoma and esophageal candidiasis are the most common opportunistic diseases without significant changes in the three-year periods analyzed. In the last five years, 15.5% of opportunistic diseases occurs in patients with CD4+ TL > 200 cells/mm3. Despite the limitations of observational studies present report describes the characteristics and evolution of the epidemics in Chile in the last 15 years. The infection occurs at younger ages in men, whereas in women there is an increase over

  11. Predicting virological decay in patients starting combination antiretroviral therapy

    PubMed Central

    2016-01-01

    Objective: Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART. Design: Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study). Methods: Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance. Results: Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one. Conclusions: Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART. PMID:27124894

  12. First-line antiretroviral therapy durability in a 10-year cohort of naïve adults started on treatment in Uganda

    PubMed Central

    Castelnuovo, Barbara; Kiragga, Agnes; Mubiru, Frank; Kambugu, Andrew; Kamya, Moses; Reynolds, Steven J

    2016-01-01

    Introduction The majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes. Methods At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence. Results Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment

  13. Changes in serum phosphate and potassium and their effects on mortality in malnourished African HIV-infected adults starting antiretroviral therapy and given vitamins and minerals in lipid-based nutritional supplements: secondary analysis from the Nutritional Support for African Adults Starting Antiretroviral Therapy (NUSTART) trial.

    PubMed

    Rehman, Andrea Mary; Woodd, Susannah Louise; Heimburger, Douglas Corbett; Koethe, John Robert; Friis, Henrik; PrayGod, George; Kasonka, Lackson; Kelly, Paul; Filteau, Suzanne

    2017-03-01

    Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.

  14. Prevalence of rilpivirine resistance in people starting antiretroviral treatment in Argentina.

    PubMed

    Bissio, Emiliano; Barbás, Maria G; Kademián, Silvia; Bouzas, Maria B; Salomón, Horacio; Cudolá, Analia; Giuliano, Silvina Fernández; Falistocco, Carlos

    2017-02-24

    Rilpivirine-based regimens are now preferred or alternative first-line regimens according to many HIV treatment guidelines. Recently, a surveillance study conducted in our country determined that prevalence of pretreatment resistance to first-generation NNRTIs was 10%. The aim of this study was to analyze the prevalence of resistance mutations to newer generation NNRTIs in the population starting ART in Argentina. We analyzed the prevalence of resistance mutations to rilpivirine and etravirine (according to the IAS list), obtained through a nationally representative pretreatment HIV-drug resistance (PDR) surveillance study performed in Argentina in 2014-2015. Briefly, 25 ART-dispensing sites throughout the country were randomly chosen to enroll 330 adults starting ART. Samples were processed with Trugene (Siemens)®, and analyzed using the Stanford algorithm. All 270 samples corresponding to participants with no prior exposure to antiretroviral drugs were included in this analysis. Median (IQR) age was 35 years (28-43); 66.7% were male; median(IQR) CD4 count was 284/mm3(112-489). The prevalence of resistance to any antiretroviral was 16% (±5%), and prevalence of NNRTI RAMs was 13% (±4%). The prevalence of resistance to rilpivirine was 8% (±3%). Prevalence of resistance to etravirine was 4% (±3%). The most frequent mutations conferring resistance to rilpivirine were: E138A (n=6) and G190A (n=4). This PDR surveillance study showed concerning levels of HIVDR in Argentina, not only for first-generation NNRTIs but also to rilpivirine. In our setting, performing resistance testing would be necessary before prescription of ART even if a second-generation NNRTI based regimen were used as first-line therapy.

  15. Improved retention of patients starting antiretroviral treatment in Karonga District, northern Malawi, 2005-2012

    PubMed Central

    Mzembe, Themba; Van Boeckel, Thomas P; Kayange, Michael; Jahn, Andreas; Chimbwandira, Frank; Glynn, Judith R; Crampin, Amelia C

    2014-01-01

    Background Patient retention in antiretroviral therapy (ART) programs remains a major challenge in sub-Saharan Africa. We examined whether and why retention in ART care has changed with increasing access. Methods Retrospective cohort study combining individual data from ART registers and interview data, enabling us to link patients across different ART clinics in Karonga District, Malawi. We recorded information on all adults (≥15 years) starting ART between July 2005 and August 2012, including those initiating due to pregnancy and breastfeeding (Option B+). Retention in care was defined as being alive and receiving ART at the end of study. Predictors of attrition were assessed using a multi-variable Cox-proportional hazards model. Results The number of clinics providing ART increased from one in 2005 to 16 in 2012. Six month retention increased from 73% (95%CI 71-76) to 93% (92-94) when comparing the 2005-06 and 2011-12 cohorts, and 12-month retention increased from 70% (67-73) to 92% (90-93). Over the study period, the proportion of patients starting ART at WHO stage 4 declined from 62% to 10%. Being a man, younger than 35 years, having a more advanced WHO stage and being part of an earlier cohort were all independently associated with attrition. Women starting ART for Option B+ experienced higher attrition than women of child-bearing age starting for other reasons. Conclusions In this area retention in care has increased dramatically. Improved health in patients starting ART and decentralization of ART care to peripheral health centres appear to be the major drivers for this change. PMID:24977375

  16. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    PubMed Central

    Rodríguez, Mónica; Flores, Paúl; Ahumada, Víctor; Vázquez-Vázquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2012-01-01

    We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV) infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes. PMID:22924046

  17. When to Start Antiretroviral Therapy in Resource-limited Settings

    PubMed Central

    Walensky, Rochelle P.; Wolf, Lindsey L.; Wood, Robin; Fofana, Mariam O.; Freedberg, Kenneth A.; Martinson, Neil A.; Paltiel, A. David; Anglaret, Xavier; Weinstein, Milton C.; Losina, Elena

    2011-01-01

    Background Results of international clinical trials assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective To inform HIV treatment decisions over the short- and long-term regarding the optimal CD4 threshold at which to initiate ART in South Africa, while awaiting “when to start” trial results. Design Cost-effectiveness analysis using a computer simulation model of HIV disease. Data Sources Published data from randomized trials and observational cohorts in South Africa. Target Population HIV-infected patients in South Africa. Time Horizon Five-year and lifetime. Perspective Modified societal. Interventions No treatment, initiate ART at CD4<250/μl, and initiate ART at CD4<350/μl. Outcome Measures Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis If 10-100% of HIV-infected patients are diagnosed and linked to care, initiating ART at CD4<350/μl would reduce severe opportunistic diseases by 22,000-221,000 and deaths by 25,000-253,000 during the next 5 years, compared to initiating ART at CD4<250/μl; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART strategy increased long-term survival by at least 7.9 years, with a mean per person life expectancy of 3.8 years for no ART and 12.5 years for ART at <350/μl. Compared to initiating ART at <250/μl, initiating ART at <350/μl had an incremental cost-effectiveness ratio of $1,200/year of life saved. Results of Sensitivity Analysis Initiating ART at CD4<350/μl remained cost-effective over the next 5 years even if the probability that the trial would demonstrate superiority to earlier therapy is as low as 17%. Limitations This model does not consider the possible benefits of ART initiation at CD4>350/μl nor reduced HIV transmission. Conclusions Earlier ART initiation in South Africa will likely reduce morbidity and mortality, improve long-term survival, and be very cost

  18. Minimal impact of an iron-fortified lipid-based nutrient supplement on Hb and iron status: a randomised controlled trial in malnourished HIV-positive African adults starting antiretroviral therapy.

    PubMed

    James, Philip; Friis, Henrik; Woodd, Susannah; Rehman, Andrea M; PrayGod, George; Kelly, Paul; Koethe, John R; Filteau, Suzanne

    2015-08-14

    Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1.81 g/l increase in Hb (95% CI 0.85, 2.76; P< 0.001), and a 0.11 log decrease in serum ferritin (95% CI - 0.22, 0.03; P= 0.012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0.78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia.

  19. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.

    PubMed

    Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A; Lundgren, Jens D; Gill, M John; Gatell, Jose M; Rauch, Andri; Montaner, Julio S; de Wolf, Frank; Reiss, Peter; Mocroft, Amanda

    2009-08-24

    This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13). Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

  20. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

    PubMed Central

    Corbett, Elizabeth L.; Connor, Myles D.; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C.A.; Bryer, Alan; Faragher, Brian; Heyderman, Robert S.; Allain, Theresa J.; Solomon, Tom

    2016-01-01

    Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43–12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44–8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21–46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID:26683649

  1. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.

    PubMed

    Günthard, Huldrych F; Aberg, Judith A; Eron, Joseph J; Hoy, Jennifer F; Telenti, Amalio; Benson, Constance A; Burger, David M; Cahn, Pedro; Gallant, Joel E; Glesby, Marshall J; Reiss, Peter; Saag, Michael S; Thomas, David L; Jacobsen, Donna M; Volberding, Paul A

    New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in

  2. Impact of antiretroviral therapy on renal function among HIV-infected Tanzanian adults: a retrospective cohort study.

    PubMed

    Mpondo, Bonaventura C T; Kalluvya, Samuel E; Peck, Robert N; Kabangila, Rodrick; Kidenya, Benson R; Ephraim, Lucheri; Fitzgerald, Daniel W; Downs, Jennifer A

    2014-01-01

    Data regarding the outcomes of HIV-infected adults with baseline renal dysfunction who start antiretroviral therapy are conflicting. We followed up a previously-published cohort of HIV-infected adult outpatients in northwest Tanzania who had high prevalence of renal dysfunction at the time of starting antiretroviral therapy (between November 2009 and February 2010). Patients had serum creatinine, proteinuria, microalbuminuria, and CD4(+) T-cell count measured at the time of antiretroviral therapy initiation and at follow-up. We used the adjusted Cockroft-Gault equation to calculate estimated glomerular filtration rates (eGFRs). In this cohort of 171 adults who had taken antiretroviral therapy for a median of two years, the prevalence of renal dysfunction (eGFR <90 mL/min/1.73 m(2)) decreased from 131/171 (76.6%) at the time of ART initiation to 50/171 (29.2%) at the time of follow-up (p<0.001). Moderate dysfunction (eGFR<60 mL/min/1.73 m(2)) decreased from 21.1% at antiretroviral therapy initiation to 1.1% at follow-up (p<0.001), as did the prevalence of microalbuminuria (72% to 44%, p<0.001). Use of tenofovir was not associated with renal dysfunction at follow-up. Mild and moderate renal dysfunction were common in this cohort of HIV-infected adults initiating antiretroviral therapy, and both significantly improved after a median follow-up time of 2 years. Our work supports the renal safety of antiretroviral therapy in African adults with mild-moderate renal dysfunction, suggesting that these regimens do not lead to renal damage in the majority of patients and that they may even improve renal function in patients with mild to moderate renal dysfunction.

  3. Acne vulgaris and acne rosacea as part of immune reconstitution disease in HIV-1 infected patients starting antiretroviral therapy.

    PubMed

    Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David

    2008-07-01

    Immune reconstitution disease (IRD) has been widely reported following the commencement of antiretrovirals. We report a case series from a cohort of HIV-1-infected patients of whom four developed acne vulgaris and one developed acne rosacea after the initiation of antiretroviral therapy. Acne vulgaris, as part of IRD, has been reported only once in the literature, whereas acne rosacea has not, to our knowledge, previously been described. This serves as a reminder not to overlook dermatological manifestations of disease in patients with HIV infection after starting antiretrovirals.

  4. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    PubMed Central

    May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413

  5. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia

    PubMed Central

    Abdissa, Alemseged; Kæstel, Pernille; Tesfaye, Markos; Yilma, Daniel; Girma, Tsinuel; Wells, Jonathan C K; Ritz, Christian; Mølgaard, Christian; Michaelsen, Kim F; Zerfu, Dilnesaw; Brage, Søren; Andersen, Åse B; Friis, Henrik

    2014-01-01

    Objectives To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. Design Randomised controlled trial. Setting Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. Outcome measures Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. Results Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (−0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (−2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not

  6. Appetite testing in HIV-infected African adults recovering from malnutrition and given antiretroviral therapy.

    PubMed

    Rehman, Andrea M; Woodd, Susannah; Chisenga, Molly; Siame, Joshua; Sampson, Gemma; PrayGod, George; Koethe, John R; Kelly, Paul; Filteau, Suzanne

    2015-03-01

    The Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial was designed to determine whether nutritional support for malnourished HIV-infected adults starting antiretroviral therapy (ART) can improve early survival. Appetite is related to health outcomes in this population, but the optimal appetite metric for field use is uncertain. We evaluated two measures of appetite with the goal of improving understanding and treatment of malnutrition in HIV-infected adults. Longitudinal cohort study embedded in a clinical trial of vitamin and mineral-fortified, v. unfortified, lipid-based nutritional supplements. HIV clinics in Mwanza, Tanzania and Lusaka, Zambia. Malnourished (BMI<18.5 kg/m2) HIV-infected adults starting ART. Appetite measurements, by short questionnaire and by weight of maize porridge consumed in a standardized test, were compared across time and correlated with changes in weight. Appetite questionnaire scores, from polychoric correlation, and porridge test results were normally distributed for Tanzanians (n 187) but clustered and unreliable for Zambians (n 297). Among Tanzanian patients, the appetite score increased rapidly from referral for ART, plateaued at the start of ART and then increased slowly during the 12-week follow-up. Change in appetite questionnaire score, but not porridge test, correlated with weight change in the corresponding two-week intervals (P=0.002) or over the whole study (P=0.05) but a point estimate of hunger did not predict weight change (P=0.4). In Tanzania change in appetite score correlated with weight change, but single point measurements did not. Appetite increases several weeks after the start of ART, which may be an appropriate time for nutritional interventions for malnourished HIV-infected adults.

  7. Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study

    PubMed Central

    Hasse, Barbara; Iff, Martin; Ledergerber, Bruno; Calmy, Alexandra; Schmid, Patrick; Hauser, Christoph; Cavassini, Matthias; Bernasconi, Enos; Marzolini, Catia; Tarr, Philip E.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kouyos, R.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schöni-Affolter, F.; Schmid, P.; Schultze, D.; Schüpbach, J.; Speck, R.; Staehelin, C.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

    2014-01-01

    Background  The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. Methods  We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. Results  In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m2 per year (95% confidence interval, .83–1.0) during year 0–1 and 0.31 kg/m2 per year (0.29–0.34) during years 1–4. In multivariable analyses, annualized BMI change during year 0–1 was associated with older age (0.15 [0.06–0.24] kg/m2) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1–4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16–0.37] kg/m2). Individual ART combinations differed little in their contribution to BMI change. Conclusions  Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0–1 being as large as the increase in years 1–4 combined. The effect of ART regimen on BMI change was limited. PMID:25734114

  8. Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study.

    PubMed

    Hasse, Barbara; Iff, Martin; Ledergerber, Bruno; Calmy, Alexandra; Schmid, Patrick; Hauser, Christoph; Cavassini, Matthias; Bernasconi, Enos; Marzolini, Catia; Tarr, Philip E; Aubert, V; Barth, J; Battegay, M; Bernasconi, E; Böni, J; Bucher, H C; Burton-Jeangros, C; Calmy, A; Cavassini, M; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, C A; Gorgievski, M; Günthard, H; Haerry, D; Hasse, B; Hirsch, H H; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kouyos, R; Kovari, H; Ledergerber, B; Martinetti, G; Martinez de Tejada, B; Metzner, K; Müller, N; Nadal, D; Pantaleo, G; Rauch, A; Regenass, S; Rickenbach, M; Rudin, C; Schöni-Affolter, F; Schmid, P; Schultze, D; Schüpbach, J; Speck, R; Staehelin, C; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S

    2014-09-01

    The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1-4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited.

  9. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

    PubMed Central

    Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

    2016-01-01

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  10. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries

    PubMed Central

    2013-01-01

    Objectives To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and high-income (HIC) countries. Methods Patients aged ≥16 years starting cART in a clinic participating in a multi-cohort collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted for age, gender and calendar year; missing CD4 counts were imputed. Findings 379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included. In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μl between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155 cells/μl (76% increase), 88 to 135 cells/μl (53%) and 209 to 274 cells/μl (31%). In 2009, compared to LIC, median counts were 13 cells/μl (95% CI -56 to +30) lower in LMIC, 22 cells/μl (-62 to +18) lower in UMIC and 112 /μl (+75 to +149) higher in HIC. They were 23 cells/μl (95% CI +18 to +28) higher in women than men. Median counts were 88 cells/μl (95% CI +35 to +141) higher in countries with an estimated national cART coverage >80%, compared to countries with <40% coverage. Conclusions Median CD4 cell counts at start of cART increased 2000-2009 but remained below 200 cells/μl in LIC and MIC and below 300 cells/μl in HIC. Earlier start of cART will require substantial efforts and resources globally. PMID:24419071

  11. Rash and hepatitis within days of starting a new antiretroviral regimen: nevirapine hypersensitivity, secondary syphilis or both?

    PubMed

    Saxon, Cara J; Helbert, Matthew R; Komolafe, Adeniyi J; Higgins, Stephen P

    2014-03-01

    We report a case in which an HIV-positive man developed general malaise, skin rash and biochemical hepatitis within days of starting a nevirapine-based antiretroviral treatment regimen. At the same time, his syphilis serology proved positive. We discuss the diagnostic dilemma: was this a nevirapine hypersensitivity reaction, secondary syphilis or both?

  12. Outcomes of infants starting antiretroviral therapy in Southern Africa, 2004-2012

    PubMed Central

    Porter, Mireille; Davies, Mary-Ann; Mapani, Muntanga K.; Rabie, Helena; Phiri, Sam; Nuttall, James; Fairlie, Lee; Technau, Karl-Günter; Stinson, Kathryn; Wood, Robin; Wellington, Maureen; Haas, Andreas D.; Giddy, Janet; Tanser, Frank; Eley, Brian

    2015-01-01

    Background There is limited published data on the outcomes of infants starting antiretroviral therapy (ART) in routine care in Southern Africa. This study aimed to examine the baseline characteristics and outcomes of infants initiating ART. Methods We analysed prospectively collected cohort data from routine ART initiation in infants from 11 cohorts contributing to the International Epidemiologic Database to Evaluate AIDS in Southern Africa. We included ART naïve HIV-infected infants <12 months of age initiating ≥ three antiretroviral drugs between 2004 and 2012. Kaplan-Meier estimates were calculated for mortality, loss to follow-up (LTFU), transfer out and virological suppression. We used Cox Proportional Hazards models stratified by cohort to determine baseline characteristics associated with outcomes mortality and virological suppression. Results The median (interquartile range) age at ART initiation of 4945 infants was 5.9 months (3.7-8.7) with follow-up of 11.2 months (2.8-20.0). At ART initiation 77% had WHO clinical stage 3 or 4 disease and 87% were severely immunosuppressed. Three-year mortality probability was 16% and LTFU 29%. Severe immunosuppression, WHO stage 3 or 4, anaemia, being severely underweight and initiation of treatment before 2010 were associated with higher mortality. At 12 months after ART initiation 17% of infants were severely immunosuppressed and the probability of attaining virological suppression was 56%. Conclusion Most infants initiating ART in Southern Africa had severe disease with high probability of LTFU and mortality on ART. Although the majority of infants remaining in care showed immune recovery and virological suppression, these responses were suboptimal. PMID:26167620

  13. No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception.

    PubMed

    Mandelbrot, Laurent; Tubiana, Roland; Le Chenadec, Jerome; Dollfus, Catherine; Faye, Albert; Pannier, Emmanuelle; Matheron, Sophie; Khuong, Marie-Aude; Garrait, Valerie; Reliquet, Veronique; Devidas, Alain; Berrebi, Alain; Allisy, Christine; Elleau, Christophe; Arvieux, Cedric; Rouzioux, Christine; Warszawski, Josiane; Blanche, Stéphane

    2015-12-01

    The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2). Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Treatment modification in HIV-Infected individuals starting antiretroviral therapy between 2011 and 2014.

    PubMed

    Rappold, Michaela; Rieger, Armin; Steuer, Andrea; Geit, Maria; Sarcletti, Mario; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Leierer, Gisela; Ledergerber, Bruno; Zangerle, Robert

    2014-01-01

    While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug was considered as stopped when the regimen was interrupted for more than eight days. Drugs of particular interest were Darunavir (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other drugs were summarized as "other." Proportional hazards regression methods were used to identify predictors of discontinuation and Kaplan-Meier estimates were used to calculate probabilities of discontinuation. Patients who died were censored at the date of death. 965 patients started ART, 282 with DRV, 161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The overall probability of modification at one year was 28.7%, at two years 40.0% and at three years 49.8%. In a multivariable proportional hazards regression analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared with men who have sex with men (MSM) have a higher risk of switch/stop. Compared with DRV, RPV showed a much lower and ATV and particularly "other" a higher risk for discontinuation (Table 1). Rates of modification and interruption were still high in recent years, particularly in the first year of ART. The decreased rate of modification found in patients treated with Rilpivirine may be attributed to selection of patients according to guidelines.

  15. Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa.

    PubMed

    Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine

    2017-01-01

    In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6-9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8-2.6), ≥6-12 months (aHR = 2.1; 95% CI: 1.6-2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2-2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1-1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0-1.4). The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation.

  16. Reasons for not starting antiretroviral therapy in HIV-1-infected individuals: a changing landscape.

    PubMed

    Fehr, Jan; Nicca, Dunja; Goffard, Jean-Christophe; Haerry, David; Schlag, Michael; Papastamopoulos, Vasileios; Hoepelman, Andy; Skoutelis, Athanasius; Diazaraque, Ruth; Ledergerber, Bruno

    2016-08-01

    A cross-sectional survey was conducted to better understand why chronically HIV-1-infected individuals stratified by CD4 count (≤349; 350-499; ≥500 cells/μL) were not on antiretroviral therapy (ART). Before the consultation, treatment-naive patients and their physicians independently completed a 90-item-questionnaire about barriers and their readiness to start/defer ART. The study was carried out at 34 sites in nine countries in Europe and Australia. Between December 2011 and October 2012, 508 pairs of patient- and physician-questionnaires were completed. 426 (84 %) patients were male and 39 (8 %), 138 (27 %), and 330 (65 %) were in the three stratified groups based on CD4 count, respectively. In the category 'Body and symptoms' the most commonly identified reason for patients not to start was: "As long as I feel good I don't have to take medication" (44 %). Less than 20 % of respondents indicated fears of side effects and toxicity or problems to manage pills. Most patients were in the lowest stage of treatment-readiness (N = 323, 68 %), especially patients with CD4 cells ≥500 cells/μL (N = 240, 79 %). Physicians answered in 92 (18 %) cases that ART was not indicated for CD4 cells <500 cells/μL. Main reasons for physicians not starting treatment for these patients were their perception that patients were 'too depressed' (13 %) or that they had not known them long enough (13 %). Nowadays patient-barriers to ART are commonly related to health-and treatment-beliefs compared to fear of toxicity or ART manageability in the past. This new barrier pattern seems to reflect the era of well tolerated, easier ART regimens and has to be considered in light of the new recommendations to treat all HIV-infected individuals regardless of the CD4 cell count.

  17. National review of first treatment change after starting highly active antiretroviral therapy in antiretroviral-naïve patients.

    PubMed

    Hart, E; Curtis, H; Wilkins, E; Johnson, M

    2007-04-01

    The aim of the study was to explore the factors surrounding modification of the first antiretroviral (ARV) regimen where drug switch occurred 3 months or more after initiation. Reference was made to the British HIV Association (BHIVA) guidelines on HIV management. A case note and questionnaire-based audit was carried out. Toxicity was the single most important reason for ARV change and was the only, or a contributory, cause in over half the patients. Virological failure, adherence issues, requirement for treatment simplification, and patient request were other significant reasons cited. In one-third of those with virological failure, six or more months had elapsed between first detection and the time of switching to a new ARV regimen. This audit demonstrated broad adherence to the BHIVA guidelines, although the long time before switching ARVs in the setting of virological failure was of some concern, particularly given the continuing and significant occurrence of primary ARV resistance in the UK.

  18. Immunologic Risk Factors for Early Mortality After Starting Antiretroviral Therapy in HIV-Infected Zambian Children

    PubMed Central

    Rainwater-Lovett, Kaitlin; Nkamba, Hope C.; Mubiana-Mbewe, Mwangelwa; Moore, Carolyn Bolton

    2013-01-01

    Abstract To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4+ and CD8+ T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4+ T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8+ effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4+ central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ≥85% for early and overall mortality, with bootstrapped sensitivities of 82–85% upon validation, supporting the predictive accuracy of the models. CD4+ and CD8+ T cell subsets may be more accurate predictors of early mortality than CD4+ T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART. PMID:23025633

  19. Variability of Growth in Children Starting Antiretroviral Treatment in Southern Africa

    PubMed Central

    Gsponer, Thomas; Weigel, Ralf; Davies, Mary-Ann; Bolton, Carolyn; Moultrie, Harry; Vaz, Paula; Rabie, Helena; Technau, Karl; Ndirangu, James; Eley, Brian; Garone, Daniela; Wellington, Maureen; Giddy, Janet; Ehmer, Jochen; Egger, Matthias

    2012-01-01

    BACKGROUND: Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa. METHODS: Treatment naïve children aged <10 years were included. We calculated weight for age z scores (WAZs), height for age z scores (HAZs), and weight for height z scores (WHZs) up to 3 years after starting ART, by using the World Health Organization standards. Multilevel regression models were used. RESULTS: A total of 17 990 children (range, 238–8975) were followed for 36 181 person-years. At ART initiation, most children were underweight (50%) and stunted (66%). Lower baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch-up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated or reversed thereafter, whereas HAZ increased continuously over time. Three years after starting ART, WAZ ranged from −2.80 (95% confidence interval [CI]: −3.66 to −2.02) to −1.98 (95% CI: −2.41 to −1.48) in children with a baseline z score < −3 and from −0.79 (95% CI: −1.62 to 0.02) to 0.05 (95% CI: −0.42 to 0.51) in children with a baseline WAZ ≥ −1. For HAZ, the corresponding range was −2.33 (95% CI: −2.62 to −2.02) to −1.27 (95% CI: −1.58 to −1.00) for baseline HAZ < −3 and −0.24 (95% CI: −0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ ≥ −1. CONCLUSIONS: Despite a sustained growth response and catch-up growth in children with advanced HIV disease treated with ART, normal weights and heights are not achieved over 3 years of ART. PMID:22987878

  20. Treatment modification in HIV-Infected individuals starting antiretroviral therapy between 2011 and 2014

    PubMed Central

    Rappold, Michaela; Rieger, Armin; Steuer, Andrea; Geit, Maria; Sarcletti, Mario; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Leierer, Gisela; Ledergerber, Bruno; Zangerle, Robert

    2014-01-01

    Introduction While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. Methods Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug was considered as stopped when the regimen was interrupted for more than eight days. Drugs of particular interest were Darunavir (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other drugs were summarized as “other.” Proportional hazards regression methods were used to identify predictors of discontinuation and Kaplan–Meier estimates were used to calculate probabilities of discontinuation. Patients who died were censored at the date of death. Results 965 patients started ART, 282 with DRV, 161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The overall probability of modification at one year was 28.7%, at two years 40.0% and at three years 49.8%. In a multivariable proportional hazards regression analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared with men who have sex with men (MSM) have a higher risk of switch/stop. Compared with DRV, RPV showed a much lower and ATV and particularly “other” a higher risk for discontinuation (Table 1). Availability of more effective/convenient treatment (28.9%) was the main reason for discontinuation, especially in the group “other” (43.5%), RAL (34.6%) and DRV (31.6%). Non-specified patient or physician wish to modify therapy was revealed in 17.4% and 9.3% respectively. EFV was modified in 52

  1. Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa

    PubMed Central

    Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine

    2017-01-01

    Background In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Results Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6–9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8–2.6), ≥6–12 months (aHR = 2.1; 95% CI: 1.6–2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2–2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1–1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0–1.4). Conclusion The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation. PMID:28122041

  2. HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen.

    PubMed

    Imaz, Arkaitz; Martinez-Picado, Javier; Niubó, Jordi; Kashuba, Angela D M; Ferrer, Elena; Ouchi, Dan; Sykes, Craig; Rozas, Nerea; Acerete, Laura; Curto, Jordi; Vila, Antonia; Podzamczer, Daniel

    2016-11-15

     The objective of this study was to quantify human immunodeficiency virus (HIV) type 1 RNA decay and dolutegravir (DTG) concentrations in the semen of HIV-infected patients receiving DTG-based first-line therapy.  This was a prospective, single-arm, open-label study including 15 HIV-1-infected, antiretroviral therapy-naive men starting once-daily treatment with DTG (50 mg) plus abacavir-lamivudine (600/300 mg). HIV-1 RNA was measured in seminal plasma (SP) and blood plasma (BP) at baseline, on days 3, 7, and 14, and at weeks 4, 12, and 24. The HIV-1 RNA decay rate was assessed using nonlinear mixed-effects models. Total and free DTG concentrations were quantified 24 hours after the dose at weeks 4 and 24 by means of a validated liquid chromatography-tandem mass spectrometry method.  Viral decay was faster in BP than in SP in the first decay phase (half-life, 4.5 vs 8.6 days; P = .001) with no statistically significant differences in the second phase. HIV-1 RNA suppression (<40 copies/mL) was reached earlier in SP (4 vs 12 weeks; P = .008) due to lower baseline HIV-1 RNA levels. The median total DTG 24 hours after the dose in SP was 119.1 ng/mL (range, 27.2-377 ng/mL), which represents 7.8% of BP exposure. The median DTG free-fraction in SP was 48% of the total drug. Seminal protein-unbound DTG concentrations exceeded the in vitro 50% inhibitory concentration (0.21 ng/mL) by a median of 214-fold.  DTG concentrations in SP are sufficient to contribute to rapid seminal HIV-1 RNA suppression. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

    PubMed Central

    Siedner, Mark J.

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  4. Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy.

    PubMed

    Stein, James H; Komarow, Lauren; Cotter, Bruno R; Currier, Judith S; Dubé, Michael P; Fichtenbaum, Carl J; Gerschenson, Mariana; Mitchell, Carol K C; Murphy, Robert L; Squires, Kathleen; Parker, Robert A; Torriani, Francesca J

    2008-12-01

    BACKGROUND: Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. OBJECTIVE: To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. METHODS: This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. RESULTS: Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (p(KW)<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (p(KW)=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. CONCLUSIONS: Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir.

  5. Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

    PubMed

    Baker, Jason V; Sharma, Shweta; Achhra, Amit C; Bernardino, Jose Ignacio; Bogner, Johannes R; Duprez, Daniel; Emery, Sean; Gazzard, Brian; Gordin, Jonathan; Grandits, Greg; Phillips, Andrew N; Schwarze, Siegfried; Soliman, Elsayed Z; Spector, Stephen A; Tambussi, Giuseppe; Lundgren, Jens

    2017-05-22

    HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4(+) cell counts >500 cells/mm(3). Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm(3), an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in

  6. Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy

    PubMed Central

    Nabeta, Henry W; Okia, Richard; Rhein, Joshua; Lukande, Robert

    2016-01-01

    Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesions. PMID:28210571

  7. Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study

    PubMed Central

    Musiime, Victor; Prendergast, Andrew; Nathoo, Kusum; Kekitiinwa, Addy; Nahirya Ntege, Patricia; Gibb, Diana M.; Thiebaut, Rodolphe; Walker, A. Sarah; Klein, Nigel; Callard, Robin

    2013-01-01

    Background Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery. Methods and Findings CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4–17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization–recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled. Conclusions Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and

  8. Site-nurse initiated Adherence and Symptom Support Telephone Calls for HIV-positive individuals starting antiretroviral therapy, ACTG 5031, a substudy of ACTG 384.

    PubMed Central

    Robbins, Gregory K.; Testa, Marcia A.; Su, Max; Safren, Steven A.; Morse, Gene; Lammert, Sara; Shafer, Robert W.; Reynolds, Nancy R.; Chesney, Margaret A.

    2013-01-01

    Background: Effective and easy to implement interventions to improve adherence to antiretroviral therapy are needed. Objective: To compare a site-nurse initiated adherence and symptom support telephone calls for HIV-positive individuals starting antiretroviral therapy compare to the study site’s standard of care. Methods: A randomized controlled trial of site-nurse initiated adherence and symptom support telephone calls for HIV-positive individuals starting antiretrovirals. Subjects were randomized to receive site-nurse initiated telephone calls (intervention) or no additional calls above the site’s standard of care (control). Subjects received calls 1-3 days after initiating antiretrovirals, weeks 1, 2, 3, 6, 10, 14, 18, 22, 26, and every 8 weeks thereafter. Self-reported adherence was captured during study visits. Results: A total of 333 subjects starting antiretrovirals as part of ACTG 384 were co-enrolled into ACTG 5031. Subjects were followed for up to 160 weeks and were contacted for 74% of scheduled calls. There was no significant difference in proportion of patients with >95% mean Total Adherence, 87.9% and 91.2% (p=0.34) and mean self-reported Total Adherence, 97.9% and 98.4% in the intervention and control, respectively, or in symptom distress and clinical endpoints. Conclusions: In the context of a clinical trial, where self-reported adherence was exceptionally high, the site-nurse initiated telephone calls did not further improve self-reported adherence, symptom distress or clinical outcomes. PMID:24144900

  9. National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines?

    PubMed

    Beck, Eduard J; Vitoria, Marco; Mandalia, Sundhiya; Crowley, Siobhan; Gilks, Charles F; Souteyrand, Yves

    2006-07-13

    To investigate the existence of national adult antiretroviral therapy (ART) guidelines in 43 World Health Organization (WHO) '3 by 5' focus countries and compare their content with the 2003 WHO ART guidelines. Questionnaires covered initiation of ART, selection of first or second-line ART, monitoring treatment response and toxicity and dissemination of national guidelines. Weighted concordance scores were created and country scores correlated with national indicators and WHO recommendations. Thirty-nine (91%) countries returned questionnaires, three of which had no national ART guidelines. Of the 36, 16 (44%) recommended to start ART based on WHO clinical staging criteria and CD4 cell count or T-lymphocyte count, 12 (33%) WHO clinical staging criteria and CD4 cell count, four (11%) only CD4 cell counts. 35 (97%) recommended a standard first-line regimen and 24 (67%) preferred stavudine + lamivudine + nevirapine; 33 (92%) recommended second-line regimens, and 24 (60%) preferred abacavir + didanosine + lopinavir/ritonavir. Thirty-one (94%) recommended CD4 cell count, possibly combined with other indicators, to monitor ART. Concordance scores were higher in countries with lower health expenditure per capita (P = 0.009) and lower GDP per capita (P < 0.03). Median concordance scores for starting ART was 100 [interquartile range (IQR), 67 to 100]; first line therapy, 70 (IQR, 60 to 80); second-line regimens, 45 (IQR, 27 to 55) and for laboratory investigations, 80 (IQR, 80 to 100). Most countries had developed national ART guidelines as part of a comprehensive national HIV program. Concordance with WHO recommendations was strong on starting first-line ART regimens and routine monitoring but lower for second-line recommendations.

  10. Project Re-Start. A Program for Homeless Adults.

    ERIC Educational Resources Information Center

    Pelzer, Dagmar F.; And Others

    Project Re-Start, of the Dade County Public Schools in Florida, was funded under the Adult Education Act and the Stewart B. McKinney Homeless Assistance Act. Classes in literacy skills, General Educational Development (GED) preparation, English for speakers of other languages, employability skills, and life coping skills were conducted at most of…

  11. Unhealthy Alcohol Use is Associated with Monocyte Activation Prior to Starting Anti-Retroviral Therapy

    PubMed Central

    Carrico, Adam W.; Hunt, Peter W.; Emenyonu, Nneka I.; Muyindike, Winnie; Ngabirano, Christine; Cheng, Debbie M.; Winter, Michael R.; Samet, Jeffrey H.; Hahn, Judith A.

    2015-01-01

    Background Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. Methods HIV-positive persons who were not on anti-retroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (sCD14), inflammation (IL-6), and coagulation (D-dimer). We defined “unhealthy alcohol use” as testing positive using the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C; ≥ 3 for women and ≥ 4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phophatidylethanol (PEth; ≥ 50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, Log10 IL-6, and D-dimer. Results Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference (95% CI) = 289 (83, 495), p < 0.01). In analyses adjusted for demographic factors, current cigarette smoking, and HIV disease markers, unhealthy drinkers continued to display significantly higher sCD14 levels compared to those who were abstinent from alcohol (adjusted mean = 1,670 vs. 1,406 ng/ml; adjusted mean difference (95% CI) = 264 (47, 480), p = 0.02). Unhealthy alcohol use was not significantly associated with IL-6 or D-dimer levels. Conclusions unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV infection. Longitudinal research should examine if unhealthy alcohol use predicts changes in sCD14 prior to and following ART initiation. PMID:26509359

  12. Hospitalization for severe malnutrition among HIV-infected children starting antiretroviral therapy.

    PubMed

    Prendergast, Andrew; Bwakura-Dangarembizi, Mutsa F; Cook, Adrian D; Bakeera-Kitaka, Sabrina; Natukunda, Eva; Nahirya Ntege, Patricia; Nathoo, Kusum J; Karungi, Christine; Lutaakome, Joseph; Kekitiinwa, Adeodata; Gibb, Diana M

    2011-04-24

    To describe early hospitalization for severe malnutrition in HIV-infected children initiating antiretroviral therapy (ART). Randomized trial of induction-maintenance and monitoring strategies in HIV-infected children. Three tertiary hospitals in Uganda and one in Zimbabwe. 1207 HIV-infected children, median age 6 years (range, 3 months to 17 years). Abacavir, lamivudine and nevirapine or efavirenz were given; children in induction-maintenance arms also received zidovudine to week 36. Pre-ART inpatient/outpatient nutritional rehabilitation for children with baseline severe malnutrition. : Hospitalization for severe malnutrition and change in CD4 cell percentage by week 12 after ART. Mortality and change in weight-for-age Z-score (WAZ) by week 24 after ART. Thirty-nine of 1207 (3.2%) children were hospitalized for severe malnutrition (20 with oedema), median 28 days [interquartile range (IQR) 14, 36] after ART for marasmus and 26 days (IQR 14, 56) after ART for kwashiorkor. Hospitalized children had lower baseline and greater 24-week rise in WAZ than nonhospitalized children (P < 0.001). Twenty-nine of 39 (74%) children admitted for severe malnutrition had underlying infections. Of 220 children with advanced disease (baseline WAZ and CD4 cell Z-scores both <-3), 7.3% [95% confidence interval (CI) 3.8, 10.7] developed kwashiorkor and 3.6% (95% CI 1.2, 6.1) developed marasmus by week 12. CD4 cell percentage rise was similar among groups (P = 0.37). Twenty-four-week mortality was 32, 20 and 1.7% among children hospitalized with marasmus, kwashiorkor and not hospitalized, respectively, (P < 0.001). One in nine children with advanced HIV required early hospitalization for severe malnutrition after ART, with a 15-fold increase in 6-month mortality compared with nonhospitalized children. Integration of HIV/malnutrition services and further research to determine optimal ART timing, role of supplementary feeding and antimicrobial prophylaxis are urgently required.

  13. Antiretroviral treatment-associated tuberculosis in a prospective cohort of HIV-infected patients starting ART.

    PubMed

    Worodria, William; Massinga-Loembe, Marguerite; Mayanja-Kizza, Harriet; Namaganda, Jane; Kambugu, Andrew; Manabe, Yukari C; Kestens, Luc; Colebunders, Robert

    2011-01-01

    Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m(2) BMI (HR 5.85 95% CI 1.24-27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36-38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.

  14. Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial.

    PubMed

    Baker, Jason V; Hullsiek, Katherine Huppler; Engen, Nicole Wyman; Nelson, Ray; Chetchotisakd, Ploenchan; Gerstoft, Jan; Jessen, Heiko; Losso, Marcelo; Markowitz, Norman; Munderi, Paula; Papadopoulos, Antonios; Shuter, Jonathan; Rappoport, Claire; Pearson, Mary T; Finley, Elizabeth; Babiker, Abdel; Emery, Sean; Duprez, Daniel

    2016-10-01

    Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm(3) on small arterial elasticity (SAE) and large artery elasticity (LAE). Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm(3) and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity.

  15. Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial

    PubMed Central

    Hullsiek, Katherine Huppler; Engen, Nicole Wyman; Nelson, Ray; Chetchotisakd, Ploenchan; Gerstoft, Jan; Jessen, Heiko; Losso, Marcelo; Markowitz, Norman; Munderi, Paula; Papadopoulos, Antonios; Shuter, Jonathan; Rappoport, Claire; Pearson, Mary T.; Finley, Elizabeth; Babiker, Abdel; Emery, Sean; Duprez, Daniel

    2016-01-01

    Background. Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm3 on small arterial elasticity (SAE) and large artery elasticity (LAE). Methods. Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. Results. Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm3 and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. Conclusions. Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity. PMID:27942541

  16. When to start antiretroviral therapy: the need for an evidence base during early HIV infection

    PubMed Central

    2013-01-01

    Background Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has always been vigorously debated. The lack of an evidence base from randomized trials, in conjunction with varying degrees of therapeutic aggressiveness and optimism tempered by the risks of drug resistance and side effects, has resulted in divided expert opinion and inconsistencies among treatment guidelines. Discussion On the basis of recent data showing that early ART initiation reduces heterosexual HIV transmission, some countries are considering adopting a strategy of universal treatment of all HIV+ persons irrespective of their CD4 count and whether ART is of benefit to the individual or not, in order to reduce onward HIV transmission. Since ART has been found to be associated with both short-term and long-term toxicity, defining the benefit:risk ratio is the critical missing link in the discussion on earlier use of ART. For early ART initiation to be justified, this ratio must favor benefit over risk. An unfavorable ratio would argue against using early ART. Summary There is currently no evidence from randomized controlled trials to suggest that a strategy of initiating ART when the CD4 count is above 350 cells/μl (versus deferring initiation to around 350 cells/μl) results in benefit to the HIV+ person and data from observational studies are inconsistent. Large, clinical endpoint-driven randomized studies to determine the individual health benefits versus

  17. Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations.

    PubMed

    von Wyl, Viktor; Yerly, Sabine; Böni, Jürg; Shah, Cyril; Cellerai, Cristina; Klimkait, Thomas; Battegay, Manuel; Bernasconi, Enos; Cavassini, Matthias; Furrer, Hansjakob; Hirschel, Bernard; Vernazza, Pietro L; Ledergerber, Bruno; Günthard, Huldrych F

    2012-01-01

    Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL). The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of

  18. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

    PubMed Central

    Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

    2012-01-01

    Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/μL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ μL (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot

  19. Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy

    PubMed Central

    Freedberg, Kenneth A.; Kumarasamy, Nagalingeswaran; Losina, Elena; Cecelia, Anitha J.; Scott, Callie A.; Divi, Nomita; Flanigan, Timothy P.; Lu, Zhigang; Weinstein, Milton C.; Wang, Bingxia; Ganesh, Aylur K.; Bender, Melissa A.; Mayer, Kenneth H.; Walensky, Rochelle P.

    2008-01-01

    Background India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. Objective To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. Methods We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/μl (SD 291 cells/μl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. Results Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 < 350 cells/μl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 < 350 cells/μl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 < 250 cells/μl to < 350 cells/μl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. Conclusions In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival

  20. Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy.

    PubMed

    Shepherd, Bryan E; Liu, Qi; Mercaldo, Nathaniel; Jenkins, Cathy A; Lau, Bryan; Cole, Stephen R; Saag, Michael S; Sterling, Timothy R

    2016-10-30

    Optimal timing of initiating antiretroviral therapy has been a controversial topic in HIV research. Two highly publicized studies applied different analytical approaches, a dynamic marginal structural model and a multiple imputation method, to different observational databases and came up with different conclusions. Discrepancies between the two studies' results could be due to differences between patient populations, fundamental differences between statistical methods, or differences between implementation details. For example, the two studies adjusted for different covariates, compared different thresholds, and had different criteria for qualifying measurements. If both analytical approaches were applied to the same cohort holding technical details constant, would their results be similar? In this study, we applied both statistical approaches using observational data from 12,708 HIV-infected persons throughout the USA. We held technical details constant between the two methods and then repeated analyses varying technical details to understand what impact they had on findings. We also present results applying both approaches to simulated data. Results were similar, although not identical, when technical details were held constant between the two statistical methods. Confidence intervals for the dynamic marginal structural model tended to be wider than those from the imputation approach, although this may have been due in part to additional external data used in the imputation analysis. We also consider differences in the estimands, required data, and assumptions of the two statistical methods. Our study provides insights into assessing optimal dynamic treatment regimes in the context of starting antiretroviral therapy and in more general settings. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

    PubMed Central

    Rappoport, C; Engen, NW; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, MJ

    2015-01-01

    Objectives The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. Methods START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. Results An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Conclusions Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem‐solving. PMID:25711319

  2. Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

    PubMed

    Grarup, J; Rappoport, C; Engen, N W; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, M J

    2015-04-01

    The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem-solving. © 2015 British HIV Association.

  3. Twelve-year mortality in adults initiating antiretroviral therapy in South Africa.

    PubMed

    Cornell, Morna; Johnson, Leigh F; Wood, Robin; Tanser, Frank; Fox, Matthew P; Prozesky, Hans; Schomaker, Michael; Egger, Matthias; Davies, Mary-Ann; Boulle, Andrew

    2017-09-25

    South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa. The study was a cohort analysis of routine data on adults with IDs starting ART 2004-2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan-Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV-negative. Viral suppression in patients with viral loads (VLs) in their last year of follow-up was the secondary outcome. Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02-3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007-2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIV-negative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV-negative population, and SMRs were similar for all baseline CD4

  4. Evaluation of adherence to highly active antiretroviral therapy in adults in Jamaica.

    PubMed

    Harvey, K M; Carrington, D; Duncan, J; Figueroa, J P; Hirschorn, L; Manning, D; Jackson, S

    2008-06-01

    Highly active antiretroviral therapy (HAART) has improved morbidity and mortality and quality of life, revitalized communities and transformed the perception of HIV/AIDS from being a "death sentence" to a chronic illness. Strict and sustained adherence to medication is essential long-term viral suppression. In April 2005, an Adherence Support Programme was introduced to Jamaica's HIV Programme, whereby Persons Living with HIV/AIDS (PLWHA) who had achieved high levels of adherence were trained to provide support to other PLWHA in order to increase their adherence to HAART regimens. A cross-sectional survey of 116 individuals with advanced HIV and on HAART was performed in June and July 2006. Many participants were unemployed, poor persons with limited education. Based on self-report of seven-day adherence, 54.8% of persons were 95-100% adherent, 37.5% were 80-94% adherent and 7.7% were < 80% adherent. Having interacted with an adherence counsellor was not associated with adherence levels. Factors associated with nonadherence were: being away from home (38%), sleeping through dose-time (37%), forgetfulness (37%) and running out of pills (31%). Having no food (26.9%), not wanting to be seen taking medication (200%) and intolerable side effects (18.8%) were also reasons given. Only 44% of persons used aids to remind them of dose times. Adherence in this study group is low and may have worsened since 2005. More emphasis must be placed on preparing adults to start HAART The use of pillboxes and other reminders such as alarm clocks and cell phones must be reinforced.

  5. Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

    PubMed Central

    Maskew, Mhairi; Fox, Matthew P.; van Cutsem, Gilles; Chu, Kathryn; MacPhail, Patrick; Boulle, Andrew; Egger, Matthias; Africa, for IeDEA Southern

    2013-01-01

    Background Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. Methods We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. Results Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm3) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm3) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment. Conclusions HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS

  6. Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

    PubMed Central

    Boulle, Andrew; Schomaker, Michael; May, Margaret T.; Hogg, Robert S.; Shepherd, Bryan E.; Monge, Susana; Keiser, Olivia; Lampe, Fiona C.; Giddy, Janet; Ndirangu, James; Garone, Daniela; Fox, Matthew; Ingle, Suzanne M.; Reiss, Peter; Dabis, Francois; Costagliola, Dominique; Castagna, Antonella; Ehren, Kathrin; Campbell, Colin; Gill, M. John; Saag, Michael; Justice, Amy C.; Guest, Jodie; Crane, Heidi M.; Egger, Matthias; Sterne, Jonathan A. C.

    2014-01-01

    Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and

  7. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012.

    PubMed

    Williams, Ian; Churchill, Duncan; Anderson, Jane; Boffito, Marta; Bower, Mark; Cairns, Gus; Cwynarski, Kate; Edwards, Simon; Fidler, Sarah; Fisher, Martin; Freedman, Andrew; Geretti, Anna Maria; Gilleece, Yvonne; Horne, Rob; Johnson, Margaret; Khoo, Saye; Leen, Clifford; Marshall, Neal; Nelson, Mark; Orkin, Chloe; Paton, Nicholas; Phillips, Andrew; Post, Frank; Pozniak, Anton; Sabin, Caroline; Trevelion, Roy; Ustianowski, Andrew; Walsh, John; Waters, Laura; Wilkins, Edmund; Winston, Alan; Youle, Mike

    2012-09-01

    The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

  8. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

    PubMed

    Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

    2016-07-12

    New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and

  9. Information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS.

    PubMed

    Lima, Ivana Cristina Vieira de; Galvão, Marli Teresinha Gimeniz; Alexandre, Herta de Oliveira; Lima, Francisca Elisângela Teixeira; Araújo, Thelma Leite de

    2016-08-01

    Information and communication technologies support interventions directed at the prevention of HIV transmission and patient monitoring by promoting improved accessibility and quality of care. To evaluate the efficacy of information and communication technologies in the adherence to antiretroviral treatment in adults with HIV/AIDS. Systematic review conducted from March to May of 2015 in three databases-the Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Latin-American and Caribbean Literature in Health Sciences (LILACS/BIREME) and SCOPUS; and the Cochrane library and the Medical Literature Analysis and Retrieval System Online portal (MEDLINE/PubMed). The sample consisted of nine randomized clinical trials based on the use of information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS. Three studies analysed the use of a short message service - SMS - two phone calls, two alarm devices, one web-enabled Hand-held device and one web electronic intervention. Improvements in the levels of adherence in the group subjected to the intervention were identified in seven studies. The phone was the type of information and communication technology with proven efficacy with respect to adherence. It was used to make calls, as well as to send alert messages and reminders about taking medications. Pagers were not considered to be effective regarding adherence to antiretroviral therapy. The integrated use of information and communication technologies with standard care promotes increased access to care, strengthening the relationship between patients and health services, with the possibility of mitigating the difficulties experienced by people with HIV in achieving optimal levels of adherence to drug therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel.

    PubMed

    Hammer, Scott M; Eron, Joseph J; Reiss, Peter; Schooley, Robert T; Thompson, Melanie A; Walmsley, Sharon; Cahn, Pedro; Fischl, Margaret A; Gatell, Jose M; Hirsch, Martin S; Jacobsen, Donna M; Montaner, Julio S G; Richman, Douglas D; Yeni, Patrick G; Volberding, Paul A

    2008-08-06

    The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial

  11. Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe

    PubMed Central

    Takarinda, K. C.; Owiti, P.; Mutasa-Apollo, T.; Mugurungi, O.; Buruwe, L.; Reid, A. J.

    2016-01-01

    Setting: A non-governmental organisation-supported clinic offering health services including antiretroviral therapy (ART). Objective: To compare ART retention between younger (age 10–14 years) vs. older (age 15–19 years) adolescents and younger (age 20–29 years) vs. older (age ⩾30 years) adults and determine adolescent- and adult-specific attrition-associated factors among those initiated on ART between 2010 and 2011. Design: Retrospective cohort study. Results: Of 110 (7%) adolescents and 1484 (93%) adults included in the study, no differences in retention were observed between younger vs. older adolescents at 6, 12 and 24 months. More younger adolescents were initiated with body mass index <16 kg/m2 compared with older adolescents (64% vs. 47%; P = 0.04). There were more females (74% vs. 52%, P < 0.001) and fewer patients initiating ART with CD4 count ⩽350 cells/mm3 (77% vs. 81%, P = 0.007) among younger vs. older adults. Younger adults demonstrated more attrition than older adults at all time-points. No attrition risk factors were observed among adolescents. Attrition-associated factors among adults included being younger, having a lower CD4 count and advanced human immunodeficiency virus disease at initiation, and initiation on a stavudine-based regimen. Conclusion: Younger adults demonstrated greater attrition and may require more attention. We were unable to demonstrate differences in attrition among younger vs. older adolescents. Loss to follow-up was the main reason for attrition across all age groups. Overall, earlier presentation for ART care appears important for improved ART retention among adults. PMID:27358802

  12. Psychosocial factors affecting medication adherence among HIV-1 infected adults receiving combination antiretroviral therapy (cART) in Botswana.

    PubMed

    Do, Natalie T; Phiri, Kelesitse; Bussmann, Hermann; Gaolathe, Tendani; Marlink, Richard G; Wester, C William

    2010-06-01

    As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1-6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value <0.02). A significant proportion (81.3%) of cART-treated adults were adherent to their prescribed treatment, with rates superior to those reported in resource-rich settings. Adherence rates were poorest among those just starting cART, most likely due to the presence of ARV-related toxicity. Adherence was lower among those who have been treated for longer periods of time (greater than 1 year), suggesting complacency, which may become a significant problem, especially among these long-term cART-treated patients who return to improved physical and mental functioning and may be less motivated to adhere to their ARV medications. Healthcare providers should encourage HIV disclosure to "at-risk" partners and provide ongoing counseling and education to help patients

  13. Cost-Effectiveness of Earlier Initiation of Antiretroviral Therapy for Uninsured HIV-Infected Adults

    PubMed Central

    Schackman, Bruce R.; Goldie, Sue J.; Weinstein, Milton C.; Losina, Elena; Zhang, Hong; Freedberg, Kenneth A.

    2001-01-01

    Objectives. This study was designed to examine the societal cost-effectiveness and the impact on government payers of earlier initiation of antiretroviral therapy for uninsured HIV-infected adults. Methods. A state-transition simulation model of HIV disease was used. Data were derived from the Multicenter AIDS Cohort Study, published randomized trials, and medical care cost estimates for all government payers and for Massachusetts, New York, and Florida. Results. Quality-adjusted life expectancy increased from 7.64 years with therapy initiated at 200 CD4 cells/μL to 8.21 years with therapy initiated at 500 CD4 cells/μL. Initiating therapy at 500 CD4/μL was a more efficient use of resources than initiating therapy at 200 CD4/μL and had an incremental cost-effectiveness ratio of $17 300 per quality-adjusted life-year gained, compared with no therapy. Costs to state payers in the first 5 years ranged from $5500 to $24 900 because of differences among the states in the availability of federal funds for AIDS drug assistance programs. Conclusions. Antiretroviral therapy initiated at 500 CD4 cells/μL is cost-effective from a societal perspective compared with therapy initiated later. States should consider Medicaid waivers to expand access to early therapy. PMID:11527782

  14. Longitudinal assessment of changes in HIV-specific effector activity in HIV-infected patients starting highly active antiretroviral therapy in primary infection.

    PubMed

    Alter, G; Hatzakis, G; Tsoukas, C M; Pelley, K; Rouleau, D; LeBlanc, R; Baril, J G; Dion, H; Lefebvre, E; Thomas, R; Côté, P; Lapointe, N; Routy, J P; Sékaly, R P; Conway, B; Bernard, N F

    2003-07-01

    Both the magnitude and breadth of HIV-specific immunity were evaluated longitudinally on samples collected from six subjects starting highly active antiretroviral therapy (HAART) preseroconversion (group 1), 11 recently infected subjects starting HAART postseroconversion (group 2), five subjects starting HAART in the second half of the first year of infection (group 3), and six persons starting treatment in the chronic phase of infection (group 4). HIV-specific immunity was measured by IFN-gamma ELISPOT, detecting the frequency of cells responding to a panel of HLA-restricted HIV-1 peptides. Intracellular cytokine staining was used to detect the frequency of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells in a subset of participants. The magnitude and breadth of HIV-specific responses persisted in all group 1 subjects and in 5 of 11 (45%) group 2 subjects. Both of these parameters declined in 6 of 11 (55%) group 2 and in all group 3 and 4 individuals. All persons who maintained detectable numbers of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells after starting HAART preserved the intensity and breadth of their HIV-specific effector response. Our results show that HIV-specific immunity can be preserved even if HAART is initiated beyond the acute phase of infection.

  15. Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia

    PubMed Central

    Mulenga, Lloyd B.; Kruse, Gina; Lakhi, Shabir; Cantrell, Ronald A.; Reid, Stewart E.; Zulu, Isaac; Stringer, Elizabeth M.; Krishnasami, Zipporah; Mwinga, Alwyn; Saag, Michael S.; Stringer, Jeffrey S. A.; Chi, Benjamin H.

    2009-01-01

    Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment. PMID:18753939

  16. Longitudinal lactate levels from routine point-of-care monitoring in adult Malawian antiretroviral therapy patients: associations with stavudine toxicities.

    PubMed

    Chagoma, Newton; Mallewa, Jane; Kaunda, Symon; Njalale, Yasin; Kampira, Elizabeth; Mukaka, Mavuto; Heyderman, Robert S; van Oosterhout, Joep J

    2013-10-01

    Stavudine is still widely used in under-resourced settings such as Malawi due to its low price. It frequently causes peripheral neuropathy and lipodystrophy and increases the risk of lactic acidosis and other high lactate syndromes. We studied the association of longitudinal lactate levels, obtained by routine, 3-monthly point-of-care monitoring, with peripheral neuropathy, lipodystrophy and high lactate syndromes in adult Malawians who were in the second year of stavudine containing antiretroviral therapy (ART). Point-of-care lactate measurements were feasible in a busy urban ART clinic. Of 1170 lactate levels collected from 253 patients over the course of one year, 487 (41.8%) were elevated (>2.2mg/dl), 58 (5.0%) were highly elevated (>3.5mg/dl). At least one elevated lactate level occurred in 210 (83.0%) of patients and sustained hyperlactatemia in 65 (26.4%). In random effects analyses lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Only five patients developed high lactate syndromes (one lactic acidosis) of whom no preceding lactate measurements were available because events had started before enrolment. Lactate levels significantly decreased over time and no high lactate syndromes were observed after the 15th month on ART. Lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Lactate levels decreased over time, coinciding with absence of new high lactate syndromes after the 15th month on ART.

  17. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  18. Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

    PubMed Central

    Laurichesse, Jean-Jacques; Taieb, Audrey; Capoulade-Metay, Corinne; Katlama, Christine; Villes, Virginie; Drobacheff-Thiebaud, Marie-Christine; Raffi, François; Chêne, Genevieve; Theodorou, Ioannis; Leport, Catherine

    2010-01-01

    Objective To examine whether CCR5 Δ32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1 infected patients. Methods The genetic sub-study of ANRS CO8 APROCO-COPILOTE cohort included 609 patients who started a protease inhibitor-containing cART in 1997–99. Patients were considered to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3–5 were <500 copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Δ32 (Δ32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV-RNA, CD4 cell counts, antiretroviral naive status, time spent on antiretroviral therapy at year 3 and 5 and adherence to treatment (month 4 to year 3 and 5). Results Sustained virological response was better in Δ32/wt than in wt/wt patients: 66% versus 52% up to year 3 (p=0.02), nearly significant after adjustment to potential cofounders (p=0.07). Δ32/wt patients had a better virological response, up to year 5, 48% versus 35% (p=0.01), and remained significantly better, after adjustment, associated with a better virological response up to 5 years post initiation of cART (p=0.04). There was no association with CD4 response. Conclusion Δ32/wt deletion is associated with a beneficial virological response to cART on the long-term. Whether this association can be a direct effect of Δ32/wt deletion remains questionable and needs confirmation in other observational studies. PMID:20050936

  19. Metabolic disorders and cardiovascular risk in treatment-naive HIV-infected patients of sub-saharan origin starting antiretrovirals: impact of westernized lifestyle.

    PubMed

    Eholié, Serge Paul; Lacombe, Karine; Krain, Alysa; Diallo, Zelica; Ouiminga, Mariama; Campa, Pauline; Bouchaud, Olivier; Bissagnene, Emmanuel; Girard, Pierre-Marie

    2015-04-01

    In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk.

  20. Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral Therapy

    PubMed Central

    Dhakal, Ishwori; Casper, Corey; Noy, Ariela; Palefsky, Joel M.; Haigentz, Missak; Krown, Susan E.; Ambinder, Richard F.; Mitsuyasu, Ronald T.

    2016-01-01

    The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (<30, 30–39, 40–49, 50–59, and >60 years) was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER) program. Standardized incidence ratios (SIRs) were estimated using their 95% confidence intervals (CIs). Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI) for Kaposi sarcoma (46.08; 38.74–48.94), non-Hodgkin lymphoma (4.22; 3.63–4.45), Hodgkin lymphoma (9.83; 7.45–10.84), and anal cancer (30.54; 25.62–32.46) and lower for colorectal cancer (0.69; 0.52–0.76), lung cancer (0.70; 0.54, 0.77), and prostate cancer (0.54; 0.45–0.58). Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers. PMID:27882054

  1. Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

    PubMed

    Sharma, S; Babiker, A G; Emery, S; Gordin, F M; Lundgren, J D; Neaton, J N; Bakowska, E; Schechter, M; Wiselka, M J; Wolff, M J

    2015-04-01

    The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/μL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/μL (IQR 584-765 cells/μL) and 12,754 HIV RNA copies/mL (IQR 3014-43,607 copies/mL), respectively. START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes. © 2015 British HIV Association.

  2. Antiretroviral treatment changes in adults from Côte d'Ivoire: the roles of tuberculosis and pregnancy.

    PubMed

    Messou, Eugène; Anglaret, Xavier; Duvignac, Julien; Konan-N'dri, Eric; Komena, Eric; Gnokoro, Joachim; Karcher, Sophie; Tanoh, Anthony; N'dri-Yoman, Thérèse; Seyler, Catherine

    2010-01-02

    To determine the rates and causes of first antiretroviral treatment changes in HIV-infected adults in Côte d'Ivoire. We evaluated adults who initiated antiretroviral treatment in an outpatient clinic in Abidjan. We recorded baseline and follow-up data, including drug prescriptions and reasons for changing to alternative first-line regimens (drug substitution for any reason but failure) or second-line regimens (switch for failure). Two thousand and twelve HIV-infected adults (73% women) initiated antiretroviral treatment. At baseline, 9% of all patients were on treatment for tuberculosis and 3% of women were pregnant. First-line antiretroviral treatment consisted of two nucleoside reverse transcriptase inhibitors (58% stavudine-lamivudine, 42% zidovudine-lamivudine) and efavirenz (63%), nevirapine (32%) or indinavir (5%). Median follow-up time was 16.9 months. During this time, 205 (10%) patients died and 261 (13%) were lost to follow-up. Overall, the rate of treatment modifications was 20.7/100 patient-years. The most common modifications were drug substitutions for intolerance (12.4/100 patient-years), pregnancy (4.5/100 patient-years) and tuberculosis (2.5/100 patient-years). The rates of intolerance-related substitutions were 17.9/100 patient-years for stavudine, 6.3/100 patient-years for nevirapine, 3.9/100 patient-years for zidovudine and 0.1/100 patient-years for efavirenz. Twenty percent of efavirenz substitutions resulted from pregnancy and 18% of nevirapine substitutions were related to tuberculosis treatment. During the first months following antiretroviral treatment initiation, a third of all treatment changes occurred for reasons other than intolerance to the drug or treatment failure. In Africa, drug forecasting is crucial to ensuring the success of HIV treatment programmes. Drugs that do not require interruptions during pregnancy or tuberculosis treatment should be made more readily available as first-line drugs in sub-Saharan Africa.

  3. Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults.

    PubMed

    Onwumeh, Jennifer; Okwundu, Charles I; Kredo, Tamara

    2017-05-25

    Human immunodeficiency virus (HIV) continues to be a leading cause of morbidity and mortality, particularly in sub-Saharan Africa. Although antiretroviral drugs have helped to improve the quality of life and life expectancy of HIV-positive individuals, there is still a need to explore other interventions that will help to further reduce the disease burden. One potential strategy is the use of interleukin-2 (IL-2) in combination with antiretroviral therapy (ART). IL-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes and may help to boost the immune system. To assess the effects of interleukin-2 (IL-2) as an adjunct to antiretroviral therapy for HIV-positive adults. We searched the following sources up to 26 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; the Web of Science; LILACS; the World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP); and ClinicalTrials.gov. We also checked conference abstracts, contacted experts and relevant organizations in the field, and checked the reference list of all studies identified by the above methods for any other potentially eligible studies. Randomized controlled trials (RCTs) that evaluated the effects of IL-2 as an adjunct to ART in reducing the morbidity and mortality in HIV-positive adults. Two review authors independently screened records and selected trials that met the inclusion criteria, extracted data, and assessed the risk of bias in the included trials. Where possible, we compared the effects of interventions using risk ratios (RR), and presented them with 95% confidence intervals (CI). We assessed the overall certainty of the evidence using the GRADE approach. Following a comprehensive literature search up to 26 May 2016, we identified 25 eligible trials. The interventions involved the use of IL-2 in combination with ART compared with ART alone. There was no difference in

  4. Jump Start: The Federal Role in Adult Literacy.

    ERIC Educational Resources Information Center

    BCEL Newsletter for the Business Community, 1989

    1989-01-01

    A study examined the Federal Government's role in adult literacy. A far-reaching plan of action for the Federal Government was proposed that was based on an understanding of national literacy need and the structure and politics of Federal Government. The focus of the current national literacy movement was found to be seriously flawed in…

  5. Creating Lessons for Adult ESOL Learners: Getting Started.

    ERIC Educational Resources Information Center

    Florez, MaryAnn Cunningham

    This paper offers a series of practical, useful tips for creating lessons for adult English language learners (ELLs). It begins by offering seven questions to help the teacher think through the lesson ahead of time. It also provides tips for creating a general lesson plan, and tips for tapping the four language modes: speaking, listening, reading,…

  6. Suboptimal antiretroviral therapy adherence among HIV-infected adults in Guangzhou, China

    PubMed Central

    Muessig, Kathryn E.; McLaughlin, Megan M.; Nie, Jing Min; Cai, Weiping; Zheng, Heping; Yang, Ligang; Tucker, Joseph D.

    2014-01-01

    Despite China“s free antiretroviral treatment (ART) program, there are high rates of treatment failure, large sociodemographic disparities in care outcomes and emerging medication resistance. Understanding patient medication adherence behaviors and challenges could inform adherence interventions to maximize the individual and prevention benefits of ART. This study assessed recent non-adherence and treatment interruption among 813 HIV-infected adult outpatients in Guangzhou, China. Participants completed a behavioral survey, underwent chart review, and were tested for syphilis, gonorrhea, and chlamydia. Factors associated with suboptimal adherence were identified using univariate and multivariate logistic regression. Among 721 HIV-infected adults receiving ART, 18.9% reported recent non-adherence (any missed ART in the past 4 weeks) and 6.8% reported treatment interruption (four or more weeks of missed ART in the past year). Lower education, living alone, alcohol use and being on ART one to three years were associated with recent non-adherence. Male gender, lower education and being on ART one to three years were associated with treatment interruption. ART medication adherence interventions are needed in China that include individualized, long-term adherence plans sensitive to patients“ educational and economic situations. These interventions should also consider possible gender disparities in treatment outcomes and address the use of alcohol during ART. Successful ART medication adherence interventions in China can inform other international settings that face similar adherence challenges and disparities. PMID:24666239

  7. Suboptimal antiretroviral therapy adherence among HIV-infected adults in Guangzhou, China.

    PubMed

    Muessig, Kathryn E; McLaughlin, Megan M; Nie, Jing Min; Cai, Weiping; Zheng, Heping; Yang, Ligang; Tucker, Joseph D

    2014-01-01

    Despite China's free antiretroviral therapy (ART) program, there are high rates of treatment failure, large sociodemographic disparities in care outcomes and emerging medication resistance. Understanding patient medication adherence behaviors and challenges could inform adherence interventions to maximize the individual and prevention benefits of ART. This study assessed recent nonadherence and treatment interruption among 813 HIV-infected adult outpatients in Guangzhou, China. Participants completed a behavioral survey, underwent chart review, and were tested for syphilis, gonorrhea, and chlamydia. Factors associated with suboptimal adherence were identified using univariate and multivariate logistic regression. Among 721 HIV-infected adults receiving ART, 18.9% reported recent nonadherence (any missed ART in the past four weeks) and 6.8% reported treatment interruption (four or more weeks of missed ART in the past year). Lower education, living alone, alcohol use, and being on ART one to three years were associated with recent nonadherence. Male gender, lower education, and being on ART one to three years were associated with treatment interruption. ART medication adherence interventions are needed in China that include individualized, long-term adherence plans sensitive to patients' educational and economic situations. These interventions should also consider possible gender disparities in treatment outcomes and address the use of alcohol during ART. Successful ART medication adherence interventions in China can inform other international settings that face similar adherence challenges and disparities.

  8. Quality of Life Among Individuals with HIV Starting Antiretroviral Therapy in Diverse Resource-Limited Areas of the World

    PubMed Central

    Hendriksen, Ellen S.; Smeaton, Laura; Celentano, David D.; Hosseinipour, Mina C.; Barnett, Ronald; Guanira, Juan; Flanigan, Timothy; Kumarasamy, N.; Klingman, Karin; Campbell, Thomas

    2011-01-01

    As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a randomized clinical trial of ART conducted in the U.S. (n = 203) and 8 resource-limited countries (n = 1,360) in the Caribbean, South America, Asia, and Africa. Participants were interviewed prior to initiation of ART using a modified version of the ACTG SF-21, a health-related QOL measure including 8 subscales: general health perception, physical functioning, role functioning, social functioning, cognitive functioning, pain, mental health, and energy/fatigue. Other measures included demographics, CD4+ lymphocyte count, plasma HIV-1 RNA viral load. Higher quality of life in each of the 8 QOL subscales was associated with higher CD4+ lymphocyte category. General health perception, physical functioning, role functioning, and energy/fatigue varied by plasma HIV-1 RNA viral load categories. Each QOL subscale included significant variation by country. Only the social functioning subscale varied by sex, with men having greater impairments than women, and only the physical functioning subscale varied by age category. This was the first large-scale international ART trial to conduct a standardized assessment of QOL in diverse international settings, thus demonstrating that implementation of the behavioral assessment was feasible. QOL indicators at study entry varied with disease severity, demographics, and country. The relationship of these measures to treatment outcomes can and should be examined in clinical trials of ART in resource-limited settings using similar methodologies. PMID:21499794

  9. Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

    PubMed Central

    Suthar, Amitabh B.; Lawn, Stephen D.; del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R.; Chaisson, Richard E.; Williams, Brian G.; Harries, Anthony D.; Granich, Reuben M.

    2012-01-01

    Background Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. Methods and Findings PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis

  10. Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study.

    PubMed

    May, Margaret T; Vehreschild, Jorg-Janne; Trickey, Adam; Obel, Niels; Reiss, Peter; Bonnet, Fabrice; Mary-Krause, Murielle; Samji, Hasina; Cavassini, Matthias; Gill, Michael John; Shepherd, Leah C; Crane, Heidi M; d'Arminio Monforte, Antonella; Burkholder, Greer A; Johnson, Margaret M; Sobrino-Vegas, Paz; Domingo, Pere; Zangerle, Robert; Justice, Amy C; Sterling, Timothy R; Miró, José M; Sterne, Jonathan A C; Boulle, Andrew; Stephan, Christoph; Miro, Jose M; Cavassini, Matthias; Chêne, Geneviève; Costagliola, Dominique; Dabis, François; Monforte, Antonella D'Arminio; Del Amo, Julia; Van Sighem, Ard; Fätkenheuer, Gerd; Gill, John; Guest, Jodie; Haerry, David Hans-Ulrich; Hogg, Robert; Justice, Amy; Shepherd, Leah; Obel, Neils; Crane, Heidi; Smith, Colette; Reiss, Peter; Saag, Michael; Sterling, Tim; Teira, Ramon; Williams, Matthew; Zangerle, Robert; Sterne, Jonathan; May, Margaret; Ingle, Suzanne; Trickey, Adam

    2016-06-15

    CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P = .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and ≥10 years, respectively. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  11. Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

    PubMed Central

    May, Margaret T.; Vehreschild, Jorg-Janne; Trickey, Adam; Obel, Niels; Reiss, Peter; Bonnet, Fabrice; Mary-Krause, Murielle; Samji, Hasina; Cavassini, Matthias; Gill, Michael John; Shepherd, Leah C.; Crane, Heidi M.; d'Arminio Monforte, Antonella; Burkholder, Greer A.; Johnson, Margaret M.; Sobrino-Vegas, Paz; Domingo, Pere; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy R.; Miró, José M.; Sterne, Jonathan A. C.

    2016-01-01

    Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5–0.9, 1–2.9, 3–4.9, 5–9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996–2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996–1997, 1998–1999, 2000–2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0–49, 50–99, 100–199, 200–349, 350–499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2–35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4–16.8) during 5–9.9 years and 14.2 (95% CI, 13.3–15.1) after 10 years’ duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94–1.00; P = .054) and 1.02 (95% CI, .98–1.07; P = .32) among patients followed for 5–9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. PMID:27025828

  12. Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study.

    PubMed

    Peck, Robert N; Shedafa, Rehema; Kalluvya, Samuel; Downs, Jennifer A; Todd, Jim; Suthanthiran, Manikkam; Fitzgerald, Daniel W; Kataraihya, Johannes B

    2014-07-29

    The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity. In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher's exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding. Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤ 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with

  13. A Randomized Controlled Trial of Real-Time Electronic Adherence Monitoring With Text Message Dosing Reminders in People Starting First-Line Antiretroviral Therapy.

    PubMed

    Orrell, Catherine; Cohen, Karen; Mauff, Katya; Bangsberg, David R; Maartens, Gary; Wood, Robin

    2015-12-15

    There are conflicting findings about whether mobile phone text message reminders impact on antiretroviral adherence. We hypothesized that text reminders sent when dosing was late would improve adherence and HIV viral suppression. Antiretroviral therapy (ART)-naive participants, from a South African outpatient ART clinic, were randomized to standard of care (SoC, 3 pretreatment education sessions), or intervention (SoC and automated text reminders if dosing >30 minutes late). Dosing time was recorded by real-time electronic adherence monitoring devices, given to participants at ART start. CD4 cell count and HIV RNA were determined at baseline, 16 and 48 weeks. Primary outcome was cumulative adherence execution by electronic adherence monitoring device. HIV-1 viral suppression (<40 copies/mL) at week 48 and count of treatment interruptions (TIs) >72 hours were secondary outcomes. Analysis was by intention to treat (missing = failure). Registration was with the Pan-African Clinical Trials Registry: PACTR201311000641402. A total of 230 participants were randomly assigned to control (n = 115) or intervention (n = 115) arms. Median adherence was 82.1% (interquartile range, 56.6%-94.6%) in the intervention arm, compared with 80.4% (interquartile range, 52.8%-93.8%) for SoC [adjusted odds ratio for adherence 1.08; 95% confidence interval (CI): 0.77 to 1.52]. Suppressed HIV RNA (<40 copies/mL) occurred in 80 (69.6%) of control and 75 (65.2%) of intervention (adjusted odds ratio for virological failure in intervention arm 0.77; 95% CI: 0.42 to 1.40). In the intervention arm, the count of TIs of >72 hours was reduced (adjusted incident rate ratio, 0.84; 95% CI: 0.75 to 0.94). Text message reminders linked to late doses detected by real-time adherence monitoring reduced the number of prolonged TIs, but did not significantly improve adherence or viral suppression.

  14. Immunologic Effects of Maraviroc in HIV-Infected Patients with Severe CD4 Lymphopenia Starting Antiretroviral Therapy: A Sub-Study of the CADIRIS Trial.

    PubMed

    Belaunzarán-Zamudio, Pablo F; Azzoni, Livio; Canaday, David H; Caro-Vega, Yanink N; Clagget, Brian; Rassool, Mohammed S; Rodriguez, Benigno; Sanne, Ian; Sereti, Irini; Sierra-Madero, Juan G; Lederman, Michael M

    2017-01-01

    We aimed to describe the mechanisms of immunological recovery and the effects of blocking CCR5 in patients starting ART with advanced HIV-infection. This was a sub-study of a 48 week double-blind, clinical trial where patients starting ART with CD4+ cell counts <100 cells/uL were randomized to receive maraviroc or a placebo. CD4+ and CD8+ cell maturation phenotypes, expression of PD-1 and CCR5, and activation indices were measured at weeks 0, 4, 12, 24, and 48. The reactivity of CD4+ and CD8+cells with peptides of CMV and MTb, and with Staphylococcal enterotoxin B (SEB) was assessed by intracellular expression of IFNγ, TNFα, and CD40 ligand at weeks 0, 4, and 12 of ART. Forty patients were included in the study (Maraviroc = 22; placebo = 18). Sustained increases in CD8+ cells and in proportions of CCR5+ CD4+ and CD8+ cells were observed in the maraviroc arm. Early increases in the proportions of activated (CD38+, HLA-DR+), PD-1+ CD4+, and CD8+ cells and more matured CD8+ cells, were observed in the maraviroc arm. T cell responses to CMV, MTb, and SEB did not differ by treatment arms. During antiretroviral therapy in advanced HIV infection, maraviroc retains mature, activated CCR5+ cells in circulation without impact on CD4+ T cell recovery or T cell reactivity to antigen or superantigen.

  15. Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts

    PubMed Central

    Haas, Andreas D.; Keiser, Olivia; Balestre, Eric; Brown, Steve; Bissagnene, Emmanuel; Chimbetete, Cleophas; Dabis, François; Davies, Mary-Ann; Hoffmann, Christopher J.; Oyaro, Patrick; Parkes-Ratanshi, Rosalind; Reynolds, Steven J.; Sikazwe, Izukanji; Wools-Kaloustian, Kara; Zannou, Djimon Marcel; Wandeler, Gilles; Egger, Matthias

    2015-01-01

    Background HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004–2013. Methods Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. Findings Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine VL, 1·21 (1·13–1·30) for targeted VL and 0·49 (0·43–0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114–133 cells/µl). Interpretation Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing. PMID:26423252

  16. Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges

    PubMed Central

    Wester, C William; Bussmann, Hermann; Koethe, John; Moffat, Claire; Vermund, Sten; Essex, Max; Marlink, Richard G

    2009-01-01

    Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment. Analyses from the region report favorable clinical/treatment outcomes and impressive declines in AIDS-related mortality among HIV-1-infected adults and children receiving cART. While immunologic recovery, virologic suppression and cART adherence rates are on par with resource-rich settings, loss to follow-up and high mortality rates, especially within the first 6 months of treatment, remain a significant problem. Over the next decade, cART coverage rates are expected to improve across the region, with attendant increases in healthcare utilization for HIV- and non-HIV-related complications and the need for expanded laboratory and clinical services. Planned and in-progress trials will evaluate the use of cART to prevent primary HIV-1 infection with so-called ‘test and treat’ expansions of coverage and treatment. Education and training programs as well as patient-retention strategies will need to be strengthened as national cART programs are expanded and more people require lifelong monitoring and care. PMID:20161344

  17. Antiretroviral Treatment Adherence: Knowledge and Experiences among Adolescents and Young Adults in Soweto, South Africa

    PubMed Central

    Tshabalala, Celokuhle; Laher, Fatima

    2017-01-01

    Human immunodeficiency virus (HIV) management of adolescents and young adults (AYAs) is particularly pertinent to sub-Saharan Africa, where the pediatric HIV burden is marked. Antiretroviral treatment (ART) adherence is a major challenge for AYAs. This qualitative study explored knowledge and experiences of adherence amongst AYAs attending treatment at the Perinatal HIV Research Unit (PHRU), Soweto, South Africa. Four focus group discussions (FGDs) and eight in-depth interviews (IDIs) were conducted with HIV-infected 15–25-year-old ART recipients. Transcripts were coded thematically. Participants (n = 26) were aged median 18.5 years, 59.1% female and 69.2% virally suppressed <400 cp/ml. Three main themes emerged during FGDs and IDIs: (i) correct knowledge about how to be adherent, benefits, and nonadherence consequences, (ii) social, personal, and medication-related barriers to adherence, and (iii) reminder, concealment, and motivational strategies to optimize adherence. Interventions to improve AYA adherence could focus on practical strategies, including status disclosure and medication concealment. PMID:28409026

  18. Correlates of Antiretroviral Therapy Adherence among HIV-Infected Older Adults

    PubMed Central

    McCoy, Katryna; Waldrop-Valverde, Drenna; Balderson, Benjamin H.; Mahoney, Christine; Catz, Sheryl

    2016-01-01

    Background Despite the success of antiretroviral therapy (ART), HIV-infected older African Americans experience higher mortality rates compared to their white counterparts. This disparity may be partly attributable to the differences in ART adherence by different racial and gender groups. The purpose of this study was to describe demographic, psychosocial, and HIV disease-related factors that influence ART adherence and to determine whether race and gender impact ART adherence among HIV-infected adults aged 50 years and older. Methods This descriptive study involved a secondary analysis of baseline data from 426 participants in “PRIME,” a telephone-based ART adherence and quality-of-life intervention trial. Logistic regression was used to examine the association between independent variables and ART adherence. Results Higher annual income and increased self-efficacy were associated with being ≥95% ART adherent. Race and gender were not associated with ART adherence. Conclusion These findings indicated that improvements in self-efficacy for taking ART may be an effective strategy to improve adherence regardless of race or gender. PMID:27071744

  19. Socioeconomic and clinical factors explaining the risk of unstructured antiretroviral therapy interruptions among Kenyan adult patients.

    PubMed

    Mûnene, Edwin; Ekman, Björn

    2016-09-01

    A cross-sectional study was conducted to assess the extent of unstructured HIV treatment interruptions (TIs) and investigate the effects of socioeconomic, socio-demographic, HIV treatment-related and clinical factors on the magnitude and rate of the same among adult patients at a Kenyan regional referral center. Four hundred and twenty-one adult patients actively receiving antiretroviral therapy at Nyeri County Referral Hospital since 2003 were randomly selected to complete a health survey questionnaire. Electronic records were used to obtain their HIV treatment utilization history. The marginal effects of selected determinants on prevalence and rate of TI were assessed by fitting multiple Poisson log-linear regression models. In total, 392 patients participated in the study. HIV TI was prevalent with 64.5% having had at least one TI of 3 months or more during treatment. The risk of TI was significantly higher in those longer on treatment (prevalence ratio = 1.2, 95% confidence interval [CI] 1.12-1.28). Greater risk of TI was also associated with lower income (prevalence rate ratio [PRR] = 0.9, 95% CI 0.83-1.00), low medication adherence (PRR = 0.3, 95% CI 0.13-0.72), inconsistent treatment engagement (PRR = 0.4, 95% CI 0.19-0.75) and, contrarily, fewer adverse drug reactions (PRR = 0.9, 95% CI 0.90-0.97). Unstructured HIV TIs appear to be fairly common at the study site. The results suggest that efforts to minimize HIV TI could benefit from treatment-continuity monitoring strategies that target the high-risk sub-samples identified.

  20. The Perfect Pairing: The Adult Learner and the Boutique Winery in the Start-Up Phase

    ERIC Educational Resources Information Center

    Heath-Simpson, Delta F.

    2011-01-01

    The purpose of this phenomenological study was to understand and describe the lived experiences of adult learners who are owners and managers of small winery businesses operating in the start-up phase of the organizational life cycle. The study explored and identified the meaning of adult learning in the entrepreneurial context and its affect on…

  1. The Perfect Pairing: The Adult Learner and the Boutique Winery in the Start-Up Phase

    ERIC Educational Resources Information Center

    Heath-Simpson, Delta F.

    2011-01-01

    The purpose of this phenomenological study was to understand and describe the lived experiences of adult learners who are owners and managers of small winery businesses operating in the start-up phase of the organizational life cycle. The study explored and identified the meaning of adult learning in the entrepreneurial context and its affect on…

  2. Life expectancy trends in adults on antiretroviral treatment in South Africa.

    PubMed

    Johnson, Leigh F; Keiser, Olivia; Fox, Matthew P; Tanser, Frank; Cornell, Morna; Hoffmann, Chris J; Prozesky, Hans; Boulle, Andrew; Davies, Mary-Ann

    2016-10-23

    Previous studies have reported improvements in life expectancies of patients on antiretroviral treatment (ART) over time, but it is not clear whether these improvements are explained by changes in baseline clinical characteristics, longer duration on ART or changes in clinical practices. Two parametric survival models were fitted to mortality data from South African ART cohorts that had linked patient records to the national vital registration system. The first model estimated mortality by age, sex, cohort, baseline CD4 cell count, time since ART initiation and period of ART initiation; the second model included only age, sex, cohort and period of follow-up. Life expectancies were calculated from the estimated mortality rates. The first model estimated little change in mortality over time: women starting ART at age 35 years, at CD4 cell counts of 200 cells/μl or higher, had life expectancies of 32.7 years [95% confidence interval (CI): 31.6-33.6], 32.4 years (95% CI: 31.3-33.4) and 33.0 years (95% CI: 32.0-34.1) in the 2001-2006, 2007-2009 and 2010-2014 periods, respectively. However, the second model estimated a significant improvement in life expectancy; for all women on ART at age 35 years, corresponding life expectancies were 13.0 years (95% CI: 12.1-14.2), 20.4 years (95% CI: 19.5-21.4) and 26.1 years (95% CI: 25.2-26.9), respectively. Although life expectancies in South African ART patients have improved over time, these improvements are not observed after controlling for changes in baseline CD4 cell count and ART duration. This suggests that changes in clinical practice and programme scale have had little impact on ART mortality in South Africa.

  3. Immune Reconstitution During the First Year of Antiretroviral Therapy of HIV-1-Infected Adults in Rural Burkina Faso

    PubMed Central

    Tiba, Fabrice; Nauwelaers, Frans; Traoré, Siaka; Coulibaly, Boubacar; Ouedraogo, Thierry; Compaoré, Adama; Kräusslich, Hans-Georg; Böhler, Thomas

    2012-01-01

    There are no data on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected adults in rural Burkina Faso. We therefore assessed CD4+ T-cell counts and HIV-1 plasma viral load (VL), the proportion of naive T-cells (co-expressing CCR7 and CD45RA) and T-cell activation (expression of CD95 or CD38) in 61 previously untreated adult patients from Nouna, Burkina Faso, at baseline and 2 weeks, 1, 3, 6, 9 and 12 months after starting therapy. Median CD4+ T-cell counts increased from 174 (10th-90th percentile: 33-314) cells/µl at baseline to 300 (114- 505) cells/µl after 3 months and 360 (169-562) cells/µl after 12 months of HAART. Median VL decreased from 5.8 (4.6- 6.6) log10 copies/ml at baseline to 1.6 (1.6-2.3) log10 copies/ml after 12 months. Early CD4+ T-cell recovery was accompanied by a reduction of the expression levels of CD95 and CD38 on T-cells. Out of 42 patients with complete virological follow-up under HAART, 19 (45%) achieved concordant good immunological (gain of ≥100 CD4+ T-cells/µl above baseline) and virological (undetectable VL) responses after 12 months of treatment (intention-to-treat analysis). Neither a decreased expression of the T-cell activation markers CD38 and CD95, nor an increase in the percentage of naive T-cells reliably predicted good virological treatment responses in patients with good CD4+ T-cell reconstitution. Repeated measurement of CD4+ T-cell counts during HAART remains the most important parameter for immunologic monitoring. Substitution of repeated VL testing by determination of T-cell activation levels (e.g., CD38 expression on CD8+ T-cells) should be applied with caution. PMID:22435082

  4. Nevirapine-related adverse events among children switched from efavirenz to nevirapine as compared to children who were started on nevirapine-based antiretroviral therapy directly.

    PubMed

    Sanjeeva, G N; Sukanya, V; Pavithra, H B; Dodderi, S K; Rewari, B B; Govindaraj, M; Shivananda, S; Premalatha, R

    2015-01-01

    In this retrospective study, incidence of nevirapine (NVP) toxicity in children who were switched from efavirenz (EFV) to NVP (treatment experienced [TE] group) was compared with that of children who had started NVP-based antiretroviral therapy directly (treatment naïve [TN] group). This study also identified risk factors associated with development of NVP toxicity in children. The incidence and risk of developing NVP toxicities were significantly higher in TE when compared to TN group. Median duration of onset of NVP toxicity from the initiation was 2.14 and 3.84 weeks in TE and TN children, respectively. Mean CD4 count was found to be significantly higher in children who developed toxicity (577 ± 81 cells/µL) as compared to the children who did not develop toxicity (403 ± 29 cells/µL). Similarly, children in TE group who developed NVP toxicity had higher mean CD4 cell count than children in TN with NVP toxicity. The risk factors for the development of NVP toxicity include female gender with CD4 count >250 cells/μL and TE children especially girls with CD4% >15% and boys with CD4 count >400 cells/μL. To conclude, the higher incidence of NVP toxicity among TE group warrants a cautious approach while switching the NVP- from EFV-based therapy.

  5. Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study.

    PubMed

    Gilson, R J C; Man, S-L; Copas, A; Rider, A; Forsyth, S; Hill, T; Bansi, L; Porter, K; Gazzard, B; Orkin, C; Pillay, D; Schwenk, A; Johnson, M; Easterbook, P; Walsh, J; Fisher, M; Leen, C; Anderson, J; Sabin, C A

    2010-02-01

    Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL). Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events. Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.

  6. Sex disparities in outcomes among adults on long-term antiretroviral treatment in northern Nigeria.

    PubMed

    Musa, Baba M; Garbati, Musa A; Nashabaru, Ibrahim M; Yusuf, Shehu M; Nalado, Aisha M; Ibrahim, Daiyabu A; Simmons, Melynda N; Aliyu, Muktar H

    2017-01-01

    There are conflicting reports of sex differences in HIV treatment outcomes in Africa. We investigated sex disparities in treatment outcomes for adults on first line antiretroviral treatment (ART) in Nigeria. We compared clinical and immunologic responses to ART between HIV-infected men (n=205) and women (n=140) enrolled in an ART program between June 2004 and December 2007, with follow-up through June 2014. We employed Kaplan-Meier estimates to examine differences in time to immunologic failure and loss to follow-up (LTFU), and generalized estimating equations to assess changes in CD4+ count by sex. Men had lower baseline mean CD4+ count compared to women (327.6 cells/µL vs 413.4, respectively, p<0.01). Women had significantly higher rates of increase in CD4+ count than men, even after adjusting for confounders, p<0.0001. There was no significant difference in LTFU by sex: LTFU rate was 2.47/1000 person-months (95% CI 1.6-3.9) in the first five years for men vs 1.98/1000 person-months (95% CI (1.3-3.0) for women. There was no difference in time to LTFU by sex over the study period. Women achieved better long-term immune response to ART at baseline and during treatment, but had similar rates of long-term retention in care to men. Targeted efforts are needed to improve immune outcomes in men in our setting. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Determinants of non-adherence to antiretroviral therapy in adult hospitalized patients, Northwest Ethiopia

    PubMed Central

    Tsega, Bayew; Srikanth, Bhagavathula Akshaya; Shewamene, Zewdneh

    2015-01-01

    Aim The aim of this study was to assess the rate of antiretroviral therapy (ART) adherence and to identify any determinants among adult patients. Methods A cross-sectional study was conducted on 351 ART patients in the ART clinic of the University of Gondar referral hospital. Data were collected by a pretested interviewer-administered structured questionnaire from May to June 2014. Multivariate logistic regression was used to determine factors significantly associated with adherence. Results Of 351 study subjects, women were more predominant than men (64.4% versus 35.6%). Three hundred and forty (96.9%) patients agreed and strongly agreed that the use of ART is essential in their life, and approximately 327 (93.2%) disclosed their sero-status to family. Seventy-nine (22.5%) participants were active substance users. The level of adherence was 284 (80.9%). Three hundred forty-one (97.2%) respondents had good or fair adherence. Among the reasons for missing doses were forgetfulness (29 [43.3%]), missing appointments (14 [20.9%]), running out of medicine (9 [13.4%]), depression, anger, or hopelessness (4 [6.0%]), side effects of the medicine used (2 [3.0%]), and nonbelief in the ART (2 [3.0%]). The variables found significantly associated with non-adherence were age (P-value 0.017), employment (P-value 0.02), HIV disclosure (P-value 0.04), and comfortability to take ART in the presence of others (P-value 0.02). Conclusion From this study, it was determined that forgetfulness (43.3%) was the most common reason for missing doses. Also, employment and acceptance in using ART in the presence of others are significant issues observed for non-adherence. Hence, the ART counselor needs to place more emphasis on the provision and use of memory aids. PMID:25784793

  8. Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania, Uganda and Zambia.

    PubMed

    Denison, Julie A; Koole, Olivier; Tsui, Sharon; Menten, Joris; Torpey, Kwasi; van Praag, Eric; Mukadi, Ya Diul; Colebunders, Robert; Auld, Andrew F; Agolory, Simon; Kaplan, Jonathan E; Mulenga, Modest; Kwesigabo, Gideon P; Wabwire-Mangen, Fred; Bangsberg, David R

    2015-01-28

    To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. A cross-sectional study. Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients.

  9. Effect of antiretroviral therapy on malaria incidence in HIV-infected Ugandan adults

    PubMed Central

    Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy

    2017-01-01

    Introduction: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. Methods: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4+ at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4+ cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events. Results: Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2–1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4+ cell count. Conclusion: There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4+ cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance. PMID:28121670

  10. Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

    PubMed Central

    Koenig, Serena P.; Bang, Heejung; Severe, Patrice; Jean Juste, Marc Antoine; Ambroise, Alex; Edwards, Alison; Hippolyte, Jessica; Fitzgerald, Daniel W.; McGreevy, Jolion; Riviere, Cynthia; Marcelin, Serge; Secours, Rode; Johnson, Warren D.; Pape, Jean W.; Schackman, Bruce R.

    2011-01-01

    Background In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. Methods and Findings Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS). Conclusions Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests. Trial registration ClinicalTrials.gov NCT00120510 Please see

  11. Is early antiretroviral therapy initiation useful in HIV(+) adults without co-infections?

    PubMed

    Chauriye, Verónica; Monsalve, Ximena

    2015-12-02

    HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects.

  12. Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection

    PubMed Central

    Anderson, Christy M.; Var, Susanna R.; Oliveira, Michelli F.; Lada, Steven M.; Vargas, Milenka V.; Little, Susan J.; Richman, Douglas D.; Strain, Matthew C.; Pérez-Santiago, Josué; Smith, Davey M.

    2016-01-01

    ABSTRACT Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and is associated with increased T-cell activation and HIV disease progression. We hypothesized that the presence of replication of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence HIV DNA decay during antiretroviral therapy (ART). We investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, HIV-infected men who have sex with men, who started ART within a median of 3 months from their estimated date of infection (EDI) and were monitored for a median of 19 months thereafter. Levels of HIV, CMV, and EBV DNA and cellular HIV RNA were measured by droplet digital PCR (ddPCR) for each time point. Using a general linear mixed-effect regression model, we evaluated associations between the presence of detectable CMV DNA and EBV DNA levels and HIV DNA decay and cellular HIV RNA levels, while adjusting for peak HIV RNA, nadir CD4+ count, CD4/CD8 ratio, CMV IgG levels, time from EDI to ART initiation, time from ART initiation to virologic suppression, detectable CMV DNA pre-ART, and age. The presence of intermittent CMV DNA in PBMC during ART was significantly associated with slower decay of HIV DNA (P = 0.011) but not with increased cellular HIV RNA transcription or more detectable 2-long terminal repeat circles. Higher levels of EBV DNA were also associated with higher levels of HIV DNA (P < 0.001) and increased unspliced cellular HIV RNA transcription (P = 0.010). These observations suggest that replication of HHV may help maintain a larger HIV DNA reservoir, but the underlying mechanisms remain unclear. IMPORTANCE Over three-fourths of HIV-infected men have at least one actively replicating human herpesvirus (HHV) in their mucosal secretions at any one time. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the most common, and although it is often asymptomatic, such CMV and EBV

  13. Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

    PubMed Central

    Siefried, Krista J.; Mao, Limin; Kerr, Stephen; Cysique, Lucette A.; Gates, Thomas M.; McAllister, John; Maynard, Anthony; de Wit, John; Carr, Andrew

    2017-01-01

    Background Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. Methods Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression. Results We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2–6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2–4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5–7.3], p = 0.004), reaching the “Medicare safety net” (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1–4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0–6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0–18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1–5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3–7.0], p = 0.012). Conclusions In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with

  14. Retention and risk factors for attrition among adults in antiretroviral treatment programmes in Tanzania, Uganda and Zambia

    PubMed Central

    Koole, Olivier; Tsui, Sharon; Wabwire-Mangen, Fred; Kwesigabo, Gideon; Menten, Joris; Mulenga, Modest; Auld, Andrew; Agolory, Simon; Mukadi, Ya Diul; Colebunders, Robert; Bangsberg, David R.; van Praag, Eric; Torpey, Kwasi; Williams, Seymour; Kaplan, Jonathan; Zee, Aaron; Denison, Julie

    2016-01-01

    OBJECTIVES We assessed retention and predictors of attrition (recorded death or loss to follow-up) in antiretroviral treatment (ART) clinics in Tanzania, Uganda and Zambia. METHODS We conducted a retrospective cohort study among adults (≥18 years) starting ART during 2003–2010. We purposefully selected six health facilities per country and randomly selected 250 patients from each facility. Patients who visited clinics at least once during the 90 days before data abstraction were defined as retained. Data on individual and programme level risk factors for attrition were obtained through chart review and clinic manager interviews. Kaplan–Meier curves for retention across sites were created. Predictors of attrition were assessed using a multivariable Cox-proportional hazards model, adjusted for site-level clustering. RESULTS From 17 facilities, 4147 patients were included. Retention ranged from 52.0% to 96.2% at 1 year to 25.8%–90.4% at 4 years. Multivariable analysis of ART initiation characteristics found the following independent risk factors for attrition: younger age [adjusted hazard ratio (aHR) and 95% confidence interval (95%CI) = 1.30 (1.14–1.47)], WHO stage 4 ([aHR (95% CI): 1.56 (1.29–1.88)], >10% bodyweight loss [aHR (95%CI) = 1.17 (1.00–1.38)], poor functional status [ambulatory aHR (95%CI) = 1.29 (1.09–1.54); bedridden aHR1.54 (1.15–2.07)], and increasing years of clinic operation prior to ART initiation in government facilities [aHR (95%CI) = 1.17 (1.10–1.23)]. Patients with higher CD4 cell count were less likely to experience attrition [aHR (95%CI) = 0.88 (0.78–1.00)] for every log (tenfold) increase. Sites offering community ART dispensing [aHR (95% CI) = 0.55 (0.30–1.01) for women; 0.40 (0.21–0.75) for men] had significantly less attrition. CONCLUSIONS Patient retention to an individual programme worsened over time especially among males, younger persons and those with poor clinical indicators. Community ART drug dispensing

  15. Retention and risk factors for attrition among adults in antiretroviral treatment programmes in Tanzania, Uganda and Zambia.

    PubMed

    Koole, Olivier; Tsui, Sharon; Wabwire-Mangen, Fred; Kwesigabo, Gideon; Menten, Joris; Mulenga, Modest; Auld, Andrew; Agolory, Simon; Mukadi, Ya Diul; Colebunders, Robert; Bangsberg, David R; van Praag, Eric; Torpey, Kwasi; Williams, Seymour; Kaplan, Jonathan; Zee, Aaron; Denison, Julie

    2014-12-01

    We assessed retention and predictors of attrition (recorded death or loss to follow-up) in antiretroviral treatment (ART) clinics in Tanzania, Uganda and Zambia. We conducted a retrospective cohort study among adults (≥18 years) starting ART during 2003-2010. We purposefully selected six health facilities per country and randomly selected 250 patients from each facility. Patients who visited clinics at least once during the 90 days before data abstraction were defined as retained. Data on individual and programme level risk factors for attrition were obtained through chart review and clinic manager interviews. Kaplan-Meier curves for retention across sites were created. Predictors of attrition were assessed using a multivariable Cox-proportional hazards model, adjusted for site-level clustering. From 17 facilities, 4147 patients were included. Retention ranged from 52.0% to 96.2% at 1 year to 25.8%-90.4% at 4 years. Multivariable analysis of ART initiation characteristics found the following independent risk factors for attrition: younger age [adjusted hazard ratio (aHR) and 95% confidence interval (95%CI) = 1.30 (1.14-1.47)], WHO stage 4 ([aHR (95% CI): 1.56 (1.29-1.88)], >10% bodyweight loss [aHR (95%CI) = 1.17 (1.00-1.38)], poor functional status [ambulatory aHR (95%CI) = 1.29 (1.09-1.54); bedridden aHR1.54 (1.15-2.07)], and increasing years of clinic operation prior to ART initiation in government facilities [aHR (95%CI) = 1.17 (1.10-1.23)]. Patients with higher CD4 cell count were less likely to experience attrition [aHR (95%CI) = 0.88 (0.78-1.00)] for every log (tenfold) increase. Sites offering community ART dispensing [aHR (95%CI) = 0.55 (0.30-1.01) for women; 0.40 (0.21-0.75) for men] had significantly less attrition. Patient retention to an individual programme worsened over time especially among males, younger persons and those with poor clinical indicators. Community ART drug dispensing programmes could improve retention. © 2014 John Wiley & Sons Ltd.

  16. Crofelemer for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy.

    PubMed

    Castro, Jose G; Chin-Beckford, Nafeesa

    2015-01-01

    Chronic diarrhea remains a common condition that affects people infected with human immunodeficiency virus (HIV) despite the widespread use of potent antiretroviral therapy. It is important that providers control this condition, as the persistence of diarrhea affects the quality of life of patients and may contribute to decreased adherence to antiretroviral therapy. Strategies to control diarrhea in patients with HIV infection include switching to a new antiretroviral regimen and/or the use of specific medications to control the diarrhea. This review aims to provide a concise evaluation of a newly approved medication (crofelemer) that has a novel mechanism of action and has received approval for the symptomatic relief of non-infectious diarrhea in adult patients with HIV on anti-retroviral therapy.

  17. HIV drug resistance in adults failing early antiretroviral treatment: results from the HIV Prevention Trials Network 052 trial

    PubMed Central

    Fogel, Jessica M.; Hudelson, Sarah E.; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G.; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi Cindy; Eron, Joseph J.; Gallant, Joel E.; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C.; Santos, Breno Riegel; Godbole, Sheela V.; Pilotto, Jose Henrique; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H.; Chen, Ying Q.; Cohen, Myron S.; Eshleman, Susan H.

    2016-01-01

    Early initiation of antiretroviral therapy (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HPTN 052 trial who started ART at CD4 counts of 350–550 cells/mm3 and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7/8 (87.5%) participants who started ART at lower CD4 cell counts. PMID:26859828

  18. Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

    PubMed

    Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2016-07-01

    Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

  19. When to Start Antiretroviral Therapy

    MedlinePlus

    Please enable Javascript in your Browser to experience full features of this website. Skip to main content U.S. Department of Health and Human Services Contact Us | En ... Search Menu Home Guidelines Understanding ...

  20. Gender differences in diet and nutrition among adults initiating antiretroviral therapy in Dar es Salaam, Tanzania.

    PubMed

    Abioye, Ajibola I; Isanaka, Sheila; Liu, Enju; Mwiru, Ramadhani S; Noor, Ramadhani A; Spiegelman, Donna; Mugusi, Ferdinand; Fawzi, Wafaie

    2015-01-01

    Human immunodeficiency virus (HIV)-infected males have poor treatment outcomes after initiation of antiretroviral therapy (ART) compared to HIV-infected women. Dietary factors might mediate the association between sex and disease progression. However, the gender difference in diet among HIV-infected individuals in sub-Saharan Africa is largely unknown. The objective of this study was to examine differences in dietary intake among HIV-infected men and women. We conducted a cross-sectional analysis of dietary questionnaire data from 2038 adults initiating ART in Dar es Salaam, Tanzania to assess whether nutrient adequacy differed by sex. We dichotomized participants' nutrient intakes by whether recommended dietary allowances (RDAs) were met and estimated the relative risk (RR) of meeting RDAs in males using binomial regression models. We also estimated the mean difference in intake of foods and food groups by gender. We found poorer dietary practices among men compared to women. Males were less likely to meet the RDAs for micronutrients critical for slowing disease progression among HIV patients: niacin (RR = 0.39, 95% confidence interval [CI]: 0.27 to 0.55), riboflavin (RR = 0.81, 95% CI: 0.73 to 0.91), vitamin C (RR = 0.94, 95% CI: 0.89 to 1.00), and zinc (RR = 0.06, 95% CI: 0.01 to 0.24). Intake of thiamine, pantothenate, vitamins B6, B12, and E did not vary by gender. Males were less likely to eat cereals (mean difference [servings per day] = -0.21, 95% CI: -0.44 to 0.001) and vegetables (mean difference = -0.47, 95% CI: -0.86 to -0.07) in their diet, but more likely to have meat (mean difference = 0.14, 95% CI: 0.06 to 0.21). We conclude that male HIV patients have poorer dietary practices than females, and this may contribute to faster progression of the disease in males.

  1. Do Sedentary Older Adults Benefit from Community-Based Exercise? Results from the Active Start Program

    ERIC Educational Resources Information Center

    Yan, Tingjian; Wilber, Kathleen H.; Aguirre, Rosa; Trejo, Laura

    2009-01-01

    Purpose: This study assessed the effectiveness of Active Start, a community-based behavior change and fitness program, designed to promote physical activity among sedentary community-dwelling older adults. Design and Methods: A quasi-experimental design was used. Data were analyzed using a within-group pretest-post-test design to calculate changes…

  2. Do Sedentary Older Adults Benefit from Community-Based Exercise? Results from the Active Start Program

    ERIC Educational Resources Information Center

    Yan, Tingjian; Wilber, Kathleen H.; Aguirre, Rosa; Trejo, Laura

    2009-01-01

    Purpose: This study assessed the effectiveness of Active Start, a community-based behavior change and fitness program, designed to promote physical activity among sedentary community-dwelling older adults. Design and Methods: A quasi-experimental design was used. Data were analyzed using a within-group pretest-post-test design to calculate changes…

  3. Tracking Adult Learning Routes. A Pilot Investigation into Adult Learners' Starting Points and Progression to Further Education and Training.

    ERIC Educational Resources Information Center

    McGivney, Veronica

    A sample of approximately 50 educational organizations in England and Wales were invited to supply statistics or other information regarding where adults start their return to learning. Approximately two-thirds responded and also commented on the feasibility of collecting such data. Responses indicated a lack of "hard" quantitative…

  4. Kinematics of the Typical Beach Flags Start for Young Adult Sprinters

    PubMed Central

    Lockie, Robert G.; Vickery, William M.; de Jonge, Xanne A.K. Janse

    2012-01-01

    This study profiled beach flags start kinematics for experienced young adult sprinters. Five males and three females (age = 20.8 ± 2.1 years; height = 1.70 ± 0.06 meters [m]; mass = 63.9 ± 6.0 kilograms) completed four sprints using their competition start technique. A high-speed camera, positioned laterally, filmed the start. Data included: start time; hand clearance time; posterior movement from the start line; feet spacing during the start; elbow, hip, knee, trunk lean, and trajectory angles at take-off; and first step length. Timing gates recorded 0-2, 0-5, and 0-20 m time. Spearman’s correlations identified variables relating (p ≤ 0.05) to faster start and sprint times. The beach flags start involved sprinters moving 0.18 ± 0.05 m posterior to the start line by flexing both legs underneath the body before turning. Following the turn, the feet were positioned 0.47 ± 0.07 apart. This distance negatively correlated with start (ρ = -0.647), 0-2 (ρ = -0.683), and 0-5 m (ρ = -0.766) time. Beach flags start kinematics at take-off resembled research analyzing track starts and acceleration. The elbow extension angle (137.62 ± 13.45°) of the opposite arm to the drive leg correlated with 0-2 (ρ = -0.762), 0-5 (ρ = -0.810), and 0-20 m (ρ = -0.810) time. Greater arm extension likely assisted with stability during the start, leading to enhanced sprint performance. The drive leg knee extension angle (146.36 ± 2.26°) correlated with start time (ρ = -0.677), indicating a contribution to a faster start completion. A longer first step following the start related to faster 0-5 m time (ρ = -0.690). Sprinters quicker over 0-2 and 0-5 m were also quicker over 20 m (ρ = 0.881-0.952). Beach flags sprinters must ensure their start is completed quickly, such that they can attain a high speed throughout the race. Key pointsThere are specific movement patterns adopted by beach flags sprinters during the start. Sprinters will move posterior to the start time prior to

  5. Kinematics of the typical beach flags start for young adult sprinters.

    PubMed

    Lockie, Robert G; Vickery, William M; Janse de Jonge, Xanne A K

    2012-01-01

    This study profiled beach flags start kinematics for experienced young adult sprinters. Five males and three females (age = 20.8 ± 2.1 years; height = 1.70 ± 0.06 meters [m]; mass = 63.9 ± 6.0 kilograms) completed four sprints using their competition start technique. A high-speed camera, positioned laterally, filmed the start. Data included: start time; hand clearance time; posterior movement from the start line; feet spacing during the start; elbow, hip, knee, trunk lean, and trajectory angles at take-off; and first step length. Timing gates recorded 0-2, 0-5, and 0-20 m time. Spearman's correlations identified variables relating (p ≤ 0.05) to faster start and sprint times. The beach flags start involved sprinters moving 0.18 ± 0.05 m posterior to the start line by flexing both legs underneath the body before turning. Following the turn, the feet were positioned 0.47 ± 0.07 apart. This distance negatively correlated with start (ρ = -0.647), 0-2 (ρ = -0.683), and 0-5 m (ρ = -0.766) time. Beach flags start kinematics at take-off resembled research analyzing track starts and acceleration. The elbow extension angle (137.62 ± 13.45°) of the opposite arm to the drive leg correlated with 0-2 (ρ = -0.762), 0-5 (ρ = -0.810), and 0-20 m (ρ = -0.810) time. Greater arm extension likely assisted with stability during the start, leading to enhanced sprint performance. The drive leg knee extension angle (146.36 ± 2.26°) correlated with start time (ρ = -0.677), indicating a contribution to a faster start completion. A longer first step following the start related to faster 0-5 m time (ρ = -0.690). Sprinters quicker over 0-2 and 0-5 m were also quicker over 20 m (ρ = 0.881-0.952). Beach flags sprinters must ensure their start is completed quickly, such that they can attain a high speed throughout the race. Key pointsThere are specific movement patterns adopted by beach flags sprinters during the start. Sprinters will move posterior to the start time prior to

  6. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial.

    PubMed

    Kunisaki, Ken M; Niewoehner, Dennis E; Collins, Gary; Aagaard, Bitten; Atako, Nafisah B; Bakowska, Elzbieta; Clarke, Amanda; Corbelli, Giulio Maria; Ekong, Ernest; Emery, Sean; Finley, Elizabeth B; Florence, Eric; Infante, Rosa M; Kityo, Cissy M; Madero, Juan Sierra; Nixon, Daniel E; Tedaldi, Ellen; Vestbo, Jørgen; Wood, Robin; Connett, John E

    2016-12-01

    Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per μL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per μL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T

  7. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial

    PubMed Central

    Kunisaki, Ken M; Niewoehner, Dennis E; Collins, Gary; Aagaard, Bitten; Atako, Nafisah B; Bakowska, Elzbieta; Clarke, Amanda; Corbelli, Giulio Maria; Ekong, Ernest; Emery, Sean; Finley, Elizabeth B; Florence, Eric; Infante, Rosa M; Kityo, Cissy M; Madero, Juan Sierra; Nixon, Daniel E; Tedaldi, Ellen; Vestbo, Jørgen; Wood, Robin; Connett, John E

    2017-01-01

    Summary Background Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. Methods We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per µL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per µL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. Findings Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age

  8. Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy

    PubMed Central

    Ezeamama, Amara E; Woolfork, Makhabele N; Guwatudde, David; Bagenda, Danstan; Manabe, Yukari C; Fawzi, Wafaie W; Smith Fawzi, Mary C

    2016-01-01

    Abstract The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up. QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time∗depression P < 0.001) and anxiety levels (time∗anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time∗social support P = 0.8943) or number of stigmatizing experiences (time∗stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults. PMID:26945347

  9. HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries.

    PubMed

    Bennett, Diane E; Jordan, Michael R; Bertagnolio, Silvia; Hong, Steven Y; Ravasi, Giovanni; McMahon, James H; Saadani, Ahmed; Kelley, Karen F

    2012-05-01

    The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.

  10. Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

    PubMed

    Hoy, Jennifer F; Grund, Birgit; Roediger, Mollie; Schwartz, Ann V; Shepherd, John; Avihingsanon, Anchalee; Badal-Faesen, Sharlaa; de Wit, Stephane; Jacoby, Simone; La Rosa, Alberto; Pujari, Sanjay; Schechter, Mauro; White, David; Engen, Nicole Wyman; Ensrud, Kristine; Aagaard, Peer D; Carr, Andrew

    2017-09-01

    Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (-2.5% versus -1.0%; difference -1.5%, 95% confidence interval [CI] -2.2 to -0.8, p < 0.001) and spine (-1.9% versus -0.4%; difference -1.6%, 95% CI -2.2 to -1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. NCT00867048. © 2017 American Society for

  11. Cost effectiveness of darunavir/ritonavir combination antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

    PubMed

    Brogan, Anita J; Smets, Erik; Mauskopf, Josephine A; Manuel, Sarah A L; Adriaenssen, Ines

    2014-09-01

    The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir-boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive adults with HIV-1 infection in Canada. A Markov model with a 3-month cycle time and six CD4 cell-count-based health states (>500, 351-500, 201-500, 101-200, 51-100, and 0-50 cells/mm(3)) followed a cohort of treatment-naive adults with HIV-1 infection through initial darunavir/r or lopinavir/r combination therapy and a common set of subsequent regimens over the course of their remaining lifetimes. Population characteristics and transition probabilities were estimated from the ARTEMIS clinical trial and other trials. Costs (in 2014 Canadian dollars), utilities, and mortality were estimated from Canadian sources and published literature. Costs and health outcomes were discounted at 5% per year. One-way and probabilistic sensitivity analyses were performed, including a simple indirect comparison of the darunavir/r initial regimen with an atazanavir/r-based regimen. In the base-case lifetime analysis, individuals receiving initial therapy with the darunavir/r regimen experienced 0.25 more quality-adjusted life-years (QALYs) with lower antiretroviral drug costs (-$14,246) and total costs (-$18,402) than individuals receiving the lopinavir/r regimen, indicating that darunavir/r dominated lopinavir/r. In an indirect comparison with an atazanavir/r-based regimen, the darunavir/r regimen remained the dominant choice, but with lower cost savings (-$2,303) and QALY gains (0.02). Results were robust to a wide range of other changes in input parameter values, population characteristics, and modeling assumptions. The

  12. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

    PubMed

    Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John; Cambiano, Valentina; Chindelevitch, Leonid; Cori, Anne; Hontelez, Jan A C; Humair, Salal; Kerr, Cliff C; Klein, Daniel J; Mishra, Sharmistha; Mitchell, Kate M; Nichols, Brooke E; Vickerman, Peter; Bakker, Roel; Bärnighausen, Till; Bershteyn, Anna; Bloom, David E; Boily, Marie-Claude; Chang, Stewart T; Cohen, Ted; Dodd, Peter J; Fraser, Christophe; Gopalappa, Chaitra; Lundgren, Jens; Martin, Natasha K; Mikkelsen, Evelinn; Mountain, Elisa; Pham, Quang D; Pickles, Michael; Phillips, Andrew; Platt, Lucy; Pretorius, Carel; Prudden, Holly J; Salomon, Joshua A; van de Vijver, David A M C; de Vlas, Sake J; Wagner, Bradley G; White, Richard G; Wilson, David P; Zhang, Lei; Blandford, John; Meyer-Rath, Gesine; Remme, Michelle; Revill, Paul; Sangrujee, Nalinee; Terris-Prestholt, Fern; Doherty, Meg; Shaffer, Nathan; Easterbrook, Philippa J; Hirnschall, Gottfried; Hallett, Timothy B

    2014-01-01

    New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per

  13. When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa

    PubMed Central

    Schomaker, Michael; Egger, Matthias; Ndirangu, James; Phiri, Sam; Moultrie, Harry; Technau, Karl; Cox, Vivian; Giddy, Janet; Chimbetete, Cleophas; Wood, Robin; Gsponer, Thomas; Bolton Moore, Carolyn; Rabie, Helena; Eley, Brian; Muhe, Lulu; Penazzato, Martina; Essajee, Shaffiq; Keiser, Olivia; Davies, Mary-Ann

    2013-01-01

    Background There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%. Methods and Findings ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The

  14. Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study.

    PubMed

    Inzaule, Seth C; Hamers, Raph L; Kityo, Cissy; Rinke de Wit, Tobias F; Roura, Maria

    2016-01-01

    Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one's lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints experienced by temporary economic

  15. Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

    PubMed Central

    Inzaule, Seth C.; Hamers, Raph L.; Kityo, Cissy; Rinke de Wit, Tobias F.; Roura, Maria

    2016-01-01

    Background Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. Methods We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. Results The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Conclusion Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints

  16. Increasing HIV-1 Pre-Treatment Drug Resistance among Antiretroviral-Naïve Adults Initiating Treatment between 2006 and 2014 in Nairobi, Kenya

    PubMed Central

    CHUNG, Michael H.; SILVERMAN, Rachel; BECK, Ingrid A.; YATICH, Nelly; DROSS, Sandra; MCKERNAN-MULLIN, Jennifer; BII, Stephen; TAPIA, Kenneth; STERN, Joshua; Chohan, Bhavna; SAKR, Samah R.; KIARIE, James N.; FRENKEL, Lisa M.

    2016-01-01

    Summary Antiretroviral-naïve adults initiating antiretroviral therapy (ART) in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay (OLA). Prevalence of pre-treatment drug resistance (PDR) increased from 3.89% in 2006 to 10.93% in 2014 (p<0.001), and 95% of those with resistance had at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006. PMID:27058353

  17. Increasing HIV-1 pretreatment drug resistance among antiretroviral-naïve adults initiating treatment between 2006 and 2014 in Nairobi, Kenya.

    PubMed

    Chung, Michael H; Silverman, Rachel; Beck, Ingrid A; Yatich, Nelly; Dross, Sandra; McKernan-Mullin, Jennifer; Bii, Stephen; Tapia, Kenneth; Stern, Joshua; Chohan, Bhavna; Sakr, Samah R; Kiarie, James N; Frenkel, Lisa M

    2016-06-19

    Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006.

  18. Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results

    PubMed Central

    Floris-Moore, Michelle A; Mollan, Katie; Wilkin, Aimee M; Johnson, Marc A; Kashuba, Angela DM; Wohl, David A; Patterson, Kristine B; Francis, Owen; Kronk, Catherine; Eron, Joseph J

    2017-01-01

    Background Etravirine (ETR), an NNRTI approved for 200 mg BID dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing. Methods In this single arm, open-label study, 79 treatment-naïve HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200mg once daily to assess antiviral activity, safety, and tolerability. Antiretroviral activity at 48 weeks was determined by proportion of subjects with HIV-1 RNA <50 copies/mL (intention-to-treat, missing = failure). Results Of 79 eligible subjects, 90% were men, 62% African-American and 29% Caucasian. At baseline, median (Q1, Q3) age was 29 years (23, 44) and HIV-1 RNA 4.52 log10 copies/mL (4.07, 5.04). Sixty-nine (87%) completed a week 48 visit and 61 (77%, 95% CI: 66 – 86%) achieved HIV-1 RNA <50 copies/mL at week 48. At time of virologic failure, genotypic resistance-associated mutations were detected in 3 participants, 2 with E138K (1 alone and 1 with additional mutations). Median (95% CI) CD4+ cell count increase was 163 (136, 203) cells/uL. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality ≥ Grade 3 and 3 participants (3.8 %) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths. Conclusions In this study of ARV-naïve HIV+ adults, once daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once daily ETR may be a plausible option as part of a combination ARV regimen for treatment-naïve individuals. PMID:26263403

  19. [Pneumocystis jiroveci pneumonia characteristics in adults with AIDS with or without antiretroviral therapy].

    PubMed

    Bahamondes M, Laura; Villar Z, M José; Orellana C, Carolina; González R, Jimena; Montenegro U, Cristian

    2006-09-01

    Highly active antiretroviral therapy (HAART) has changed the epidemiology of Pneumocystis jiroveci pneumonia (PCP) in AIDS patients. Global incidence of PCP has decreased and now it is prevalent in AIDS patients who do not receive HAART or are unsuccessfully treated with persistent immune depression. Moreover, the immunologic response to HAART has caused a PCP form which is included in the immune restoration inflammatory syndrome (IRIS). As of late 2004, 75.5% of patients cared for at Dr. Lucio Córdova Infectious Diseases Hospital were receiving HAART. This study compares PCP clinical characteristics in patients under the effect of HAART (n: 6) with those without antiretroviral therapy (n: 12). Among those with HAART, 83.3% (5/6) were without immunologic responses and 16.7% with virologic response. The median CD4 counts were low in both groups: 20 cells/mm(3) without HAART and 51 cells/mm(3) with HAART. There were no differences in most of PCP characteristics, and no IRIS cases were observed. HAART-receiving group had less severe disease and lower frequency of both, complications and steroidal therapy prescription (P 0.023).

  20. Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi, 2007-2014.

    PubMed

    Tanuma, Junko; Lee, Kyu Ha; Haneuse, Sebastien; Matsumoto, Shoko; Nguyen, Dung Thi; Nguyen, Dung Thi Hoai; Do, Cuong Duy; Pham, Thuy Thanh; Nguyen, Kinh Van; Oka, Shinichi

    2016-01-01

    Although the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings. HIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014. Of 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03-75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8-54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months. ADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up.

  1. Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study

    PubMed Central

    Chakravarty, Jaya; Tiwary, Narendra K.; Prasad, Shashi Ranjan; Shukla, Saurabh; Tiwari, Anurag; Mishra, Rabindra Nath; Sundar, Shyam

    2014-01-01

    Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. By 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme. PMID:25488442

  2. Hypertension among HIV-Infected Adults Receiving Highly Active Antiretroviral Therapy (HAART) in Malaysia

    PubMed Central

    Hejazi, Nazisa; MSL, Huang; Lin, Khor Geok; Choong, Lee Christopher Kwok

    2014-01-01

    There are increasing researches about non-communicable disease such as elevated blood pressure among people living with HIV before and after initiation of highly active antiretroviral therapy (HAART). This cross-sectional study was designed to determine the prevalence of hypertension and associated risk factors among 340 HIV-infected patients on antiretroviral therapy at a Malaysian public hospital providing HIV-related treatment. Data on socioeconomic background, anthropometry, medical history and dietary intake of the patients were collected. Hypertension is defined as blood pressure ≥130/85 (mm Hg). Prevalence of hypertension was 45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024-1.078), higher body mass index (OR 1.18, 95% CI 1.106-2.71), bigger waist circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070, 95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95% CI 0.845-2.100) and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were significant risk factors for hypertension (p<0.001). After adjusting for other variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124, p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with hypertension. None of the antiretroviral therapy and immunologic factors was linked to hypertension. In conclusion hypertension among PLHIV was linked to the well-known risk factors such as age, gender and body mass index. With HAART, people can live longer by making monitoring and control of some reversible factors, especially excessive weight gain for maintaining quality of life. PMID:24576366

  3. Hypertension among HIV-infected adults receiving highly active antiretroviral therapy (HAART) in Malaysia.

    PubMed

    Hejazi, Nazisa; Huang, M S L; Lin, Khor Geok; Choong, Lee Christopher Kwok

    2013-12-01

    There are increasing researches about non-communicable disease such as elevated blood pressure among people living with HIV before and after initiation of highly active antiretroviral therapy (HAART). This cross-sectional study was designed to determine the prevalence of hypertension and associated risk factors among 340 HIV-infected patients on antiretroviral therapy at a Malaysian public hospital providing HIV-related treatment. Data on socioeconomic background, anthropometry, medical history and dietary intake of the patients were collected. Hypertension is defined as blood pressure >=130/85 (mm Hg). Prevalence of hypertension was 45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024-1.078), higher body mass index (OR 1.18, 95%CI 1.106-2.71), bigger waist circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070, 95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95%CI 0.845-2.100) and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were significant risk factors for hypertension (p<0.001). After adjusting for other variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124, p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with hypertension. None of the antiretroviral therapy and immunologic factors was linked to hypertension. In conclusion hypertension among PLHIV was linked to the well-known risk factors such as age, gender and body mass index. With HAART, people can live longer by making monitoring and control of some reversible factors, especially excessive weight gain for maintaining quality of life.

  4. HIV viral load suppression in adults and children receiving antiretroviral therapy - results from the IeDEA collaboration.

    PubMed

    Jiamsakul, Awachana; Kariminia, Azar; Althoff, Keri N; Cesar, Carina; Cortes, Claudia P; Davies, Mary-Ann; Do, Viet Chau; Eley, Brian; Gill, John; Kumarasamy, Nagalingeswaran; Machado, Daisy Maria; Moore, Richard; Prozesky, Hans; Zaniewski, Elizabeth; Law, Matthew

    2017-07-08

    Having 90% of patients on antiretroviral therapy (ART) and achieving an undetectable viral load (VL) is one of the 90:90:90 by 2020 targets. In this global analysis, we investigated the proportions of adult and paediatric patients with VL suppression in the first three years after ART initiation. Patients from the IeDEA cohorts who initiated ART between 2010 and 2014 were included. Proportions with VL suppression (<1000 copies/mL) were estimated using: (i) strict intention-to-treat (ITT) - loss to follow-up (LTFU) and dead patients counted as having detectable VL; and (ii) modified ITT - LTFU and dead patients were excluded. Logistic regression was used to identify predictors of viral suppression at one year after ART initiation using modified ITT. A total of 35561 adults from 38 sites/16 countries and 2601 children from 18 sites/6 countries were included. When comparing strict with modified ITT methods, the proportion achieving VL suppression at three years from ART initiation changed from 45.1% to 90.2% in adults, and 60.6% to 80.4% in children. In adults, older age, higher CD4 count pre-ART, and homosexual/bisexual HIV exposure were associated VL suppression. In children, older age and higher CD4 percentage pre-ART showed significant associations with VL suppression. Large increases in the proportion of VL suppression in adults were observed when we excluded those who were LTFU or had died. The increases were less pronounced in children. Greater emphasis should be made to minimise LTFU and maximise patient retention in HIV-infected patients of all age groups.

  5. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults

    PubMed Central

    Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O’Cleirigh, Conall; Pinkston, Megan M.; Safren, Steven A.

    2015-01-01

    There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting. PMID:26688659

  6. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.

    PubMed

    Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A

    2015-11-01

    There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.

  7. Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults.

    PubMed

    Alvarez, M; Monge, S; Chueca, N; Guillot, V; Viciana, P; Anta, L; Rodriguez, C; Gomez-Sirvent, J L; Navarro, G; de los Santos, I; Moreno, S; García, F

    2015-01-01

    We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. HIV infection and arterial stiffness among older-adults taking antiretroviral therapy in rural Uganda

    PubMed Central

    Siedner, Mark J.; Kim, June-Ho; Nakku, Ruth Sentongo; Hemphill, Linda; Triant, Virginia A.; Haberer, Jessica E.; Martin, Jeffrey N.; Boum, Yap; Kwon, Douglas S.; Tsai, Alexander C.; Hunt, Peter W.; Okello, Samson; Bangsberg, David R.

    2015-01-01

    HIV infection is associated with arterial stiffness, but no studies have assessed this relationship in sub-Saharan Africa. We enrolled 205 participants over 40 years old in Uganda: 105 on antiretroviral therapy for a median of 7 years, and a random sample of 100 age and gender-matched HIV-uninfected controls from the clinic catchment area. The prevalence of arterial stiffness (ABI>1.2) was 33%, 18%, 19% and 2% in HIV+ men, HIV- men, HIV+ women, and HIV- women. In multivariable models adjusted for cardiovascular risk factors, HIV+ individuals had over double the prevalence of arterial stiffness (APR 2.86, 95%CI 1.41–5.79, P=0.003). PMID:26636926

  9. Antiretroviral therapy enrollment characteristics and outcomes among HIV-infected adolescents and young adults compared with older adults--seven African countries, 2004-2013.

    PubMed

    Auld, Andrew F; Agolory, Simon G; Shiraishi, Ray W; Wabwire-Mangen, Fred; Kwesigabo, Gideon; Mulenga, Modest; Hachizovu, Sebastian; Asadu, Emeka; Tuho, Moise Zanga; Ettiegne-Traore, Virginie; Mbofana, Francisco; Okello, Velephi; Azih, Charles; Denison, Julie A; Tsui, Sharon; Koole, Olivier; Kamiru, Harrison; Nuwagaba-Biribonwoha, Harriet; Alfredo, Charity; Jobarteh, Kebba; Odafe, Solomon; Onotu, Dennis; Ekra, Kunomboa A; Kouakou, Joseph S; Ehrenkranz, Peter; Bicego, George; Torpey, Kwasi; Mukadi, Ya Diul; van Praag, Eric; Menten, Joris; Mastro, Timothy; Dukes Hamilton, Carol; Swaminathan, Mahesh; Dokubo, E Kainne; Baughman, Andrew L; Spira, Thomas; Colebunders, Robert; Bangsberg, David; Marlink, Richard; Zee, Aaron; Kaplan, Jonathan; Ellerbrock, Tedd V

    2014-11-28

    Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

  10. Diminished physical function in older HIV-infected adults in the Southeastern U.S. despite successful antiretroviral therapy.

    PubMed

    Khoury, Audrey L; Morey, Miriam C; Wong, Tammy C; McNeil, Donna Lynn; Humphries, Barlett; Frankey, Katherine; Pieper, Carl F; Hicks, Charles B; Huffman, Kim; McKellar, Mehri S

    2017-01-01

    As antiretroviral therapy efficacy improves, HIV is gradually being recognized more as a chronic disease within the aging HIV-infected population. While these individuals are surviving into old age, they may, however, be experiencing "accelerated aging" with greater declines in physical function than that observed among comparably matched individuals free of HIV. This decline is not well understood and it remains unclear if physical decline correlates with the degree of immunosuppression based on CD4 lymphocyte nadir. In a cross-sectional study of accelerated aging in the older HIV-infected population on antiretroviral therapy (ART), physical performance evaluations were completed on a cohort of 107 HIV-infected subjects, age 50 years or older (with no HIV-1 RNA >200 copies/mL in the prior 12 months), and compared to reference ranges for age- and gender-matched HIV-uninfected persons. Physical performance testing consisted of four validated assessments: the 2.4-meter walk, 30-second chair stand, grip strength and 6-minute walk test. When compared to age- and gender-matched HIV-uninfected reference controls, older HIV-infected persons had diminished physical function. No correlation was found between physical function and degree of immunosuppression as determined by pre-ART CD4 nadir. Despite improved survival, HIV-infected adults on suppressive ART have diminished physical function compared to HIV-uninfected persons. The degree of HIV-associated immunosuppression does not correlate with the observed degree of physical function decline in older HIV-infected persons, suggesting the decline is mediated by other mechanisms.

  11. Community-Based Accompaniment with Supervised Antiretrovirals for HIV-Positive Adults in Peru: A Cluster-Randomized Trial.

    PubMed

    McLaughlin, Megan M; Franke, Molly F; Muñoz, Maribel; Nelson, Adrianne K; Saldaña, Olga; Cruz, Janeth Santa; Wong, Milagros; Zhang, Zibiao; Lecca, Leonid; Ticona, Eduardo; Arevalo, Jorge; Sanchez, Eduardo; Sebastián, Jose Luis; Shin, Sonya

    2017-01-10

    We conducted a cluster-randomized trial to estimate effects of directly observed combination antiretroviral therapy (DOT-cART) on retention with viral suppression among HIV-positive adults in Peru. We randomly allocated facilities to receive the 12-month intervention plus the standard of care, including adherence support provided through accompaniment. In the intervention arm, health workers supervised doses, twice daily, and accompanied patients to appointments. Among 356 patients, intention-to-treat analyses showed no statistically significant benefit of DOT, relative to no-DOT, at 12 or 24 months (adjusted probability of primary outcome: 0.81 vs. 0.73 and 0.76 vs. 0.68, respectively). A statistically significant benefit of DOT was found in per-protocol and as-treated analyses at 12 months (0.83 for DOT vs. 0.73 for no DOT, p value: 0.02 per-protocol, 0.01 as-treated), but not 24 months. Rates of retention with viral suppression were high in both arms. Among adults receiving robust adherence support, the added effect of time-limited DOT, if any, is small-to-moderate.

  12. A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 – 2011

    PubMed Central

    Dube, Nomathemba Michell; Summers, Robert; Tint, Khin-San; Mayayise, Guistee

    2012-01-01

    Background Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. Methods A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. Results After HAART initiation, with an average lapse of 17.8 months (range: 0 – 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). Conclusion The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should

  13. Modeling the impact of early antiretroviral therapy for adults coinfected with HIV and hepatitis B or C in South Africa.

    PubMed

    Martin, Natasha K; Devine, Angela; Eaton, Jeffrey W; Miners, Alec; Hallett, Timothy B; Foster, Graham R; Dore, Gregory J; Easterbrook, Philippa J; Legood, Rosa; Vickerman, Peter

    2014-01-01

    There has been discussion about whether individuals coinfected with HIV and hepatitis C virus (HCV) or hepatitis B virus (HBV) (∼30% of all people living with HIV) should be prioritized for early HIV antiretroviral therapy (ART). We assess the relative benefits of providing ART at CD4 count below 500  cells/μl or immediate ART to HCV/HIV or HBV/HIV-coinfected adults compared with HIV-monoinfected adults. We evaluate individual outcomes (HIV/liver disease progression) and preventive benefits in a generalized HIV epidemic setting. We modeled disease progression for HIV-monoinfected, HBV/HIV-coinfected, and HCV/HIV-coinfected adults for differing ART eligibility thresholds (CD4 <350  cells/μl, CD4 <500  cells/μl, immediate ART eligibility upon infection). We report disability-adjusted life-years averted per 100 person-years on ART (DALYaverted/100PYonART) as a measure of the health benefits generated from incremental changes in ART eligibility. Sensitivity analyses explored impact on sexual HIV and vertical HIV, HCV, and HBV transmission. For HBV/HIV-coinfected adults, a switch to ART initiation at CD4 count below 500  cells/μl from CD4 below 350  cells/μl generates 9% greater health benefits per year on ART (48 DALYaverted/100PYonART) than for HIV-monoinfected adults (44 DALYaverted/100PYonART). Additionally, ART at CD4 below 500  cells/μl could prevent 25% and 32% of vertical transmissions of HIV and HBV, respectively. For HCV/HIV-coinfected adults, ART at CD4 below 500  cells/μl generates 10% fewer health benefits (40 DALYaverted/100PYonART) than for HIV monoinfection, unless ART reduces progression to cirrhosis by more than 70% (33% in base-case). The additional therapeutic benefits of ART for HBV-related liver disease results in ART generating more health benefits among HBV/HIV-coinfected adults than HIV-monoinfected individuals, whereas less health benefits are generated amongst HCV/HIV coinfection in a generalized HIV epidemic

  14. Incidence of serious morbidity in HIV-infected adults on antiretroviral therapy in a West African care centre, 2003-2008

    PubMed Central

    2013-01-01

    Background In resource-limited settings, scaling-up antiretroviral treatment (ART) has required the involvement of decentralized health facilities with limited equipment. We estimated the incidence of serious morbidity among HIV-infected adults receiving ART in one of these HIV routine care center in sub-Saharan Africa. Methods We conducted a prospective study at the Centre Medical de Suivi des Donneurs de Sang (CMSDS), which is affiliated with the National Centre for Blood Transfusion in Abidjan, Côte d’Ivoire. Adult patients infected with HIV-1 or HIV-1/HIV-2 who initiated ART between January 2003 and December 2008 were eligible for the study. Standardized clinical data were collected at each visit. Serious morbidity was defined as a new episode of malaria, WHO stage 3–4 event, ANRS grade 3–4 adverse event, or any event leading to death or to hospitalization. Results 1008 adults, 67% women, with a median age of 35 years, and a median pre-ART CD4 count of 186/mm3 started ART and were followed for a median of 17.3 months. The overall incidences of loss to follow-up, death, and attrition were 6.2/100 person-years (PY) [95% CI 5.1-7.2], 2.3/100 PY [95% CI 1.6-2.9], and 8.1/100 PY [95% CI 7.0-9.4], respectively. The incidence of first serious event was 11.5/100 PY overall, 15.9/100 PY within the first year and 8.3/100 PY thereafter. The most frequently documented specific diagnoses were malaria, tuberculosis, bacterial septicemia and bacterial pneumonia. Conclusion Among HIV-infected adults followed in routine conditions in a West African primary care clinic, we recorded a high incidence of serious morbidity during the first year on ART. Providing care centers with diagnostic tools and standardizing data collection are necessary steps to improve the quality of care in primary care facilities in sub-Saharan Africa. PMID:24373303

  15. Vitamin E concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

    PubMed

    Itinoseki Kaio, Daniella J Itinoseki; Rondó, Patricia Helen C; Luzia, Liania Alves; Souza, José Maria P; Firmino, Aline Vale; Santos, Sigrid Sousa

    2014-09-15

    HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 μmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment.

  16. Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. Methods Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider’s perspective using site- and country-level data and are reported in 2011 USD. Results Patients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293), ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months’ worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site. Conclusions Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were

  17. Effect of Intercurrent Infections and Vaccinations on Immune and Inflammatory Biomarkers Among Human Immunodeficiency Virus-Infected Adults on Suppressive Antiretroviral Therapy

    PubMed Central

    Tan, Darrell H. S.; Szadkowski, Leah; Raboud, Janet; Yi, Tae Joon; Shannon, Brett; Kaul, Rupert; Liles, W. Conrad; Walmsley, Sharon

    2015-01-01

    We used generalized estimating equations to quantify the impact of recent vaccination or intercurrent infections on immune and inflammatory biomarkers among 144 human immunodeficiency virus (HIV)-infected adults with HIV RNA < 50 copies/mL on antiretroviral therapy. These events were associated with a 2.244 µg/mL increase in high sensitivity C-reactive protein and should be routinely assessed in future studies. PMID:26380337

  18. Effects of highly active antiretroviral therapy on the survival of HIV-infected adult patients in urban slums of Kenya.

    PubMed

    Muhula, Samuel Opondo; Peter, Memiah; Sibhatu, Biadgilign; Meshack, Ndirangu; Lennie, Kyomuhangi

    2015-01-01

    Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated with mortality among adult patients on ART in resource poor, urban, sub-Saharan African setting. A prospective open cohort study was conducted with adult patients on ART at a clinic in Kibera slums, Nairobi, Kenya. The patients' enrollment to care was between March 2005 and November 2011. Descriptive statistics were computed and Kaplan-Meier (KM) methods used to estimate survival time while Cox's proportional hazards (CPH) model fitted to determine mortality predictors. A total of 2,011 adult patients were studied, 69% being female. Female gender (p=0.0016), zidovudine-based regimen patients (p<0.0001), CD4 count>351 patients (p<0.0001), WHO stage I patients (p<0.0001) and "Working" functional status patients recorded better survival probability on ART. In CPH analysis, the hazard of dying was higher in patients on Stavudine-based regimen(hazard ratio (HR)=.8; 95% CI, 1.5-2.2; p<0.0001),CD4 count<50 cells/µl (HR=1.6; 95% CI, 1.5-1.7;p<0.0001), WHO Stage IV at ART initiation (HR=1.3; 95% CI, 1.1-1.6; p=0.016) and bedridden patients (HR=2.7; 95% CI, 1.7-4.4;p<0.0001). There was increased mortality among the males, those with advanced Immunosuppression, late WHO stage and bedridden patients. The findings further justify the need to switch patients on Stavudine-based regimen as per the WHO recommendations.

  19. Relationship between total bilirubin, endothelial function, inflammation and oxidative stress in HIV-infected adults on stable antiretroviral therapy

    PubMed Central

    Hileman, Corrilynn O.; Longenecker, Chris T.; Carman, Teresa L.; Milne, Ginger L.; Labbato, Danielle E.; Storer, Norma J.; White, Cynthia A.; McComsey, Grace A.

    2012-01-01

    Objective Enhanced inflammation is evident in HIV, even with virologic suppression. Outside HIV, studies show an independent association between higher total bilirubin and better endothelial function as well as lower prevalence of coronary heart disease possibly due to the anti-inflammatory and antioxidant effect of bilirubin. Methods A cross-sectional study was performed in HIV-1 infected adults on stable antiretroviral therapy (ART) to determine if a relationship exists between total bilirubin and endothelial function (flow mediated dilation (FMD) of the brachial artery), inflammation (interleukin-6 (IL-6), soluble tumor necrosis factor receptors, C-reactive protein, adhesion molecules), coagulation markers (fibrinogen and D-Dimer) and oxidative stress (F2-Isoprostanes). Endpoints were compared based on total bilirubin levels and atazanavir status using distributionally-appropriate, two-sample tests. Correlation coefficients were determined between total bilirubin and end points. Linear regression was used to model the relationship between total bilirubin (and atazanavir status) and FMD. Results 98 adults were included. Total bilirubin was higher in atazanavir group (median (IQR) 1.8 (1.1–2.6) vs. 0.6 (0.4–1.4) mg/dL; p<0.01) as was insulin, HOMA-IR and fibrinogen. Total bilirubin was positively correlated with fibrinogen and was not correlated with other outcomes. After adjustment, neither total bilirubin nor atazanavir status was associated with FMD. Conclusions In virologically-suppressed, HIV-infected adults on stable ART, neither total bilirubin nor atazanavir use was associated with improved endothelial function as measured by FMD, inflammation or oxidative stress as measured by biomarkers. PMID:22624591

  20. Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy in Tanzania

    PubMed Central

    LIU, Enju; MAKUBI, Abel; DRAIN, Paul; SPIEGELMAN, Donna; SANDO, David; LI, Nan; CHALAMILLA, Guerino; SUDFELD, Christopher R.; HERTZMARK, Ellen; FAWZI, Wafaie W.

    2015-01-01

    Objective To determine the incidence rate and risk factors of tuberculosis (TB) among HIV-infected adults accessing antiretroviral therapy (ART) in Tanzania. Design A prospective observational study among HIV-infected adults attending 47 HIV clinics in Dar es Salaam. Methods We estimated TB incidence rates among HIV-infected patients prior to and after ART initiation. We used Cox proportional hazard regressions to determine the predictors of incident TB among HIV-infected adults enrolled in the HIV care and treatment program. Results We assessed 67,686 patients for a median follow-up period of 24 (interquartile range: 8–49) months; 7,602 patients were diagnosed with active TB. The TB incidence rate was 7.9 (95% Confidence Interval (CI), 7.6–8.2)/100 person-years prior to ART initiation, and 4.4(95%CI, 4.2–4.4)/100 person-years for patients receiving ART. In multivariate analyses, patients on ART in the first 3 months had a 57% higher risk of TB (Hazard Ratio:1.57, 95%CI:1.47–1.68) compared to those not on ART, but the risk significantly decreased with increasing duration of ART. Risk factors for incident TB included being male, having low body mass index or middle upper arm circumference, lower CD4 cell count, and advanced WHO disease stage. There was seasonal variation for incident TB, with higher risk observed following the rainy seasons (May, June, and November). Conclusion In TB endemic regions, HIV-infected patients initiating ART, particularly males and those with poor nutritional status, should be closely monitored for active TB in the months following ART initiation. In addition to increasing the access to ART, interventions should be considered to improve nutritional status among HIV-infected patients. PMID:26091295

  1. [National consensus document by GESIDA/National Aids Plan on antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2011 update)].

    PubMed

    2011-03-01

    The update of these adult antiretroviral treatment (cART) recommendations has been carried out by consensus of a panel consisting of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) who have reviewed the antiretroviral efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase), or presented in medical scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend antiretroviral treatment (ART) was established by consensus in each situation. The current treatment of choice for HIV infection is the combination of three drugs. Combined ART is recommended in patients with symptomatic HIV infection, and guidelines on this treatment in patients with an opportunistic type C infection are included. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: a) therapy should be started in patients with CD4 counts <350 cells/μL; b) Therapy should be recommended when CD4 counts are between 350 and 500 cells/μL, except when CD4 are stabilized, there is low plasma viral load, or the patient not willing; c) Therapy could be deferred when CD4 counts are above 500 cells/ μL, but should be considered in cases of cirrhosis, chronic hepatitis C, hepatitis B fulfilling treatment criteria, high cardiovascular risk, HIV nephropathy, viral load > 100,000 copies/ mL, proportion of CD4 cells < 14%, in people aged >55 years, and in cases of discordant serological sexual couples in order to reduce transmission. cART should include 2 reverse transcriptase inhibitor nucleoside analogues (AN) and a non-analogue reverse transcriptase inhibitor (NN) or 2 AN and a

  2. Initiation of antiretroviral therapy in HIV-infected adults with skin complaints in northern Tanzania

    PubMed Central

    Mavura, Daudi R.; Masenga, E. John; Minja, Eli; Grossmann, Henning; Crump, John A.; Bartlett, John A.

    2015-01-01

    Abnormal skin findings are identified in over 90% of human immunodeficiency virus (HIV)-infected persons globally. A prospective cohort study of HIV-infected patients with skin complaints commencing antiretroviral therapy (ART) in northern Tanzania was undertaken. Consecutive HIV-infected subjects presenting with skin complaints, who met criteria for ART initiation, were recruited at a Tanzanian Regional Dermatology Training Center. A single dermatologist evaluated all subjects; baseline skin biopsies were performed, and CD4+ cell counts and plasma HIV RNA levels were measured. All subjects received a fixed-dose combination of stavudine, lamivudine, and nevirapine. A total of 100 subjects were enrolled; 86 subjects completed six months of follow-up. Median baseline CD4+ cell counts and plasma HIV RNA levels were 120 cells/μl and 5.2 log10 copies/ml. The most common dermatologic condition was papular pruritic eruption (47%). The median baseline score on the Burn Scale was 38%. After six months, 10 subjects had achieved the complete resolution of skin abnormalities. In those without complete resolution, the median Burn Scale score improved to 7%. Five patients developed new eruptions by month 3, which in two cases were attributed to drug reactions. In the 86 subjects remaining on ART after six months, the median CD4+ cell count had increased to 474 cells/μl, and plasma HIV RNA levels were <400 copies/ml in 85 (99%) subjects. Patients with HIV infection with skin complaints experienced marked clinical improvements following ART initiation. PMID:25256912

  3. Use, perceptions, and acceptability of a ready-to-use supplementary food among adult HIV patients initiating antiretroviral treatment: a qualitative study in Ethiopia

    PubMed Central

    Olsen, Mette Frahm; Tesfaye, Markos; Kaestel, Pernille; Friis, Henrik; Holm, Lotte

    2013-01-01

    Objectives Ready-to-use supplementary foods (RUSF) are used increasingly in human immunodeficiency virus (HIV) programs, but little is known about how it is used and viewed by patients. We used qualitative methods to explore the use, perceptions, and acceptability of RUSF among adult HIV patients in Jimma, Ethiopia. Methods The study obtained data from direct observations and 24 in-depth interviews with HIV patients receiving RUSF. Results Participants were generally very motivated to take RUSF and viewed it as beneficial. RUSF was described as a means to fill a nutritional gap, to “rebuild the body,” and protect it from harmful effects of antiretroviral treatment (ART). Many experienced nausea and vomiting when starting the supplement. This caused some to stop supplementation, but the majority adapted to RUSF. The supplement was eaten separately from meal situations and only had a little influence on household food practices. RUSF was described as food with “medicinal qualities,” which meant that many social and religious conventions related to food did not apply to it. The main concerns about RUSF related to the risk of HIV disclosure and its social consequences. Conclusion HIV patients view RUSF in a context of competing livelihood needs. RUSF intake was motivated by a strong wish to get well, while the risk of HIV disclosure caused concerns. Despite the motivation for improving health, the preservation of social networks was prioritized, and nondisclosure was often a necessary strategy. Food sharing and religious fasting practices were not barriers to the acceptability of RUSF. This study highlights the importance of ensuring that supplementation strategies, like other HIV services, are compatible with the sociocultural context of patients. PMID:23766634

  4. Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam

    PubMed Central

    Pollack, Todd M.; Duong, Hao T.; Pham, Thuy T.; Do, Cuong D.; Colby, Donn

    2017-01-01

    High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1–10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15–3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75–2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use

  5. Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam.

    PubMed

    Pollack, Todd M; Duong, Hao T; Pham, Thuy T; Do, Cuong D; Colby, Donn

    2017-01-01

    High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1-10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15-3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75-2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among

  6. Utility of Cryptococcal Antigen Screening and Evolution of Asymptomatic Cryptococcal Antigenemia among HIV-Infected Women Starting Antiretroviral Therapy in Thailand.

    PubMed

    Kwan, Candice K; Leelawiwat, Wanna; Intalapaporn, Poj; Anekthananon, Thanomsak; Raengsakulrach, Boonyos; Peters, Philip J; McNicholl, Janet M; Park, Benjamin J; McConnell, Michelle S; Weidle, Paul J

    2014-01-01

    Cryptococcal meningitis (CM) remains a significant HIV-associated opportunistic infection in Southeast Asia and Africa, with a high burden of disease and a high mortality rate despite the availability of antiretroviral therapy (ART). We retrospectively examined the utility of cryptococcal antigen screening to identify risk for CM among 211 Thai women initiating ART. Antigenemia prevalence was 11% (n = 9) among 84 women with a CD4 count <100 cells/mm(3). Screening identified all women who later developed CM. Cryptococcal antigen titers decreased over time with ART. Our study confirmed findings from previous studies in Thailand and South Africa and provided novel observational data regarding the course of cryptococcal antigenemia in patients initiating ART and the poor efficacy of low-dose fluconazole prophylaxis in preventing CM among patients with antigenemia.

  7. Short Communication: Limited HIV Pretreatment Drug Resistance Among Adults Attending Free Antiretroviral Therapy Clinic of Pune, India.

    PubMed

    Karade, Santosh; Patil, Ajit A; Ghate, Manisha; Kulkarni, Smita S; Kurle, Swarali N; Risbud, Arun R; Rewari, Bharat B; Gangakhedkar, Raman R

    2016-04-01

    In India, the roll out of the free antiretroviral therapy (ART) program completed a decade of its initiation in 2014. The success of first-line ART is influenced by prevalence of HIV pretreatment drug resistance (PDR) in the population. In this cross-sectional study, we sought to determine the prevalence of PDR among adults attending the state-sponsored free ART clinic in Pune in western India. Fifty-two individuals eligible for ART as per national guidelines with median CD4 cell count of 253 cells/mm(3) (inter quartile range: 149-326) were recruited between January 2014 and April 2015. Population-based sequencing of partial pol gene sequences from plasma specimen revealed predominant HIV-1 subtype C infection (96.15%) and presence of single-drug resistance mutations against non-nucleoside reverse transcriptase inhibitor in two sequences. The study supports the need for periodic surveillance, when offering PDR testing at individual level is not feasible.

  8. Nutritional status of Malawian adults on antiretroviral therapy 1 year after supplementary feeding in the first 3 months of therapy.

    PubMed

    Ndekha, Macdonald; van Oosterhout, Joep J G; Saloojee, Haroon; Pettifor, John; Manary, Mark

    2009-09-01

    To test the hypothesis that individuals on antiretroviral therapy (ART) for 3 months with a greater body mass index (BMI) as a result of supplementary feeding with ready-to-use fortified spread would maintain a higher BMI 9 months after the feeding ended. Two cohorts of wasted adults with AIDS, after 12 months of ART and 3 months of supplementary feeding with either ready-to-use fortified spread, an energy dense lipid paste; or corn/soy blended flour, were assessed for clinical and anthropometric status, quality of life, and ART adherence after 3 and 9 months. 336 ART patients participated: 162 who had received ready-to-use fortified spread and 174 who had received corn/soy blended flour. 9 months after stopping food supplements, both groups had a similar BMI, fat-free body mass, hospitalization rate and mortality. Binary logistic regression modelling showed that lower BMI, lower CD4 count, and older age at baseline were associated with a higher risk of death (odds ratio for BMI = 0.63, 95% CI 0.47-0.79). Adherence to the ART regimen and quality of life were similar in both cohorts. While supplementary feeding with ready-to-use fortified spread can ameliorate the BMI, an established risk factor for mortality, this effect is sustained only during the time of the intervention. Supplementary feeding of wasted patients for longer than 3 months should be investigated.

  9. Prevalence, trend and risk factors for antiretroviral therapy discontinuation among HIV-infected adults in Ethiopia in 2003-2015.

    PubMed

    Gesesew, Hailay Abrha; Ward, Paul; Woldemichael, Kifle; Mwanri, Lillian

    2017-01-01

    It is well acknowledged that antiretroviral therapy (ART) discontinuation hampers the progress towards achieving the UNAIDS treatment targets that aim to treat 90% of HIV diagnosed patients and achieve viral suppression for 90% of those on treatment. Nevertheless, the magnitude, trend and risk factors for ART discontinuation have not been explored extensively. We carried out a retrospective data analysis to assess prevalence, trend and risk factors for ART discontinuation among adults in Southwest Ethiopia. 12 years retrospective cohort analysis was performed with 4900 HIV-infected adult patients between 21 June 2003 and 15 March 2015 registered at the ART clinic at Jimma University Teaching Hospital. ART discontinuation could be loss to follow-up, defaulting and/or stopping medication while remaining in care. Because data for 2003 and 2015 were incomplete, the 10 years data were used to describe trends for ART discontinuation using a line graph. We used binary logistic regression to identify factors that were correlated with ART discontinuation. To handle missing data, we applied multiple imputations assuming missing at random pattern. In total, 4900 adult patients enrolled on ART, of whom 1090 (22.3%) had discontinued, 954 (19.5%) had transferred out, 300 (6.1%) had died, 2517 (51.4%) were alive and on ART, and the remaining 39 (0.8%) had unknown outcome status. The trend of ART discontinuation showed an upward direction in the recent times and reached a peak, accounting for a magnitude of 10%, in 2004 and 2005. Being a female (AOR = 2.1, 95%CI: 1.7-2.8), having an immunological failure (AOR = 2.3, 1.9-8.2), having tuberculosis/HIV co-infection (AOR = 1.5, 1.1-2.1) and no previous history of HIV testing (AOR = 1.8, 1.4-2.9) were the risk factors for ART discontinuation. One out of five adults had discontinued from ART, and the trend of ART discontinuation increased recently. Discontinued adults were more likely to be females, tuberculosis/HIV co-infected, with

  10. Quality assurance program for clinical measurement of antiretrovirals: AIDS clinical trials group proficiency testing program for pediatric and adult pharmacology laboratories.

    PubMed

    Holland, Diane T; DiFrancesco, Robin; Stone, Judith; Hamzeh, Fayez; Connor, James D; Morse, Gene D

    2004-03-01

    Clinical trials designed to compare antiretroviral regimens, investigate therapeutic drug monitoring, or measure pharmacometrics often include protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and nucleoside reverse transcriptase inhibitors, requiring the measurement of these antiretrovirals in plasma. Within the adult and pediatric AIDS Clinical Trials Group (ACTG), a network of Pharmacology Support Laboratories (PSLs) is a component of the group laboratory infrastructure and conducts these types of pharmacologic assays. The adult ACTG has developed a comprehensive quality assurance program for the conduct of clinical pharmacology protocols, one component of which is the antiretroviral proficiency testing (PT) program that has been implemented between the adult and pediatric pharmacology laboratories of the ACTG. PT testing samples were prepared and distributed in July 2001, February 2002, and July 2002. High, medium, and low concentrations of PIs (indinavir, saquinavir, amprenavir, lopinavir, ritonavir, and nelfinavir) and NNRTIs (nevirapine and efavirenz) were added to drug-free EDTA plasma and distributed, on dry ice, to eight ACTG PSLs. One testing laboratory used liquid chromatography-tandem mass spectrometry, and seven used high-performance liquid chromatography-UV analysis. A result was considered acceptable if it was within 20% deviation of the assigned concentration. For all concentrations of PIs evaluated, 96% of samples tested (430 of 448 measurements) met the acceptance criteria. For both NNRTIs, 100% of samples tested (140 of 140 measurements) met the acceptance criteria. In conclusion, the PT program results presented demonstrate excellent interlaboratory agreement for all antiretrovirals tested and provide support for the merger of plasma concentration data among laboratories for large clinical trials.

  11. Quality Assurance Program for Clinical Measurement of Antiretrovirals: AIDS Clinical Trials Group Proficiency Testing Program for Pediatric and Adult Pharmacology Laboratories

    PubMed Central

    Holland, Diane T.; DiFrancesco, Robin; Stone, Judith; Hamzeh, Fayez; Connor, James D.; Morse, Gene D.

    2004-01-01

    Clinical trials designed to compare antiretroviral regimens, investigate therapeutic drug monitoring, or measure pharmacometrics often include protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and nucleoside reverse transcriptase inhibitors, requiring the measurement of these antiretrovirals in plasma. Within the adult and pediatric AIDS Clinical Trials Group (ACTG), a network of Pharmacology Support Laboratories (PSLs) is a component of the group laboratory infrastructure and conducts these types of pharmacologic assays. The adult ACTG has developed a comprehensive quality assurance program for the conduct of clinical pharmacology protocols, one component of which is the antiretroviral proficiency testing (PT) program that has been implemented between the adult and pediatric pharmacology laboratories of the ACTG. PT testing samples were prepared and distributed in July 2001, February 2002, and July 2002. High, medium, and low concentrations of PIs (indinavir, saquinavir, amprenavir, lopinavir, ritonavir, and nelfinavir) and NNRTIs (nevirapine and efavirenz) were added to drug-free EDTA plasma and distributed, on dry ice, to eight ACTG PSLs. One testing laboratory used liquid chromatography-tandem mass spectrometry, and seven used high-performance liquid chromatography-UV analysis. A result was considered acceptable if it was within 20% deviation of the assigned concentration. For all concentrations of PIs evaluated, 96% of samples tested (430 of 448 measurements) met the acceptance criteria. For both NNRTIs, 100% of samples tested (140 of 140 measurements) met the acceptance criteria. In conclusion, the PT program results presented demonstrate excellent interlaboratory agreement for all antiretrovirals tested and provide support for the merger of plasma concentration data among laboratories for large clinical trials. PMID:14982771

  12. Effect of cotrimoxazole on mortality in HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis

    PubMed Central

    Suthar, Amitabh B; Mermin, Jonathan; Van Rie, Annelies

    2012-01-01

    Abstract Objective To determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in low- and middle-income countries through a systematic review and meta-analysis. Methods PubMed and Embase were searched for randomized controlled trials and prospective and retrospective cohort studies that compared mortality or morbidity in HIV-infected individuals aged ≥ 13 years on cotrimoxazole and ART and on ART alone. The Newcastle–Ottawa Quality Assessment Scale was used to assess selection, confounding and measurement bias. Publication bias was assessed using Egger’s and Begg’s tests. Sensitivity analysis was performed because the I-squared statistic indicated substantial heterogeneity in study results. A random-effects model was used for meta-analysis. Findings Nine studies were included. Begg and Egger P-values for the seven that reported the effect of cotrimoxazole on mortality were 0.29 and 0.49, respectively, suggesting no publication bias. The I-squared statistic was 93.2%, indicating high heterogeneity in study results. The sensitivity analysis showed that neither the follow-up duration nor the percentage of individuals with World Health Organization stage 3 or 4 HIV disease at baseline explained the heterogeneity. The summary estimate of the effect of cotrimoxazole on the incidence rate of death was 0.42 (95% confidence interval: 0.29–0.61). Since most studies followed participants for less than 1 year, it was not possible to determine whether cotrimoxazole can be stopped safely after ART-induced immune reconstitution. Conclusion Cotrimoxazole significantly increased survival in HIV-infected adults on ART. Further research is needed to determine the optimum duration of cotrimoxazole treatment in these patients. PMID:22423164

  13. Kaposi sarcoma-associated herpesvirus and response to antiretroviral therapy: A prospective study of HIV-infected adults

    PubMed Central

    Maskew, Mhairi; MacPhail, A Patrick; Whitby, Denise; Egger, Matthias; Fox, Matthew P.

    2013-01-01

    Background The possible impact of co-infection with Kaposi’s sarcoma associated herpes virus on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. Methods We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. Subjects were defined as seropositive to KSHV if reactive to either KSHV lytic K8.1 or latent Orf73 antigen or both. Subjects were followed from ART initiation until 18-months on treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response as well as HIV viral load suppression within 18-months after ART initiation. Results 385 subjects initiating ART from November 2008-March 2009 were eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV− in terms of age, gender, initiating CD4 count, body mass index, tuberculosis and haemoglobin levels. The KSHV+ group gained a similar number of cells at 6- (difference of 10 cells/mm3, 95% CI: −11–31), 12- (3 cells/mm3, 95% CI: −19–25) and 18-months (24 cells/mm3, 95% CI: −13–61) compared to the KSHV− group. Adjusted relative risk of failure to suppress viral load to <400 copies/mL (1.03; 95% CI: 0.90–1.17) were similar for KSHV+ and KSHV− by 6-months on treatment. Conclusions In a population with a high KSHV prevalence, HIV-positive adults co-infected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared to those KSHV−. PMID:23614996

  14. Antiretroviral Therapy Adherence, Virologic and Immunologic Outcomes in Adolescents Compared With Adults in Southern Africa

    PubMed Central

    Nachega, Jean B.; Hislop, Michael; Nguyen, Hoang; Dowdy, David W.; Chaisson, Richard E.; Regensberg, Leon; Cotton, Mark; Maartens, Gary

    2009-01-01

    Objective To determine adherence to and effectiveness of ART in adolescents versus adults in southern Africa Design Observational cohort study Setting Aid for AIDS, a private-sector disease-management program in southern Africa Subjects Adolescents (age 11–19 years; n=154) and adults (n=7,622) initiating ART between 1999 and 2006 and having a viral-load measurement within one year after ART initiation Main Outcome Measures Primary: virologic suppression (HIV viral load ≤400 copies/mL), viral rebound and CD4+ T-cell count at 6, 12, 18, 24 months after ART initiation. Secondary: adherence assessed by pharmacy refills at 6, 12 and 24 months. Multivariate analyses: log-linear regression and Cox proportional hazards. Results A significantly smaller proportion of adolescents achieved 100% adherence at each time point (adolescents: 20.7% at 6 months, 14.3% at 12 months, 6.6% at 24 months; adults: 40.5%, 27.9%, and 20.6% at each time point, respectively; p<0.01). Patients achieving 100% 12-month adherence were significantly more likely to exhibit virologic suppression at 12 months, regardless of age. However, adolescents achieving virologic suppression had significantly shorter time to viral rebound (adjusted hazard ratio 2.03; 95% CI 1.31–3.13; p<0.003). Adolescents were less likely to experience long-term immunologic recovery despite initial CD4+ T-cell counts comparable to adults. Conclusions Compared to adults, adolescents in southern Africa are less adherent to ART and have lower rates of virologic suppression and immunologic recovery and a higher rate of virologic rebound after initial suppression. Studies must determine specific barriers to adherence in this population and develop appropriate interventions. PMID:19282780

  15. “I was thinking too much”: experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe

    PubMed Central

    Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirgh, Conall; Chibanda, Dixon; Abas, Melanie

    2015-01-01

    Objective To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. Methods In-depth qualitative interviews were conducted with 47 (female =31) HIV-positive adults who scored above the cut-point on a locally-validated scale for common mental disorders. Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. Results The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of common mental disorders (“thinking too much”, changes to appetite and sleep, “burdened heart”, and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with common mental disorders. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income generating activities, and family engagement in mental health care. Conclusions Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce common mental disorders and poor adherence to antiretroviral therapy. PMID:25754063

  16. 'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe.

    PubMed

    Kidia, Khameer; Machando, Debra; Bere, Tarisai; Macpherson, Kirsty; Nyamayaro, Primrose; Potter, Lucy; Makadzange, Tariro; Munjoma, Ronald; Marufu, Marshall; Araya, Ricardo; Safren, Steven; O'Cleirigh, Conall; Chibanda, Dixon; Abas, Melanie

    2015-07-01

    To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy. © 2015 John Wiley & Sons Ltd.

  17. [AIDS Study Group/Spanish AIDS Plan consensus document on antiretroviral therapy in adults with human immunodeficiency virus infection (updated January 2010)].

    PubMed

    2010-01-01

    This consensus document is an update of antiretroviral therapy recommendations for adult patients with human immunodeficiency virus infection. To formulate these recommendations a panel made up of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) reviewed the advances in the current understanding of the pathophysiology of human immunodeficiency virus (HIV) infection, the efficacy and safety of clinical trials, and cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend ART was established in each situation. Currently, the treatment of choice for chronic HIV infection is the combination of three drugs of two different classes, including 2 nucleosides or nucleotide analogs (NRTI) plus 1 non-nucleoside (NNRTI) or 1 boosted protease inhibitor (PI/r), but other combinations are possible. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts below 350 cells/microl; 2) When CD4 counts are between 350 and 500 cells/microl, therapy should be started in case of cirrhosis, chronic hepatitis C, high cardiovascular risk, HIV nephropathy, HIV viral load above 100,000 copies/ml, proportion of CD4 cells under 14%, and in people aged over 55; 3) Therapy should be deferred when CD4 are above 500 cells/microl, but could be considered if any of previous considerations concurs. Treatment should be initiated in case of hepatitis B requiring treatment and should be considered for reduce sexual transmission

  18. [Recommendations from the GESIDA/Spanish AIDS Plan regarding antiretroviral treatment in adults with human immunodeficiency virus infection (update February 2009)].

    PubMed

    2009-04-01

    This consensus document is an update of antiretroviral therapy recommendations for adult patients with human immunodeficiency virus (HIV) infection. To formulate these recommendations, a panel comprised of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) reviewed the advances in current understanding of the pathophysiology of HIV infection, and the efficacy and safety results from clinical trials, cohort studies, and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last 2 years. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider, or not recommend antiretroviral therapy (ART) was established in each situation. The current treatment of choice for chronic HIV infection is a combination of 3 drugs from 2 different classes; that is, 2 nucleoside or nucleotide analogs (NRTI) plus 1 non-nucleoside (NNRTI) or 1 boosted protease inhibitor (PI/r). ART initiation is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and the patient's comorbid conditions, as follows: a) therapy should be started in patients with CD4 counts of <350 cells/microl; b) when CD4 count is between 350 and 500 cells/microl, therapy should be started in patients with chronic hepatitis C or cirrhosis, coinfection with hepatitis B requiring treatment, high cardiovascular risk, HIV nephropathy, HIV viral load >10(5)copies/ml, or<14% CD4 cells; c) therapy should be deferred when CD4 count is >500 cells/microl, but can be considered if any of the previous circumstances concur. The objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral

  19. Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe.

    PubMed

    Matyanga, C M J; Takarinda, K C; Owiti, P; Mutasa-Apollo, T; Mugurungi, O; Buruwe, L; Reid, A J

    2016-06-21

    Contexte : Un centre de santé soutenu par une organisation non gouvernementale offrant des services de santé, notamment les services de traitement antirétroviral (TAR).Objectif : Comparer la rétention du TAR entre des adolescents plus jeunes (10–14 ans) et plus âgés (15–19 ans) et des adultes plus jeunes (20–29 ans) et plus âgés (⩾30 ans) et déterminer les facteurs associés à l'attrition et spécifiques des adolescents et des adultes parmi ceux qui ont mis en route du TAR en 2010–2011.Schéma : Etude rétrospective de cohorte.Résultats : L'étude a inclus 110 (7%) adolescents et 1484 (93%) adultes. Aucune différence en termes de rétention n'a été observée entre les adolescents plus jeunes et plus âgés à 6, 12 et 24 mois. Davantage des plus jeunes adolescents ont été initiés au traitement avec un index de masse corporelle <16 kg/m(2) comparé aux adolescents plus âgés (64% contre 47% ; P = 0,04). Il y avait plus de femmes (74% contre 52% ; P < 0,001) et moins de patients démarrant le TAR avec un comptage de CD4 ⩽ 350 cellules/mm(3) (77% contre 81% ; P = 0,007) parmi les adultes plus jeunes comparés aux plus âgés. Les adultes plus jeunes ont eu davantage d'attrition à tout moment que les plus âgés. Aucun facteur de risque d'attrition n'a été observé parmi les adolescents. Chez les adultes, les facteurs associés à l'attrition ont inclus l'âge plus jeune, un comptage de CD4 plus faible et une infection au virus de l'immunodéficience humaine plus avancée lors de la mise en route du traitement et son initiation dans le cadre d'un protocole basé sur la stavudine.Conclusion : Les adultes plus jeunes ont eu davantage d'attrition et devraient susciter davantage d'attention. Nous n'avons pas pu démontrer de différences d'attrition entre les adolescents plus jeunes et plus âgés. La perte de vue a été la cause principale d'attrition dans tous les groupes d'âge. Dans l'ensemble, un démarrage plus précoce du TAR parait

  20. Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

    PubMed Central

    Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

    2006-01-01

    OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

  1. Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi, 2007-2014

    PubMed Central

    Tanuma, Junko; Lee, Kyu Ha; Haneuse, Sebastien; Matsumoto, Shoko; Nguyen, Dung Thi; Nguyen, Dung Thi Hoai; Do, Cuong Duy; Pham, Thuy Thanh; Nguyen, Kinh Van; Oka, Shinichi

    2016-01-01

    Background Although the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings. Methods HIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014. Results Of 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03–75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8–54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months. Conclusion ADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up. PMID:26939050

  2. Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

    PubMed Central

    Polyak, Christina S.; Yuhas, Krista; Singa, Benson; Khaemba, Monica; Walson, Judd; Richardson, Barbra A.; John-Stewart, Grace

    2016-01-01

    Background Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings. Methods and Findings Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression. Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected. Conclusions CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence

  3. Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study

    PubMed Central

    Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Binelli, Andrea; De Castro, Paola; Terlizzi, Roberta; Fucili, Luca; Di Gregorio, Massimiliano; Mirra, Marco; Olivieri, Erika; Teklu, Tsigemariam; Zegeye, Teame; Haile, Amanuel; Vella, Stefano; Abraham, Loko; Godefay, Hagos

    2015-01-01

    Introduction Although Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia. Methods We used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation. Results The four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition. Conclusions Although Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific

  4. Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

    PubMed

    Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

    2014-01-01

    A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

  5. Determinants of adherence to antiretroviral therapy among HIV-positive adults in sub-Saharan Africa: a systematic review

    PubMed Central

    Heestermans, Tessa; Browne, Joyce L; Aitken, Susan C; Vervoort, Sigrid C; Klipstein-Grobusch, Kerstin

    2016-01-01

    Objective The rapid scale up of antiretroviral treatment (ART) in sub-Saharan Africa (SSA) has resulted in an increased focus on patient adherence. Non-adherence can lead to drug-resistant HIV caused by failure to achieve maximal viral suppression. Optimal treatment requires the identification of patients at high risk of suboptimal adherence and targeted interventions. The aim of this review was to identify and summarise determinants of adherence to ART among HIV-positive adults. Design Systematic review of adherence to ART in SSA from January 2002 to October 2014. Methods A systematic search was performed in 6 databases (PubMed, Cochrane Library, EMBASE, Web of Science, Popline, Global Health Library) for qualitative and quantitative articles. Risk of bias was assessed. A meta-analysis was conducted for pooled estimates of effect size on adherence determinants. Results Of the 4052 articles screened, 146 were included for final analysis, reporting on determinants of 161 922 HIV patients with an average adherence score of 72.9%. Main determinants of non-adherence were use of alcohol, male gender, use of traditional/herbal medicine, dissatisfaction with healthcare facility and healthcare workers, depression, discrimination and stigmatisation, and poor social support. Promoters of adherence included counselling and education interventions, memory aids, and active disclosure among people living with HIV. Determinants of health status had conflicting influence on adherence. Conclusions The sociodemographic, psychosocial, health status, treatment-related and intervention-related determinants are interlinked and contribute to optimal adherence. Clinics providing ART in SSA should therefore design targeted interventions addressing these determinants to optimise health outcomes. PMID:28588979

  6. Incidence and predictors of tuberculosis among HIV-infected adults after initiation of antiretroviral therapy in Nigeria, 2004-2012

    PubMed Central

    Dokubo, E. Kainne; Shiraishi, Ray W.; Agolory, Simon G.; Auld, Andrew F.; Onotu, Dennis; Odafe, Solomon; Dalhatu, Ibrahim; Abiri, Oseni; Debem, Henry C.; Bashorun, Adebobola; Ellerbrock, Tedd

    2017-01-01

    Background Nigeria had the most AIDS-related deaths worldwide in 2014 (170,000), and 46% were associated with tuberculosis (TB). Although treatment of people living with HIV (PLHIV) with antiretroviral therapy (ART) reduces TB-associated morbidity and mortality, incident TB can occur while on ART. We estimated incidence and characterized factors associated with TB after ART initiation in Nigeria. Methods We analyzed retrospective cohort data from a nationally representative sample of adult patients on ART. Data were abstracted from 3,496 patient records, and analyses were weighted and controlled for a complex survey design. We performed domain analyses on patients without documented TB disease and used a Cox proportional hazard model to assess factors associated with TB incidence after ART. Results At ART initiation, 3,350 patients (95.8%) were not receiving TB treatment. TB incidence after ART initiation was 0.57 per 100 person-years, and significantly higher for patients with CD4<50/μL (adjusted hazard ratio [AHR]: 4.2, 95% confidence interval [CI]: 1.4–12.7) compared with CD4≥200/μL. Patients with suspected but untreated TB at ART initiation and those with a history of prior TB were more likely to develop incident TB (AHR: 12.2, 95% CI: 4.5–33.5 and AHR: 17.6, 95% CI: 3.5–87.9, respectively). Conclusion Incidence of TB among PLHIV after ART initiation was low, and predicted by advanced HIV, prior TB, and suspected but untreated TB. Study results suggest a need for improved TB screening and diagnosis, particularly among high-risk PLHIV initiating ART, and reinforce the benefit of early ART and other TB prevention efforts. PMID:28282390

  7. Changes in Body Fat Distribution on Dual-Energy X-Ray Absorptiometry in Black South Africans Starting First-Line Antiretroviral Therapy.

    PubMed

    Abrahams, Zulfa; Levitt, Naomi; Lesosky, Maia; Maartens, Gary; Dave, Joel

    2016-10-01

    Long-term use of antiretroviral therapy (ART) increases the risk of developing lipodystrophy. Few studies from Africa have used longitudinal data to assess the development of lipoatrophy and lipohypertrophy. We use clinical anthropometry and dual-energy X-ray absorptiometry (DEXA) to describe changes in body fat distribution over a 24-month period in individuals initiated on ART. A convenience sample of black South Africans (55 men and 132 women) were recruited and followed for 24 months after commencing ART. Body fat distribution was assessed using anthropometric measurements and DEXA scans at baseline and then at 3, 6, 12, 18, and 24 months after commencing ART. DEXA was also used to estimate abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Women gained more overall weight and more regional fat in all areas analyzed on DEXA scans. Women, not men, experienced a significant increasing trend in trunk fat and a significant decreasing trend in limb fat, when expressed as a percentage of total body fat. In men, the risk of developing lipoatrophy was more than two times greater than that of women, after adjusting for age, baseline body mass index, and ART regimen. Lipohypertrophy occurred similarly in men and women. VAT and SAT increased significantly in men and women, with women gaining considerably more than men. These findings are of great concern as an increased waist circumference is associated with increased mortality in HIV-infected populations. Further investigation is required to understand the mechanisms underlying the sex differences in changes in body fat distribution and its effects on cardiovascular risk.

  8. The reliability of the modified lower extremity functional scale among adults living with HIV on antiretroviral therapy, in Rwanda, Africa.

    PubMed

    Tumusiime, D K; Stewart, A; Venter, F W D; Musenge, E

    2014-01-01

    Peripheral neuropathy (PN) is common among people living with HIV (PLHIV) on antiretroviral therapy (ART), and affects their daily functional ability and quality of life. Lower extremity functional ability, which is most commonly compromised in patients with PN, has not been clearly evaluated in an African setting, with regard to functional limitations. The lower extremity functional scale (LEFS) was originally developed and validated among elderly people in the USA, where the environment and activities of daily life are very different from those in Rwanda. The purpose of this study was to adapt and establish the reliability of LEFS, among adults living with HIV on ART, in a Rwandan environment. The study translated LEFS from English to Kinyarwanda, the local language spoken in Rwanda, the LEFS was then modified accordingly, and tested for test-retest reliability among 50 adult PLHIV on ART. An average Spearman rank order correlation coefficient, ρ ≥ 0.7, was considered optimal for reliability. Prior to the modification of the LEFS and in the initial testing of the translated LEFS, none of the activities was strongly correlated (ρ ≥ 0.8); most of the activities (90%, 18/20) were moderately correlated (ρ ≥ 0.5) and 10% (2/20) were weakly correlated (ρ ≤ 0.5). The ρ of most of the functional activities improved after modification by an expert group to ρ ≥ 0.7, establishing reliability and validity of LEFS among PLHIV on ART with lower extremity functional limitations, in this environment. In conclusion, this study demonstrated the importance of modifying and establishing test - retest reliability of tools derived from developed world contexts to local conditions in developing countries, such as in Rwanda. The modified LEFS in this study can be used in Rwanda by clinicians, specifically at ART clinics to screen and identify people with functional limitations at an early stage of the limitations, for treatment, rehabilitation and

  9. Predictors of loss to follow-up in antiretroviral treatment for adult patients in the Oromia region, Ethiopia

    PubMed Central

    Megerso, Abebe; Garoma, Sileshi; Eticha, Tolosa; Workineh, Tilaye; Daba, Shallo; Tarekegn, Mihretu; Habtamu, Zelalem

    2016-01-01

    Purpose It is known that antiretroviral treatment (ART) reduces mortality from acquired immunodeficiency syndrome related causes. Patient’s lost to follow-up (LTFU) in this treatment poses a paramount problem to the public and health care services. Information on predictors of loss to follow-up is scarce in this study area and similar settings. Therefore, this study aimed at identifying correlates of loss to follow-up in ART among adult patients in the Oromia region of Ethiopia. Methods A case–control study was conducted between February 2015 and April 2015 using medical records. The stratified sampling technique was used to select health facilities. The number of patient records to be included in the study was proportionally allocated to each stratum based on their patient proportion in the regional data. Specific health facilities from which to include the records were randomly selected from a list of the health facilities per stratum. All adult patient records registered as LTFU (416) in the selected health facilities during the 12-month period prior to the data collection date, and 832 patients with good adherence to ART were included. Data were double-entered into Epi Info 7 and analyzed using SPSS 20. Descriptive statistics and binary logistic regression were used to report the results. Qualitative data were thematically analyzed using open code computer software. Results Age 15–24 years (adjusted odds ratio [AOR], 19.82 95% CI: 6.80, 57.73); day laborers (AOR, 5.36; 95% confidence interval [CI]: 3.23, 8.89), rural residents (AOR, 2.35; 95% CI: 1.45, 3.89), World Health Organization clinical stage IV (AOR, 2.29; 95% CI: 1.45, 3.62), baseline CD4 <350 cells/mL (AOR, 2.06; 95% CI: 1.36, 3.13), suboptimal adherence to ART (AOR, 7.42; 95% CI: 1.87, 29.41), were factors which increased the risk of loss to follow-up in ART. Conclusion Multiple risk factors, both socioeconomic and clinical, were associated with loss to follow-up. Attention is required to

  10. The reliability of the modified lower extremity functional scale among adults living with HIV on antiretroviral therapy, in Rwanda, Africa

    PubMed Central

    Tumusiime, D.K.; Stewart, A.; Venter, F.W.D.; Musenge, E.

    2014-01-01

    Abstract Peripheral neuropathy (PN) is common among people living with HIV (PLHIV) on antiretroviral therapy (ART), and affects their daily functional ability and quality of life. Lower extremity functional ability, which is most commonly compromised in patients with PN, has not been clearly evaluated in an African setting, with regard to functional limitations. The lower extremity functional scale (LEFS) was originally developed and validated among elderly people in the USA, where the environment and activities of daily life are very different from those in Rwanda. The purpose of this study was to adapt and establish the reliability of LEFS, among adults living with HIV on ART, in a Rwandan environment. The study translated LEFS from English to Kinyarwanda, the local language spoken in Rwanda, the LEFS was then modified accordingly, and tested for test-retest reliability among 50 adult PLHIV on ART. An average Spearman rank order correlation coefficient, ρ ≥ 0.7, was considered optimal for reliability. Prior to the modification of the LEFS and in the initial testing of the translated LEFS, none of the activities was strongly correlated (ρ ≥ 0.8); most of the activities (90%, 18/20) were moderately correlated (ρ ≥ 0.5) and 10% (2/20) were weakly correlated (ρ ≤ 0.5). The ρ of most of the functional activities improved after modification by an expert group to ρ ≥ 0.7, establishing reliability and validity of LEFS among PLHIV on ART with lower extremity functional limitations, in this environment. In conclusion, this study demonstrated the importance of modifying and establishing test – retest reliability of tools derived from developed world contexts to local conditions in developing countries, such as in Rwanda. The modified LEFS in this study can be used in Rwanda by clinicians, specifically at ART clinics to screen and identify people with functional limitations at an early stage of the limitations, for treatment

  11. Metabolic abnormalities in adult HIV infected population on antiretroviral medication in Malaysia: a cross-sectional survey

    PubMed Central

    2013-01-01

    Background In the current two decades, dyslipidemia and increased blood glucose as metabolic abnormalities are the most common health threats with a high incidence among HIV/AIDS patients on antiretroviral (ARV) treatment. Scientific investigations and reports on lipid and glucose disorders among HIV infected communities are inadequate especially in those developing such as Malaysia. This cross-sectional survey was mainly aimed to evaluate the prevalence of metabolic abnormalities and associated risk factors among HIV infected population patients on ARV medication. Methods In a single reference health center in Malaysia, 2739 adult HIV positive patients on antiretroviral therapy (ART) were studied cross-sectionally using medical records. Besides demographic variables and associated health disorders, those factors which can change the lipid and glucose levels were collected. Logistic Regression was used to find the potential risk factors (p < 0.05). Results Majority of the studied population were male (81.1%) and aged between 30–49 (68.6%). Mean CD4 count was 474.25 (cells/mm3) while undetectable RNA viral load was common among 83.3 (%) of subjects. Among 1,583 patients with the recent blood lipid and glucose tests, increased levels of triglyceride (TG) and total cholesterol (TC) were frequently prevalent in half of the population as 59 (%) and 54.2 (%) while 28.7 (%), 35.1 (%) and 38.2 (%) had declined level of high-density lipoprotein (HDL), raised low-density lipoprotein (LDL) and fasting plasma glucose (FPG) which were less common. Dyslipidemia was common in 82.3 (%) of the subjects. Notably, medication with protease inhibitor (PI) was a potential risk for elevated triglyceride (odds ratio (OR) = 2.309, 95% confidence interval (CI) = 1.605–3.324, P = 0.001), high TC (OR = 1.561, 95% CI = 1.123–2.169, P = 0.008) and low HDL (OR = 1.449, 95% CI = 1.037–2.024, P = 0.029). As lifestyle factor, alcohol consumption

  12. Overcoming Barriers to HIV Treatment Adherence: A Brief Cognitive Behavioral Intervention for HIV-Positive Adults on Antiretroviral Treatment

    PubMed Central

    Olem, David; Sharp, Kelly M.; Taylor, Jonelle M.; Johnson, Mallory O.

    2014-01-01

    Maximizing HIV treatment adherence is critical in efforts to optimize health outcomes and to prevent further HIV transmission. The Balance Project intervention uses cognitive behavioral approaches to improve antiretroviral medication adherence through promoting adaptive coping with medication side effect and distress related to HIV. This 5-session intervention has been documented to prevent nonadherence among persons living with HIV who experience high levels of distress associated with their antiretroviral medication side effects. We describe the theoretical underpinnings of the intervention, provide details of the training and session protocols with a case example, and discuss implications for future applications of the intervention in both research and clinical settings. PMID:24855332

  13. Excellent clinical outcomes and retention in care for adults with HIV-associated Kaposi sarcoma treated with systemic chemotherapy and integrated antiretroviral therapy in rural Malawi.

    PubMed

    Herce, Michael E; Kalanga, Noel; Wroe, Emily B; Keck, James W; Chingoli, Felix; Tengatenga, Listern; Gopal, Satish; Phiri, Atupere; Mailosi, Bright; Bazile, Junior; Beste, Jason A; Elmore, Shekinah N; Crocker, Jonathan T; Rigodon, Jonas

    2015-01-01

    HIV-associated Kaposi sarcoma (HIV-KS) is the most common cancer in Malawi. In 2008, the non-governmental organization, Partners In Health, and the Ministry of Health established the Neno Kaposi Sarcoma Clinic (NKSC) to treat HIV-KS in rural Neno district. We aimed to evaluate 12-month clinical outcomes and retention in care for HIV-KS patients in the NKSC, and to describe our implementation model, which featured protocol-guided chemotherapy, integrated antiretroviral therapy (ART) and psychosocial support delivered by community health workers. We conducted a retrospective cohort study using routine clinical data from 114 adult HIV-KS patients who received ART and ≥1 chemotherapy cycle in the NKSC between March 2008 and February 2012. At enrolment 97% of patients (n/N=103/106) had advanced HIV-KS (stage T1). Most patients were male (n/N=85/114, 75%) with median age 36 years (interquartile range, IQR: 29-42). Patients started ART a median of 77 days prior to chemotherapy (IQR: 36-252), with 97% (n/N=105/108) receiving nevirapine/lamivudine/stavudine. Following standardized protocols, we treated 20 patients (18%) with first-line paclitaxel and 94 patients (82%) with bleomycin plus vincristine (BV). Of the 94 BV patients, 24 (26%) failed to respond to BV requiring change to second-line paclitaxel. A Division of AIDS grade 3/4 adverse event occurred in 29% of patients (n/N=30/102). Neutropenia was the most common grade 3/4 event (n/N=17/102, 17%). Twelve months after chemotherapy initiation, 83% of patients (95% CI: 74-89%) were alive, including 88 (77%) retained in care. Overall survival (OS) at 12 months did not differ by initial chemotherapy regimen (p=0.6). Among patients with T1 disease, low body mass index (BMI) (adjusted hazard ratio, aHR=4.10, 95% CI: 1.06-15.89) and 1 g/dL decrease in baseline haemoglobin (aHR=1.52, 95% CI: 1.03-2.25) were associated with increased death or loss to follow-up at 12 months. The NKSC model resulted in infrequent adverse events

  14. Excellent clinical outcomes and retention in care for adults with HIV-associated Kaposi sarcoma treated with systemic chemotherapy and integrated antiretroviral therapy in rural Malawi

    PubMed Central

    Herce, Michael E; Kalanga, Noel; Wroe, Emily B; Keck, James W; Chingoli, Felix; Tengatenga, Listern; Gopal, Satish; Phiri, Atupere; Mailosi, Bright; Bazile, Junior; Beste, Jason A; Elmore, Shekinah N; Crocker, Jonathan T; Rigodon, Jonas

    2015-01-01

    Introduction HIV-associated Kaposi sarcoma (HIV-KS) is the most common cancer in Malawi. In 2008, the non-governmental organization, Partners In Health, and the Ministry of Health established the Neno Kaposi Sarcoma Clinic (NKSC) to treat HIV-KS in rural Neno district. We aimed to evaluate 12-month clinical outcomes and retention in care for HIV-KS patients in the NKSC, and to describe our implementation model, which featured protocol-guided chemotherapy, integrated antiretroviral therapy (ART) and psychosocial support delivered by community health workers. Methods We conducted a retrospective cohort study using routine clinical data from 114 adult HIV-KS patients who received ART and ≥1 chemotherapy cycle in the NKSC between March 2008 and February 2012. Results At enrolment 97% of patients (n/N=103/106) had advanced HIV-KS (stage T1). Most patients were male (n/N=85/114, 75%) with median age 36 years (interquartile range, IQR: 29–42). Patients started ART a median of 77 days prior to chemotherapy (IQR: 36–252), with 97% (n/N=105/108) receiving nevirapine/lamivudine/stavudine. Following standardized protocols, we treated 20 patients (18%) with first-line paclitaxel and 94 patients (82%) with bleomycin plus vincristine (BV). Of the 94 BV patients, 24 (26%) failed to respond to BV requiring change to second-line paclitaxel. A Division of AIDS grade 3/4 adverse event occurred in 29% of patients (n/N=30/102). Neutropenia was the most common grade 3/4 event (n/N=17/102, 17%). Twelve months after chemotherapy initiation, 83% of patients (95% CI: 74–89%) were alive, including 88 (77%) retained in care. Overall survival (OS) at 12 months did not differ by initial chemotherapy regimen (p=0.6). Among patients with T1 disease, low body mass index (BMI) (adjusted hazard ratio, aHR=4.10, 95% CI: 1.06–15.89) and 1 g/dL decrease in baseline haemoglobin (aHR=1.52, 95% CI: 1.03–2.25) were associated with increased death or loss to follow-up at 12 months. Conclusions

  15. Washington State Even Start 1993-1994: Final Evaluation. A Report to the Office of Adult Literacy.

    ERIC Educational Resources Information Center

    Iglitzin, Lynne; Wandschneider, Mary

    All 18 Washington State Even Start sites participated in the program's evaluation. Site coordinators administered the assessment and evaluation measures to the adults served by the program and to teachers working with children at both entry and exit from the program. An indepth study was conducted of 134 families for whom there were complete sets…

  16. Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial.

    PubMed

    Achhra, Amit C; Mocroft, Amanda; Ross, Michael; Ryom-Nielson, Lene; Avihingsanon, Anchalee; Bakowska, Elzbieta; Belloso, Waldo; Clarke, Amanda; Furrer, Hansjakob; Lucas, Gregory M; Ristola, Matti; Rassool, Mohammed; Ross, Jonathan; Somboonwit, Charurut; Sharma, Shweta; Wyatt, Christina

    2017-09-01

    The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4(+) (cells/mm(3)) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m(2), calculated by CKD-EPI equation), over time using longitudinal mixed models. Of 4685 START participants, 4629 (2294 in immediate and 2335 deferred arm) were included. Median baseline CD4(+) and eGFR were 651 and 111.5, respectively. ART was initiated in 2271 participants (99.0%) in the immediate and 1127 (48.3%) in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 (95% CI 0.003-1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21-2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84-4.97) versus non-Blacks (1.05, 95% CI 0.33-1.77) (P < 0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55-1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  17. Long-term outcomes of second-line antiretroviral treatment in an adult and adolescent cohort in Myanmar.

    PubMed

    Kyaw, Nang Thu Thu; Kumar, Ajay M V; Oo, Myo Minn; Oo, Htun Nyunt; Kyaw, Khine Wut Yee; Thiha, Soe; Aung, Thet Ko; Win, Than; Mon, Yin Yin; Harries, Anthony D

    2017-01-01

    Myanmar has a high burden of Human Immunodeficiency Virus (HIV) and second-line antiretroviral treatment (ART) has been available since 2008 in the public health sector. However, there have been no published data about the outcomes of such patients until now. To assess the treatment and programmatic outcomes and factors associated with unfavorable outcomes (treatment failure, death and loss to follow-up from care) among people living with HIV (aged ≥ 10 years) receiving protease inhibitor-based second-line ART under the Integrated HIV Care Program in Myanmar between October 2008 and June 2015. Retrospective cohort study using routinely collected program data. Of 824 adults and adolescents on second-line ART, 52 patients received viral load testing and 19 patients were diagnosed with virological failure. However, their treatment was not modified. At the end of a total follow-up duration of 7 years, 88 (11%) patients died, 35 (4%) were lost to follow-up, 21 (2%) were transferred out to other health facilities and 680 (83%) were still under care. The incidence rate of unfavorable outcomes was 7.9 patients per 100 person years follow-up. Patients with a history of injecting drug use, with a history of lost to follow-up, with a higher baseline viral load and who had received didanosine and abacavir had a higher risk of unfavorable outcomes. Patients with higher baseline C4 counts, those having taken first-line ART at a private clinic, receiving ART at decentralized sites and taking zidovudine and lamivudine had a lower risk of unfavorable outcomes. Long-term outcomes of patients on second-line ART were relatively good in this cohort. Virological failure was relatively low, possibly because of lack of viral load testing. No patient who failed on second-line ART was switched to third-line treatment. The National HIV/AIDS Program should consider making routine viral load monitoring and third-line ART drugs available after a careful cost-benefit analysis.

  18. Long-term outcomes of second-line antiretroviral treatment in an adult and adolescent cohort in Myanmar

    PubMed Central

    Kyaw, Nang Thu Thu; Kumar, Ajay M. V.; Oo, Myo Minn; Oo, Htun Nyunt; Kyaw, Khine Wut Yee; Thiha, Soe; Aung, Thet Ko; Win, Than; Mon, Yin Yin; Harries, Anthony D.

    2017-01-01

    ABSTRACT Background: Myanmar has a high burden of Human Immunodeficiency Virus (HIV) and second-line antiretroviral treatment (ART) has been available since 2008 in the public health sector. However, there have been no published data about the outcomes of such patients until now. Objective: To assess the treatment and programmatic outcomes and factors associated with unfavorable outcomes (treatment failure, death and loss to follow-up from care) among people living with HIV (aged ≥ 10 years) receiving protease inhibitor-based second-line ART under the Integrated HIV Care Program in Myanmar between October 2008 and June 2015. Design: Retrospective cohort study using routinely collected program data. Results: Of 824 adults and adolescents on second-line ART, 52 patients received viral load testing and 19 patients were diagnosed with virological failure. However, their treatment was not modified. At the end of a total follow-up duration of 7 years, 88 (11%) patients died, 35 (4%) were lost to follow-up, 21 (2%) were transferred out to other health facilities and 680 (83%) were still under care. The incidence rate of unfavorable outcomes was 7.9 patients per 100 person years follow-up. Patients with a history of injecting drug use, with a history of lost to follow-up, with a higher baseline viral load and who had received didanosine and abacavir had a higher risk of unfavorable outcomes. Patients with higher baseline C4 counts, those having taken first-line ART at a private clinic, receiving ART at decentralized sites and taking zidovudine and lamivudine had a lower risk of unfavorable outcomes. Conclusions: Long-term outcomes of patients on second-line ART were relatively good in this cohort. Virological failure was relatively low, possibly because of lack of viral load testing. No patient who failed on second-line ART was switched to third-line treatment. The National HIV/AIDS Program should consider making routine viral load monitoring and third-line ART drugs

  19. Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV

    PubMed Central

    Kahana, Shoshana Y.; Jenkins, Richard A.; Bruce, Douglas; Fernandez, Maria I.; Hightow-Weidman, Lisa B.; Bauermeister, Jose A.

    2016-01-01

    Background The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States. Methods The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer–assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability). Results Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single

  20. Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

    PubMed

    Kahana, Shoshana Y; Jenkins, Richard A; Bruce, Douglas; Fernandez, Maria I; Hightow-Weidman, Lisa B; Bauermeister, Jose A

    2016-01-01

    The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States. The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability). Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent

  1. Prevalence, Correlates and Under-Diagnosis of Clinical Depression among Adults on Highly Active Antiretroviral Therapy in a Tertiary Health Institution in Northeastern Nigeria

    PubMed Central

    Jidda, Mohammed Said; Wakil, Musa Abba; Rabbebe, Isa Bukar; Omeiza, Asuku Beida; Yusuph, Haruna; Ogunlesi, Adegboyega; Suleiman, Umar Garba

    2014-01-01

    Clinical depression is a highly debilitating illness, which is often under-diagnosed and negatively impacts on the quality of life of its sufferers. When it co-exists with other medical conditions, its effect is even more incapacitating. Undiagnosed depression in the context of HIV infection leads to accelerated decline in CD4+ cell counts with concomitant increase in the viral load and poor adherence to the antiretroviral medications which lead to viral mutation and the evolution of resistant strains. This study examined the prevalence of depression, its correlates and the frequency of the diagnosis of the condition among HIV+ subjects on highly active antiretroviral therapy (HAART) by the internists and general physicians at the University of Maiduguri Teaching Hospital in Northeastern Nigeria. Three hundred and fifty representative samples of HIV+ adults on HAART were drawn from the Antiretroviral Therapy Clinic of the Institution. Diagnosis of depression was made using the International Classification of Diseases-10 criteria based on Composite International Diagnostic Interview generated data. Socio-demographic and clinical variables were also analyzed for their correlation with depression in the subjects. About 20% of the respondents were diagnosed with clinical depression and no diagnosis of the condition was hitherto entertained in all the respondents. The independent determinants of depression in the participants were: female gender [odds ratio (OR)=3.87 (95% confidence interval, CI: 2.089-7.183)], past history of psychiatric illness [OR=43.81 (95% CI: 9.731-197.30)] and family history of psychiatric illness in first-degree relatives of the subjects [OR=14.364 (95% CI=5.327-38.729)]. Depression is a relatively common psychiatric condition among adults on HAART, there is therefore the need for routine screening of this condition among HIV+ subjects in order to optimize patient care and improve clinical outcomes.

  2. Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial

    PubMed Central

    Arathoon, Eduardo; Bhorat, Asad; Silaghi, Rodica; Crauwels, Herta; Lavreys, Ludo; Tambuyzer, Lotke; Van Baelen, Ben; Vanveggel, Simon; Opsomer, Magda

    2017-01-01

    Objective: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. Methods: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors. Results: Of 211 treated patients, 73% (n = 155) had baseline viral load ⩾ 50 copies/mL and 27% (n = 56) had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%). Diarrhea was the most frequent adverse event (17%). Serious adverse events (no rash) occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC12h was 5390 ng h/mL and C0h was 353 ng/mL (N = 199). Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm) were 48% (74/155) (baseline viral load ⩾ 50 copies/mL) and 75% (42/56) (baseline viral load < 50 copies/mL). Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79) (non-adherent) versus 64% (44/69) (adherent subset). Conclusion: Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent

  3. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience.

    PubMed

    van der Ploeg, A T; Kruijshaar, M E; Toscano, A; Laforêt, P; Angelini, C; Lachmann, R H; Pascual Pascual, S I; Roberts, M; Rösler, K; Stulnig, T; van Doorn, P A; Van den Bergh, P Y K; Vissing, J; Schoser, B

    2017-06-01

    Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in adult patients were developed and reported here. Three consensus meetings were organized through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative synthesis is presented. Consensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43 observational studies, covering a total of 586 individual adult patients, provided evidence of a beneficial effect of ERT at group level. At individual patient level, the response to treatment varied, but factors associated with a patient's response to ERT were not described in many studies. Eleven observational studies focused on more severely affected patients, suggesting that ERT can also be beneficial in these patients. There are no studies on the effects of ERT in pre-symptomatic patients. This is the first European consensus recommendation for starting and stopping ERT in adult patients with Pompe disease, based on the extensive experience of experts from different countries. © 2017 EAN.

  4. Efficacy of Initial Antiretroviral Therapy for HIV-1 Infection in Adults: A Systematic Review and Meta-Analysis of 114 Studies with up to 144 Weeks' Follow-Up

    PubMed Central

    Lee, Frederick J.; Amin, Janaki; Carr, Andrew

    2014-01-01

    Background A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines. Methods Group-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy. Outcome Measures Antiviral efficacy (undetectable plasma viral load) and premature cessation of therapy. Results 114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log10 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with ‘Preferred’ than ‘Alternative’ regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; p<0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ≥100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; p<0.001). This difference persisted within ‘Preferred’ regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes). Conclusion Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads

  5. Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models.

    PubMed

    Keebler, Daniel; Revill, Paul; Braithwaite, Scott; Phillips, Andrew; Blaser, Nello; Borquez, Annick; Cambiano, Valentina; Ciaranello, Andrea; Estill, Janne; Gray, Richard; Hill, Andrew; Keiser, Olivia; Kessler, Jason; Menzies, Nicolas A; Nucifora, Kimberly A; Vizcaya, Luisa Salazar; Walker, Simon; Welte, Alex; Easterbrook, Philippa; Doherty, Meg; Hirnschall, Gottfried; Hallett, Timothy B

    2014-01-01

    WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or

  6. Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy: A Prospective Cohort Study.

    PubMed

    Ezeamama, Amara E; Woolfork, Makhabele N; Guwatudde, David; Bagenda, Danstan; Manabe, Yukari C; Fawzi, Wafaie W; Smith Fawzi, Mary C

    2016-03-01

    The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up.QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time*depression P < 0.001) and anxiety levels (time*anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time*social support P = 0.8943) or number of stigmatizing experiences (time*stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults.

  7. Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial.

    PubMed

    Hosseinipour, Mina C; Bisson, Gregory P; Miyahara, Sachiko; Sun, Xin; Moses, Agnes; Riviere, Cynthia; Kirui, Fredrick K; Badal-Faesen, Sharlaa; Lagat, David; Nyirenda, Mulinda; Naidoo, Kogieleum; Hakim, James; Mugyenyi, Peter; Henostroza, German; Leger, Paul D; Lama, Javier R; Mohapi, Lerato; Alave, Jorge; Mave, Vidya; Veloso, Valdilea G; Pillay, Sandy; Kumarasamy, Nagalingeswaran; Bao, Jing; Hogg, Evelyn; Jones, Lynne; Zolopa, Andrew; Kumwenda, Johnstone; Gupta, Amita

    2016-03-19

    Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080. Between Oct 31, 2011, and June 9, 2014, we enrolled 850

  8. Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

    PubMed Central

    Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

    2011-01-01

    The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication. PMID:22654926

  9. The effects of HIV self-testing on the uptake of HIV testing and linkage to antiretroviral treatment among adults in Africa: a systematic review protocol.

    PubMed

    Njau, Bernard; Damian, Damian J; Abdullahi, Leila; Boulle, Andrew; Mathews, Catherine

    2016-04-05

    HIV is still a global public health problem. More than 75 % of HIV-infected people are in Africa, and most of them are unaware of their HIV status, which is a barrier to accessing antiretroviral treatment. Our review aims, firstly, to determine whether HIV self-testing is an effective method to increase the uptake of testing, the yield of new HIV-positive diagnoses, and the linkage to antiretroviral treatment. Secondly, we aim to review the factors that facilitate or impede the uptake of HIV self-testing. Participants will be adults living in Africa. For the first aim, the intervention will be HIV self-testing either alone or in addition to HIV testing standard of care. The comparison will be HIV testing standard of care. The primary outcomes will be (i) uptake of HIV testing and (ii) yield of new HIV-positive diagnoses. The secondary outcomes will be (a) linkage to antiretroviral (ARV) treatment and (b) incidence of social harms. For the second aim, we will review barriers and facilitators to the uptake of self-testing. We will search PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide, and CINAHL for eligible studies from 1998, with no language limits. We will check reference lists of included studies for other eligible reports. Eligible studies will include experimental and observational studies. Two authors will independently screen the search output, select studies, and extract data, resolving discrepancies by consensus and discussion. Two authors will use Cochrane risk of bias tools for experimental studies, the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Critical Appraisal Skills Programme (CASP) quality assessment tool for qualitative studies. Innovative and cost-effective community-based HIV testing strategies, such as self-testing, will contribute to universal coverage of HIV testing in Africa. The findings from this systematic review will guide development of self

  10. [Evaluation of antiretroviral therapy in HIV-infected adults in the Department of Haematology, University Hospital of Brazzavllle, Congo].

    PubMed

    Dokekias, A Elira; Galiba, F O Atipo; Bokilo, A Dzia Lepfoundzou; Ntsimba, P; Nsitou, M B; Malanda, F; Basseila, G Boukatou

    2008-04-01

    A retrospective study was conducted during 32 months; from 1 May 2003 to 30 December 2005 in haematology department. The objective of the study was to assess the effectiveness of the anti retroviral therapy 157 patients receiving antiretroviral treatment for at least a twelve month-period and presenting AIDS symptoms based on revised CDC criteria were included. The average number of initial T4 lymphocytes is 133/mm3 (extremes 1 and 385) and the initial plasmatic average viral load, quantified in 96 patients is 214,000 copies (extreme 30,000 et 999,000) The initial antiretroviral combinations were as follows: ZDV or D4T + LMV + NVP (59.2%); ZDV or D4T + LMV + EFV (28.7%), ZDV or D4T + LMV + IDNV (8.9%); ZDV or D4T + DDI + NVP (3.2%). The results of the study are: observance rate during the first 12 months (84%), antiretroviral therapy taken irregularly (10.8%), early submission of therapy (5.2%), weight gain after 24 months: +18 kgs, clinical response globally positive. The immune response is characterised by an average increase of 353/mm3 of CD4 after 24 months. Among 96 patients tested, the plasmatic viral load was undetectable in 71% of cases after a 12 month-follow up. Mild adverse drug effects have been noticed, represented by cutaneous and nervous toxicity anaemia and digestive disorders due to indinavir These therapeutic results confirm the importance of the antiretroviral therapy in the improvement of the quality of life of HIV/AIDS patients but a concern remains on the possible drug resistance still not documented.

  11. A Seven Step Approach To Starting an Exercise Program for Older Adults.

    ERIC Educational Resources Information Center

    Resnick, Barbara

    2000-01-01

    To help older adults (N=212) initiate and adhere to a regular exercise program, a seven step approach was developed and implemented in a continuing care retirement community. Results indicate that older adults can exercise safely and that regular exercise will improve physical fitness, prevent injury and disease and improve quality of life.…

  12. Child Safety: A Healthy Start. Teacher's Guide. Health Promotion for Adult Literacy Students: An Empowering Approach.

    ERIC Educational Resources Information Center

    Hudson River Center for Program Development, Glenmont, NY.

    This guide is intended to help adult literacy teachers in New York present a learning module in which an empowering approach is used to provide adult students with information about child-rearing and prevention techniques to keep their children safe. The first half of the guide consists of reading materials concerning the following: home and road…

  13. Pharmacy Refill Adherence Compared with CD4 Count Changes for Monitoring HIV-Infected Adults on Antiretroviral Therapy

    PubMed Central

    Bisson, Gregory P; Gross, Robert; Bellamy, Scarlett; Chittams, Jesse; Hislop, Michael; Regensberg, Leon; Frank, Ian; Maartens, Gary; Nachega, Jean B

    2008-01-01

    Background World Health Organization (WHO) guidelines for monitoring HIV-infected individuals taking combination antiretroviral therapy (cART) in resource-limited settings recommend using CD4+ T cell (CD4) count changes to monitor treatment effectiveness. In practice, however, falling CD4 counts are a consequence, rather than a cause, of virologic failure. Adherence lapses precede virologic failure and, unlike CD4 counts, data on adherence are immediately available to all clinics dispensing cART. However, the accuracy of adherence assessments for predicting future or detecting current virologic failure has not been determined. The goal of this study therefore was to determine the accuracy of adherence assessments for predicting and detecting virologic failure and to compare the accuracy of adherence-based monitoring approaches with approaches monitoring CD4 count changes. Methodology and Findings We conducted an observational cohort study among 1,982 of 4,984 (40%) HIV-infected adults initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid for AIDS Disease Management Program, which serves nine countries in southern Africa. Pharmacy refill adherence was calculated as the number of months of cART claims submitted divided by the number of complete months between cART initiation and the last refill prior to the endpoint of interest, expressed as a percentage. The main outcome measure was virologic failure defined as a viral load > 1,000 copies/ml (1) at an initial assessment either 6 or 12 mo after cART initiation and (2) after a previous undetectable (i.e., < 400 copies/ml) viral load (breakthrough viremia). Adherence levels outperformed CD4 count changes when used to detect current virologic failure in the first year after cART initiation (area under the receiver operating characteristic [ROC] curves [AUC] were 0.79 and 0.68 [difference = 0.11; 95% CI 0.06 to 0.16; χ2 = 20.1] respectively at 6 mo, and 0.85 and 0.75 [difference = 0.10; 95% CI

  14. Starting an adolescent and young adult program: some success stories and some obstacles to overcome.

    PubMed

    Ferrari, Andrea; Thomas, David; Franklin, Anna R K; Hayes-Lattin, Brandon M; Mascarin, Maurizio; van der Graaf, Winette; Albritton, Karen H

    2010-11-10

    Adolescent and young adult (AYA) patients seem to be in a sort of no-man's land, halfway between the two different worlds of pediatric and adult medical oncology and bearing the brunt, in terms of inclusion in clinical trials and quality of professional care, of the lack of integration between these two worlds. This article discusses the different organization models of care used in pediatric oncology (mainly family-focused) and in adult medical oncology (disease-focused). There is a growing awareness that these models are not ideally suited to the complex needs of AYA patients, which require a different, new, patient-focused multidisciplinary approach. A comprehensive, multipronged effort is required to bridge the gap in the care of AYA patients, with the ultimate challenge of creating a new discipline, AYA oncology. In this article, we review the experiences of AYA oncology programs in Europe, North America, and Australia, focusing on similarities and differences in strategy, as well as the major challenges and opportunities faced by these programs. Among the most important factors for the successful establishment of an AYA oncology service are the degree of engagement of both pediatric and adult medical oncologists, the philanthropic support of powerful charities, and the role of dedicated professionals across a range of disciplines in driving the development of services for AYA patients.

  15. "Starting from Ground Zero:" Constraints and Experiences of Adult Women Returning to College

    ERIC Educational Resources Information Center

    Deutsch, Nancy L.; Schmertz, Barbara

    2011-01-01

    Women adult students face particular constraints when pursuing degrees. This paper uses focus group data to explore the educational pathways, barriers, and supports of women students. Women's educations are shaped by personal and structural gendered forces, including family, economic, and workplace issues. Women report conflict over short-term…

  16. Start Young!

    ERIC Educational Resources Information Center

    Rubin, Penni

    2002-01-01

    Discusses the importance of early interest in science and how effective it is on career choice in adult stages of life. Recommends starting mathematics and science activities in preschool and kindergarten. Describes how to create a career-oriented learning center in the classroom with examples of kitchen chemistry, nutrition/botany, zoology,…

  17. Start Young!

    ERIC Educational Resources Information Center

    Rubin, Penni

    2002-01-01

    Discusses the importance of early interest in science and how effective it is on career choice in adult stages of life. Recommends starting mathematics and science activities in preschool and kindergarten. Describes how to create a career-oriented learning center in the classroom with examples of kitchen chemistry, nutrition/botany, zoology,…

  18. Oakland Readers. A Book of Life Stories Told by Students in the Second Start Adult Literacy Program. Levels One-Four.

    ERIC Educational Resources Information Center

    Lamb, Jessica, Ed.

    This set of Oakland Readers consists of four books of oral histories edited on four reading levels. Each book contains life stories told by students in the Second Start Adult Literacy Program. The books are intended for use by tutors and adult students/new readers in adult literacy programs. Life stories of eight students appear in each book. In…

  19. Sepsis carries a high mortality among hospitalised adults in Malawi in the era of antiretroviral therapy scale-up: a longitudinal cohort study.

    PubMed

    Waitt, Peter I; Mukaka, Mavuto; Goodson, Patrick; SimuKonda, Felanji D; Waitt, Catriona J; Feasey, Nick; Allain, Theresa J; Downie, Paul; Heyderman, Robert S

    2015-01-01

    To assess mortality risk among adults presenting to an African teaching hospital with sepsis and severe sepsis in a setting of high HIV prevalence and widespread ART uptake. Prospective cohort study of adults (age ≥16 years) admitted with clinical suspicion of severe infection between November 2008 and January 2009 to Queen Elizabeth Central Hospital, a 1250-bed government-funded hospital in Blantyre, Malawi. Demographic, clinical and laboratory information, including blood and cerebrospinal fluid cultures were obtained on admission. Data from 213 patients (181 with sepsis and 32 with severe sepsis; M:F = 2:3) were analysed. 161 (75.6%) patients were HIV-positive. Overall mortality was 22%, rising to 50% amongst patients with severe sepsis. The mortality of all sepsis patients commenced on antiretroviral therapy (ART) within 90 days was 11/28 (39.3%) compared with 7/42 (16.7%) among all sepsis patients on ART for greater than 90 days (p = 0.050). Independent associations with death were hypoxia (OR = 2.4; 95% CI, 1.1-5.1) and systolic hypotension (OR 7.0; 95% CI: 2.4-20.4). Sepsis and severe sepsis carry high mortality among hospitalised adults in Malawi. Measures to reduce this, including early identification and targeted intervention in high-risk patients, especially HIV-positive individuals recently commenced on ART, are urgently required. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. When to start paediatric testing of the adult HIV cure research agenda?

    PubMed Central

    Shah, Seema K

    2017-01-01

    Ethical guidelines recommend that experimental interventions should be tested in adults first before they are tested and approved in children. Some challenge this paradigm, however, and recommend initiating paediatric testing after preliminary safety testing in adults in certain cases. For instance, commentators have argued for accelerated testing of HIV vaccines in children. Additionally, HIV cure research on the use of very early therapy (VET) in infants, prompted in part by the Mississippi baby case, is one example of a strategy that is currently being tested in infants before it has been well tested in adults. Because infants’ immune systems are still developing, the timing of HIV transmission is easier to identify in infants than in adults, and infants who receive VET might never develop the viral reservoirs that make HIV so difficult to eradicate, infants may be uniquely situated to achieve HIV cure or sustained viral remission. Several commentators have now argued for earlier initiation of HIV cure interventions other than (or in addition to) VET in children. HIV cure research is therefore a good case for re-examining the important question of when to initiate paediatric research. I will argue that, despite the potential for HIV cure research to benefit children and the scientific value of involving children in this research, the HIV cure agenda should not accelerate the involvement of children for the following reasons: HIV cure research is highly speculative, risky, aimed at combination approaches and does not compare favourably with the available alternatives. I conclude by drawing general implications for the initiation of paediatric testing, including that interventions that have to be used in combination with others and cures for chronic diseases may not be valuable enough to justify early paediatric testing. PMID:27259546

  1. Older adults recently started on psychotropic medication: where are the symptoms?

    PubMed

    Maust, Donovan T; Chen, Shirley H; Benson, Amy; Mavandadi, Shahrzad; Streim, Joel E; DiFilippo, Suzanne; Snedden, Thomas M; Oslin, David W

    2015-06-01

    The objective of this study is to understand the characteristics of older adults on newly prescribed psychotropic medication with minimal psychiatric symptoms. Naturalistic cohort study of non-institutionalized older adults in Pennsylvania participating in the Pharmaceutical Assistance Contract for the Elderly. Persons newly prescribed antidepressant or anxiolytic monotherapy or combination therapy were contacted for clinical assessment by a telephone-based behavioral health service. The initial assessment included standardized mental health screening instruments and scales including the Blessed Orientation-Memory-Concentration test, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Medical Outcomes Survey (SF-12). In addition, patients were asked for their understanding of the prescription indication. Of the 254 participants who met minimal symptom criteria (Patient Health Questionnaire-9 < 5 and Generalized Anxiety Disorder-7 < 5), women comprised slightly more of the anxiolytic compared with antidepressant monotherapy group (88.9% vs. 76.7%, p = 0.04). The most common self-reported reason for prescription of an antidepressant or anxiolytic was depression or anxiety, respectively, despite near-absence of these symptoms on clinical assessment. Comparing monotherapy to combination therapy groups, those with combination therapy were more likely to report a history of depression (12.6% vs. 1.8%, p < 0.001) and also report depression as the reason for the prescription (40.2% vs. 21.0%, p < 0.01). In this sample of older adults on new psychotropic medication with minimal psychiatric symptoms, there are few patient characteristics that distinguish those on antidepressant versus anxiolytic monotherapy or those on monotherapy versus combination therapy. While quality of care in late-life mental health has focused on improving detection and treatment, there should be further attention to low-symptom patients potentially receiving inappropriate

  2. Effect of nutritional factors on adherence to antiretroviral therapy among HIV-infected adults: a case control study in Northern Ethiopia

    PubMed Central

    2013-01-01

    Background Adherence to antiretroviral treatment is critical for suppression of viral replication, reduced destruction of CD4 cells, prevention of viral resistance, promotion of immune reconstitution and slowed disease progression. This study sought to determine the effect of nutritional factors on adherence to ART among HIV-infected adults on ART. Methods Matched case control study design (matched by age and sex) was employed. Data was collected from ART registration chart, pre-tested structured data extraction format, anthropometric measurements and by interview. Conditional logistic regression was used to compute the relevant associations among the variables by STATA version 10. Results From 174 paired subjects participated in the study 80 (46%) pair were males and 94 (54%) pair were females on ART for at least one year prior to the survey. The mean age (±SD) for the non-adherent was 38.4 ± 8.1years and for the adherent subjects was 38.5 ± 8.4 years. Malnutrition with BMI less than 18.5 Kg/m2 in the adherent group was 14 (8%) and that of the non-adherent group was 74 (42.5%) which was associated with non-adherence to ART (AOR 10.0, 95%CI 4.3 – 54.7). Inability to get enough and quality food was also associated with non-adherence to ART (AOR 2.1, 95%CI 1.1 – 11.5). Conclusions Malnutrition, inability to get enough and/or quality food and consumption pattern which is less than three meals per day were significantly associated with non-adherence to ART. Therefore, the capacity to effectively manage the food and nutrition implications of ART adherence is a critical factor in the success of antiretroviral therapy in resource limited settings. PMID:23701864

  3. Initial response to highly active antiretroviral therapy in HIV-1C-infected adults in a public sector treatment program in Botswana.

    PubMed

    Wester, C William; Kim, Soyeon; Bussmann, Hermann; Avalos, Ava; Ndwapi, Ndwapi; Peter, Trevor F; Gaolathe, Tendani; Mujugira, Andrew; Busang, Lesego; Vanderwarker, Chris; Cardiello, Peter; Johnson, Onalethata; Thior, Ibou; Mazonde, Patson; Moffat, Howard; Essex, Max; Marlink, Richard

    2005-11-01

    To describe the response to highly active antiretroviral treatment (HAART) in a public sector pilot antiretroviral (ARV) treatment program in Botswana. The response to HAART is described in adult HIV-infected ARV-naive patients initiating treatment from April 2001 to January 2002 at Princess Marina Hospital in Gaborone, Botswana. Patients had medical and laboratory evaluations before initiating ARV treatment and were followed longitudinally. For analysis, data were collected from charts and patient management records. One hundred fifty-three ARV-naive patients initiated HAART. Most received didanosine plus stavudine (ddI + d4T) with efavirenz or nevirapine. The mean CD4 cell count increase was 149 cells/mm at 24 weeks and 204 cells/mm at 48 weeks. The percentage of patients with an HIV-1 RNA level < or =400 copies/mL was 87.0% at 24 weeks and 78.8% at 48 weeks. The Kaplan-Meier 1-year survival estimate was 84.7% (79.0%, 90.8%), with a 3.2-fold increased risk (P = 0.004) of mortality among patients with a CD4 cell count <50 cells/mm. The 1-year Kaplan-Meier estimate of toxicity-related drug switches was 32.2% (20.3%, 40.4%). The most common toxicity was peripheral neuropathy, occurring more frequently in patients with a preexisting diagnosis of peripheral neuropathy and among those placed on ddI + d4T-containing regimens. An excellent response to HAART was observed among HIV-1C-infected patients, paralleling those seen elsewhere. Despite excellent responses, high rates of toxicity were observed for ddI + d4T-containing regimens.

  4. Effects of Antiretroviral Therapy on Immune Function of HIV-infected Adults with Pulmonary Tuberculosis and CD4+ >350 Cells/mm3

    PubMed Central

    Mahan, C. Scott; Johnson, Denise F.; Walusimbi, Maria; Chervenak, Keith A.; Nalukwago, Sophie; Charlebois, Edwin; Havlir, Diane; Mayanja-Kizza, Harriet; Whalen, Christopher C.; Boom, W. Henry

    2011-01-01

    Background. Human immunodeficiency virus (HIV)–tuberculosis coinfection is associated with heightened immune activation, viral replication, and T cell dysfunction. We compared changes in T cell activation and function between patients receiving concurrent treatment for HIV-tuberculosis coinfection and those receiving treatment for tuberculosis alone. Methods. HIV-infected adults with tuberculosis and CD4+ T cell counts >350 cells/mm3 were randomized to receive tuberculosis treatment alone (control arm; n = 36) or 6 months of antiretroviral therapy (ART) concurrent with tuberculosis treatment (intervention arm; n = 38). HIV viral load, T cell subsets, T cell activation, and cytokine production were measured at enrollment and every 3 months for 12 months. Results. Differences in absolute CD4+ and CD8+ T cell counts were not observed between arms. Viral load was reduced while participants received ART; control patients maintained viral load at baseline levels. Both arms had significant reductions in T cell expression of CD38 and HLA-DR. Interferon-γ production in response to mitogen increased significantly in the intervention arm. Conclusions. In HIV-infected adults with tuberculosis and CD4+ T cell counts >350 cells/mm3, both tuberculosis treatment and concurrent HIV-tuberculosis treatment reduce T cell activation and stabilize T cell counts. Concurrent ART with tuberculosis treatment does not provide additional, sustained reductions in T cell activation among individuals with preserved immunologic function. PMID:21402550

  5. Effect of Raltegravir-containing Intensification on HIV Burden and T Cell Activation in Multiple Gut Sites of HIV+ Adults on Suppressive Antiretroviral Therapy

    PubMed Central

    Yukl, Steven A.; Shergill, Amandeep; McQuaid, Kenneth; Gianella, Sara; Lampiris, Harry; Hare, C. Bradley; Pandori, Mark; Sinclair, Elizabeth; Günthard, Huldrych F.; Fischer, Marek; Wong, Joseph K.; Havlir, Diane V.

    2010-01-01

    Objective To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Design Open-label study in HIV+ adults on ART with plasma HIV RNA<40 copies/ml. Methods Seven HIV+ adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from PBMC and 4 gut sites, T cell subsets, and activation markers. Results Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, 5 of 7 participants had a decrease in unspliced HIV RNA per 106 CD4+ T cells in the ileum. There was a trend towards decreased T cell activation in all sites, which was greatest for CD8+ T cells in the ileum and PBMC, and a trend towards increased CD4+ T cells in the ileum. Conclusion Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible. PMID:20827162

  6. Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study.

    PubMed

    Cerutti, Bernard; Broers, Barbara; Masetsibi, Motlomelo; Faturiyele, Olatunbosun; Toti-Mokoteli, Likabelo; Motlatsi, Mokete; Bader, Joelle; Klimkait, Thomas; Labhardt, Niklaus D

    2016-09-08

    Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001). The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001). Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77) and alcohol use disorder (2.73, 95 % CI: 1.68-4.42) were significantly associated with poor adherence. There was, however, no significant association with viral suppression. Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. April 28th 2014; NCT02126696 .

  7. An evaluation of quality of life among Cambodian adults living with HIV/AIDS and using antiretroviral therapy: a short report.

    PubMed

    Yang, Youngran; Thai, Sopheak; Choi, Jongsan

    2016-12-01

    The aim of this study was to evaluate quality of life (QOL) and analyze its determinants among Cambodian adults living with HIV/AIDS who are on antiretroviral therapy (ART). A cross-sectional study was conducted using convenience sampling to select 150 adults 18 years of age or older from the patient population at the HIV/AIDS care hospital in Phnom Penh, Cambodia. QOL was assessed using the World Health Organization Quality of Life HIV BREF; socio-demographic characteristics, time elapsed since HIV diagnosis, months on ART, CD4 cell count, family and community support, depression, and anxiety were included in the survey. Results of the multiple regression analysis indicate that positive predictors of QOL included being female, being less 40 years old, having a household monthly income greater than 300 USD, having an education beyond the secondary level, or being employed. However, time elapsed since HIV diagnosis and duration of ART were not significantly associated with QOL and CD4 cell count and the World Health Organization clinical stage had little association with QOL. Perceiving oneself as healthy and happy and reporting no depression or anxiety were associated with a positive QOL. These findings suggest the importance of group-specific interventions to improve the QOL for those people living with HIV/AIDS in Cambodia who are male, have a low household income or education level, are unemployed, or are anxious or depressed.

  8. Stigma and Discrimination faced by HIV-infected Adults on Antiretroviral Therapy for more than 1 Year in Raichur Taluk, Karnataka, India.

    PubMed

    Muralidharan, Shrikanth; Acharya, Arun Kumar; Margabandu, Shanthi; Purushotaman, Shalini; Kannan, Ranjit; Mahendrakar, Sangeeta; Kulkarni, Dinraj

    2017-09-01

    The aim of this study was to evaluate the stress and discrimination faced by human immunodeficiency virus (HIV)-affected adult patients on antiretroviral therapy (ART) for more than 1 year. A cross-sectional study was carried out among 170 adults on ART, reporting to the ART center of the District Civil Hospital, for more than 1 year in Raichur Taluk, Karnataka, India. Convenience sampling technique was followed. Descriptive statistics was performed (Chi-square test) using Statistical Package for the Social Sciences version 16.0. A total of 156 (91.8%) patients' families had knowledge about their seropositive status. Seventeen (10.9%) HIV-positive patients reported of change in the attitude of their family members. The main reasons for not revealing the HIV status were the internalized stigma and fear of rejection. Women faced greater discrimination from family, friends, and neighbors than men. It is necessary to not undermine the effect of rejection due to HIV. It is the only infection that has so many associated social and psychological norms which we need to tend at the earnest. Till date, there is an existence of condescendence toward treatment approach. The presence of stigma and the fear of being discriminated could be a major hurdle in the rehabilitation of these patients into the mainstream society. Furthermore, it serves as an existing challenge to ascertain these individuals to achieve overall health.

  9. The Impact of Comorbid Clinical Depression on The Health-Related Quality of Life of Adults on Highly Active Antiretroviral Therapy in Maiduguri, Northeastern Nigeria

    PubMed Central

    Wakawa, Ibrahim Abdu; Said, Jidda Mohammed; Abba, Wakil Musa; Shehu, Saleh; Rabbebe, Isa Bukar; Beida, Omeiza

    2014-01-01

    Background: Globally, depression compromises the quality of life (QOL) of people suffering from it. We assessed the impact of comorbid depression on the health-related quality of life (HRQOL) of adults on highly active antiretroviral therapy (HAART) in northeastern Nigeria in this study. Materials and Methods: Three hundred and three adults on HAART were recruited for this study from the ART clinic of the University of Maiduguri Teaching Hospital in northeastern Nigeria. The depressive disorder module of the Composite international diagnostic interview (CIDI version 3.0) and the WHO quality of life instrument (WHOQOL-BREF) were used for the evaluation of depression and quality of life respectively. Results: The prevalence of depression in this study was 19.8%. The depressed respondents rated their HRQOL poorer than their nondepressed counterparts on the physical, psychological, social relationships and environmental domains as well as the global outcome, as shown by these statistically significant findings (T = 9.739, P = <0.001), (T = 8.972, P = <0.001), (T = 6.533, P = <0.001), (T = 8.913, P = <0.001), and (T = 10.018, P = <0.001), respectively. Female gender, CD4 counts <200/mm3 and diagnosis of depression were significant predictors poor QOL. Conclusion: Depression has a negative impact on the QOL of the respondents. We therefore recommend incorporation of the routine screening of this important psychiatric comorbidity into the care of this vulnerable group in order to optimize patient care. PMID:25336775

  10. Incidence of malaria by cotrimoxazole use in HIV-infected Ugandan adults on antiretroviral therapy: a randomised, placebo-controlled study

    PubMed Central

    Kasirye, Ronnie P.; Baisley, Kathy; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Grosskurth, Heiner

    2016-01-01

    Introduction: Previous unblinded trials have shown increased malaria among HIV-infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV-infected adults on ART in a double-blind, placebo-controlled trial. Methods: HIV-infected Ugandan adults stable on ART and CTX with CD4+ cell count at least 250 cells/μl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes. Results: A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2–10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74–4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18–0.49). There was one malaria-related death (CTX arm). Conclusion: HIV-infected adults – who are stable on ART and stop prophylactic CTX – experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis. PMID:26558729

  11. Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era

    PubMed Central

    Lewden, Charlotte; Drabo, Youssoufou J; Zannou, Djimon M; Maiga, Moussa Y; Minta, Daouda K; Sow, Papa S; Akakpo, Jocelyn; Dabis, François; Eholié, Serge P

    2014-01-01

    Objective We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. Method We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. Results Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women), 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm3 (IQR: 25–177) and 48% had previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36%), cerebral toxoplasmosis (10%), cryptococcosis (9%) and sepsis (7%). Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. Conclusions AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease

  12. [Recommendations of GESIDA (Grupo de Estudio de SIDA)/National Plan on AIDS with respect to the anti-retroviral treatment in adult patients infected with the human immunodeficiency virus in the year 2000 (II)].

    PubMed

    Miró, J M; Antela, A; Arrizabalaga, J; Clotet, B; Gatell, J M; Guerra, L; Antonio Iribarren, J; Laguna, F; Moreno, S; Parras, F; Rubio, R; Santamaría, J M; Viciana, P

    2000-10-01

    To update the recommendations for antiretroviral therapy (ART) in adult HIV-infected persons according to the new scientific advances and the existence of new antiretroviral drugs in the last two years. The ART recommendations have been condensed by a panel of experts from the Spanish AIDS Study Group (Grupo de Estudio de Sida-GESIDA) of the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC) and from the Clinical Advisory Panel (CAP) of the Secretariat of the Spanish National Plan on AIDS (SPNS) of the Ministry of Health. Three levels of evidence have been established depending if the data came from randomized and controlled studies, from cohort or case-control studies or from descriptive studies and expert opinions, for that purpose we have reviewed the advanced in HIV pathophysiology and results of efficacy (clinical, virologic and immunologic) and security (toxicity) from clinical trials involving ART lasting at least 12 months, from cohort studies and pharmacokinetic and security data of antoiretrovírico drugs, presented in international conferences or published in biomedical journals in the last two years. In each situation we have established either to recommend or to consider or not recommend ART. Nowadays, ART consistent of at least three drugs constitutes the election therapy for chronic HIV infection, since it delays clinical progression, increases significantly the survival and diminishes hospital admissions and associated costs. The decision to start ART must be based upon three elements: presence or absence of symptoms, plasma vírica load and CD4+ cells counts. Thus, in asymptomatic cases with a high CD4+ cells count (> 500/microliter) and low vírica load (< 10,000 copies/ml by branched DNA bDNA or < 20,000 copies/ml by reverse-transcription polymerase chain reaction [RT-PCR] or nucleic acid sequence based amplification [NASBA]) we recommend to delay ART. In symptomatic patients we recommend to start it, and in asymptomatic

  13. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

    PubMed

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred; Emery, Sean; Grund, Birgit; Sharma, Shweta; Avihingsanon, Anchalee; Cooper, David A; Fätkenheuer, Gerd; Llibre, Josep M; Molina, Jean-Michel; Munderi, Paula; Schechter, Mauro; Wood, Robin; Klingman, Karin L; Collins, Simon; Lane, H Clifford; Phillips, Andrew N; Neaton, James D

    2015-08-27

    Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. The initiation of

  14. Correlates of Combination Antiretroviral Adherence Among Recently Diagnosed Older HIV-Infected Adults Between 50 and 64 years

    PubMed Central

    Abara, Winston E.; Adekeye, Oluwatoyosi A.; Xu, Junjun; Heiman, Harry J.; Rust, George

    2016-01-01

    Optimal adherence to combination antiretroviral therapy is essential to the health of older people living with HIV (PLWH), however, the literature on adherence and aging is limited. Using Medicaid data from 29 states (N = 5177), we explored correlates of optimal adherence among older PLWH. The prevalence of optimal adherence was low (32 %) in this study. Males were more adherent than females (APR = 1.11, 95 % CI 1.02–1.21, P = 0.0127); persons with three or more co-morbidities (APR = 0.67, 95 % CI 0.60–0.74, P < 0.001), two co-morbidities (APR = 0.86, 95 % CI 0.75–0.98, P = 0.0319) and one co-morbidity (APR = 0.82, 95 % CI 0.73–0.92, P = 0.0008) were less adherent than those without any co-morbidity; and residents of rural areas (APR = 0.90, 95 % CI 0.63–0.98, P = 0.0385) and small metropolitan areas (APR = 0.82, 95 % CI 0.72–0.94, P = 0.0032) were less adherent than residents of large metropolitan areas. There were no racial differences in optimal adherence. Targeted interventions that provide adherence support, case management, and peer navigation services may be of benefit in achieving optimal adherence in this population. PMID:26885812

  15. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  16. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  17. Incidence and Predictors of Antiretroviral Treatment Modification in HIV-Infected Adults: A Brazilian Historical Cohort from 2001 to 2010

    PubMed Central

    Pinto Mendicino, Cássia Cristina; Reis, Edna Afonso; Carmo, Ricardo Andrade; Menezes de Pádua, Cristiane

    2017-01-01

    This study estimated the incidence of and time to first antiretroviral therapy (ART) modification. This longitudinal analysis comprised a sample of 236 patients from three HIV/AIDS referral centers in Belo Horizonte, Brazil—part of a major historical cohort. Inclusion criteria were as follows: having been treatment-naive patient ≥18 years old who initiated ART between 2001 and 2005 in these three referral centers. The main endpoint was time to first ART modification. Patients were followed up for five years, covering the period 2001–2010, during which time Pearson's chi-square test was performed to compare ART modification between groups. Kaplan-Meier inverse survival curves were employed to describe the probability of ART modification and Cox proportional hazard regression was used to estimate the adjusted hazard ratio (aHR) of ART modification. Among 247 patients from the major cohort, 236 were eligible. Median follow-up time was 37.2 months and the contribution in person-months was 7,615.4 months. A total of 108 (45.8%) patients had their ART regimen modified at least once (incidence rate: 1.42 per 100 person-months). Adverse drug reactions were the main reason for ART modification. Women (aHR = 1.62; p = 0.022) and patients on protease inhibitor- (PI-) based regimens (aHR = 2.70; p < 0.001) were at higher risk of ART modification. PMID:28348602

  18. Ratio of Monocytes to Lymphocytes in Peripheral Blood Identifies Adults at Risk of Incident Tuberculosis Among HIV-Infected Adults Initiating Antiretroviral Therapy

    PubMed Central

    Naranbhai, Vivek; Hill, Adrian V. S.; Abdool Karim, Salim S.; Naidoo, Kogieleum; Abdool Karim, Quarraisha; Warimwe, George M.; McShane, Helen; Fletcher, Helen

    2014-01-01

    Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases. Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted. Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002). Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis. PMID:24041796

  19. A meta-analysis of adherence to antiretroviral therapy and virologic responses in HIV-infected children, adolescents, and young adults.

    PubMed

    Kahana, Shoshana Y; Rohan, Jennifer; Allison, Susannah; Frazier, Thomas W; Drotar, Dennis

    2013-01-01

    The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) <100, VL < 400, and continuously measured VL. The analyses included 5,344 HIV+ children, adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report indices elicited very small to small magnitude effects across both VL < 100 and VL < 400 outcomes and combined informant reporting (youth/adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials reported smaller relationships between adherence and categorical clinical outcomes, such that year of publication significantly negatively correlated with VL < 100 (r = -.71(14), p < .005) and VL < 400 (r = -.43(26), p < .02). The data suggest that the magnitude of the relationship between ART adherence and virologic outcomes among heterogeneous samples of HIV+ children, adolescents and young adults varies across virologic outcomes and

  20. Effect of Optional Home Initiation of HIV Care Following HIV Self-testing on Antiretroviral Therapy Initiation Among Adults in Malawi

    PubMed Central

    MacPherson, Peter; Lalloo, David G.; Webb, Emily L.; Maheswaran, Hendramoorthy; Choko, Augustine T.; Makombe, Simon D.; Butterworth, Anthony E.; van Oosterhout, Joep J.; Desmond, Nicola; Thindwa, Deus; Squire, Stephen Bertel; Hayes, Richard J.; Corbett, Elizabeth L.

    2014-01-01

    IMPORTANCE Self-testing for HIV infection may contribute to early diagnosis of HIV, but without necessarily increasing antiretroviral therapy (ART) initiation. OBJECTIVE To investigate whether offering optional home initiation of HIV care after HIV self-testing might increase demand for ART initiation, compared with HIV self-testing accompanied by facility-based services only. DESIGN, SETTING, AND PARTICIPANTS Cluster randomized trial conducted in Blantyre, Malawi, between January 30 and November 5, 2012, using restricted 1:1 randomization of 14 community health worker catchment areas. Participants were all adult (≥16 years) residents (n = 16 660) who received access to home HIV self-testing through resident volunteers. This was a second-stage randomization of clusters allocated to the HIV self-testing group of a parent trial. INTERVENTIONS Clusters were randomly allocated to facility-based care or optional home initiation of HIV care (including 2 weeks of ART if eligible) for participants reporting positive HIV self-test results. MAIN OUTCOMES AND MEASURES The preplanned primary outcome compared between groups the proportion of all adult residents who initiated ART within the first 6 months of HIV self-testing availability. Secondary outcomes were uptake of HIV self-testing, reporting of positive HIV self-test results, and rates of loss from ART at 6 months. RESULTS A significantly greater proportion of adults in the home group initiated ART (181/8194, 2.2%) compared with the facility group (63/8466, 0.7%; risk ratio [RR], 2.94, 95% CI, 2.10-4.12; P < .001). Uptake of HIV self-testing was high in both the home (5287/8194, 64.9%) and facility groups (4433/8466, 52.7%; RR, 1.23; 95% CI, 0.96-1.58; P = .10). Significantly more adults reported positive HIV self-test results in the home group (490/8194 [6.0%] vs the facility group, 278/8466 [3.3%]; RR, 1.86; 95% CI, 1.16-2.97; P = .006). After 6 months, 52 of 181 ART initiators (28.7%) and 15 of 63 ART initiators (23

  1. Using Health Surveillance Systems Data to Assess the Impact of AIDS and Antiretroviral Treatment on Adult Morbidity and Mortality in Botswana

    PubMed Central

    Stoneburner, Rand; Korenromp, Eline; Lazenby, Mark; Tassie, Jean-Michel; Letebele, Judith; Motlapele, Diemo; Granich, Reuben; Boerma, Ties; Low-Beer, Daniel

    2014-01-01

    Introduction Botswana's AIDS response included free antiretroviral treatment (ART) since 2002, achieving 80% coverage of persons with CD4<350 cells/µl by 2009–10. We explored impact on mortality and HIV prevalence, analyzing surveillance and civil registration data. Methods Hospital natural cause admissions and deaths from the Health Statistics Unit (HSU) over 1990–2009, all-cause deaths from Midnight Bed Census (MNC) over 1990–2011, institutional and non-institutional deaths recorded in the Registry of Birth and Deaths (RBD) over 2003–2010, and antenatal sentinel surveillance (ANC) over 1992–2011 were compared to numbers of persons receiving ART. Mortality was adjusted for differential coverage and completeness of institutional and non-institutional deaths, and compared to WHO and UNAIDS Spectrum projections. Results HSU deaths per 1000 admissions declined 49% in adults 15–64 years over 2003–2009. RBD mortality declined 44% (807 to 452/100,000 population in adults 15–64 years) over 2003–2010, similarly in males and females. Generally, death rates were higher in males; declines were greater and earlier in younger adults, and in females. In contrast, death rates in adults 65+, particularly females increased over 2003–2006. MNC all-age post-neonatal mortality declined 46% and 63% in primary and secondary level hospitals, over 2003–2011. We estimated RBD captured 80% of adult deaths over 2006–2011. Comparing empirical, completeness-adjusted deaths to Spectrum estimates, declines over 2003–2009 were similar overall (47% vs. 54%); however, Spectrum projected larger and earlier declines particularly in women. Following stabilization and modest decreases over 1998–2002, HIV prevalence in pregnant women 15–24 and 25–29-years declined by >50% and >30% through 2011, while continuing to increase in older women. Conclusions Adult mortality in Botswana fell markedly as ART coverage increased. HIV prevalence declines may reflect ART

  2. Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa.

    PubMed

    Mekuria, Legese A; Sprangers, Mirjam A G; Prins, Jan M; Yalew, Alemayehu W; Nieuwkerk, Pythia T

    2015-01-01

    Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify patients most in need of additional support and to design appropriate interventions. A cross-sectional study was conducted between September 2012 and April 2013 in 10 healthcare facilities in Addis Ababa, Ethiopia. Patients who were at least 6 months on cART were randomly selected and individual patient data were retrieved from medical records. HRQoL was measured by the WHOQoL-HIVBREF, depressive-symptoms by the Kessler-6 scale, and stigma by the Kalichman internalized AIDS-related stigma scale. Multivariate linear regression analysis was carried-out to examine associations between HRQoL and the other variables. A total of 664 patients (response-rate 95%) participated in the study. A higher level of depressive-symptoms was most strongly and consistently associated with a lower HRQoL, both in terms of the magnitude of the relationship and in the number of HRQoL domains associated with it. Also, a higher level of HIV-stigma was associated with a lower HRQoL except for the physical domain, while obtaining sufficient nutritious food and job opportunity were associated with a better HRQoL except for the spiritual and social domains, respectively. Demographics, clinical, and treatment characteristics yielded few significant associations with HRQoL. Our study findings suggest that interventions to improve HRQoL should focus on reducing depressive-symptoms and HIV-stigma, and on enhancing food security and job opportunity.

  3. Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa

    PubMed Central

    Petersen, Maya L.; Tran, Linh; Geng, Elvin H.; Reynolds, Steven J.; Kambugu, Andrew; Wood, Robin; Bangsberg, David R.; Yiannoutsos, Constantin T.; Deeks, Steven G.; Martin, Jeffrey N.

    2015-01-01

    Objective Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design A cohort. Methods We examined patients with confirmed virologic failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27–33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1 –4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99–5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality. PMID:24977440

  4. Knowledge, attitudes, and practices of antiretroviral therapy among HIV-infected adults attending private and public clinics in India.

    PubMed

    Ramchandani, Suneil R; Mehta, Shruti H; Saple, Dattatray G; Vaidya, Satish B; Pandey, Ved P; Vadrevu, Ravi; Rajasekaran, Sikhamani; Bhatia, Vandana; Chowdhary, Abhay; Bollinger, Robert C; Gupta, Amita

    2007-02-01

    India has approximately 5.2 million persons infected with HIV. Although antiretroviral therapy (ART) is being widely introduced in public clinics, many HIV-infected persons still seek care via the private sector. A cross-sectional survey was conducted in 2004 at six public and private sites to characterize the knowledge, attitudes, and practices (KAP) of ART among patients with HIV receiving care in India. Of 1667 persons surveyed, 609 (36%) had heard of ART and 19% of these persons reported that ART could cure HIV. Twenty-four percent reported that they were currently taking ART, with 18% of these patients not actually on ART according to their provider. Major barriers to taking ART were cost (33%), lack of knowledge of ART (41%), and deferral by physician (30%). More than half of all public and private patients had not heard of CD4 (57%) or viral load testing (80%), and even fewer had received these tests (32% and 11%, respectively). Private clinic attendees were almost 4 times more likely to be on ART (35% versus 9%, p < 0.0001), more likely to be male, have a higher education, be partnered, have a higher income, and have had a CD4 or viral load (p < 0.0001). Overall, low levels of ART knowledge and access were observed among HIV infected patients, with access to ART being particularly low among patients attending public clinics. In order to make widespread dissemination of ART effective in India, further educational and programmatic efforts are likely needed to optimize access, treatment awareness, and compliance among patients with HIV.

  5. Effects of 96 Weeks of Rosuvastatin on Bone, Muscle, and Fat in HIV-Infected Adults on Effective Antiretroviral Therapy

    PubMed Central

    Jiang, Ying; Debanne, Sara M.; McComsey, Grace A.

    2016-01-01

    Abstract Heightened inflammation and immune activation are associated with lower bone mineral density (BMD) and lean body mass (LBM) among HIV-infected persons. We hypothesized that a reduction in inflammation with rosuvastatin would be associated with improvements in BMD and LBM. HIV-infected participants on stable antiretroviral therapy without statin indication and with heightened immune activation (≥19% CD8+CD38+HLA-DR+ T cells) or inflammation (hsCRP ≥2 mg/liter) were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Among 72 participants randomized to rosuvastatin and 75 to placebo, there were no significant differences in the relative changes in BMD (p > 0.29) or in fat (p ≥ 0.19). A trend toward increased LBM (p = 0.059) was seen in the rosuvastatin arm without differences in creatinine kinase or self-reported physical activity (p ≥ 0.10). In a multivariable regression model, rosuvastatin was associated with a significant positive effect on LBM after adjusting for age, sex, race, smoking status, and detectable HIV-1 viral load. Higher baseline sCD163 correlated with increases in LBM from weeks 0 to 96 (p = 0.023); greater changes in total and leg lean mass were seen among statin users with higher compared to lower baseline IP-10 levels (LBM 1.8 vs. −0.3%; p = 0.028 and leg lean mass 2.9 vs. −1.7%; p = 0.012). Rosuvastatin is associated with an absence of toxicity on BMD and a potential benefit on LBM over 96 weeks of therapy. The preservation of LBM in the rosuvastatin arm over the 2 years of the study is of major clinical relevance in delaying loss of muscle mass with aging. PMID:26477698

  6. Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya.

    PubMed

    Chung, Michael H; Beck, Ingrid A; Dross, Sandra; Tapia, Kenneth; Kiarie, James N; Richardson, Barbra A; Overbaugh, Julie; Sakr, Samah R; John-Stewart, Grace C; Frenkel, Lisa M

    2014-11-01

    Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at the time of ART initiation. Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1000 copies/mL) at 6-month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. Among 386 participants, TDR was detected by OLA in 3.89% (95% confidence interval: 2.19 to 6.33) and was associated with a 10-fold higher rate of virologic failure (hazard ratio: 10.39; 95% confidence interval: 3.23 to 32.41; P < 0.001) compared with those without TDR. OLA detected 24 TDR mutations (K103N: n = 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15; 3TC: n = 3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared with frequencies ≥2% (22% vs. 63%; P < 0.001). Detection of TDR by a point mutation assay may prevent the use of suboptimal ART.

  7. Oligonucleotide Ligation Assay Detects HIV Drug Resistance Associated with Virologic Failure among Antiretroviral-Naïve Adults in Kenya

    PubMed Central

    Chung, Michael H.; Beck, Ingrid A.; Dross, Sandra; Tapia, Kenneth; Kiarie, James N.; Richardson, Barbra A.; Overbaugh, Julie; Sakr, Samah R.; John-Stewart, Grace C.; Frenkel, Lisa M.

    2014-01-01

    Background Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at time of ART initiation. Methods Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1,000 copies/mL) at 6 month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. Results Among 386 participants, TDR was detected by OLA in 3.89% [95% Confidence Interval (CI), 2.19-6.33], and was associated with a 10-fold higher rate of virologic failure [Hazard Ratio (HR), 10.39; 95% CI, 3.23-32.41; p<0.001) compared to those without TDR. OLA detected 24 TDR mutations (K103N, n=13; Y181C, n=5; G190A, n=3; M184V, n=3) in 15 subjects (NNRTI, n=15; 3TC, n=3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared to frequencies ≥2% (22% vs. 63%; p<0.001). Conclusions Detection of TDR by a point mutation assay may prevent use of sub-optimal ART. PMID:25140907

  8. A randomized trial of ready-to-use supplementary food versus corn-soy blend plus as food rations for HIV-infected adults on antiretroviral therapy in rural Haiti.

    PubMed

    Ivers, Louise C; Teng, Jessica E; Jerome, J Gregory; Bonds, Matthew; Freedberg, Kenneth A; Franke, Molly F

    2014-04-01

    The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities. We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth. A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/µL (interquartile range [IQR], 197-475 cells/µL) for the CSB+ group, and 341 cells/µL (IQR, 213-464/µL) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant. In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti.

  9. A Randomized Trial of Ready-to-Use Supplementary Food Versus Corn-Soy Blend Plus as Food Rations for HIV-Infected Adults on Antiretroviral Therapy in Rural Haiti

    PubMed Central

    Ivers, Louise C.; Teng, Jessica E.; Gregory Jerome, J.; Bonds, Matthew; Freedberg, Kenneth A.; Franke, Molly F.

    2014-01-01

    Background. The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities. Methods. We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth. Results. A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/µL (interquartile range [IQR], 197–475 cells/µL) for the CSB+ group, and 341 cells/µL (IQR, 213–464/µL) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant. Conclusions. In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti. PMID:24536058

  10. 100 Things Every Adult College Student Ought To Know: A Self-Orientation Guide with Definitions, Customs, Procedures, and Advice To Assist Adults in Adjusting to the Start of College.

    ERIC Educational Resources Information Center

    Hardin, Carlette Jackson

    The information for this book was obtained by asking hundreds of adults students, and instructors with experience teaching adult learners, what they felt were the most important things adult students needed to know. Chapter 1, "Getting Started," provides information about what a student needs to know before enrolling in college. It is designed to…

  11. [Consensus document of Gesida and Spanish Secretariat for the National Plan on AIDS (SPNS) regarding combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2012)].

    PubMed

    2012-06-01

    This consensus document has been prepared by a panel consisting of members of the AIDS Study Group (Gesida) and the Spanish Secretariat for the National Plan on AIDS (SPNS) after reviewing the efficacy and safety results of clinical trials, cohort and pharmacokinetic studies published in medical journals, or presented in medical scientific meetings. Gesida has prepared an objective and structured method to prioritise combined antiretroviral treatment (cART) in naïve patients. Recommendations strength (A, B, C) and the evidence which supports them (I, II, III) are based on a modification of the Infectious Diseases Society of America criteria. The current antiretroviral treatment (ART) of choice for chronic HIV infection is the combination of three drugs. ART is recommended in patients with symptomatic HIV infection, in pregnancy, in serodiscordant couples with high transmission risk, hepatitis B fulfilling treatment criteria, and HIV nephropathy. Guidelines on ART treatment in patients with concurrent diagnosis of HIV infection and an opportunistic type C infection are included. In asymptomatic patients ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts <350 cells/μL; 2) when CD4 counts are between 350 and 500 cells/μL, therapy will be recommended and only delayed if patient is reluctant to take it, the CD4 are stabilised, and the plasma viral load is low; 3) therapy could be deferred when CD4 counts are above 500 cells/μL, but should be considered in cases of cirrhosis, chronic hepatitis C, high cardiovascular risk, plasma viral load >10(5) copies/mL, proportion of CD4 cells <14%, and in people aged >55 years. ART should include 2 reverse transcriptase inhibitors nucleoside analogues and a third drug (non-analogue reverse transcriptase inhibitor, ritonavir boosted protease inhibitor or integrase inhibitor). The panel has consensually

  12. Awareness about antiretroviral treatment, intentions to use condoms, and decisions to have an HIV test among rural Northern Lowland Thai and ethnic minority young adults.

    PubMed

    Srithanaviboonchai, Kriengkrai; Celentano, David D; Visaruratana, Surasing; Kawichai, Surinda; Wichajarn, Monjun; Genberg, Becky; Chariyalertsak, Chonlisa; Kulich, Michal; Chariyalertsak, Suwat

    2010-04-01

    Young adults aged 18 to 32 years were randomly selected from a household probability sample participating in Project Accept in the remote areas of Chiang Mai province in northern Thailand in 2005. Among 2989 respondents, 44.4% had never heard of antiretroviral treatment (ART). Lack of awareness of ART was independently associated with having had no formal education compared with some formal education and being an ethnic minority compared with being Thai. In all, 57% of the respondents who had ever heard of ART stated that if ART were easily available in their communities it would affect their intentions to be tested for HIV, whereas only 36% stated that this would affect their intentions to use condoms. Younger participants were less likely to intend to get an HIV test as compared with older individuals, and ethnic minorities were less likely to report that they would get an HIV test compared with Thai lowlanders. Single individuals and people who lived separately from their spouses were more likely to have the intention to use condoms if ART were available.

  13. Pill Burden Influences the Association Between Time-Based Prospective Memory and Antiretroviral Therapy Adherence in Younger But Not Older HIV-Infected Adults.

    PubMed

    Sheppard, David P; Weber, Erica; Casaletto, Kaitlin B; Avci, Gunes; Woods, Steven Paul

    2016-01-01

    Prospective memory (PM) is associated with antiretroviral (ARV) adherence in HIV, but little is known about how pill burden and age might affect this association. One hundred seventeen older (≥50 years) and 82 younger (<50 years) HIV-infected adults were administered a measure of PM in the laboratory and subsequently were monitored for ARV adherence for 30 days using the Medication Event Monitoring System. In the older group, better time-based PM performance was associated with higher likelihood of adherence, irrespective of pill burden. Within the younger sample, time-based PM was positively related to adherence only in participants with lower pill burdens. Younger HIV-infected individuals with higher pill burdens may overcome the normal effects of time-based PM on adherence through compensatory medication-taking strategies, whereas suboptimal use of these strategies by younger HIV-infected individuals with lower pill burdens may heighten their risk of ARV nonadherence secondary to deficits in time-based PM.

  14. Crofelemer: a review of its use in the management of non-infectious diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy.

    PubMed

    Frampton, James E

    2013-07-01

    Crofelemer (Fulyzaq) is a botanical drug substance (oligomeric proanthocyanidin) extracted from the stem bark latex of the Croton lechleri tree. Crofelemer undergoes minimal systemic absorption following oral administration; it acts locally within the gastrointestinal (GI) tract by inhibiting the two principal chloride ion channels in the luminal membrane of enterocytes. Crofelemer is the first (and so far only) agent to be approved by the US FDA specifically for the symptomatic relief of non-infectious (i.e. secretory) diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy (ART). This approval was based on findings from the ADVENT study, a large (n = 376 randomized patients), multicentre, phase III trial in which the recommended dosage of oral crofelemer (125 mg twice daily) significantly reduced secretory diarrhoea in HIV-positive individuals on ART compared with placebo, as assessed over a 4-week period. Crofelemer was generally well tolerated in ADVENT (which included a 5-month placebo-free extension phase) and a 48-week, open-label, phase III safety study; infections and GI disorders were the most frequently reported treatment-emergent adverse events (TEAEs) in patients receiving the drug. Of note, the overall incidence of TEAEs was similar in the crofelemer and placebo groups during the 4-week placebo-controlled phase of ADVENT. Treatment with crofelemer had no appreciable effect on immune parameters, such as HIV viral load and CD4+ cell counts.

  15. Relationship of Medication Management Test-Revised (MMT-R) performance to neuropsychological functioning and antiretroviral adherence in adults with HIV.

    PubMed

    Patton, Doyle E; Woods, Steven Paul; Franklin, Donald; Cattie, Jordan E; Heaton, Robert K; Collier, Ann C; Marra, Christina; Clifford, David; Gelman, Benjamin; McArthur, Justin; Morgello, Susan; Simpson, David; McCutchan, J Allen; Grant, Igor

    2012-11-01

    While performance-based tests of everyday functioning offer promise in facilitating diagnosis and classification of HIV-associated neurocognitive disorders (HAND), there remains a dearth of well-validated instruments. In the present study, clinical correlates of performance on one such measure (i.e., Medication Management Test-Revised; MMT-R) were examined in 448 HIV+ adults who were prescribed antiretroviral therapy. Significant bivariate relationships were found between MMT-R scores and demographics (e.g., education), hepatitis C co-infection, estimated premorbid IQ, neuropsychological functioning, and practical work abilities. MMT-R scores were not related to HIV disease severity, psychiatric factors, or self-reported adherence among participants with a broad range of current health status. However, lower MMT-R scores were strongly and uniquely associated with poorer adherence among participants with CD4 T cell counts <200. In multivariate analyses, MMT-R scores were predicted by practical work abilities, estimated premorbid functioning, attention/working memory, learning, and education. Findings provide overall mixed support for the construct validity of the MMT-R and are discussed in the context of their clinical and research implications for evaluation of HAND.

  16. Use of and Adherence to Antiretroviral Therapy in a Large U.S. Sample of HIV-infected Adults in Care, 2007-2008

    PubMed Central

    Beer, Linda; Heffelfinger, James; Frazier, Emma; Mattson, Christine; Roter, Brad; Barash, Elizabeth; Buskin, Susan; Rime, Todd; Valverde, Eduardo

    2012-01-01

    Background: Antiretroviral therapy (ART) is the cornerstone of HIV clinical care and is increasingly recognized as a key component of HIV prevention. However, the benefits of ART can be realized only if HIV-infected persons maintain high levels of adherence. Methods: We present interview data (collected from June 2007 through September 2008) from a national HIV surveillance system in the United States—the Medical Monitoring Project (MMP)—to describe persons taking ART. We used multivariate logistic regression to assess behavioral, sociodemographic, and medication regimen factors associated with three measures that capture different dimensions of nonadherence to ART: dose, schedule, and instruction. Results: The use of ART among HIV-infected adults in care was high (85%), but adherence to ART was suboptimal and varied across the three measures of nonadherence. Of MMP participants currently taking ART, the following reported nonadherence during the past 48 hours: 13% to dose, 27% to schedule, and 30% to instruction. The determinants of the three measures also varied, although younger age and binge drinking were associated with all aspects of nonadherence. Conclusion: Our results support the measurement of multiple dimensions of medication-taking behavior in order to avoid overestimating adherence to ART. PMID:23056163

  17. Relationship of Medication Management Test-Revised (MMT-R) Performance to Neuropsychological Functioning and Antiretroviral Adherence in Adults with HIV

    PubMed Central

    Patton, Doyle E.; Woods, Steven Paul; Franklin, Donald; Cattie, Jordan E.; Heaton, Robert K.; Collier, Ann C.; Marra, Christina; Clifford, David; Gelman, Benjamin; McArthur, Justin; Morgello, Susan; Simpson, David; McCutchan, J. Allen; Grant, Igor

    2013-01-01

    While performance-based tests of everyday functioning offer promise in facilitating diagnosis and classification of HIV-associated neurocognitive disorders (HAND), there remains a dearth of well-validated instruments. In the present study, clinical correlates of performance on one such measure (i.e., Medication Management Test—Revised; MMT-R) were examined in 448 HIV+ adults who were prescribed antiretroviral therapy. Significant bivariate relationships were found between MMT-R scores and demographics (e.g., education), hepatitis C co-infection, estimated premorbid IQ, neuropsychological functioning, and practical work abilities. MMT-R scores were not related to HIV disease severity, psychiatric factors, or self-reported adherence among participants with a broad range of current health status. However, lower MMT-R scores were strongly and uniquely associated with poorer adherence among participants with CD4 T-cell counts <200. In multivariate analyses, MMT-R scores were predicted by practical work abilities, estimated premorbid functioning, attention/working memory, learning, and education. Findings provide overall mixed support for the construct validity of the MMT-R and are discussed in the context of their clinical and research implications for evaluation of HAND. PMID:22722882

  18. Partner Disclosure and Early CD4 Response among HIV-Infected Adults Initiating Antiretroviral Treatment in Nairobi Kenya

    PubMed Central

    Trinh, T. Tony; Yatich, Nelly; Ngomoa, Richard; McGrath, Christine J.; Richardson, Barbra A.; Sakr, Samah R.; Langat, Agnes; John-Stewart, Grace C.; Chung, Michael H.

    2016-01-01

    Background Disclosure of HIV serostatus can have significant benefits for people living with HIV/AIDS. However, there is limited data on whether partner disclosure influences ART treatment response. Methods We conducted a retrospective cohort study of newly diagnosed, ART-naïve HIV-infected adults (>18 years) who enrolled at the Coptic Hope Center in Nairobi, Kenya between January 1st 2009 and July 1st 2011 and initiated ART within 3 months. Analysis was restricted to adults who reported to have either disclosed or not disclosed their HIV status to their partner. Analysis of CD4 response at 6 and 12 months post-ART was stratified by age group. Results Among 615 adults newly initiating ART with partner disclosure data and 12 month follow-up, mean age was 38 years and 52% were male; 76% reported that they had disclosed their HIV-status to their partner. Those who disclosed were significantly younger and more likely to be married/cohabitating than non-disclosers. At baseline, median CD4 counts were similar between disclosure groups. Among younger adults (< 38 years) those who disclosed had higher CD4 recovery than those who did not at 6 months post- ART (mean difference = 31, 95% CI 3 to 58 p = 0.03) but not at 12 months (mean difference = 17, 95% CI -19 to 52, p = 0.4). Among older adults (≥ 38years) there was no observed difference in CD4 recovery at 6 or 12 months between disclosure groups. Conclusion Among younger adults, disclosure of HIV status to partners may be associated with CD4 recovery following ART. PMID:27711164

  19. Mortality and immunological recovery among older adults on antiretroviral therapy at a large urban HIV clinic in Kampala, Uganda

    PubMed Central

    Semeere, Aggrey Semwendero; Lwanga, Isaac; Sempa, Joseph; Parikh, Sujal; Nakasujja, Noeline; Cumming, Robert; Kambugu, Andrew; Mayanja-Kizza, Harriet

    2014-01-01

    Background We describe older (> 50 years) HIV-infected adults after ART initiation, evaluating immunological recovery by age category, considering individual trajectories based on the pre-treatment CD4. We also describe mortality on ART and its risk factors by age category including the contribution of poor immunological recovery at a large urban clinic in Kampala, Uganda. Methods We performed a cohort analysis of adult (>18 years) HIV-infected patients who initiated ART between January 1, 2004 and January 3, 2012. Immunological response was evaluated using mixed-effects linear regression. We described mortality using Kaplan Meier survival methods analyzing for risk factors of mortality using multivariate Weibull survival regression stratified by age category. Results Among 9,806 individuals who initiated ART, mean age was 37 years (S.D 8.8), average follow-up 5.7 years (S.D 1.7) and median baseline CD4 was 115 cells/mm3 (IQR; 42-184). Adults <50 years had on average a higher CD4 increase of 45 cells/mm3 (95% CI; 17, 72, p=0.001) compared to counterparts aged ≥ 60 years. Mortality was highest among older adults compared to younger counterparts. Only CD4 count <100 cells/mm3 after 1 year on ART and a CD4 count less than baseline were associated with a statistically significant higher rate of death among older adults. Conclusion Older adults had a slower immunological response which was associated with mortality, but this mortality was not typically associated with opportunistic infections. Future steps would require more evaluation of possible causes of death among these older individuals if survival on ART is to be further improved. PMID:25171733

  20. [GeSIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2014)].

    PubMed

    2014-01-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: <350cells/μL, A-I; 350-500 cells/μL, A-II, and >500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2

  1. Outcomes of antiretroviral treatment in HIV-infected adults: a dynamic and observational cohort study in Shenzhen, China, 2003-2014.

    PubMed

    Huang, Peng; Tan, Jingguang; Ma, Wenzhe; Zheng, Hui; Lu, Yan; Wang, Ning; Peng, Zhihang; Yu, Rongbin

    2015-05-22

    To report 10-year outcomes of virological and immunological treatment failure rates and risk factors. Prospective cohort study. Shenzhen, China. 2172 HIV-positive adults in the national treatment database of Shenzhen from December 2003 to January 2014. Antiretroviral therapy according to the Chinese national treatment guidelines. Virological and immunological treatment failure rates. Of the 3099 patients surveyed, 2172 (70.1%) were included in the study. The median age was 33 years; 78.2% were male and 51.8% were infected through heterosexual contact. The median follow-up time was 31 months (IQR, 26-38). A total of 81 (3.7%) patients died, whereas 292 (13.4%) and 400 (18.4%) patients experienced virological and immunological failures, respectively. Adjusted Cox regression analysis indicated that baseline viral load (HR=2.19, 95% CI 1.52 to 4.48 for patients with a baseline viral load greater than or equal to 1,000,000 copies/mL compared to those with less than 10,000 copies/mL) and WHO stage (HR=4.16, 95% CI 2.01 to 10.57 for patients in WHO stage IV compared with those in stage I) were significantly associated with virological failure. The strongest risk factors for immunological treatment failure were a low CD4 cell count (HR=0.46, 95% CI 0.32 to 0.66 for patients with CD4 cell counts of 50-99 cells/mm(3) compared to those with less than 50 cells/mm(3)) and higher baseline WHO stage at treatment initiation (HR=2.15, 95% CI 1.38 to 3.34 for patients in WHO stage IV compared to those in stage I). Sustained virological and immunological outcomes show that patients have responded positively to long-term antiretroviral treatment with low mortality. This 10-year data study provides important information for clinicians and policymakers in the region as they begin to evaluate and plan for the future needs of their own rapidly expanding programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

  2. Non-AIDS-defining events among HIV-1-infected adults receiving combination antiretroviral therapy in resource-replete versus resource-limited urban setting

    PubMed Central

    Wester, C. William; Koethe, John R.; Shepherd, Bryan E.; Stinnette, Samuel E.; Rebeiro, Peter F.; Kipp, Aaron M.; Hong, Hwanhee; Bussmann, Hermann; Gaolathe, Tendani; McGowan, Catherine C.; Sterling, Timothy R.; Marlink, Richard G.

    2011-01-01

    Objective To compare incidence and distribution of non-AIDS-defining events (NADEs) among HIV-1-infected adults receiving combination antiretroviral therapy (cART) in urban sub-Saharan African versus United States settings. Design Retrospective cohort analysis of clinical trial and observational data. Methods Compared crude and standardized (to US cohort by age and sex) NADE rates from two urban adult HIV-infected cART-initiating populations: a clinical trial cohort in Gaborone, Botswana (Botswana) and an observational cohort in Nashville, Tennessee (USA). Results Crude NADE incidence rates were similar: 10.0 [95% confidence interval 6.3–15.9] per 1000 person-years in Botswana versus 12.4 [8.4–18.4] per 1000 person-years in the United States. However, after standardizing to an older, predominantly male US population, the overall NADE incidence rates were higher in Botswana [18.7 (8.3–33.1) per 1000 person-years]. Standardized rates differed most for cardiovascular events (8.4 versus 5.0 per 1000 person-years) and non-AIDS-defining malignancies (8.0 versus 0.5 per 1000 person-years) – both higher in Botswana. Conversely, hepatic NADE rates were higher in the United States (4.0 versus 0.0 per 1000 person-years), whereas renal NADE rates [3.0 per 1000 person-years (United States) versus 2.4 per 1000 person-years (Botswana)] were comparable. Conclusion Crude NADE incidence rates were similar between cART-treated patients in a US observational cohort and a sub-Saharan African clinical trial. However, when standardized to the US cohort, overall NADE rates were higher in Botswana. NADEs appear to be a significant problem in our sub-Saharan African setting, and the monitoring, prevention, and treatment of NADEs should be a critical component of care in resource-limited settings. PMID:21572309

  3. The Impact of a Community-Based Intervention Including a Monthly Food Ration on Food Insecurity Among HIV-Positive Adults During the First Year of Antiretroviral Therapy.

    PubMed

    Rothman, Jessica; Kayigamba, Felix; Hills, Victoria; Gupta, Neil; Machara, Faustin; Niyigena, Peter; Franke, Molly F

    2017-08-28

    The objective of this study was to examine how food insecurity changed among HIV-positive adults during the first 12 months of combination antiretroviral therapy (cART) and whether any change differed according to the receipt of food support, which was provided in the context of a comprehensive community-based intervention. We conducted secondary data analyses of data from a prospective cohort study of the effectiveness of a community-based cART delivery model when added to clinic-based cART delivery in Rwanda. We included patients from four health centers that implemented a clinic-based cART delivery model alone and five health centers that additionally implemented the intervention, which included 10 months of food support. We compared food insecurity at 3, 6, and 12 months, relative to baseline, and stratified by receipt of the intervention. Relative to baseline, median food insecurity score decreased after 3, 6, and 12 months (p value <0.0001 for all) for patients receiving a food ration through the community-based model for cART delivery. Among patients receiving care under the clinic-based cART model, food insecurity scores remained unchanged at 3 and 12 months and were significantly higher after 6 months. In adjusted analyses, participants enrolled in the community-based intervention with a food ration had a lower risk of severe food insecurity and a lower risk of moderate or severe food insecurity after 12 months. A comprehensive community-based HIV program including a food ration likely contributes to an alleviation of food insecurity among adults newly initiating cART.

  4. Antiretroviral Therapy Adherence Enhancing Interventions for Adolescents and Young Adults 13–24 Years of Age: A Review of the Evidence Base

    PubMed Central

    Shaw, Sarah

    2016-01-01

    Introduction: Youth living with HIV are highly under-represented in the evidence base for adherence interventions, despite their diverse and unique needs and barriers. Objective: This systematic review aimed to identify antiretroviral therapy (ART) adherence interventions specifically targeting adolescents and young adults (defined as ages 13–24) with the goal of characterizing the evidence base. Methods: Articles were identified using the PubMed database and cover work published through September 14, 2015. Inclusion criteria: (1) average age 13 to 24, (2) HIV positive, (3) on or beginning ART, (4) intervention targeted ART adherence in full or in part, (5) reported adherence, viral load, and/or CD4 count outcomes. Strength of evidence was defined as level 1 [randomized controlled trial (RCT) with significance testing on outcomes], 2 (within group studies with statistical testing on outcomes), 3 (RCTs with descriptive results), or 4 (within group studies with descriptive results). Results: Of 151 articles, 10 met inclusion criteria. Published between 2003 and 2014, these studies evaluated diverse intervention approaches. Most were conducted in the US and were small pilots that have yet to be replicated despite promising results. Only 3 studies met criteria for highest level strength of evidence; 2 supported a phone-based counseling approach with adherence monitors and 1 for weekly individual and family counseling. Conclusions: Despite nearly 20 years passing since the wide-scale availability of ART, and clear recognition that adolescents and youth adults fair worse on the cascade of HIV care, the evidence base remains sparse and underdeveloped. Promising approaches need replication and more rigorous studies are desperately needed. PMID:26959190

  5. Are social support and HIV coping strategies associated with lower depression in adults on antiretroviral treatment? Evidence from rural KwaZulu-Natal, South Africa.

    PubMed

    Yeji, Francis; Klipstein-Grobusch, Kerstin; Newell, Marie-Louise; Hirschhorn, Lisa R; Hosegood, Victoria; Bärnighausen, Till

    2014-01-01

    We assess depression rates and investigate whether depression among HIV-infected adults receiving antiretroviral treatment (ART) is associated with social support and HIV coping strategies in rural South Africa (SA). The study took place in a decentralised public-sector ART programme in a poor, rural area of KwaZulu-Natal, SA, with high-HIV prevalence and high-ART coverage. The 12-item General Health Questionnaire (GHQ12), validated in this setting, was used to assess depression in 272 adults recently initiated on ART. Estimates of depression prevalence ranged from 33% to 38%, depending on the method used to score the GHQ12. Instrumental social support (providing tangible factors for support, such as financial assistance, material goods or services), but not emotional social support (expressing feelings, such as empathy, love, trust or acceptance, to support a person), was significantly associated with lower likelihood of depression [adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) 0.52-0.81, P < 0.001], when controlling for sex, age, marital status, education, household wealth and CD4 cell count. In addition, using "avoidance of people" as a strategy to cope with HIV was associated with an almost three times higher odds of depression (aOR = 2.79, CI: 1.34-5.82, P = 0.006), whereas none of the other five coping strategies we assessed was significantly associated with depression. In addition to antidepressant drug treatment, interventions enhancing instrumental social support and behavioural therapy replacing withdrawal behaviours with active HIV coping strategies may be effective in reducing the burden of depression among patients on ART.

  6. Virological response and resistance profiles after 24 months of first-line antiretroviral treatment in adults living in Bangui, Central African Republic.

    PubMed

    Péré, Hélène; Charpentier, Charlotte; Mbelesso, Pascal; Dandy, Marius; Matta, Mathieu; Moussa, Sandrine; De Dieu Longo, Jean; Grésenguet, Gérard; Abraham, Bruno; Bélec, Laurent

    2012-04-01

    The rate of virological failure was assessed in 386 adult patients attending the Centre National Hospitalier Universitaire of Bangui, the capital city of the Central African Republic (CAR), receiving their first-line antiretroviral (ARV) drug regimen for 24 months, according to the World Health Organization (WHO) recommendations. In addition, genotypic resistance testing was carried out in 45 of 145 randomly selected patients whose plasma HIV-1 RNA load was detectable. Overall, 28.5% of ARV-treated patients were in virological failure (e.g., HIV-1 RNA >3.7 log(10) copies/ml). Twenty-four percent of patients in virological failure showed wild-type viruses, likely indicating poor adherence. Even after excluding the M184V mutation, all 76% of patients in virological failure displayed viruses harboring at least one major drug resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI), non-NRTI, or protease inhibitors. Whereas the second-line regimen proposed by the 2010 WHO recommendations, including zidovudine, tenofovir, lopinavir, and atazanavir, could be effective in more than 90% of patients in virological failure with resistant viruses, the remaining patients showed genotypic profiles highly predictive of resistance to the usual WHO second-line regimen, including complex genotypic profiles diagnosed only by genotypic resistance tests in some patients. In conclusion, our observations highlight the high frequency of therapeutic failure in ARV-treated adults in this study, as well as the urgent and absolute need for improving viral load assessment in the CAR to prevent and/or, from now on, to monitor therapeutic failure.

  7. Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria.

    PubMed

    Chang, Charlotte A; Meloni, Seema Thakore; Eisen, Geoffrey; Chaplin, Beth; Akande, Patrick; Okonkwo, Prosper; Rawizza, Holly E; Tchetgen Tchetgen, Eric; Kanki, Phyllis J

    2015-12-01

    Background.  Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods.  This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results.  Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7-27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4(+) cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions.  The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections.

  8. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.

    PubMed

    Cahn, Pedro; Pozniak, Anton L; Mingrone, Horacio; Shuldyakov, Andrey; Brites, Carlos; Andrade-Villanueva, Jaime F; Richmond, Gary; Buendia, Carlos Beltran; Fourie, Jan; Ramgopal, Moti; Hagins, Debbie; Felizarta, Franco; Madruga, Jose; Reuter, Tania; Newman, Tamara; Small, Catherine B; Lombaard, John; Grinsztejn, Beatriz; Dorey, David; Underwood, Mark; Griffith, Sandy; Min, Sherene

    2013-08-24

    Dolutegravir (GSK1349572), a once-daily HIV integrase inhibitor, has shown potent antiviral response and a favourable safety profile. We evaluated safety, efficacy, and emergent resistance in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance. ING111762 (SAILING) is a 48 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began in October, 2010. Eligible patients had two consecutive plasma HIV-1 RNA assessments of 400 copies per mL or higher (unless >1000 copies per mL at screening), resistance to two or more classes of antiretroviral drugs, and had one to two fully active drugs for background therapy. Participants were randomly assigned (1:1) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg, with investigator-selected background therapy. Matching placebo was given, and study sites were masked to treatment assignment. The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48, evaluated in all participants randomly assigned to treatment groups who received at least one dose of study drug, excluding participants at one site with violations of good clinical practice. Non-inferiority was prespecified with a 12% margin; if non-inferiority was established, then superiority would be tested per a prespecified sequential testing procedure. A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance. The trial is registered at ClinicalTrials.gov, NCT01231516. Analysis included 715 patients (354 dolutegravir; 361 raltegravir). At week 48, 251 (71%) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 (64%) patients on raltegravir (adjusted difference 7·4%, 95% CI 0·7 to 14·2); superiority of dolutegravir versus raltegravir was then concluded (p=0·03). Significantly fewer patients had virological failure with treatment

  9. Prevalence and risk factors of micronutrient deficiencies pre- and post-antiretroviral therapy (ART) among a diverse multicountry cohort of HIV-infected adults.

    PubMed

    Shivakoti, Rupak; Christian, Parul; Yang, Wei-Teng; Gupte, Nikhil; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Tang, Alice M; Semba, Richard D; Campbell, Thomas B; Gupta, Amita

    2016-02-01

    HIV-infected adults have increased risk of several individual micronutrient deficiencies. However, the prevalence and risk factors of concurrent and multiple micronutrient deficiencies and whether micronutrient concentrations change after antiretroviral therapy (ART) initiation have not been well described. The objective of this study was to determine the prevalence and risk factors of individual, concurrent and multiple micronutrient deficiencies among ART-naïve HIV-infected adults from nine countries and assess change in micronutrient status 48 weeks post-ART initiation. A random sub-cohort (n = 270) stratified by country was selected from the multinational PEARLS clinical trial (n = 1571 ART-naïve, HIV-infected adults). We measured serum concentrations of vitamins A, D (25-hydroxyvitamin), E, carotenoids and selenium pre-ART and 48 weeks post-ART initiation, and measured vitamins B6, B12, ferritin and soluble transferrin receptor at baseline only. Prevalence of single micronutrient deficiencies, concurrent (2 coexisting) or conditional (a deficiency in one micronutrient given a deficiency in another) and multiple (≥3) were determined using defined serum concentration cutoffs. We assessed mean changes in micronutrient concentrations from pre-ART to week 48 post-ART initiation using multivariable random effects models. Of 270 participants, 13.9%, 29.2%, 24.5% and 32.4% had 0, 1, 2 and multiple deficiencies, respectively. Pre-ART prevalence was the highest for single deficiencies of selenium (53.2%), vitamin D (42.4%), and B6 (37.3%) with 12.1% having concurrent deficiencies of all three micronutrients. Deficiency prevalence varied widely by country. 48 weeks post-ART initiation, mean vitamin A concentration increased (p < 0.001) corresponding to a 9% decrease in deficiency. Mean concentrations also increased for other micronutrients assessed 48 weeks post-ART (p < 0.001) but with minimal change in deficiency status. Single and multiple micronutrient

  10. Antiretroviral Treatment 2010: Progress and Controversies

    PubMed Central

    Gulick, Roy M.

    2011-01-01

    Effective antiretroviral therapy (ART) changes the clinical course of HIV infection. There are 25 antiretroviral drugs approved for the treatment of HIV infection, and current antiretroviral drug regimens are highly effective, convenient, and relatively nontoxic. ART regimens should be chosen in consideration of a patient’s particular clinical situation. Successful treatment is associated with durable suppression of HIV viremia over years, and consequently, ART reduces the risk of clinical progression. In fact, current models estimate that an HIV-infected individual appropriately treated with antiretroviral drugs has a life expectancy that approaches that of the general HIV-uninfected population, although some patient groups such as injection drug users do less well. Despite these advances, continued questions about ART persist: What is the optimal time to start ART? What is the best regimen to start? When is the optimal time to change ART? What is the best regimen to change to? In addition, newer antiretroviral agents are in development, both in existing classes and in new classes such as the CD4 receptor attachment inhibitors and the maturation inhibitors. Further research will help optimize current antiretroviral treatments and strategies. PMID:21045599

  11. Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy.

    PubMed

    Winston, A; Stöhr, W; Antinori, A; Arenas-Pinto, A; Llibre, J M; Amieva, H; Cabié, A; Williams, I; Di Perri, G; Tellez, M J; Rockstroh, J; Babiker, A; Pozniak, A; Raffi, F; Richert, L

    2016-06-01

    Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors. © 2015 British HIV Association.

  12. High perceived social standing is associated with better health in HIV-infected Ugandan adults on highly active antiretroviral therapy.

    PubMed

    Ezeamama, A E; Guwatudde, D; Wang, M; Bagenda, D; Brown, K; Kyeyune, R; Smith, Emily; Wamani, H; Manabe, Y C; Fawzi, W W

    2016-06-01

    Perceived social standing (PSS) was evaluated as a determinant of differences in health outcomes among Ugandan HIV-infected adults from Kampala using cross-sectional study design. PSS was defined using the MacArthur scale of subjective social status translated and adapted for the study setting. Socio-demographic and psychosocial correlates of PSS ranking at enrollment were determined using linear regression models. High versus low PSS was defined based on the median PSS score and evaluated as a determinant of body mass index, hemoglobin, quality of life (QOL) and frailty-related phenotype via linear regression. A log-binomial regression model estimated the relative-risk of good, very good or excellent versus fair or poor self-rated health (SRH) in relation to PSS. Older age, increasing social support and material wealth were correlated with high PSS ranking, whereas female sex, experience of multiple stigmas and multiple depressive symptoms were correlated with low PSS ranking. High PSS participants were on average 1.1 kg/m(2) heavier, had 4.7 % lower frailty scores and 3.6 % higher QOL scores compared to low PSS patients (all p < 0.05); they were also more likely to self-classify as high SRH (RR 1.4, 95 % confidence interval 1.1, 1.7) but had comparable hemoglobin levels (p = 0.634). Low PSS correlated with poor physical and psychosocial wellbeing in HIV-positive Ugandan adults. The assessment of PSS as part of clinical management, combined with efforts to reduce stigma and improve social support, may identify and possibly reduce PSS-associated health inequality in Ugandan adults with HIV.

  13. “The sky is the limit”: adhering to antiretroviral therapy and HIV self-management from the perspectives of adolescents living with HIV and their adult caregivers

    PubMed Central

    Denison, Julie A; Banda, Harry; Dennis, Alexis C; Packer, Catherine; Nyambe, Namakau; Stalter, Randy M; Mwansa, Jonathan K; Katayamoyo, Patrick; McCarraher, Donna R

    2015-01-01

    Introduction Worldwide, HIV-related mortality among adolescents living with HIV (ALHIV) increased by 50% from 2005 to 2012 and is attributed in part to a lack of support for adolescent retention to care and adherence to antiretroviral therapy (ART). This vulnerability reinforces the need to better understand incomplete ART adherence among ALHIV, particularly in sub-Saharan Africa, where the majority of the world's 2.1 million ALHIV reside. Methods From December 2011 to February 2012, we conducted in-depth interviews with 32 ALHIV (aged 15 to 18) and 23 of their adult caregivers in the Copperbelt Province of Zambia. Interviews were transcribed and translated. An iterative qualitative process was used to code and analyze the data and main themes were summarized regarding the barriers to and facilitators of ART adherence. Results More than a quarter of ALHIV reported missing a day or more of ART (ranging from one day to six months). Barriers to ART adherence included fear of disclosure and anticipated stigma. Few youth were willing to take their drugs outside of the home, which led to missed doses of ART. Similarly, families tended to manage HIV within the home only. As a result, although caregivers and families were often the greatest source of emotional and instrumental support, they coped with HIV in isolation of other potential support from their communities, schools or churches. Factors that supported ART adherence included attending clinic-sponsored youth groups, wanting to maintain one's health and using phone and clock alarms. Involvement of adult caregivers in HIV management varied greatly and was often based on the age and health status of the youth. Some caregivers struggled with letting the adolescents assume responsibility for their medication, and ALHIV had few self-management skills and tools to help them regularly take ART. Conclusions These data highlight the importance of families and home environments in supporting adherence to ART among ALHIV

  14. Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV-1-Infected Patients Starting Efavirenz, Lopinavir-Ritonavir, or Atazanavir-Ritonavir Plus Tenofovir/Emtricitabine: Final 48-Week Results (The Advanz-3 Trial).

    PubMed

    Miro, Jose M; Manzardo, Christian; Ferrer, Elena; Loncà, Montserrat; Guardo, Alberto C; Podzamczer, Daniel; Domingo, Pere; Curran, Adrian; Clotet, Bonaventura; Cruceta, Anna; Lozano, Francisco; Pérez, Iñaki; Plana, Montserrat; Gatell, Jose M

    2015-06-01

    Few randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens. Randomized, controlled, open-label, multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naive patients with <100 CD4 cells per cubic millimeter were randomly assigned in a 1:1:1 ratio to efavirenz (n = 29), atazanavir/ritonavir (n = 30), or lopinavir/ritonavir (n = 30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary end points were the proportion of patients with HIV-1 RNA <50 copies per milliliter, adverse events, disease progression, and death. In the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was +193 (129-349) cells per microliter in the efavirenz arm, +197 (146-238) cells per microliter in the ritonavir-boosted atazanavir arm, and +205 (178-327) cells per microliter in the ritonavir-boosted lopinavir arm (P = 0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks {efavirenz, 85.71% [95% confidence interval (CI): 68.5 to 94.3]; atazanavir, 80% [95% CI: 62.7 to 90.5]; and lopinavir, 82.8% [95% CI: 65.5 to 92.4]; P = 0.88}. Bacterial translocation, inflammation, immune activation, and apoptotic markers, but not D-dimer, declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died. The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).

  15. [Treatment of opportunistic infections in adolescent and adult patients infected with the human immunodeficiency virus during the era of highly active antiretroviral therapy. AIDS Study Group (GESIDA) and National AIDS Plan Expert Committee].

    PubMed

    2008-01-01

    Despite the huge advance that highly active antiretroviral therapy has represented for the prognosis of infection by human immunodeficiency virus (HIV), opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. This is often the case because of severe immunodepression, poor adherence to antiretroviral therapy, failure of therapy, or the fact that patients are unaware of their HIV-positive status and debut with an opportunistic infection. This article updates the guidelines on treatment of acute episodes of various opportunistic infections in HIV-infected patients, including infections due to parasites, fungi, viruses, mycobacteria, and bacteria. This edition has a new chapter on imported parasite infections as well as additional information on endemic mycoses in the chapter on fungal infections, taking into account the growing number of immigrants in our setting. Lastly, the chapter on the immune reconstitution syndrome has also been updated, providing relevant data on a phenomenon that has clinical and diagnostic repercussions in patients who start antiretroviral therapy while they are severely immunodepressed (English version available at http://www.gesida.seimc.org).

  16. Barriers and Facilitators of Adherence to Antiretroviral Drug Therapy and Retention in Care among Adult HIV-Positive Patients: A Qualitative Study from Ethiopia

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.; Bimirew, Mekides A.; Kassie, Desalew M.

    2014-01-01

    Background Antiretroviral therapy (ART) has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country’s ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. Methods Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. Results Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. Conclusions Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved patient outcomes

  17. The use of cell phone reminder calls for assisting HIV-infected adolescents and young adults to adhere to highly active antiretroviral therapy: a pilot study.

    PubMed

    Puccio, Joseph A; Belzer, Marvin; Olson, Johanna; Martinez, Miguel; Salata, Cathy; Tucker, Diane; Tanaka, Diane

    2006-06-01

    Long-term medication regimen adherence is challenging in all populations, but in the HIV-infected adolescent population the frequency of poverty, homelessness, substance abuse, and mental illness make highly active antiretroviral therapy (HAART) adherence even more challenging. In 2003, we developed a pilot program for HIV-infected adolescents and young adults between the ages of 16 and 24 who were either going to begin a HAART regimen for the first time or begin a new HAART regimen. Participants received a free cell phone with a local service plan for approximately 6 months. Participants received phone call reminders for 12 weeks. Call frequency was tapered at 4-week intervals. Patients were assessed at 4-week intervals to determine the perceived intrusiveness or helpfulness of receiving calls, and missed medication doses. Eight consecutive patients were recruited for the study, and five were able to complete it through the 24 weeks. Most participants found the calls to be helpful and the level of intrusion into their daily lives acceptable. Using cell phone reminders to assist patients does not require an extensive amount of daily staff time. Tapering calls rapidly over 3 months, followed by discontinuation of calls provided inadequate support for subjects, especially those with significant psychosocial issues such as substance abuse. Use of cell phone reminders to assist adolescents adhere with HIV medications was practical and acceptable to pilot study participants. Viral suppression waned for all but two patients after termination of cell phone reminders and suggests that a 12-week intervention was not adequate for most subjects. Larger prospective studies of cell phone observation of therapy will be needed to determine if this intervention can improve long-term adherence and health outcomes.

  18. Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa

    PubMed Central

    Sempa, Joseph B.; Ujeneza, Eva L.; Nieuwoudt, Martin

    2017-01-01

    Introduction In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. Methods ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: ‘slope’, ‘survival’, and ‘asymptote’ models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. Results 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Conclusion Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to

  19. Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008–2013

    PubMed Central

    Fox, Matthew P; MPA, Sydney Rosen

    2015-01-01

    Background We previously published systematic reviews of retention in care after antiretroviral therapy initiation among general adult populations in sub-Saharan Africa. We estimated 36-month retention at 73% for publications from 2007–2010. This report extends the review to cover 2008–2013 and expands it to all low- and middle-income countries. Methods We searched PubMed, Embase, Cochrane Register, and ISI Web of Science from January 1, 2008 to December 31, 2013 and abstracts from AIDS and IAS from 2008–2013. We estimated retention across cohorts using simple averages and interpolated missing times through the last time reported. We estimated all-cause attrition (death, loss to follow-up) for patients receiving first-line ART in routine settings in low- and middle-income countries. Results We found 123 papers and abstracts reporting retention for 154 patient cohorts and 1,554,773 patients in 42 countries. Overall, 43% of all patients not retained were known to have died. Unweighted averages of reported retention was 78%, 71% and 69% at 12, 24, and 36 months after treatment initiation, respectively. We estimated 36-month retention at 65% in Africa, 80% in Asia, and 64% in Latin America and the Caribbean. From lifetable analysis, we estimated retention at 12, 24, 36, 48 and 60 months at 83%, 74%, 68%, 64% and 60%, respectively. Conclusions Retention at 36 months on treatment averages 65–70%. There are several important gaps in the evidence-base, which could be filled by further research, especially in terms of geographic coverage and duration of follow-up. PMID:25942461

  20. Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa.

    PubMed

    Sempa, Joseph B; Ujeneza, Eva L; Nieuwoudt, Martin

    2017-01-01

    In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. 'Preferred Reporting Items for Systematic Review and Meta-Analyses' guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: 'slope', 'survival', and 'asymptote' models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to define 'prior' knowledge in the Bayesian sense. Such

  1. New Antiretroviral Therapies for Pediatric HIV Infection

    PubMed Central

    Morris, Jennifer L.; Kraus, Donna M.

    2005-01-01

    Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

  2. CROI 2014: Advances in antiretroviral therapy.

    PubMed

    Taylor, Barbara S; Shalev, Noga; Wilkin, Timothy J

    2014-05-01

    The 2014 Conference on Retroviruses and Opportunistic Infections (CROI) highlighted important advances in antiretroviral therapy, with an emphasis on HIV eradication strategies. Follow-up information about the Mississippi baby who remains free of HIV infection off antiretroviral therapy was presented, and a second baby and 1 adult may also have been cured with very early initiation of antiretroviral therapy. The HIV care cascade was again a major focus of the conference. Investigators from around the world presented data on the implementation, and limitations, of the care cascade paradigm. Scale-up of antiretroviral therapy continues and a number of presentations featured optimal ways to measure the impact of these efforts by applying lessons from implementation science and health care economics. Encouraging results from expanded prevention of mother-to-child transmission programs, especially Option B+, were highlighted. Extensive data on transmitted (primary) drug resistance in the United States and Europe were presented.

  3. Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

    PubMed

    Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

    2017-06-01

    To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

  4. Predictors of treatment failure on second-line antiretroviral therapy among adults in northwest Ethiopia: a multicentre retrospective follow-up study

    PubMed Central

    Tsegaye, Adino Tesfahun; Wubshet, Mamo; Awoke, Tadesse; Addis Alene, Kefyalew

    2016-01-01

    Background The number of patients using second-line antiretroviral therapy (ART) has increased over time. In Ethiopia, 1.5% of HIV infected patients on ART are using a second-line regimen and little is known about its effect in this setting. Objective To estimate the rate and predictors of treatment failure on second-line ART among adults living with HIV in northwest Ethiopia. Setting An institution-based retrospective follow-up study was conducted at three tertiary hospitals in northwest Ethiopia from March to May 2015. Participants 356 adult patients participated and 198 (55.6%) were males. Individuals who were on second-line ART for at least 6 months of treatment were included and the data were collected by reviewing their records. Primary outcome measure The primary outcome was treatment failure defined as immunological failure, clinical failure, death, or lost to follow-up. To assess our outcome, we used the definitions of the WHO 2010 guideline. Result The mean±SD age of participants at switch was 36±8.9 years. The incidence rate of failure was 61.7/1000 person years. The probability of failure at the end of 12 and 24 months were 5.6% and 13.6%, respectively. Out of 67 total failures, 42 (62.7%) occurred in the first 2 years. The significant predictors of failure were found to be: WHO clinical stage IV at switch (adjusted HR (AHR) 2.1, 95% CI 1.1 to 4.1); CD4 count <100 cells/mm3 at switch (AHR 2.0, 95% CI 1.2 to 3.5); and weight change (AHR 0.92, 95% CI 0.88 to 0.95). Conclusions The rate of treatment failure was highest during the first 2 years of treatment. WHO clinical stage, CD4 count at switch, and change in weight were found to be predictors of treatment failure. PMID:27932339

  5. Empiric Tuberculosis Therapy versus Isoniazid in Advanced HIV-infected Adult Outpatients Initiating Antiretroviral Therapy: a Multi-Country Randomized Controlled Trial

    PubMed Central

    Hosseinipour, Mina C.; Bisson, Gregory P.; Miyahara, Sachiko; Sun, Xin; Moses, Agnes; Riviere, Cynthia; Kirui, F.K.; Badal-Faesen, Sharla; Lagat, David; Nyirenda, Mulinda; Naidoo, K; Hakim, James; Mugyenyi, Peter; Henostroza, German; Leger, P.D; Lama, Javier.R; Mohapi, Lerato; Alave, Jorge; Mave, V; Veloso, Valdilea.G; Pillay, Sandy; Kumarasamy, N.; Bao, Jing; Hogg, Evelyn; Jones, Lynne; Zolopa, Andrew; Kumwenda, Johnstone; Gupta, Amita

    2016-01-01

    Summary Background Mortality within the first 6 months after initiating antiretroviral therapy (ART) is common in resource-limited settings and is often due to tuberculosis (TB) among patients with advanced HIV disease. Isoniazid preventive therapy (IPT) is recommended in HIV-infected adults, but sub-clinical TB can be difficult to diagnose. We hypothesized that empiric TB treatment would reduce early mortality compared to IPT in high-burden settings. Methods We conducted a multi-country randomized clinical trial comparing empiric TB therapy (Empiric) vs. isoniazid preventive therapy (IPT) in HIV-infected outpatients initiating ART with CD4 counts <50 cells/mm3. Individuals were screened for TB using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available. The primary endpoint was survival (death or unknown status) at 24 weeks post randomization. Kaplan Meier estimates of the endpoint rates across arms were compared by the z-test. Registered at ClinicalTrials.gov (NCT01380080). Findings From October 31, 2011 until June 9, 2014, we randomized 850 participants (424 in Empiric arm and 426 in IPT arm); the median CD4 count at baseline was 18 cells/mm3 (IQR: 9, 32). At week 24, each arm had 22 primary endpoints, for rates of 5.2% in each arm (95% CI: 3.5% to 7.8% for Empiric and 3.4% to 7.8% for IPT; absolute risk difference of -0.06% (95% CI: −3.05% to 2.94%). Grade 3 or 4 signs or symptoms occurred in 50 (12%) in the Empiric arm and 46 (11%) in the IPT arm. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) in the Empiric arm and 97 (23%) in the IPT arm. Incident TB was more common in the Empiric arm (31 vs. 18 events, p=0.01). Interpretation Empiric TB therapy did not reduce mortality at 24 weeks in outpatient adults initiating ART with advanced HIV disease. The low mortality rate of the trial supports implementation of systematic TB screening and IPT in outpatients with advanced HIV disease. PMID:27025337

  6. HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study

    PubMed Central

    2014-01-01

    Background An increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya. Methods HIV-infected adults on first-line ART for ≥6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ≥400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively. Results Of the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 – 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 – 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15–34 vs. ≥35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1–0.6], p = 0.002) and unsatisfactory adherence (<95% vs. ≥95%: 3.0 [1.5–6.5], p = 0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR. Conclusions High levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance

  7. Incidence and predictors of attrition from antiretroviral care among adults in a rural HIV clinic in Coastal Kenya: a retrospective cohort study.

    PubMed

    Hassan, Amin S; Mwaringa, Shalton M; Ndirangu, Kennedy K; Sanders, Eduard J; de Wit, Tobias F Rinke; Berkley, James A

    2015-05-10

    Scale up of antiretroviral therapy (ART) has led to substantial declines in HIV related morbidity and mortality. However, attrition from ART care remains a major public health concern and has been identified as one of the key reportable indicators in assessing the success of ART programs. This study describes the incidence and predictors of attrition among adults initiating ART in a rural HIV clinic in Coastal Kenya. A retrospective cohort study design was used. Adults (≥ 15 years) initiated ART between January 2008 and December 2010 were followed up for two years. Attrition was defined as individuals who were either reported dead or lost to follow up (LFU, ≥ 180 days late since the last clinic visit). Kaplan Meier survival probabilities and Weibull baseline hazard regression analyses were used to model the incidence and predictors of time to attrition. Of the 928 eligible participants, 308 (33.2% [95% CI, 30.2 - 36.3]) underwent attrition at an incident rate of 23.1 (95% CI, 20.6 - 25.8)/100 pyo. Attrition at 6 and 12 months was 18.4% (95% CI, 16.0 - 21.1) and 23.2% (95% CI, 19.9 - 25.3) respectively. Gender (male vs. female, adjusted hazard ratio [95% CI], p-value: 1.5 [1.1 - 2.0], p = 0.014), age (15 - 24 vs. ≥ 45 years, 2.2 [1.3 - 3.7], p = 0.034) and baseline CD4 T-cell count (100 - 350 cells/uL vs. < 100 cells/uL, 0.5 [0.3 - 0.7], p = 0.002) were independent predictors of time to attrition. A third of individuals initiating ART were either reported dead or LFU during two years of care, with more than a half of these occurring within six months of treatment initiation. Practical and sustainable biomedical interventions and psychosocial support systems are warranted to improve ART retention in this setting.

  8. Twice-daily versus once-daily antiretroviral therapy and coformulation strategies in HIV-infected adults: benefits, risks, or burden?

    PubMed Central

    Nachega, Jean B; Rosenkranz, Bernd; Pham, Paul A

    2011-01-01

    The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices. PMID:22259241

  9. Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART) Clients in Bale Zone Hospitals, South Eastern Ethiopia

    PubMed Central

    Takele, Abulie; Gashaw, Ketema; Demelash, Habtamu; Nigatu, Dabere

    2016-01-01

    Background Treatment failure defined as progression of disease after initiation of ART or when the anti-HIV medications can’t control the infection. One of the major concerns over the rapid scaling up of ART is the emergence and transmission of HIV drug resistant strains at the population level due to treatment failure. This could lead to the failure of basic ART programs. Thus this study aimed to investigate the predictors of treatment failure among adult ART clients in Bale Zone Hospitals, South east Ethiopia. Methods Retrospective cohort study was employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A total of 4,809 adult ART clients were included in the analysis from these four hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM) curve was used to describe the survival time of ART patients without treatment failure. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of treatment failure. Result The incidence rate of treatment failure was found 9.38 (95% CI 7.79–11.30) per 1000 person years. Male ART clients were more likely to experience treatment failure as compared to females [AHR = 4.49; 95% CI: (2.61–7.73)].Similarly, lower CD4 count (<100 m3/dl) at initiation of ART was found significantly associated with higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46–5.84).Bedridden [AHR = 5.02; 95% CI: (1.98–12.73)] and ambulatory [AHR = 2.12; 95% CI: (1.08–4.07)] patients were more likely to experience treatment failure as compared to patients with working functional status. TB co-infected clients had also higher odds to experience treatment failure [AHR = 3.06; 95% CI: (1.72–5.44)]. Those patients who had developed TB after ART initiation had higher odds to experience treatment failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99–9.54]. Having other opportunistic infection during ART initiation was also

  10. Sub-optimal adherence to combination anti-retroviral therapy and its associated factors according to self-report, clinician-recorded and pharmacy-refill assessment methods among HIV-infected adults in Addis Ababa.

    PubMed

    Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

    2017-04-01

    Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients' response of less than "all-of the time" to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of <95% medication possession ratio (MPR). Logistic regression models were fitted to identify factors associated with sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.

  11. Short Communication: Population-Based Surveillance of HIV-1 Drug Resistance in Cameroonian Adults Initiating Antiretroviral Therapy According to the World Health Organization Guidelines.

    PubMed

    Fokam, Joseph; Takou, Désiré; Santoro, Maria Mercedes; Akonie, Haniel Ze; Kouanfack, Charles; Ceccherini-Silberstein, Francesca; Colizzi, Vittorio; Perno, Carlo-Federico; Ndjolo, Alexis

    2016-04-01

    With ongoing earlier enrollment on and rapid scale-up of antiretroviral therapy (ART) in Cameroon, there are increasing risks of transmitted HIV drug resistance (HIVDR) at population levels. We, therefore, evaluated the threshold of HIVDR in a population initiating ART, to inform on the effectiveness of first-line regimens, considering HIV-1 diversity, plasma viral load (PVL), and CD4-based disease progression. A total of 53 adults [median (interquartile range, IQR) CD4: 162 cell/mm(3) (48-284); median (IQR) PVL: 5.34 log10 RNA (4.17-6.42) copies/ml] initiating ART in 2014 at the Yaoundé Central Hospital were enrolled for HIV-1 protease-reverse transcriptase sequencing. Drug resistance mutations (DRMs) were interpreted using the 2009 World Health Organization (WHO) list versus the Stanford HIVdb algorithm version 7.0. Level of DRMs was low (3.77%) versus moderate (7.55%), respectively, following the WHO list (T69D, K103N) versus Stanford HIVdb (T69D, A98G, K103N, K238T), respectively. Prevailing clade was CRF02_AG (71.70%). Based on Stanford HIVdb, a slightly higher proportion of patients with DRMs were found among ones infected with CRF02_AG than in those non-CRF02_AG infected (7.89% vs. 6.67%, p = 1.000), with lower PVL (7.69% <5.5 vs. 0% ≥5.5 log10 RNA copies/ml, p = .488) and with higher CD4 counts (9.52% CD4 ≥200 vs. 3.33% CD4 <200 cells/mm(3), p = .749). Thresholds of DRMs suggest that standard first-line regimens currently used in Cameroon may remain effective at population levels, despite scale-up of ART in the country, pending adherence, and closed virological monitoring. With an intent-to-diagnose approach, the discrepant levels of DRMs support using Stanford HIVdb to evaluate initial ART, while revising the WHO list for surveillance.

  12. From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults.

    PubMed

    Namakoola, Ivan; Kasamba, Ivan; Mayanja, Billy N; Kazooba, Patrick; Lutaakome, Joseph; Lyagoba, Fred; Kapaata, Anne A; Kaleebu, Pontiano; Munderi, Paula

    2016-12-23

    HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes. Between July 2013 and August 2014, 953 individuals were enrolled, 119 (12.5%) had HIV-RNA ≥1000 copies/ml and 110 were successfully genotyped; 74 (67.3%) were on first-line and 36 (32.7%) on second-line ART regimens. The predominant HIV-1 subtypes were D (34.5%), A (33.6%) and Recombinant forms (21.8%). The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor (NRTI) were; the Non-thymidine analogue mutations (Non-TAMS) M184V-20.7% and K65R-8.0%; and the TAMs M41L and K70R (both 8.0%). The major Non-NRTI (NNRTI) mutations were K103N-19.0%, G190A-7.0% and Y181C-6.0%. A relatively nonpolymorphic accessory mutation A98G-12.0% was also common. Seven of the 36 patients on second line ART had major Protease Inhibitor (PI) associated DRMS including; V82A-7.0%, I54V, M46I and L33I (all 5.0%). Also common were the accessory PI mutations L10I-27%, L10V-12.0% and L10F-5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. Of the 7 patients with major PI DRMs, five had high level resistance to ritonavir boosted Lopinavir and Atazanavir, with Darunavir as the only susceptible PI tested. In resource-limited settings, HIV care programs that have previously concentrated on ART access, should now consider availing access to routine HIV viral load

  13. Risk Factors for Mortality among Adult HIV/AIDS Patients Following Antiretroviral Therapy in Southwestern Ethiopia: An Assessment through Survival Models

    PubMed Central

    Seyoum, Dinberu; Degryse, Jean-Marie; Kifle, Yehenew Getachew; Taye, Ayele; Tadesse, Mulualem; Birlie, Belay; Banbeta, Akalu; Rosas-Aguirre, Angel; Duchateau, Luc; Speybroeck, Niko

    2017-01-01

    Introduction: Efforts have been made to reduce HIV/AIDS-related mortality by delivering antiretroviral therapy (ART) treatment. However, HIV patients in resource-poor settings are still dying, even if they are on ART treatment. This study aimed to explore the factors associated with HIV/AIDS-related mortality in Southwestern Ethiopia. Method: A non-concurrent retrospective cohort study which collected data from the clinical records of adult HIV/AIDS patients, who initiated ART treatment and were followed between January 2006 and December 2010, was conducted, to explore the factors associated with HIV/AIDS-related mortality at Jimma University Specialized Hospital (JUSH). Survival times (i.e., the time from the onset of ART treatment to the death or censoring) and different characteristics of patients were retrospectively examined. A best-fit model was chosen for the survival data, after the comparison between native semi-parametric Cox regression and parametric survival models (i.e., exponential, Weibull, and log-logistic). Result: A total of 456 HIV patients were included in the study, mostly females (312, 68.4%), with a median age of 30 years (inter-quartile range (IQR): 23–37 years). Estimated follow-up until December 2010 accounted for 1245 person-years at risk (PYAR) and resulted in 66 (14.5%) deaths and 390 censored individuals, representing a median survival time of 34.0 months ( IQR: 22.8–42.0 months). The overall mortality rate was 5.3/100 PYAR: 6.5/100 PYAR for males and 4.8/100 PYAR for females. The Weibull survival model was the best model for fitting the data (lowest AIC). The main factors associated with mortality were: baseline age (>35 years old, AHR = 3.8, 95% CI: 1.6–9.1), baseline weight (AHR = 0.93, 95% CI: 0.90–0.97), baseline WHO stage IV (AHR = 6.2, 95% CI: 2.2–14.2), and low adherence to ART treatment (AHR = 4.2, 95% CI: 2.5–7.1). Conclusion: An effective reduction in HIV/AIDS mortality could be achieved through timely ART

  14. [Consensus Statement by GeSIDA/National AIDS Plan Secretariat on antiretroviral treatment in adults infected by the human immunodeficiency virus (Updated January 2013)].

    PubMed

    2013-11-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the GeSIDA/National AIDS Plan Secretariat (Grupo de Estudio de Sida and the Secretaría del Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations and the evidence which support them are based on a modification of the criteria of Infectious Diseases Society of America. cART is recommended in patients with symptoms of HIV infection, in pregnant women, in serodiscordant couples with high risk of transmission, in hepatitisB co-infection requiring treatment, and in HIV nephropathy. cART is recommended in asymptomatic patients if CD4 is <500cells/μl. If CD4 are >500cells/μl cART should be considered in the case of chronic hepatitisC, cirrhosis, high cardiovascular risk, plasma viral load >100.000 copies/ml, proportion of CD4 cells <14%, neurocognitive deficits, and in people aged >55years. The objective of cART is to achieve an undetectable viral load. The first cART should include 2 reverse transcriptase inhibitors (RTI) nucleoside analogs and a third drug (a non-analog RTI, a ritonavir boosted protease inhibitor, or an integrase inhibitor). The panel has consensually selected some drug combinations, for the first cART and specific criteria for cART in acute HIV infection, in tuberculosis and other HIV related opportunistic infections, for the women and in pregnancy, in hepatitisB or C co-infection, in HIV-2 infection, and in post-exposure prophylaxis. These new guidelines update previous recommendations related to first cART (when to begin and what drugs should be used), how to monitor, and what to do in case of viral failure or adverse drug reactions. cART specific criteria in

  15. Factors Associated with Virological Failure and Suppression after Enhanced Adherence Counselling, in Children, Adolescents and Adults on Antiretroviral Therapy for HIV in Swaziland

    PubMed Central

    Jobanputra, Kiran; Parker, Lucy Anne; Azih, Charles; Okello, Velephi; Maphalala, Gugu; Kershberger, Bernard; Khogali, Mohammed; Lujan, Johnny; Antierens, Annick; Teck, Roger; Ellman, Tom; Kosgei, Rose; Reid, Tony

    2015-01-01

    Introduction This study explores factors associated with virological detectability, and viral re-suppression after enhanced adherence counselling, in adults and children on antiretroviral therapy (ART) in Swaziland. Methods This descriptive study used laboratory data from 7/5/2012 to 30/9/2013, which were linked with the national ART database to provide information on time on ART and CD4 count; information on enhanced adherence counselling was obtained from file review in health facilities. Multivariable logistic regression was used to explore the relationship between viral load, gender, age, time on ART, CD4 count and receiving (or not receiving) enhanced adherence counselling. Results From 12,063 patients undergoing routine viral load monitoring, 1941 (16%) had detectable viral loads. Children were more likely to have detectable viral loads (AOR 2.6, 95%CI 1.5–4.5), as were adolescents (AOR 3.2, 95%CI 2.2–4.8), patients with last CD4<350 cells/µl (AOR 2.2, 95%CI 1.7–2.9) or WHO Stage 3/4 disease (AOR 1.3, 95%CI 1.1–1.6), and patients on ART for longer (AOR 1.1, 95%CI 1.1–1.2). At retesting, 450 (54% of those tested) showed viral re-suppression. Children were less likely to re-suppress (AOR 0.2, 95%CI 0.1–0.7), as were adolescents (AOR 0.3, 95%CI 0.2–0.8), those with initial viral load> 1000 copies/ml (AOR 0.3, 95%CI 0.1–0.7), and those with last CD4<350 cells/µl (AOR 0.4, 95%CI 0.2–0.7). Receiving (or not receiving) enhanced adherence counselling was not associated with likelihood of re-suppression. Conclusions Children, adolescents and those with advanced disease were most likely to have high viral loads and least likely to achieve viral suppression at retesting; receiving adherence counselling was not associated with higher likelihood of viral suppression. Although the level of viral resistance was not quantified, this study suggests the need for ART treatment support that addresses the adherence problems of younger people; and to define the

  16. Factors associated with virological failure and suppression after enhanced adherence counselling, in children, adolescents and adults on antiretroviral therapy for HIV in Swaziland.

    PubMed

    Jobanputra, Kiran; Parker, Lucy Anne; Azih, Charles; Okello, Velephi; Maphalala, Gugu; Kershberger, Bernard; Khogali, Mohammed; Lujan, Johnny; Antierens, Annick; Teck, Roger; Ellman, Tom; Kosgei, Rose; Reid, Tony

    2015-01-01

    This study explores factors associated with virological detectability, and viral re-suppression after enhanced adherence counselling, in adults and children on antiretroviral therapy (ART) in Swaziland. This descriptive study used laboratory data from 7/5/2012 to 30/9/2013, which were linked with the national ART database to provide information on time on ART and CD4 count; information on enhanced adherence counselling was obtained from file review in health facilities. Multivariable logistic regression was used to explore the relationship between viral load, gender, age, time on ART, CD4 count and receiving (or not receiving) enhanced adherence counselling. From 12,063 patients undergoing routine viral load monitoring, 1941 (16%) had detectable viral loads. Children were more likely to have detectable viral loads (AOR 2.6, 95%CI 1.5-4.5), as were adolescents (AOR 3.2, 95%CI 2.2-4.8), patients with last CD4<350 cells/µl (AOR 2.2, 95%CI 1.7-2.9) or WHO Stage 3/4 disease (AOR 1.3, 95%CI 1.1-1.6), and patients on ART for longer (AOR 1.1, 95%CI 1.1-1.2). At retesting, 450 (54% of those tested) showed viral re-suppression. Children were less likely to re-suppress (AOR 0.2, 95%CI 0.1-0.7), as were adolescents (AOR 0.3, 95%CI 0.2-0.8), those with initial viral load> 1000 copies/ml (AOR 0.3, 95%CI 0.1-0.7), and those with last CD4<350 cells/µl (AOR 0.4, 95%CI 0.2-0.7). Receiving (or not receiving) enhanced adherence counselling was not associated with likelihood of re-suppression. Children, adolescents and those with advanced disease were most likely to have high viral loads and least likely to achieve viral suppression at retesting; receiving adherence counselling was not associated with higher likelihood of viral suppression. Although the level of viral resistance was not quantified, this study suggests the need for ART treatment support that addresses the adherence problems of younger people; and to define the elements of optimal enhanced adherence support for

  17. [GESIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2015)].

    PubMed

    2015-10-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines and recommendations for HIV-1 infected adult patients. To formulate these recommendations, a panel composed of members of the AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, and cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations, and the evidence that supports them, are based on modified criteria of the Infectious Diseases Society of America. In this update, cART is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and level of the recommendation depends on the CD4+T-lymphocyte count, the presence of opportunistic diseases or comorbid conditions, age, and prevention of transmission of HIV. The objective of cART is to achieve an undetectable plasma viral load. Initial cART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third drug from a different family. Three out of the ten recommended regimes are regarded as preferential (all of them with an integrase inhibitor as the third drug), and the other seven (based on a non-nucleoside reverse transcriptase inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as alternatives. This update presents the causes and criteria for switching cART in patients with undetectable plasma viral load, and in cases of virological failure where rescue cART should comprise 3 (or at least 2) drugs that are fully active against the virus. An update is also provided for the specific criteria for cART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). These new guidelines

  18. Effects of Antiretroviral Therapy on the Survival of Human Immunodeficiency Virus-positive Adult Patients in Andhra Pradesh, India: A Retrospective Cohort Study, 2007-2013

    PubMed Central

    Chaturvedi, Himanshu; Jayaseelan, Lakshmanan; Harvey, Pauline; Seguy, Nicole; Chavan, Laxmikant; Raj, Pinnamaneni; Pandey, Arvind

    2016-01-01

    Objectives The survival outcomes of antiretroviral treatment (ART) programs have not been systematically evaluated at the state level in India. This retrospective study assessed the survival rates and factors associated with survival among adult human immunodeficiency virus (HIV)-infected patients in Andhra Pradesh, India. Methods The present study used data from 139 679 HIV patients aged ≥15 years on ART who were registered from 2007 to 2011 and were followed up through December 2013. The primary end point was death of the patient. Mortality densities (per 1000 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore the factors associated with survival. Results The overall median follow-up time was 16.0 months (2.0 months for the deceased and 14.0 months for those lost to follow-up). Approximately 13.2% of those newly initiated on ART died during follow-up. Of those deaths, 56% occurred in the first three months. The crude mortality rate was 80.9 per 1000 person-years at risk. The CD4 count (adjusted hazard ratio [aHR],4.88; 95% confidence interval [CI], 4.36 to 5.46 for <100 cells/mm3 vs. >350 cells/mm3), functional status (aHR, 3.05; 95% CI, 2.82 to 3.30 for bedridden vs. normal), and body weight (aHR, 3.69; 95% CI, 3.42 to 3.97 for <45 kg vs. >60 kg) were strongly associated with the survival of HIV patients. Conclusions The study findings revealed that high mortality was observed within the first three months of ART initiation. Patients with poor baseline clinical characteristics had a higher risk of mortality. Expanded testing and counseling should be encouraged, with the goal of ensuring early enrollment into the program followed by the initiation of ART in HIV-infected patients. PMID:27951632

  19. Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana A Randomized Clinical Trial

    PubMed Central

    Baum, Marianna K.; Campa, Adriana; Lai, Shenghan; Martinez, Sabrina Sales; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W.; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

    2015-01-01

    IMPORTANCE Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of

  20. Trends and risk factors for obesity among HIV positive Nigerians on antiretroviral therapy.

    PubMed

    Ezechi, L O; Musa, Z A; Otobo, V O; Idigbe, I E; Ezechi, O C

    2016-06-01

    The increased access to antiretroviral therapy has changed the once deadly infection to a chronic medical condition, resulting in a dramatic change in causes of morbidity and mortality among HIV infected individuals. Obesity and its cardiovascular sequelae are increasingly reported in the literature. However, data on the burden, trends and risk factors for obesity are sparse in countries worst hit by the epidemic. To investigate the trend and risk factors for obesity among a cohort of HIV infected adults on antiretroviral therapy. We analysed prospectively collected data in an ongoing longitudinal observational study conducted at the HIV treatment centre, Nigerian Institute of Medical Research, Lagos, Nigeria. Patients who started treatment between June 2004 and December 2009, and completed a five year follow up were included in the analysis. Multivariate analysis was used to determine the risk factors for obesity among the cohort. A total of 12 585 adults were enrolled in the treatment programme during the study period. Of which, 8819 (70.1%) met the inclusion criteria. At the start of treatment, 27.0% were either overweight (19.6%) or obese (7.4%) compared to 62.2% that were either overweight (35.7%) or obese (26.5%) at the end of 5 years. The observed differences were statistically significant (p<0.01). Female gender (aOR: 2.2; 95% CI: 1.81-2.67), low baseline BMI less than 20 (aOR: 1.9; 95% CI: 1.3-2.2) and baseline CD4 count less than 350/μl (aOR: 2.51; 95% CI: 2.13 - 3.09) were associated with the development of obesity at multivariate analysis. Type of antiretroviral drug, age, marital status, viral load and haemoglobin level were not associated with obesity after controlling for confounding variables. Obesity is common among HIV infected Nigerians on antiretroviral therapy and is associated with.

  1. Short communication: emerging transmitted HIV type 1 drug resistance mutations among patients prior to start of first-line antiretroviral therapy in middle and low prevalence sites in China.

    PubMed

    Wang, Xia; He, Cui; Xing, Hui; Liao, Lingjie; Xu, Xiaoqin; He, Jianmei; Liu, Yong; Ling, Hua; Liang, Shu; Hsi, Jenny H; Ruan, Yuhua; Shao, Yiming

    2012-12-01

    It is known that transmitted drug resistance (TDR) will most likely emerge in regions where antiretroviral therapy (ART) has been widely available for years. However, after a decade of rapid scale-up of ART in China, there are few data regarding TDR among HIV-infected patients prior to initiating first-line ART in China. A prospective, observational cohort study was performed at sentinel sites in five provinces or municipalities. Study participants were recruited at the county- or city-level centers for disease control (CDCs), during routine monitoring visits following referral from diagnosing parties (e.g., hospitals). Each province or municipality recruited 140 patients through sequential sampling throughout the 2011 calendar year. A total of 627 eligible subjects were included in the analysis. the median CD4(+) cell count was 206 cells/ml at the baseline survey. The majority of patients (93.5%) had plasma HIV viral load ≥1,000 copies/ml. Of the 627 patients, 17 (2.7%) had drug resistance mutations for any type of HIV drugs. The prevalence of drug resistance mutations to nonnucleoside reverse transcriptase inhibitor (NNRTI) drugs (8/627, 1.3%) was higher than to nucleoside reverse transcriptase inhibitor (NRTI) drugs (5/627, 0.8%) and protease inhibitor (PI) drugs (4/627, 0.6%). A logistic regression model showed that the only predictive factor was the route of infection through homosexual intercourse, i.e., men who have sex with men (MSM) status. As HIV prevalence is rising rapidly among Chinese MSM, it is essential to continue surveying this risk group and related high-risk populations with low awareness of HIV, and to develop new public health interventions that help to reduce the spread of drug-resistant HIV.

  2. HIV Treatment and Prevention: An Overview of Recommendations From the IAS-USA Antiretroviral Guidelines Panel.

    PubMed

    Volberding, Paul A

    Updated recommendations from the IAS-USA Antiretroviral Guidelines Panel on antiretroviral therapy for the treatment and prevention of HIV infection in adults were published in the Journal of the American Medical Association in 2016. The updated, evidence-based recommendations address when to initiate antiretroviral therapy, recommended initial antiretroviral regimens, including integrase strand transfer inhibitor (InSTI)-based regimens, recommended regimens for persons in whom an InSTI is not an option, and special treatment considerations. The interface between antiretroviral therapy and opportunistic infections, when and how to switch antiretroviral therapy, laboratory monitoring, engagement in care, adherence to antiretroviral therapy, and use of antiretroviral therapy as HIV prevention are also discussed, as well as future directions in HIV treatment. This article summarizes an IAS-USA continuing education webinar presented by Paul A. Volberding, MD, in August 2016.

  3. Phenotypic plasticity in adult life-history strategies compensates for a poor start in life in Trinidadian guppies (Poecilia reticulata).

    PubMed

    Auer, Sonya K

    2010-12-01

    Low food availability during early growth and development can have long-term negative consequences for reproductive success. Phenotypic plasticity in adult life-history decisions may help to mitigate these potential costs, yet adult life-history responses to juvenile food conditions remain largely unexplored. I used a food-manipulation experiment with female Trinidadian guppies (Poecilia reticulata) to examine age-related changes in adult life-history responses to early food conditions, whether these responses varied across different adult food conditions, and how these responses affected overall reproductive success. Guppy females reared on low food as juveniles matured at a later age, at a smaller size, and with less energy reserves than females reared on high food as juveniles. In response to this setback, they changed their investment in growth, reproduction, and fat storage throughout the adult stage such that they were able to catch up in body size, increase their reproductive output, and restore their energy reserves to levels comparable to those of females reared on high food as juveniles. The net effect was that adult female guppies did not merely mitigate but surprisingly were able to fully compensate for the potential long-term negative effects of poor juvenile food conditions on reproductive success.

  4. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial.

    PubMed

    Raffi, François; Jaeger, Hans; Quiros-Roldan, Eugenia; Albrecht, Helmut; Belonosova, Elena; Gatell, Jose M; Baril, Jean-Guy; Domingo, Pere; Brennan, Clare; Almond, Steve; Min, Sherene

    2013-11-01

    In the primary analysis of SPRING-2 at week 48, dolutegravir showed non-inferior efficacy to and similar tolerability to raltegravir in adults infected with HIV-1 and naive for antiretroviral treatment. We present the 96 week results. SPRING-2 is an ongoing phase 3, randomised, double-blind, active-controlled, non-inferiority study in treatment-naive adults infected with HIV-1 that started in Oct 19, 2010. We present results for the safety cutoff date of Jan 30, 2013. Patients had to be aged 18 years or older and have HIV-1 RNA concentrations of 1000 copies per mL or more. Patients were randomly assigned (1:1) to receive either dolutegravir (50 mg once daily) or raltegravir (400 mg twice daily), plus investigator-selected tenofovir-emtricitabine or abacavir-lamivudine. Prespecified 96 week secondary endpoints included proportion of patients with HIV-1 RNA less than 50 copies per mL, CD4 cell count changes from baseline, safety, tolerability, and genotypic or phenotypic resistance. We used an intention-to-treat exposed population (received at least one dose of study drug) for the analyses. Sponsor staff were masked to treatment assignment until primary analysis at week 48; investigators, site staff, and patients were masked until week 96. Of 1035 patients screened, 827 were randomly assigned to study group, and 822 received at least one dose of the study drug (411 patients in each group). At week 96, 332 (81%) of 411 patients in the dolutegravir group and 314 (76%) of 411 patients in the raltegravir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 4∙5%, 95% CI -1∙1% to 10∙0%) confirming non-inferiority. Secondary analyses of efficacy such as per protocol (HIV RNA <50 copies per mL: 83% for dolutegravir and 80% for raltegravir) and treatment-related discontinuation equals failure (93% without failure for dolutegravir; 91% for raltegravir) supported non-inferiority. Virological non-response occurred less frequently in the dolutegravir group

  5. Factors associated with timely initiation of antiretroviral therapy in two HIV clinics in Lilongwe, Malawi.

    PubMed

    Johnson, D C; Feldacker, C; Tweya, H; Phiri, S; Hosseinipour, M C

    2013-01-01

    The World Health Organization (WHO) estimates that only 30% of eligible, HIV-infected individuals start antiretroviral therapy (ART). This study seeks to explore the geographic and individual factors associated with starting ART on time. This retrospective study includes 15,734 HIV-positive adults initiating ART at two HIV clinics in Lilongwe, Malawi. The outcome was starting ART within two weeks of meeting ART eligibility as defined by the Malawi ART guidelines. Euclidean distance from patient neighbourhood to their clinic was calculated using Google Earth. Logistic regression models assessed factors influencing starting ART on time. Of 15,734 adults initiating ART, 8178 were from Lighthouse (LH) and 7556 were from Martin Preuss Center (MPC). Combined, 68.7% started treatment on time. Patients who were eligible for ART based on a CD4 cell count <250 cells/mm(3) versus WHO stage were less likely to begin ART on time at both LH (odds ratio [OR] 0.16; 95% CI 0.13-0.19) and MPC (OR 0.24; 95% CI 0.21-0.28). Likelihood of starting on time decreased with each kilometer further from clinic location among LH patients (OR 0.97; 95% CI 0.94-0.99); distance was not significant at MPC. In conclusion, predictors differed by clinic. Distance to clinic and type of eligibility for ART significantly influence starting ART on time.

  6. The Majority of the Pre-Antiretroviral Population Who Were Lost to Follow-Up Stopped Their Care in Freetown, Sierra Leone: A 12-Month Prospective Cohort Study Starting with HIV Diagnosis

    PubMed Central

    Kelly, J. Daniel; Schlough, Gabriel Warren; Conteh, Sulaiman; Barrie, M. Bailor; Kargbo, Brima; Giordano, Thomas P.

    2016-01-01

    Background The heterogeneity of the pre-antiretroviral (pre-ART) population calls for more granular depictions of the cascade of HIV care. Methods We studied a prospective cohort of persons newly diagnosed with HIV infection from a single center in Freetown, Sierra Leone, over a 12-month period and then traced those persons who were lost to follow-up (LTFU) during pre-ART care (before ART initiation). ART eligibility was based on a CD4 cell count result of ≤ 350 mm/cells and/or WHO clinical stage 3 or 4. Persons who attended an appointment in the final three months were considered to be retained in care. Adherence to ART was measured using pharmacy refill dates. “Effective HIV care” was defined as completion of the cascade of care at 12-months regardless of whether patients are on ART. Tracing outcomes were obtained for those who were LTFU during pre-ART care. Results 408 persons newly diagnosed with HIV infection were screened, 338 were enrolled, and 255 persons were staged for ART. ART-ineligible persons had higher retention rates than ART-eligible persons (59.6% vs 41.8%, p = 0.03). 77 (22.8%) of 338 persons received effective HIV care. Most attrition (61.9%) occurred with persons during pre-ART care. 123 of 138 persons (89.1%) who were LTFU prior to ART initiation were found, and 91 of those 123 (74.0%) were alive. Of the 74 persons who were alive and described their engagement in care, 40 (54.1%) stopped care. Nearly half (42.5%) of those 40 stopped after assessment of ART-eligibility but before ART initiation. The main limitation of this study was the lack of tracing outcomes for those lost during ART care. Conclusions The majority of the pre-ART LTFU population stopped their care, particularly after ART-eligibility but before ART initiation. Interventions to hasten ART initiation and retain this at-risk group may have significant downstream impact on effective HIV care. PMID:26901765

  7. Effects of Adolescent Sport Practice on Health Outcomes of Adult Amateur Endurance Cyclists: Adulthood Is Not Too Late to Start.

    PubMed

    Munguia-Izquierdo, Diego; Mayolas-Pi, Carmen; Peñarrubia-Lozano, Carlos; Paris-Garcia, Federico; Bueno-Antequera, Javier; Oviedo-Caro, Miguel Angel; Legaz-Arrese, Alejandro

    2017-05-30

    We investigated the effects of adolescent sport practice on the training, performance, and health outcomes of adult amateur endurance cyclists and compared health outcomes of 3 adult groups: amateur endurance cyclists who practiced sports during adolescence, amateur endurance cyclists who did not practice sports during adolescence, and inactive individuals. In 859 (751 men, 108 women) adult cyclists and 718 inactive subjects (307 men, 411 women), we examined adolescent sport practice, current training status, quality of life, quality of sleep, anxiety and depression and cardiometabolic risk: body mass index, physical activity, physical fitness, adherence to Mediterranean diet, and alcohol and tobacco consumption. Independent of gender, no significant differences in training, performance, or health outcomes were observed between amateur endurance cyclists who practiced sports during adolescence and those who did not. Independent of gender, cyclists reported significantly better health outcomes than inactive individuals in all variables, except depression. Training, performance, and health outcomes did not differ between adult amateur endurance cyclists who practiced sports during adolescence and those who did not, but their health outcomes were significantly improved compared to inactive individuals, except for depression.

  8. Learning Center Ideas in Action. A How-to Handbook for Starting an Individualized Adult Learning Center. Revised Edition 1973.

    ERIC Educational Resources Information Center

    Los Angeles City Schools, CA. Div. of Career and Continuing Education.

    This handbook provides guidelines for administrators and teachers for establishing classes that emphasize individualized programed learning. The suggestions are primarily for use in community adult school classrooms of standard size. Some of the "hows" of setting up the program are: (1) the utilization of the classroom (space, size, and…

  9. A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy.

    PubMed

    Spivak, Adam M; Andrade, Adriana; Eisele, Evelyn; Hoh, Rebecca; Bacchetti, Peter; Bumpus, Namandjé N; Emad, Fatemeh; Buckheit, Robert; McCance-Katz, Elinore F; Lai, Jun; Kennedy, Margene; Chander, Geetanjali; Siliciano, Robert F; Siliciano, Janet D; Deeks, Steven G

    2014-03-01

    Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4(+) T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4(+) T cells at concentrations achieved in vivo. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1-infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4(+) T cells. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug.

  10. A Pilot Study Assessing the Safety and Latency-Reversing Activity of Disulfiram in HIV-1–Infected Adults on Antiretroviral Therapy

    PubMed Central

    Spivak, Adam M.; Andrade, Adriana; Eisele, Evelyn; Hoh, Rebecca; Bacchetti, Peter; Bumpus, Namandjé N.; Emad, Fatemeh; Buckheit, Robert; McCance-Katz, Elinore F.; Lai, Jun; Kennedy, Margene; Chander, Geetanjali; Siliciano, Robert F.; Siliciano, Janet D.; Deeks, Steven G.

    2014-01-01

    Background. Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4+ T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4+ T cells at concentrations achieved in vivo. Methods. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1–infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4+ T cells. Results. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Conclusions. Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug. PMID:24336828

  11. Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact.

    PubMed

    Hill-Taylor, B; Sketris, I; Hayden, J; Byrne, S; O'Sullivan, D; Christie, R

    2013-10-01

    Potentially inappropriate prescribing (PIP) has significant clinical, humanistic and economic impacts. Identifying PIP in older adults may reduce their burden of adverse drug events. Tools with explicit criteria are being developed to screen for PIP in this population. These tools vary in their ability to identify PIP in specific care settings and jurisdictions due to such factors as local prescribing practices and formularies. One promising set of screening tools are the STOPP (Screening Tool of Older Person's potentially inappropriate Prescriptions) and START (Screening Tool of Alert doctors to the Right Treatment) criteria. We conducted a systematic review of research studies that describe the application of the STOPP/START criteria and examined the evidence of the impact of STOPP/START on clinical, humanistic and economic outcomes in older adults. We performed a systematic review of studies from relevant biomedical databases and grey literature sources published from January 2007 to January 2012. We searched citation and reference lists and contacted content experts to identify additional studies. Two authors independently selected studies using a predefined protocol. We did not restrict selection to particular study designs; however, non-English studies were excluded during the selection process. Independent extraction of articles by two authors used predefined data fields. For randomized controlled trials and observational studies comparing STOPP/START to other explicit criteria, we assessed risk of bias using an adapted tool. We included 13 studies: a single randomized controlled trial and 12 observational studies. We performed a descriptive analysis as heterogeneity of study populations, interventions and study design precluded meta-analysis. All observational studies reported the prevalence of PIP; however, the application of the criteria was not consistent across all studies. Seven of the observational studies compared STOPP/START with other explicit

  12. Getting a Head Start: Diet, Sub-Adult Growth, and Associative Learning in a Seed-Eating Passerine

    PubMed Central

    Bonaparte, Kristina M.; Riffle-Yokoi, Christina; Burley, Nancy Tyler

    2011-01-01

    Developmental stress, and individual variation in response to it, can have important fitness consequences. Here we investigated the consequences of variable dietary protein on the duration of growth and associative learning abilities of zebra finches, Taeniopygia guttata, which are obligate graminivores. The high-protein conditions that zebra finches would experience in nature when half-ripe seed is available were mimicked by the use of egg protein to supplement mature seed, which is low in protein content. Growth rates and relative body proportions of males reared either on a low-protein diet (mature seed only) or a high-protein diet (seed plus egg) were determined from body size traits (mass, head width, and tarsus) measured at three developmental stages. Birds reared on the high-protein diet were larger in all size traits at all ages, but growth rates of size traits showed no treatment effects. Relative head size of birds reared on the two diets differed from age day 95 onward, with high-diet birds having larger heads in proportion to both tarsus length and body mass. High-diet birds mastered an associative learning task in fewer bouts than those reared on the low-protein diet. In both diet treatments, amount of sub-adult head growth varied directly, and sub-adult mass change varied inversely, with performance on the learning task. Results indicate that small differences in head growth during the sub-adult period can be associated with substantial differences in adult cognitive performance. Contrary to a previous report, we found no evidence for growth compensation among birds on the low-protein diet. These results have implications for the study of vertebrate cognition, developmental stress, and growth compensation. PMID:21949684

  13. Rates of switching to second-line antiretroviral therapy and impact of delayed switching on immunologic, virologic, and mortality outcomes among HIV-infected adults with virologic failure in Rakai, Uganda.

    PubMed

    Ssempijja, Victor; Nakigozi, Gertrude; Chang, Larry; Gray, Ron; Wawer, Maria; Ndyanabo, Anthony; Kasule, Jingo; Serwadda, David; Castelnuovo, Barbara; Hoog, Anja Van't; Reynolds, Steven James

    2017-08-22

    Switch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90' of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005. Retrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients. The cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001-10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9-3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9-6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul (aHR = 2.30, 95% CI = 1.5-3.6). Mortality in patients not switched to second-line ART was 11

  14. Determinant factors associated with occurrence of tuberculosis among adult people living with HIV after antiretroviral treatment initiation in Addis Ababa, Ethiopia: a case control study.

    PubMed

    Kibret, Kelemu Tilahun; Yalew, Alemayehu Worku; Belaineh, Belaineh Girma; Asres, Muluken Melese

    2013-01-01

    Tuberculosis (TB) is a leading morbidity and mortality, and the first presenting sign in majority of people living with Human Immune deficiency Virus (PLWH). Determinants of active TB among HIV patients on anti retroviral treatment (ART) are not well described in resource limited settings. The aim of this study was to assess determinant factors for the occurrence of TB among people living with HIV after ART initiation in public hospitals and health centers in Addis Ababa, Ethiopia. A case control study was conducted from December 2011 to February 2012 in 2 public hospitals and 13 health centers in Addis Ababa. The study population consisted of 204 cases and 409 controls. Cases were adult people living with HIV who developed TB after ART initiation and controls were adult people living with HIV who did not develop TB after ART initiation. An interviewer administered structured questionnaire was used to collect information. After adjustment for potential confounders, presence of isoniazid prophylaxis (adjusted odd ratio [AOR] 0.35, 95% confidence interval [CI] 0.125, 0.69) and cotrimoxazole prophylaxis (AOR = 0.19; 95% CI: 0.06, 0.62) had protective benefit against risk of TB. In contrary, bedridden (AOR = 9.36; 95% CI: 3.39, 25.85), having World Health Organization (WHO) clinical stage III/IV (AOR = 3.40; 95% CI: 1.69, 6.87) and hemoglobin level <10 mg/dl (AOR = 7.43; 95% CI; 3.04, 18.31) at enrollment to ART care were predictors for increased risk of tuberculosis in PLWH after ART initiation. Increasing coverage of isoniazid preventive therapy and cotrimoxazole preventive therapy reduced risk of TB among HIV patients who started treatment. All PLWH should be screened for TB, but for patients who have advanced disease condition (WHO clinical stage III/IV, being bedridden and having hemoglobin level <10 mg/dl) intensified screening is highly recommended during treatment follow up.

  15. Determinant Factors Associated with Occurrence of Tuberculosis among Adult People Living with HIV after Antiretroviral Treatment Initiation in Addis Ababa, Ethiopia: A Case Control Study

    PubMed Central

    Kibret, Kelemu Tilahun; Yalew, Alemayehu Worku; Belaineh, Belaineh Girma; Asres, Muluken Melese

    2013-01-01

    Introduction Tuberculosis (TB) is a leading morbidity and mortality, and the first presenting sign in majority of people living with Human Immune deficiency Virus (PLWH). Determinants of active TB among HIV patients on anti retroviral treatment (ART) are not well described in resource limited settings. The aim of this study was to assess determinant factors for the occurrence of TB among people living with HIV after ART initiation in public hospitals and health centers in Addis Ababa, Ethiopia. Methods and Findings A case control study was conducted from December 2011 to February 2012 in 2 public hospitals and 13 health centers in Addis Ababa. The study population consisted of 204 cases and 409 controls. Cases were adult people living with HIV who developed TB after ART initiation and controls were adult people living with HIV who did not develop TB after ART initiation. An interviewer administered structured questionnaire was used to collect information. After adjustment for potential confounders, presence of isoniazid prophylaxis (adjusted odd ratio [AOR] 0.35, 95% confidence interval [CI] 0.125, 0.69) and cotrimoxazole prophylaxis (AOR = 0.19; 95% CI: 0.06, 0.62) had protective benefit against risk of TB. In contrary, bedridden (AOR = 9.36; 95% CI: 3.39, 25.85), having World Health Organization (WHO) clinical stage III/IV (AOR = 3.40; 95% CI: 1.69, 6.87) and hemoglobin level <10 mg/dl (AOR = 7.43; 95% CI; 3.04, 18.31) at enrollment to ART care were predictors for increased risk of tuberculosis in PLWH after ART initiation. Conclusion Increasing coverage of isoniazid preventive therapy and cotrimoxazole preventive therapy reduced risk of TB among HIV patients who started treatment. All PLWH should be screened for TB, but for patients who have advanced disease condition (WHO clinical stage III/IV, being bedridden and having hemoglobin level <10 mg/dl) intensified screening is highly recommended during treatment follow up. PMID:23762214

  16. The Start of Head Start

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2010-01-01

    The creation of the Head Start program occurred at break-neck speed with many dramatic turns and many colorful players. No one tells the story better than Edward Zigler in "Head Start: The Inside Story of America's Most Successful Educational Experiment"--a detailed and personal, behind the scenes look at the program's inception. From this…

  17. The Start of Head Start

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2010-01-01

    The creation of the Head Start program occurred at break-neck speed with many dramatic turns and many colorful players. No one tells the story better than Edward Zigler in "Head Start: The Inside Story of America's Most Successful Educational Experiment"--a detailed and personal, behind the scenes look at the program's inception. From this…

  18. Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2014).

    PubMed

    Berenguer, Juan; Polo, Rosa; Lozano, Fernando; López Aldeguer, José; Antela, Antonio; Arribas, José Ramón; Asensi, Víctor; Blanco, José Ramón; Clotet, Bonaventura; Domingo, Pere; Galindo, María José; Gatell, José María; González-García, Juan; Iribarren, José Antonio; Locutura, Jaime; López, Juan Carlos; Mallolas, Josep; Martínez, Esteban; Miralles, Celia; Miró, José M; Moreno, Santiago; Palacios, Rosario; Pérez Elías, María Jesús; Pineda, Juan Antonio; Podzamczer, Daniel; Portilla, Joaquín; Pulido, Federico; Ribera, Esteban; Riera, Melchor; Rubio, Rafael; Santos, Jesús; Sanz, Jesús; Tuset, Montserrat; Vidal, Francesc; Rivero, Antonio

    2014-01-01

    In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer).

  19. Continued Slow Decay of the Residual Plasma Viremia Level in HIV-1–Infected Adults Receiving Long-term Antiretroviral Therapy

    PubMed Central

    Riddler, Sharon A.; Aga, Evgenia; Bosch, Ronald J.; Bastow, Barbara; Bedison, Margaret; Vagratian, David; Vaida, Florin; Eron, Joseph J.; Gandhi, Rajesh T.; Mellors, John W.

    2016-01-01

    We measured plasma human immunodeficiency virus type 1 (HIV-1) RNA levels by means of single-copy assay in 334 participants receiving virologically suppressive antiretroviral therapy (ART). A residual viremia load of ≥1 copy/mL after 4 years of ART was predicted by a higher pre-ART HIV-1 RNA level, higher CD8+ T-cell count during treatment, and a lower ratio of CD4+ T cells to CD8+ T cells during treatment but not by initial ART regimen. In a longitudinal subset of 64 individuals, continued decay of the plasma HIV-1 RNA level was observed, with an average annual decrease of 6% and an estimated half-life of 11.5 years. In contrast to prior reports, the persistent viremia level continues to slowly decline during years 4–12 of suppressive ART. Clinical Trials Registration: NCT00001137. PMID:26333941

  20. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults.

    PubMed

    Jacobson, Jeffrey M; Kuritzkes, Daniel R; Godofsky, Eliot; DeJesus, Edwin; Larson, Jeffrey A; Weinheimer, Steven P; Lewis, Stanley T

    2009-02-01

    Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log(10)) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4(+) T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4(+) T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.

  1. Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks

    PubMed Central

    Tebas, Pablo; Kumar, Princy; Hicks, Charles; Granier, Catherine; Wynne, Brian; Min, Sherene; Pappa, Keith

    2015-01-01

    Objective: Antiretroviral therapy initiation has been linked to bone mineral density and bone biomarker changes. We assessed long-term bone turnover biomarker effects over 144 weeks in patients initiating dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC) versus efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Methods: Patients randomized in SINGLE received DTG (50 mg once daily) + ABC/3TC or fixed-dose combination EFV/FTC/TDF. We evaluated vitamin D serum levels and bone turnover markers (BTMs), including type 1 collagen cross-linked C-telopeptide (CTx), osteocalcin, bone-specific alkaline phosphatase (BSAP), and procollagen type 1 N-terminal propeptide (P1NP), at baseline and weeks 48, 96, and 144. Results: Among the 833 enrolled patients (68% white, 85% men), baseline median age was 35 years (range 18–85), median CD4+ was 338 cells/μl, and median BMI was 24 kg/m2. Fifty-three percent of patients smoked, and 6% reported baseline vitamin D use, with no meaningful differences between groups. Relative to baseline, CTx, osteocalcin, BSAP, and P1NP increased; vitamin D decreased in both groups at weeks 48, 96, and 144. Changes from baseline typically peaked at weeks 48 or 96 and for the four analytes, excluding vitamin D, with the EFV/FTC/TDF group having significantly greater changes from baseline at all time points. Conclusion: DTG + ABC/3TC in antiretroviral therapy-naive patients resulted in significantly lower increases in BTMs (CTx, osteocalcin, BSAP, P1NP) compared with EFV/FTC/TDF over 144 weeks. The observed changes are consistent with results from other smaller, randomized trials. These differences in BTMs likely correlate with changes in bone mineral density over time. PMID:26355674

  2. [The antiretroviral agent Fullevir].

    PubMed

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D

    2009-01-01

    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

  3. "If you want me to treat you like an adult, start acting like one!" Comparing the criteria that emerging adults and their parents have for adulthood.

    PubMed

    Nelson, Larry J; Padilla-Walker, Laura M; Carroll, Jason S; Madsen, Stephanie D; Barry, Carolyn McNamara; Badger, Sarah

    2007-12-01

    The purpose of this study was (a) to identify the criteria parents of emerging adults consider necessary and important for their children to achieve adulthood, (b) to compare parents' criteria for adulthood with the criteria espoused by emerging adults, and (c) to examine how these criteria might differ on the basis of gender of the parent and gender of the child. Participants included 392 unmarried college students, ages 18-25, and at least 1 of their parents (271 fathers, 319 mothers). Results revealed that (a) as did their children, most parents did not yet view their children as adults, (b) there was disagreement between children and their parents in the emphasis they placed on various criteria for adulthood, (c) mothers and fathers did not always agree on the importance of various criteria, and (d) the gender of both the parent and the child played a role in the criteria parents deemed important for adulthood. Taken together, the findings suggest that parents and children view the transition to adulthood differently, which might have implications for the parent-child relationship during this period of development.

  4. Design, Recruitment and Start Up of a Primary Care Weight Loss Trial Targeting African American and Hispanic Adults

    PubMed Central

    Kumanyika, Shiriki; Fassbender, Jennifer; Phipps, Etienne; Tan-Torres, Susan; Localio, Russell; Morales, Knashawn H.; Sarwer, David B.; Harralson, Tina; Allison, Kelly; Wesby, Lisa; Kessler, Ronni; Tsai, Adam Gilden; Wadden, Thomas A.

    2011-01-01

    Primary care offices are critical access points for obesity treatment, but evidence for approaches that can be implemented within these settings is limited. The Think Health! (¡Vive Saludable!) Study was designed to assess the feasibility and effectiveness of a behavioral weight loss program, adapted from the Diabetes Prevention Program, for implementation in routine primary care. Recruitment of clinical sites targeted primary care practices serving African American and Hispanic adults. The randomized design compares (a) a moderate-intensity treatment consisting of primary care provider counseling plus additional counseling by an auxiliary staff member (i.e., lifestyle coach), with (b) a low-intensity, control treatment involving primary care provider counseling only. Treatment and follow up duration are 1 to 2 years. The primary outcome is weight change from baseline at 1 and 2 years post-randomization. Between November 2006 and January 2008, 14 primary care providers (13 physicians; 1 physician assistant) were recruited at five clinical sites. Patients were recruited between October 2007 and November 2008. A total of 412 patients were pre-screened, of whom 284 (68.9%) had baseline assessments and 261 were randomized, with the following characteristics: 65% African American; 16% Hispanic American; 84% female; mean (SD) age of 47.2 (11.7) years; mean (SD) BMI of 37.2(6.4) kg/m2; 43.7% with high blood pressure; and 18.4% with diabetes. This study will provide insights into the potential utility of moderate-intensity lifestyle counseling delivered by motivated primary care clinicians and their staff. The study will have particular relevance to African Americans and women. PMID:21062645

  5. The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial.

    PubMed

    Howard, Andrea A; Hirsch-Moverman, Yael; Frederix, Koen; Daftary, Amrita; Saito, Suzue; Gross, Tal; Wu, Yingfeng; Maama, Llang Bridget

    2016-01-01

    Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6-9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. The START Study evaluates a CIP targeting barriers to

  6. The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial.

    PubMed

    Howard, Andrea A; Hirsch-Moverman, Yael; Frederix, Koen; Daftary, Amrita; Saito, Suzue; Gross, Tal; Wu, Yingfeng; Maama, Llang Bridget

    2016-01-01

    Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6-9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START Study

  7. The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial

    PubMed Central

    Howard, Andrea A.; Hirsch-Moverman, Yael; Frederix, Koen; Daftary, Amrita; Saito, Suzue; Gross, Tal; Wu, Yingfeng; Maama, Llang Bridget

    2016-01-01

    Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START

  8. Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015).

    PubMed

    Berenguer, Juan; Polo, Rosa; Aldeguer, José López; Lozano, Fernando; Aguirrebengoa, Koldo; Arribas, José Ramón; Blanco, José Ramón; Boix, Vicente; Casado, José Luis; Clotet, Bonaventura; Crespo, Manuel; Domingo, Pere; Estrada, Vicente; García, Federico; Gatell, José María; González-García, Juan; Gutiérrez, Félix; Iribarren, José Antonio; Knobel, Hernando; Llibre, Josep María; Locutura, Jaime; López, Juan Carlos; Miró, José M; Moreno, Santiago; Podzamczer, Daniel; Portilla, Joaquín; Pulido, Federico; Ribera, Esteban; Riera, Melchor; Rubio, Rafael; Santos, Jesús; Sanz-Moreno, José; Sanz, Jesús; Téllez, María Jesús; Tuset, Montserrat; Rivero, Antonio

    2015-10-01

    In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

  9. Development of Severe Anemia and Changes in Hemoglobin in a Cohort of HIV-Infected Ugandan Adults Receiving Zidovudine-, Stavudine-, and Tenofovir-Containing Antiretroviral Regimens.

    PubMed

    Parkes-Ratanshi, Rosalind; Katende, David; Levin, Jonathan; Wakeham, Katie; Heiner, Grosskurth; Kamali, Anatoli; Lalloo, David G

    2015-01-01

    Anemia is a common problem in HIV in sub-Saharan Africa. We describe the contribution of antiretroviral therapy (ART) regimen to the incidence of anemia and changes in hemoglobin (Hb) in HIV-infected patients in Uganda. This study was nested in a prevention of cryptococcal disease trial (CRYPTOPRO; ISCRTN7648152). Patients received 3 different backbones of nucleoside reverse transcriptase inhibitor in a nonrandomized manner. Of the 852 patients (161 on zidovudine [ZDV], 628 on stavudine [d4T], and 63 on tenofovir [TDF]; all received lamuvidine), the risk of developing grade 4 anemia was higher (adjusted hazard ratio 2.7) for those receiving ZDV than those receiving d4T. Those receivingd4T had a higher average increase in Hb than those receiving ZDV (P = .024) or TDF (P = .014). In this observational study, ZDV was associated with severe anemia compared to d4T or TDF; those receiving ZDV and TDF had smaller increases in Hb after ART initiation. We encourage publication of data on cohorts using TDF from Africa. © The Author(s) 2014.

  10. Executive summary of the GESIDA/National AIDS Plan Consensus Document on Antiretroviral Therapy in Adults Infected by the Human Immunodeficiency Virus (Updated January 2017).

    PubMed

    2017-05-31

    Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer). Copyright © 2017. Publicado por Elsevier España, S.L.U.

  11. Feasibility and Acceptability of a Smartphone App for Daily Reports of Substance Use and Antiretroviral Therapy Adherence among HIV-Infected Adults

    PubMed Central

    2016-01-01

    While substance use is one of the most consistent predictors of poor adherence to antiretroviral therapy (ART), few studies among people living with HIV (PLH) have utilized mobile phone-based assessment of these health behaviors. PLH were recruited from primary care clinics to report ART and substance use using a smartphone application (app) for 14 consecutive days. The app's feasibility as a data collection tool was evaluated quantitatively via surveys and qualitatively via in-depth interviews to assess daily report completion, compliance, and study satisfaction. Overall, 26 participants (M = 49.5 years, 76% male) completed 95.3% of time-based daily reports. Participants reported high satisfaction with the app and expressed future interest in using smartphones to report daily behaviors. High completion rates and participant acceptability suggest that smartphones are a feasible, acceptable method for collecting substance use and ART data among PLH. Potential areas of concern such as sufficient training and assistance for those with limited smartphone experience should be considered for future app-based research studies among PLH. PMID:27610243

  12. Feasibility and Acceptability of a Smartphone App for Daily Reports of Substance Use and Antiretroviral Therapy Adherence among HIV-Infected Adults.

    PubMed

    Przybyla, Sarahmona M; Eliseo-Arras, Rebecca K; Krawiec, Gabriela; Gower, Emily; Dermen, Kurt

    2016-01-01

    While substance use is one of the most consistent predictors of poor adherence to antiretroviral therapy (ART), few studies among people living with HIV (PLH) have utilized mobile phone-based assessment of these health behaviors. PLH were recruited from primary care clinics to report ART and substance use using a smartphone application (app) for 14 consecutive days. The app's feasibility as a data collection tool was evaluated quantitatively via surveys and qualitatively via in-depth interviews to assess daily report completion, compliance, and study satisfaction. Overall, 26 participants (M = 49.5 years, 76% male) completed 95.3% of time-based daily reports. Participants reported high satisfaction with the app and expressed future interest in using smartphones to report daily behaviors. High completion rates and participant acceptability suggest that smartphones are a feasible, acceptable method for collecting substance use and ART data among PLH. Potential areas of concern such as sufficient training and assistance for those with limited smartphone experience should be considered for future app-based research studies among PLH.

  13. Executive summary of the GESIDA/National AIDS Plan Consensus Document on Antiretroviral Therapy in Adults Infected by the Human Immunodeficiency Virus (Updated January 2016).

    PubMed

    2016-01-01

    In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise 3 drugs, namely, 2 nucleoside reverse transcriptase inhibitors (NRTI), and 1 drug from another family. Four of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further 6 regimens, which are based on an INSTI, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with cobicistat or ritonavir (PI/COBI, PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include 3 (or at least 2) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

  14. Antiretroviral therapy in a thousand patients with AIDS in Haiti.

    PubMed

    Severe, Patrice; Leger, Paul; Charles, Macarthur; Noel, Francine; Bonhomme, Gerry; Bois, Gyrlande; George, Erik; Kenel-Pierre, Stefan; Wright, Peter F; Gulick, Roy; Johnson, Warren D; Pape, Jean William; Fitzgerald, Daniel W

    2005-12-01

    The one-year survival rate of adults and children with the acquired immunodeficiency syndrome (AIDS), without antiretroviral therapy, has been about 30 percent in Haiti. Antiretroviral therapy has recently become available in Haiti and in other developing countries. Data on the efficacy of antiretroviral therapy in developing countries are limited. High rates of coinfection with tropical diseases and tuberculosis, along with malnutrition and limited laboratory monitoring of therapy, may decrease the efficacy of antiretroviral therapy in these countries. We studied the efficacy of antiretroviral therapy in the first 1004 consecutive patients with AIDS and without previous antiretroviral therapy who were treated beginning in March 2003 in Port-au-Prince, Haiti. During a 14-month period, three-drug antiretroviral therapy was initiated in 1004 patients, including 94 children under 13 years of age. At enrollment, the median CD4 T-cell count in adults and adolescents was 131 per cubic millimeter (interquartile range, 55 to 211 per cubic millimeter); in children, a median of 13 percent of T cells were CD4-positive (interquartile range, 8 to 20 percent). According to a Kaplan-Meier survival analysis, 87 percent of adults and adolescents and 98 percent of children were alive one year after beginning treatment. In a subgroup of 100 adult and adolescent patients who were followed for 48 to 56 weeks, 76 patients had fewer than 400 copies of human immunodeficiency virus RNA per milliliter. In adults and adolescents, the median increase in the CD4 T-cell count from baseline to 12 months was 163 per cubic millimeter (interquartile range, 77 to 251 per cubic millimeter). In children, the median percentage of CD4 T cells rose from 13 percent at baseline to 26 percent (interquartile range, 22 to 36 percent) at 12 months. Treatment-limiting toxic effects occurred in 102 of the 910 adults and adolescents (11 percent) and 5 of the 94 children (5 percent). This report documents the

  15. Severe Thrombocytopenia During Dolutegravir-containing Antiretroviral Therapy.

    PubMed

    Nakaharai, Kazuhiko; Miyajima, Makiko; Kobayashi, Hiroaki; Shimizu, Akihiro; Hosaka, Yumiko; Horino, Tetsuya; Hori, Seiji

    2017-08-15

    A 56-year-old Japanese man diagnosed with acquired immunodeficiency syndrome, Pneumocystis jirovecii pneumonia and cytomegalovirus infection presented with thrombocytopenia after starting antiretroviral therapy, which included dolutegravir (DTG). Although good control of the human immunodeficiency virus and cytomegalovirus infections was achieved, the patient's thrombocytopenia persisted. The patient's platelet count decreased to ≤50,000/μL even after the cessation of valganciclovir, which can cause bone marrow suppression. At five months after starting antiretroviral therapy, DTG was replaced by ritonavir-boosted darunavir. Soon after, his platelet count improved and was maintained at a level of >100,000/μL. This is the first reported case of severe thrombocytopenia during DTG-containing antiretroviral therapy.

  16. Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study.

    PubMed

    Gunda, Daniel W; Kilonzo, Semvua B; Kamugisha, Erasmus; Rauya, Engelbert Z; Mpondo, Bonaventura C

    2017-06-08

    Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body's capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania. A retrospective analysis of adult HIV patients' data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies. A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage. Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome.

  17. Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013).

    PubMed

    2013-11-01

    In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is <500cells/μL; if the CD4(+) lymphocyte count is >500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >10(5)copies/mL, CD4(+) lymphocyte percentage <14%, cognitive impairment, and age >55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined.

  18. Can pricing deter adolescents and young adults from starting to drink: An analysis of the effect of alcohol taxation on drinking initiation among Thai adolescents and young adults.

    PubMed

    Sornpaisarn, Bundit; Shield, Kevin D; Cohen, Joanna E; Schwartz, Robert; Rehm, Jürgen

    2015-12-01

    The objective of this study is to assess the relationship between alcohol taxation changes and drinking initiation among adolescents and young adults (collectively "youth") in Thailand (a middle-income country). Using a survey panel, this study undertook an age-period-cohort analysis using four large-scale national cross-sectional surveys of alcohol consumption performed in Thailand in 2001, 2004, 2007 and 2011 (n=87,176 Thai youth, 15-24 years of age) to test the hypothesis that changes in the inflation-adjusted alcohol taxation rates are associated with drinking initiation. Regression analyses were used to examine the association between inflation-adjusted taxation increases and the prevalence of lifetime drinkers. After adjusting for potential confounders, clear cohort and age effects were observed. Furthermore, a 10% increase of the inflation-adjusted taxation rate of the total alcohol market was significantly associated with a 4.3% reduction in the prevalence of lifetime drinking among Thai youth. In conclusion, tax rate changes in Thailand from 2001 to 2011 were associated with drinking initiation among youth. Accordingly, increases in taxation may prevent drinking initiation among youth in countries with a high prevalence of abstainers and may reduce the harms caused by alcohol. Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  19. Press Start

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    This level sets the stage for the design philosophy called “Triadic Game Design” (TGD). This design philosophy can be summarized with the following sentence: it takes two to tango, but it takes three to design a meaningful game or a game with a purpose. Before the philosophy is further explained, this level will first delve into what is meant by a meaningful game or a game with a purpose. Many terms and definitions have seen the light and in this book I will specifically orient at digital games that aim to have an effect beyond the context of the game itself. Subsequently, a historical overview is given of the usage of games with a serious purpose which starts from the moment we human beings started to walk on our feet till our contemporary society. It turns out that we have been using games for all kinds of non-entertainment purposes for already quite a long time. With this introductory material in the back of our minds, I will explain the concept of TGD by means of a puzzle. After that, the protagonist of this book, the game Levee Patroller, is introduced. Based on the development of this game, the idea of TGD, which stresses to balance three different worlds, the worlds of Reality, Meaning, and Play, came into being. Interested? Then I suggest to quickly “press start!”

  20. Starting Points

    ERIC Educational Resources Information Center

    Wicks, Karen

    2011-01-01

    In this article, the author discusses the findings of a micro research project which explores students' perceptions of learning mathematics when embarking on undergraduate studies in education. The theme for this study is the consideration of a possible link between adults' perceptions of learning mathematics and the effect this may have on their…

  1. Starting Points

    ERIC Educational Resources Information Center

    Wicks, Karen

    2011-01-01

    In this article, the author discusses the findings of a micro research project which explores students' perceptions of learning mathematics when embarking on undergraduate studies in education. The theme for this study is the consideration of a possible link between adults' perceptions of learning mathematics and the effect this may have on their…

  2. Non-Classical Monocytes and Monocyte Chemoattractant Protein-1 (MCP-1) Correlate with Coronary Artery Calcium Progression in Chronically HIV-1 Infected Adults on Stable Antiretroviral Therapy

    PubMed Central

    Zungsontiporn, Nath; Tello, Raquel R.; Zhang, Guangxiang; Mitchell, Brooks I.; Budoff, Matthew; Kallianpur, Kalpana J.; Nakamoto, Beau K.; Keating, Sheila M.; Norris, Philip J.; Ndhlovu, Lishomwa C.; Souza, Scott A.; Shikuma, Cecilia M.; Chow, Dominic C.

    2016-01-01

    Background Persistent inflammation and immune activation has been hypothesized to contribute to increased prevalence of subclinical atherosclerosis and cardiovascular disease (CVD) risk in patients with chronic HIV infection. In this study, we examined the correlation of peripheral monocyte subsets and soluble biomarkers of inflammation to coronary artery calcium (CAC) progression, as measured by cardiac computed tomography scan. Methods We conducted a longitudinal analysis utilizing baseline data of 78 participants with HIV infection on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV-Cardiovascular study who had available baseline monocyte subset analysis as well as CAC measurement at baseline and at 2-year follow up. Monocyte phenotypes were assessed from cryopreserved blood by flow cytometry and plasma was assayed for soluble biomarkers using antibody-coated beads in a high sensitivity Milliplex Luminex platform. Change in CAC over 2 years was analyzed as the primary outcome variable. Results Of all monocyte subsets and biomarkers tested, higher non-classical monocyte percentage (ρ = 0.259, p = 0.022), interleukin (IL)-6 (ρ = 0.311, p = 0.012), and monocyte chemoattractant protein (MCP)-1 (ρ = 0.524, p = <0.001) were significantly correlated to higher 2-year CAC progression in unadjusted Spearman’s correlation. Non-classical monocyte percentage (ρ = 0.247, p = 0.039), and MCP-1 (ρ = 0.487, p = <0.001), remained significantly correlated to 2-year CAC progression, while IL-6 was not (ρ = 0.209, p = 0.120) after adjustment for age, hypertension, diabetes mellitus, total/HDL cholesterol ratio, smoking history, and BMI. Conclusion The percentage of non-classical monocytes and plasma MCP-1 levels were independently associated with CAC progression and may be related to the progression of atherosclerosis and increased CVD risk associated with chronic HIV infection on stable ART. PMID:26867220

  3. Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Mirani, Gayatri; Williams, Paige L.; Chernoff, Miriam; Abzug, Mark J.; Levin, Myron J.; Seage, George R.; Oleske, James M.; Purswani, Murli U.; Hazra, Rohan; Traite, Shirley; Zimmer, Bonnie; Van Dyke, Russell B.

    2015-01-01

    Background. Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)–related opportunistic infections and deaths in US youth, but both continue to occur. Methods. We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004–2007). Causes of death and relevant demographic and clinical features were reviewed. Results. Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Conclusions. Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed. PMID:26270680

  4. Antiretroviral treatment sequencing strategies to overcome HIV type 1 drug resistance in adolescents and adults in low-middle-income countries.

    PubMed

    De Luca, Andrea; Hamers, Raphael L; Schapiro, Jonathan M

    2013-06-15

    Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success.

  5. [Analysis of costs and cost-effectiveness of preferred GESIDA/National AIDS Plan regimens for initial antiretroviral therapy in human immunodeficiency virus infected adult patients in 2013].

    PubMed

    Blasco, Antonio Javier; Llibre, Josep M; Arribas, José Ramón; Boix, Vicente; Clotet, Bonaventura; Domingo, Pere; González-García, Juan; Knobel, Hernando; López, Juan Carlos; Lozano, Fernando; Miró, José M; Podzamczer, Daniel; Santamaría, Juan Miguel; Tuset, Montserrat; Zamora, Laura; Lázaro, Pablo; Gatell, Josep M

    2013-11-01

    The GESIDA and National AIDS Plan panel of experts have proposed "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2013. The objective of this study is to evaluate the costs and effectiveness of initiating treatment with these "preferred regimens". An economic assessment of costs and effectiveness (cost/effectiveness) was performed using decision tree analysis models. Effectiveness was defined as the probability of having viral load <50copies/mL at week48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance analyses) during the first 48weeks. The perspective of the analysis is that of the National Health System was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, resistance studies, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was performed, constructing three scenarios for each regimen: baseline, most favourable, and most unfavourable cases. In the baseline case scenario, the cost of initiating treatment ranges from 6,747euros for TDF/FTC+NVP to 12,059euros for TDF/FTC+RAL. The effectiveness ranges between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.87 for TDF/FTC+RAL and ABC/3TC+RAL. Effectiveness, in terms of cost/effectiveness, varies between 8,396euros and 13,930euros per responder at 48weeks, for TDF/FTC/RPV and TDF/FTC+RAL, respectively. Taking ART at official prices, the most effective regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. Effect of Early Antiretroviral Therapy on Sexual Behaviors and HIV-1 Transmission Risk Among Adults With Diverse Heterosexual Partnership Statuses in Côte d'Ivoire

    PubMed Central

    Jean, Kévin; Gabillard, Delphine; Moh, Raoul; Danel, Christine; Fassassi, Raïmi; Desgrées-du-Loû, Annabel; Eholié, Serge; Lert, France; Anglaret, Xavier; Dray-Spira, Rosemary

    2014-01-01

    Background. The effect of early initiation of antiretroviral therapy (ART; ie, at CD4+ T-cell counts >350 cells/mm3) on sexual behaviors and human immunodeficiency virus type 1 (HIV) transmission risk has not been documented in populations other than HIV-serodiscordant couples in stable relationships. Methods. On the basis of data from a behavioral study nested in a randomized, controlled trial (Temprano-ANRS12136) of early ART, we compared proportions of risky sex (ie, unprotected sex with a partner of negative/unknown HIV status) reported 12 months after inclusion between participants randomly assigned to initiate ART immediately (hereafter, “early ART”) or according to ongoing World Health Organization criteria. Group-specific HIV transmission rates were estimated on the basis of sexual behaviors and viral load–specific per-act HIV transmission probabilities. The ratio of transmission rates was computed to estimate the protective effect of early ART. Results. Among 957 participants (baseline median CD4+ T-cell count, 478 cells/mm3), 46.0% reported sexual activity in the past month; of these 46.0%, sexual activity for 41.5% involved noncohabiting partners. The proportion of subjects who engaged in risky sex was 10.0% in the early ART group, compared with 12.8% in the standard ART group (P = .17). After accounting for sexual behaviors and viral load, we estimated that the protective effect of early ART was 90% (95% confidence interval, 81%–95%). Conclusion. Twelve months after inclusion, patients in the early and standard ART groups reported similar sexual behaviors. Early ART decreased the estimated risk of HIV transmission by 90%, suggesting a major prevention benefit among seronegative sex partners in stable or casual relationships with seropositive individuals. PMID:23990567

  7. Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy.

    PubMed

    Mirani, Gayatri; Williams, Paige L; Chernoff, Miriam; Abzug, Mark J; Levin, Myron J; Seage, George R; Oleske, James M; Purswani, Murli U; Hazra, Rohan; Traite, Shirley; Zimmer, Bonnie; Van Dyke, Russell B

    2015-12-15

    Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Serum amyloid P (SAP) is associated with impaired brachial artery flow-mediated dilation in chronically HIV-1 infected adults on stable antiretroviral therapy.

    PubMed

    Zungsontiporn, Nath; Ndhlovu, Lishomwa C; Mitchell, Brooks I; Stein, James H; Kallianpur, Kalpana J; Nakamoto, Beau; Keating, Sheila M; Norris, Philip J; Souza, Scott A; Shikuma, Cecilia M; Chow, Dominic C

    2015-11-01

    This study aimed to evaluate the relationship between inflammatory biomarkers and endothelial dysfunction (ED), as measured by brachial artery flow-mediated dilation (FMD). We conducted a cross-sectional analysis utilizing baseline data of 135 participants with HIV infection on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV-Cardiovascular (HAHC-CVD) study who had available baseline inflammatory biomarkers and brachial artery FMD measurements. We observed significant associations between brachial artery FMD and baseline brachial artery diameter, age, male gender, traditional cardiovascular disease (CVD) risk factors such as BMI, waist to hip ratio, hypertension, systolic blood pressure (BP), diastolic BP, and LDL cholesterol, and 10-year coronary heart disease (CHD) risk estimated by Framingham risk score (FRS). Of all biomarkers tested, higher level of C-reactive protein (CRP) (beta =  - 0.695, P = 0.030) and serum amyloid P (SAP) (beta =  - 1.318, P = 0.021) were significantly associated with lower brachial artery FMD in univariable regression analysis. After adjusting for baseline brachial artery diameter, age, and selected traditional CVD risk factors in multivariable model, SAP remained significantly associated with brachial artery FMD (beta =  - 1.094, P = 0.030), while CRP was not (beta =  - 0.391, P = 0.181). Serum amyloid P was independently associated with impaired brachial artery FMD and may potentially relate to ED and increased CVD risk in HIV-infected patients on stable ART.

  9. Antiretrovirals: reality or illusion?

    PubMed

    Mazin, R; Zacarias, F

    1998-10-01

    The use of antiretroviral drugs and combination therapy to treat HIV disease has been widely favored, despite obstacles such as cost, difficult dosing schedules, management of side effects, and inexperience of health practitioners in customizing treatment and counseling patients on use and adherence. Several benefits of drug therapy are discussed. One benefit is that the cost of therapy is lower than the overall cost of a patient not on therapy who will need more services and hospitalizations and will have higher incidences of opportunistic infections. Drug therapy also enables individuals to continue contributing to society by slowing the development of HIV and improving the quality of life. The Pan American Health Organization and UNAIDS are investigating ways to improve access to drugs in Latin America, the Caribbean, and other countries by working with pharmaceutical companies to coordinate drug purchases or negotiate price reductions. In addition, in order for antiretroviral therapy to be most effective, treatment should also include counseling, testing, and education.

  10. Pharmacogenetics of antiretroviral therapy.

    PubMed

    Barreiro, Pablo; Fernández-Montero, José Vicente; de Mendoza, Carmen; Labarga, Pablo; Soriano, Vincent

    2014-08-01

    Human genetic testing is rapidly entering into most medical disciplines, mainly as a way to predict hereditary conditions including predisposition to cancers or degenerative diseases. Another area of interest for human genomics is to ascertain the therapeutic effect and prevent potential toxicities and/or drug-drug interactions of medication. Several human genotypes have been associated with differences in the metabolism and transport of antiretroviral agents that ultimately affect drug exposure. The accelerated discovery of new gene mutations and polymorphisms that influence the effects of antiretroviral drugs provides a unique opportunity for a personalized medicine approach in the management of lifelong HIV therapy. Integration of human genomic screening into HIV clinical management will be cost-effective, maximizing the benefit of drugs with the lowest risk of side effects for a given patient.

  11. Where is the evidence? The use of routinely-collected patient data to retain adults on antiretroviral treatment in low and middle income countries-a state of the evidence review.

    PubMed

    do Nascimento, Nena; Barker, Catherine; Brodsky, Isabel

    2017-09-25

    Retention rates in antiretroviral treatment (ART) in low- and middle-income countries are suboptimal for meeting global "90-90-90" treatment targets. Interventions using routinely collected patient data to follow up with ART defaulters is recommended to improve retention; yet, little is documented on how these data are used in practice. This state of the evidence review summarizes how facilities and programmes use patient data to retain adults on ART in low- and middle-income countries, and what effect, if any, these interventions have on retention. The authors searched peer-reviewed and grey literature in PubMed, POPLINE, OVID, Google Scholar, and select webpages; screened publications for relevance; and applied eligibility criteria to select articles for inclusion. Over 4,000 records were found, of which 19 were eligible. Interventions assessed within the studies were sorted into three categories: patient tracing (18), data reviews (3), and improved data capture systems (9). Nine studies demonstrated increased retention or reduced lost to follow-up; however, the quality of evidence was weak. We recommend that future research investigates how various combinations of these interventions are being implemented and their effectiveness on ART retention across diverse country contexts, taking into account cultural, social and economic barriers and differences in countries' HIV epidemics and health information systems.

  12. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study.

    PubMed

    Clotet, Bonaventura; Feinberg, Judith; van Lunzen, Jan; Khuong-Josses, Marie-Aude; Antinori, Andrea; Dumitru, Irina; Pokrovskiy, Vadim; Fehr, Jan; Ortiz, Roberto; Saag, Michael; Harris, Julia; Brennan, Clare; Fujiwara, Tamio; Min, Sherene

    2014-06-28

    Dolutegravir has been shown to be non-inferior to an integrase inhibitor and superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI). In FLAMINGO, we compared dolutegravir with darunavir plus ritonavir in individuals naive for antiretroviral therapy. In this multicentre, open-label, phase 3b, non-inferiority study, HIV-1-infected antiretroviral therapy-naive adults with HIV-1 RNA concentration of 1000 copies per mL or more and no resistance at screening were randomly assigned (1:1) to receive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily, with investigator-selected tenofovir-emtricitabine or abacavir-lamivudine. Randomisation was stratified by screening HIV-1 RNA (≤100,000 or >100,000 copies per mL) and nucleoside reverse transcriptase inhibitor (NRTI) selection. The primary endpoint was the proportion of patients with HIV-1 RNA concentration lower than 50 copies per mL (Food and Drug Administration [FDA] snapshot algorithm) at week 48 with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, NCT01449929. Recruitment began on Oct 31, 2011, and was completed on May 24, 2012, in 64 research centres in nine countries worldwide. Of 595 patients screened, 484 patients were included in the analysis (242 in each group). At week 48, 217 (90%) patients receiving dolutegravir and 200 (83%) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 copies per mL (adjusted difference 7·1%, 95% CI 0·9-13·2), non-inferiority and on pre-specified secondary analysis dolutegravir was superior (p=0·025). Confirmed virological failure occurred in two (<1%) patients in each group; we recorded no treatment-emergent resistance in either group. Discontinuation due to adverse events or stopping criteria was less frequent for dolutegravir (four [2%] patients) than for darunavir plus ritonavir (ten [4%] patients) and contributed to the difference in response rates. The most commonly

  13. Discontinuation from Antiretroviral Therapy: A Continuing Challenge among Adults in HIV Care in Ethiopia: A Systematic Review and Meta-Analysis

    PubMed Central

    Gesesew, Hailay Abrha; Hajito, Kifle Woldemichael; Feyissa, Garumma Tolu; Mwanri, Lillian

    2017-01-01

    Background Discontinuation of antiretroviral therapy (ART) reduces the immunological benefit of treatment and increases complications related to human immune-deficiency virus (HIV). However, the risk factors for ART discontinuation are poorly understood in developing countries particularly in Ethiopia. This review aimed to assess the best available evidence regarding risk factors for ART discontinuation in Ethiopia. Methods Quantitative studies conducted in Ethiopia between 2002 and 2015 that evaluated factors associated with ART discontinuation were sought across six major databases. Only English language articles were included. This review considered studies that included the following outcome: ART treatment discontinuation, i.e. ‘lost to follow up’, ‘defaulting’ and ‘stopping medication’. Meta- analysis was performed with Mantel Haenszel method using Revman-5 software. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals at a p-value of <0.05. Results Nine (9) studies met the criteria of the search. Five (5) were retrospective studies, 3 were case control studies, and 1 was a prospective cohort study. The total sample size in the included studies was 62,156. Being rural dweller (OR = 2.1, 95%CI: 1.5–2.7, I2 = 60%), being illiterate (OR = 1.5, 95%CI: 1.1–2.1), being not married (OR = 1.4, 95%CI: 1.1–1.8), being alcohol drinker (OR = 2.9, 95%CI: 1.9–4.4, I2 = 39%), being tobacco smoker (OR = 2.6, 95%CI: 1.6–4.3, I2 = 74%), having mental illness (OR = 2.7, 95%CI: 1.6–4.6, I2 = 0%) and being bed ridden functional status (OR = 2.3, 95%CI: 1.5–3.4, I2 = 37%) were risk factors for ART discontinuation. Whereas, having HIV positive partner (OR = 0.4, 95%CI: 0.3–0.6, I2 = 69%) and being co-infected with Tb/HIV (OR = 0.6, 95%CI: 0.4–0.9, I2 = 0%) were protective factors. Conclusion Demographic, behavioral and clinical factors influenced ART treatment discontinuation. Hence, we recommend strengthening

  14. Costs and cost-efficacy analysis of the 2014 GESIDA/Spanish National AIDS Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

    PubMed

    Blasco, Antonio Javier; Llibre, Josep M; Berenguer, Juan; González-García, Juan; Knobel, Hernando; Lozano, Fernando; Podzamczer, Daniel; Pulido, Federico; Rivero, Antonio; Tuset, Montserrat; Lázaro, Pablo; Gatell, Josep M

    2015-03-01

    GESIDA and the National AIDS Plan panel of experts suggest preferred (PR) and alternative (AR) regimens of antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2014. The objective of this study is to evaluate the costs and the efficiency of initiating treatment with these regimens. An economic assessment was made of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied by considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and costs correspond to those of 2014. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base case scenario, the cost of initiating treatment ranges from 5133 Euros for ABC/3TC+EFV to 11,949 Euros for TDF/FTC+RAL. The efficacy varies between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.89 for TDF/FTC/EVG/COBI. Efficiency, in terms of cost/efficacy, ranges from 7546 to 13,802 Euros per responder at 48 weeks, for ABC/3TC+EFV and TDF/FTC+RAL respectively. Considering ART official prices, the most efficient regimen was ABC/3TC+EFV (AR), followed by the non-nucleoside containing PR (TDF/FTC/RPV and TDF/FTC/EFV). The sensitivity analysis confirms the robustness of these findings. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  15. Costs and cost-efficacy analysis of the 2017 GESIDA/Spanish National AIDS Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

    PubMed

    Rivero, Antonio; Pérez-Molina, José Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Asensi, Víctor; Crespo, Manuel; Domingo, Pere; Iribarren, José Antonio; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Martínez, Esteban; Moreno, Santiago; Palacios, Rosario; Pineda, Juan Antonio; Pulido, Federico; Rubio, Rafael; Santos, Jesús; de la Torre, Javier; Tuset, Montserrat; Gatell, Josep M

    2017-05-19

    GESIDA and the Spanish National AIDS Plan panel of experts have recommended preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral therapy (ART) as initial therapy in HIV-infected patients for 2017. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Economic assessment of costs and efficiency (cost-efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, resistance studies and HLA B*5701 screening. The setting was Spain and the costs correspond to those of 2017. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base case scenario, the cost of initiating treatment ranged from 6882 euro for TFV/FTC/RPV (AR) to 10,904 euros for TFV/FTC+RAL (PR). The efficacy varied from 0.82 for TFV/FTC+DRV/p (AR) to 0.92 for TAF/FTC/EVG/COBI (PR). The efficiency, in terms of cost-efficacy, ranged from 7923 to 12,765 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TFV/FTC+RAL (PR), respectively. Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TFV/FTC/RPV (AR) and TAF/FTC/EVG/COBI (PR). Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Costs and cost-effectiveness analysis of 2015 GESIDA/Spanish AIDS National Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

    PubMed

    Berenguer, Juan; Rivero, Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Boix, Vicente; Clotet, Bonaventura; Domingo, Pere; González-García, Juan; Knobel, Hernando; Lázaro, Pablo; López, Juan Carlos; Llibre, Josep M; Lozano, Fernando; Miró, José M; Podzamczer, Daniel; Tuset, Montserrat; Gatell, Josep M

    2016-01-01

    GESIDA and the AIDS National Plan panel of experts suggest a preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2015. The objective of this study is to evaluate the costs and the effectiveness of initiating treatment with these regimens. Economic assessment of costs and effectiveness (cost/effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2015. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,902 Euros for TDF/FTC+RAL (PR). The effectiveness varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/effectiveness, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR) and RAL+DRV/r (OR), respectively. The most efficient regimen was 3TC+LPV/r (OR). Among the PR and AR, the most efficient regimen was TDF/FTC/RPV (AR). Among the PR regimes, the most efficient was ABC/3TC+DTG. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Costs and cost-efficacy analysis of the 2016 GESIDA/Spanish AIDS National Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

    PubMed

    Rivero, Antonio; Pérez-Molina, José Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Crespo, Manuel; Domingo, Pere; Estrada, Vicente; Iribarren, José Antonio; Knobel, Hernando; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Moreno, Santiago; Palacios, Rosario; Pineda, Juan Antonio; Pulido, Federico; Rubio, Rafael; de la Torre, Javier; Tuset, Montserrat; Gatell, Josep M

    2017-02-01

    GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Projected Uptake of New Antiretroviral (ARV) Medicines in Adults in Low- and Middle-Income Countries: A Forecast Analysis 2015-2025.

    PubMed

    Gupta, Aastha; Juneja, Sandeep; Vitoria, Marco; Habiyambere, Vincent; Nguimfack, Boniface Dongmo; Doherty, Meg; Low-Beer, Daniel

    2016-01-01

    With anti-retroviral treatment (ART) scale-up set to continue over the next few years it is of key importance that manufacturers and planners in low- and middle-income countries (LMICs) hardest hit by the HIV/AIDS pandemic are able to anticipate and respond to future changes to treatment regimens, generics pipeline and demand, in order to secure continued access to all ARV medicines required. We did a forecast analysis, using secondary WHO and UNAIDS data sources, to estimate the number of people living with HIV (PLHIV) and the market share and demand for a range of new and existing ARV drugs in LMICs up to 2025. UNAIDS estimates 24.7 million person-years of ART in 2020 and 28.5 million person-years of ART in 2025 (24.3 million on first-line treatment, 3.5 million on second-line treatment, and 0.6 million on third-line treatment). Our analysis showed that TAF and DTG will be major players in the ART regimen by 2025, with 8 million and 15 million patients using these ARVs respectively. However, as safety and efficacy of dolutegravir (DTG) and tenofovir alafenamide (TAF) during pregnancy and among TB/HIV co-infected patients using rifampicin is still under debate, and ART scale-up is predicted to increase considerably, there also remains a clear need for continuous supplies of existing ARVs including TDF and EFV, which 16 million and 10 million patients-respectively-are predicted to be using in 2025. It will be important to ensure that the existing capacities of generics manufacturers, which are geared towards ARVs of higher doses (such as TDF 300mg and EFV 600mg), will not be adversely impacted due to the introduction of lower dose ARVs such as TAF 25mg and DTG 50mg. With increased access to viral load testing, more patients would be using protease inhibitors containing regimens in second-line, with 1 million patients on LPV/r and 2.3 million on ATV/r by 2025. However, it will remain important to continue monitoring the evolution of ARV market in LMICs to guarantee

  19. Projected Uptake of New Antiretroviral (ARV) Medicines in Adults in Low- and Middle-Income Countries: A Forecast Analysis 2015-2025

    PubMed Central

    Gupta, Aastha; Juneja, Sandeep; Vitoria, Marco; Habiyambere, Vincent; Nguimfack, Boniface Dongmo; Doherty, Meg; Low-Beer, Daniel

    2016-01-01

    With anti-retroviral treatment (ART) scale-up set to continue over the next few years it is of key importance that manufacturers and planners in low- and middle-income countries (LMICs) hardest hit by the HIV/AIDS pandemic are able to anticipate and respond to future changes to treatment regimens, generics pipeline and demand, in order to secure continued access to all ARV medicines required. We did a forecast analysis, using secondary WHO and UNAIDS data sources, to estimate the number of people living with HIV (PLHIV) and the market share and demand for a range of new and existing ARV drugs in LMICs up to 2025. UNAIDS estimates 24.7 million person-years of ART in 2020 and 28.5 million person-years of ART in 2025 (24.3 million on first-line treatment, 3.5 million on second-line treatment, and 0.6 million on third-line treatment). Our analysis showed that TAF and DTG will be major players in the ART regimen by 2025, with 8 million and 15 million patients using these ARVs respectively. However, as safety and efficacy of dolutegravir (DTG) and tenofovir alafenamide (TAF) during pregnancy and among TB/HIV co-infected patients using rifampicin is still under debate, and ART scale-up is predicted to increase considerably, there also remains a clear need for continuous supplies of existing ARVs including TDF and EFV, which 16 million and 10 million patients—respectively—are predicted to be using in 2025. It will be important to ensure that the existing capacities of generics manufacturers, which are geared towards ARVs of higher doses (such as TDF 300mg and EFV 600mg), will not be adversely impacted due to the introduction of lower dose ARVs such as TAF 25mg and DTG 50mg. With increased access to viral load testing, more patients would be using protease inhibitors containing regimens in second-line, with 1 million patients on LPV/r and 2.3 million on ATV/r by 2025. However, it will remain important to continue monitoring the evolution of ARV market in LMICs to

  20. Early Mortality in Adults Initiating Antiretroviral Therapy (ART) in Low- and Middle-Income Countries (LMIC): A Systematic Review and Meta-Analysis

    PubMed Central

    Gupta, Amita; Nadkarni, Girish; Yang, Wei-Teng; Chandrasekhar, Aditya; Gupte, Nikhil; Bisson, Gregory P.; Hosseinipour, Mina; Gummadi, Naveen

    2011-01-01

    Background We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known. Methods and Findings Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3–55 months and 11–192 cells/mm3, respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%–27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11–0.24) versus 0.11 (95% CI 0.10–0.13) for Asia, and 0.07 (95% CI 0.007–0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%–44%), wasting (5%–53%), advanced HIV (20%–37%), and chronic diarrhea (10%–25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA. Conclusions Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early

  1. Starting motor

    SciTech Connect

    Tanaka, T.; Hamano, I

    1989-05-23

    This patent describes a starting motor having a housing, planetary reduction gears including an internal gear in the housing. The improvement consists of an elastic member having a first annular portion mounted in engagement with a fixed annular member of the housing and a plurality of protruding axially extending elastic portions providing a corrugated surface pressed into engagement with an end portion of the internal gear, the elastic member being sandwiched between the internal gear and the housing member, the protruding axially extending elastic portions providing resilient means which flex and incline circumferentially under turning force from the internal gear and exert reactive thrust on the internal gear elastically so that the frictional force at the abutting surfaces of the protruding portions holds the internal gear in resilient engagement with the elastic member and the resilient means acts as a buffer to absorb rotary impact force developing in the planetary reduction gears.

  2. Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort

    PubMed Central

    Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

    2013-01-01

    Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID:22778335

  3. Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania

    PubMed Central

    Hamza, Omar JM; Matee, Mecky IN; Simon, Elison NM; Kikwilu, Emil; Moshi, Mainen J; Mugusi, Ferdinand; Mikx, Frans HM; Verweij, Paul E; van der Ven, André JAM

    2006-01-01

    Background The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count. Methods Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2–17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells. Results A total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (χ2 = 4.31; df = 1; p = 0.03) and parotid enlargement (χ2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22 – 0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18 – 0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04 – 0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11–1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (χ2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (χ2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (χ2 = 8.17; df = 2; p = 0.04). Conclusion Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children

  4. High rate of lymphoma among a UK cohort of adolescents with vertically acquired HIV-1 infection transitioning to adult care in the era of antiretroviral therapy.

    PubMed

    Eades, Chris P; Herbert, Sophie A; Edwards, Simon G; Waters, Laura J; Peake, Tabitha; Miller, Robert F; Jungmann, Eva

    2016-01-02

    Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424-0.426). Previously described risk factors, including low nadir CD4 cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients.

  5. An update and review of antiretroviral therapy.

    PubMed

    Piacenti, Frank J

    2006-08-01

    The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden

  6. Saquinavir, the pioneer antiretroviral protease inhibitor.

    PubMed

    la Porte, Charles J L

    2009-10-01

    The treatment of HIV infection underwent a major change in 1995 when saquinavir was the first protease inhibitor introduced into the market. This drug made the use of combination therapy in the treatment of HIV possible and increased the success rate of treatment. This article will review recent literature on saquinavir to define its current role in HIV treatment, among the newer antiretroviral drugs. Scientific literature and conference presentations were evaluated for relevant information pertaining to saquinavir. Although underused, saquinavir has good efficacy and tolerability when compared to other protease inhibitors. The film-coated tablet formulation improved pill burden. Saquinavir still has potential in the treatment of adults, children and pregnant women.

  7. Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network.

    PubMed

    Wolff, Marcelo; Shepherd, Bryan E; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Wagner Cardoso, Sandra; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C

    2016-01-01

    HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.

  8. Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

    PubMed Central

    Low, Andrea; Gavriilidis, Georgios; Larke, Natasha; B-Lajoie, Marie-Renee; Drouin, Olivier; Stover, John; Muhe, Lulu; Easterbrook, Philippa

    2016-01-01

    Background. To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)–infected adults in low- and middle-income countries (LMICs). Methods. Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case. Results. We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%–91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032–874 853), with cost savings of $46.7 million (95% CI, $43.8–$49.4 million). Conclusions. There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted. PMID:26951573

  9. Causes of death in the era of highly active antiretroviral therapy: a retrospective analysis of a hybrid hematology-oncology and HIV practice and the Seattle/King county adult/adolescent spectrum of HIV-related diseases project.

    PubMed

    Uhlenkott, Matthew C; Buskin, Susan E; Kahle, Erin M; Barash, Elizabeth; Aboulafia, David M

    2008-09-01

    HIV-infected patients continue to die in the era of highly active antiretroviral therapy (HAART). To describe the cause of mortality in the HAART era between 2 cohorts by conducting a comparative retrospective analysis. The Virginia Mason Medical Center (VMMC) cohort was composed of 60 died HIV-infected patients from 600 patients. The second cohort was comprised of 351 died patients from the Seattle portion of the Adult and Adolescent Spectrum of Diseases Project (Seattle-ASD) of 4721 patients. Among the abstracted data were the conditions present at death, defined as any major cause of morbidity present at death for both cohorts. Non-AIDS defining illnesses (non-ADI) were a major source of mortality in 60% and 45% for the VMMC and Seattle-ASD cohorts, respectively. The most common fatal non-ADI in both cohorts were cancer (7% and 19%), bacterial infections (15%), and liver failure (9% and 14%). Cancer (10%) and wasting (7%) were prominent fatal ADI in both cohorts. In each cohort, patients died despite a nondetectable HIV viral load and a CD4 lymphocyte count >200 cells/microL. This included 11 of 60 (18%) VMMC patients (all of whom died of non-ADI) and 35 of 351 (10%) Seattle-ASD patients (81% died with non-ADI). In 2 well-characterized urban HIV cohorts, non-ADI were a major cause of mortality in the HAART era. A substantial number of these patients died despite nondetectable HIV viral loads and reasonably well-preserved immune function measured by CD4 cell counts.

  10. Pulmonary function in an international sample of HIV-positive, treatment-naïve adults with CD4 counts >500 cells/μL: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    KUNISAKI, Ken M.; NIEWOEHNER, Dennis E.; COLLINS, Gary; NIXON, Daniel E.; TEDALDI, Ellen; AKOLO, Christopher; KITYO, Cissy; KLINKER, Hartwig; LA ROSA, Alberto; CONNETT, John E.

    2014-01-01

    Objectives To describe the prevalence and correlates of chronic obstructive pulmonary disease (COPD) in a multicentre international cohort of persons living with HIV (PLWH). Methods We performed a cross-sectional analysis of adult PLWH, naïve to HIV treatment, with baseline CD4 cell count >500 cells/μL enrolled in the Pulmonary Substudy of the Strategic Timing of AntiRetroviral Treatment trial. We collected standardised, quality-controlled spirometry. COPD was defined as forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio less than the lower limit of normal. Results Among 1026 participants from 80 sites and 20 countries, median (IQR) age was 36 (30, 44) years, 29% were female, and time since HIV diagnosis was 1.2 (0.4, 3.5) years. Baseline CD4 cell count was 648 (583, 767) cells/μL, viral load was 4.2 (3.5, 4.7) log10 copies/mL, and 10% had viral load ≤400 copies/mL despite lack of HIV treatment. Current/former/never smokers comprised 28%/11%/61% of the cohort, respectively. COPD was present in 6.8% of participants, and varied by age, smoking status, and region. 48% of those with COPD reported lifelong nonsmoking. In multivariable regression, age and pack-years of smoking had the strongest associations with FEV1/FVC ratio (p<0.0001). There were significant differences between the effect of region on FEV1/FVC ratio (p=0.010). Conclusions Our data suggest that among PLWH, naïve to HIV treatment and with CD4 cell count >500 cells/μL, smoking and age are important factors related to COPD. Smoking cessation should remain a high global priority for clinical care and research in PLWH. PMID:25711330

  11. A lot of mental illness starts in adolescence. Therefore should we shift some of the spending from adult to adolescent mental health services?

    PubMed

    Neal, David

    2015-09-01

    In May 2015 the UK elected a new government. In election campaigns, health is one of the most important areas of debate and over the preceding 12 months, the state of child and adolescent mental health services (CAMHS) had held a particularly high profile in the media and in political debate. Many had suggested that the rate of mental illness starting in adolescence is increasing and that service provision is not of sufficient quality or scale to meet this need. A brief review of the sources for these statistics reveals that whilst this may be true, there is a dearth of accurate and up to date data on the scale of the need for CAMHS or the extent to which it is being met. Nonetheless, members of all parties claimed to support improvements in mental health service provision for children and adolescents through increases in funding. A key question for policy makers has therefore become, from where any additional funding might be derived. One suggestion has been that funding be transferred from spending on adult mental health services. The exact practical nature of such a policy is yet to be explored in detail by government or stakeholders. The primary purpose of the present discussion is therefore to consider the possible ethical implications of such a policy in principle. The discussion forms part of a wider and evolving political and professional discourse on society's and government's attitude towards mental illness, towards the balance of individual and societal needs and towards the balance between preventative and supportive interventions to improve health.

  12. The next generation of the World Health Organization's global antiretroviral guidance

    PubMed Central

    Hirnschall, Gottfried; Harries, Anthony D; Easterbrook, Philippa J; Doherty, Meg C; Ball, Andrew

    2013-01-01

    The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm3); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and

  13. Improvement in mortality and retention among adult HIV-infected patients in the first 12 months of antiretroviral therapy in Dodoma urban district, Tanzania.

    PubMed

    Tweve, Escor N; Kayabu, David; Nassari, Nahum O; Todd, Jim

    2015-06-01

    To determine mortality and retention in ART programmes in Tanzania, between 2010 and 2013. Retrospective routinely collected data were analysed from people starting ART in the period 2010-2013. Mortality and retention over the first 12 months on ART were compared across the 4 years, and adjustment was made for individual level potential confounders. Data from 3844 people (70.6% female) starting ART were analysed. Mortality in the first year declined from 11.4% in 2010 to 4.9% in 2013, and retention after 12 months increased from 77.8% in 2010 to 98.1% in 2013. Mortality was inversely associated with CD4 count, lowest among those with CD4 350+ cells/μl [adjusted odds ratio (AOR) = 0.03, 95% CI 0.01-0.03], associated with male sex (AOR = 1.79, 95% CI 1.39-2.31), but not age. Lost to follow-up (LTFU) was lowest among those with CD4 = 350+ cells/μl AOR = 0.20, 95% CI 0.10-0.30), but not associated with age or sex, and higher in urban health facilities (AOR = 1.88, 95% CI 1.15-3.09). After adjustment for individual level characteristics, there was a statistically significant yearly improvement in mortality (AOR = 0.31, 95% CI (0.21-0.44) and LTFU (AOR = 0.06, 95% CI 0.04-0.10). Mortality and retention in the first 12 months on ART have significantly improved over the 4 years from 2010 to 2013. These improvements may indicate better services, earlier initiation on ART, and strengthened systems to provide ART in Tanzania. These results refute the worries that earlier initiation on ART might lead to lower retention in the ART programme. © 2015 John Wiley & Sons Ltd.

  14. HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa.

    PubMed

    Rossouw, T M; Nieuwoudt, M; Manasa, J; Malherbe, G; Lessells, R J; Pillay, S; Danaviah, S; Mahasha, P; van Dyk, G; de Oliveira, T

    2017-02-01

    Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison. HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared. Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/μL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration. The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen. © 2016 British HIV Association.

  15. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel.

    PubMed

    Yeni, Patrick G; Hammer, Scott M; Hirsch, Martin S; Saag, Michael S; Schechter, Mauro; Carpenter, Charles C J; Fischl, Margaret A; Gatell, Jose M; Gazzard, Brian G; Jacobsen, Donna M; Katzenstein, David A; Montaner, Julio S G; Richman, Douglas D; Schooley, Robert T; Thompson, Melanie A; Vella, Stefano; Volberding, Paul A

    2004-07-14

    Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection. To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails. Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management. Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004. Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached. Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel). Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.

  16. Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study

    PubMed Central

    2012-01-01

    Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ≥350 cells/μL and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/μL. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/μL, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved. PMID:23095460

  17. Risky sexual practice and associated factors among HIV positive adults attending anti-retroviral treatment clinic at Gondar University Referral Hospital, Northwest Ethiopia

    PubMed Central

    2017-01-01

    Introduction Risky sexual practice among people living with HIV/AIDS is a public health concern because of the risk of transmission of the virus to sero-discordant partner/s. There is also the risk of re-infection with new, drug resistant viral strains between sero-concordant partners. However, there is lack of information on risky sexual practices among HIV positive adults. Therefore, this study aimed to assess risky sexual practice and associated factors among adult HIV positive clients at Gondar University Referral Hospital, Northwest Ethiopia, 2015. Methods An institution based cross sectional study was conducted at Gondar University Referral Hospital from May to June 2015. A pretested structured questionnaire was used to collect the data. Using systematic random sampling technique, a total of 513 respondents were participated in this study. The data were entered into EPI info version 3.5.3 and transferred to SPSS version 20 for analysis. Descriptive, bivariate and multivariate analyses were done. A P-value <0.05 was considered to determine the statistical significance of the association between factors (independent variables) and risky sexual practice. The Odds ratio was also used to determine the presence and the degree of association between the dependent and independent variables. Results A total of 513 respondents were participated in this study. The prevalence of risky sexual practices in the past three months was 38% (95% CI: 33.3%, 42.3%). Being in the age range of 18–29 years (AOR = 2.63, 95% CI: 1.55, 4.47) and 30–39 years (AOR = 2.29, 95% CI: 1.48, 3.53), being single (AOR = 6.32, 95%CI: 2.43, 16.44),being married (AOR = 6.06, 95% CI: 2.81, 13.07), having no child (AOR = 2.58, 95% CI: 1.17, 5.72), and a CD4 count of greater than 500/mm3 were factors significantly associated with risky sexual practices. Conclusions A considerable number of HIV positive clients had risky sexual practices. It is strongly recommended that the Regional Health Bureau

  18. Clinical Pharmacokinetics of Antiretroviral Drugs in Older Persons

    PubMed Central

    Schoen, John C.; Erlandson, Kristine Mace

    2013-01-01

    Introduction Combination antiretroviral therapy has enabled HIV infected persons to reach older ages in high numbers. Hepatic and renal changes that normally occur with advancing age occur earlier and with higher incidence in HIV-infected individuals. A limited number of prospective controlled studies have demonstrated small reductions (17% to 41%) in lopinavir, atazanavir, and lamivudine clearance in older versus younger adults. A much larger number of retrospective studies in adults (age range ~20 to 60 years), including all antiretroviral drugs, have evaluated age as a covariate for pharmacokinetics. Most studies did not detect substantial associations between drug exposures and age. Areas Covered This review summarizes antiretroviral drug pharmacokinetics in older persons. The authors review articles from PubMed (search terms: elderly, antiretroviral, pharmacokinetics) in addition to the bibliographies of those selected. Expert Opinion The evidence to date does not support major pharmacokinetic changes in adults between ~20 and 60 years of age. However, additional prospective, well-controlled studies are needed in more persons > 60 years, including those with frailty and comorbidities, with assessment of unbound drug clearance, and incorporation of adherence, pharmacogenetics, and concomitant medications. Until then, guidelines for drug-drug interactions and dosing in renal and hepatic impairment should be followed in older HIV infected individuals. PMID:23514375

  19. Comparative durability of nevirapine versus efavirenz in first-line regimens during the first year of initiating antiretroviral therapy among Swaziland HIV-infected adults.

    PubMed

    Takuva, Simbarashe; Evans, Denise; Zuma, Khangelani; Okello, Velephi; Louwagie, Goedele

    2013-01-01

    Nevirapine (NVP) and Efavirenz (EFV) have generally comparable clinical and virologic efficacy. However, data comparing NVP durability to EFV are imprecise. We analyzed cohort data to compare durability of NVP to EFV among patients initiating ART in Mbabane, Swaziland. The primary outcome was poor regimen durability defined as any modification of NVP or EFV to the ART regimen. Multivariate Cox proportional hazards models were employed to estimate the risk of poor regimen durability (all-cause) for the two regimens and also separately to estimate risk of drug-related toxicity. We analyzed records for 769 patients initiating ART in Mbabane, Swaziland from March 2006 to December 2007. 30 patients (3.9%) changed their NVP or EFV-based regimen during follow up. Cumulative incidence for poor regimen durability was 5.3% and 2.7% for NVP and EFV, respectively. Cumulative incidence for drug-related toxicity was 1.9% and 2.7% for NVP and EFV, respectively. Burden of TB was high and 14 (46.7%) modifications were due to patients substituting NVP due to beginning TB treatment. Though the estimates were imprecise, use of NVP - based regimens seemed to be associated with higher risk of modifications compared to use of EFV - based regimens (HR 2.03 95%CI 0.58 - 7.05) and NVP - based regimens had a small advantage over EFV - based regimens with regard to toxicity - related modifications (HR 0.87 95%CI 0.26 - 2.90). Due to the high burden of TB and a significant proportion of patients changing their ART regimen after starting TB treatment, use of EFV as the preferred NNRTI over NVP in high TB endemic settings may result in improved first-line regimen tolerance. Further studies comparing the cost-effectiveness of delivering these two NNRTIs in light of their different limitations are required.

  20. The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

    PubMed Central

    Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

    2016-01-01

    Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794

  1. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial.

    PubMed

    Raffi, François; Babiker, Abdel G; Richert, Laura; Molina, Jean-Michel; George, Elizabeth C; Antinori, Andrea; Arribas, Jose R; Grarup, Jesper; Hudson, Fleur; Schwimmer, Christine; Saillard, Juliette; Wallet, Cédrick; Jansson, Per O; Allavena, Clotilde; Van Leeuwen, Remko; Delfraissy, Jean-François; Vella, Stefano; Chêne, Geneviève; Pozniak, Anton

    2014-11-29

    Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962. Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively). Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck

  2. Mortality, AIDS-morbidity and loss to follow-up by current CD4 cell count among HIV-1 infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration

    PubMed Central

    Gabillard, Delphine; Lewden, Charlotte; Ndoye, Ibra; Moh, Raoul; Ségéral, Olivier; Tonwe-Gold, Besigin; Etard, Jean-François; Pagnaroat, Men; Fournier-Nicolle, Isabelle; Eholié, Serge; Konate, Issouf; Minga, Albert; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Zannou, Djimon Marcel; Anglaret, Xavier; Laurent, Christian

    2013-01-01

    Background In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses and inform decisions. Methods We pooled data from 13 research cohorts in five sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire and Senegal) and two Asian (Cambodia and Laos) countries. HIV-infected adults (≥18 years) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results Overall 3,917 adults (62% women) on ART were followed-up during 10,154 person-years. In the ≤50, 51-100, 101-200, 201-350, 351-500, 501-650 and >650/mm3 CD4 cells strata, death rates were: 20.6, 11.8, 6.7, 3.3, 1.8, 0.9 and 0.3 per 100 person-years; AIDS rates were: 50.5, 32.9, 11.5, 4.8, 2.8, 2.2 and 2.2 per 100 person-years; and loss to follow-up rates were: 4.9, 6.1, 3.5, 3.1, 2.9, 1.7 and 1.2 per 100 person-years, respectively. Mortality and morbidity were higher during the first year following ART initiation. Conclusion In these resource-limited settings, death and AIDS rates remained substantial after ART initiation, even in individuals with high CD4 cell counts. Ensuring earlier ART initiation and optimizing case finding and treatment for AIDS-defining diseases should be seen as priorities. PMID:23274931

  3. Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

    PubMed

    Johnson, Steven C

    Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.

  4. Potential drug interactions in patients given antiretroviral therapy

    PubMed Central

    dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

    2016-01-01

    ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. PMID:27878224

  5. Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy.

    PubMed

    Montoya, Jessica L; Iudicello, Jennifer; Fazeli, Pariya L; Hong, Suzi; Potter, Michael; Ellis, Ronald J; Grant, Igor; Letendre, Scott L; Moore, David J

    2017-02-01

    HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected. HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (β = 0.41, P < 0.01) and VEGF (β = -0.43, P = 0.01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P < 0.01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.

  6. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial.

    PubMed

    Bernardino, Jose I; Mocroft, Amanda; Mallon, Patrick W; Wallet, Cedrick; Gerstoft, Jan; Russell, Charlotte; Reiss, Peter; Katlama, Christine; De Wit, Stephane; Richert, Laura; Babiker, Abdel; Buño, Antonio; Castagna, Antonella; Girard, Pierre-Marie; Chene, Genevieve; Raffi, Francois; Arribas, Jose R

    2015-11-01

    Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen. Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants. Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the

  7. Clinical and virologic outcomes after changes in first antiretroviral regimen at 7 sites in the Caribbean, Central and South America Network (CCASAnet)

    PubMed Central

    Wolff, Marcelo; Shepherd, Bryan E.; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Cardoso, Sandra Wagner; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C.

    2015-01-01

    Background HIV-infected persons in lower income countries may experience high rates of antiretroviral therapy (ART) change, particularly due to toxicity or other non-failure reasons. Few reports address patient outcomes after these modifications. Methods HIV-infected adults from 7 Caribbean, Central and South America network (CCASAnet) clinical cohorts who modified > or = 1 drug from first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. Results 5,565 ART-naïve HAART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 due to toxicity and 11% due to failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4% and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio[aHR]=1.5 vs. failure, 95% confidence interval[CI]=1.0–2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at start of ART-2, and starting ART-2 because of failure (aHR=2.1 vs. toxicity, 95% CI=1.5–2.8). Conclusions Among patients modifying first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success. PMID:26761273

  8. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel.

    PubMed

    Hammer, Scott M; Saag, Michael S; Schechter, Mauro; Montaner, Julio S G; Schooley, Robert T; Jacobsen, Donna M; Thompson, Melanie A; Carpenter, Charles C J; Fischl, Margaret A; Gazzard, Brian G; Gatell, Jose M; Hirsch, Martin S; Katzenstein, David A; Richman, Douglas D; Vella, Stefano; Yeni, Patrick G; Volberding, Paul A

    2006-08-16

    Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to

  9. Drug Abuse Prevention Starts with Parents

    MedlinePlus

    ... Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Abuse Young Adult Healthy Children > Ages & Stages > Teen > Substance Abuse > Drug Abuse Prevention Starts with Parents Ages & Stages ...

  10. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study

    PubMed Central

    Ekouevi, Didier K.; Balestre, Eric; Coffie, Patrick A.; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P.; Gottlieb, Geoffrey S.; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d’Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N’Gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Østergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'Diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S.; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; PAC-CI; Abidjan

    2013-01-01

    Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d’Ivoire, Mali, and Senegal, in the West Africa region. Results Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3–51.7) and 42.4 years, IQR (37.0–47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm3, IQR (83–247) among HIV-2 infected patients and 146 cells/mm3, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm3 after 24 months on ART for HIV-2 patients and 169 cells/mm3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7–4.3). Conclusions This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population. PMID:23824279

  11. Pilot study of a multi-pronged intervention using social norms and priming to improve adherence to antiretroviral therapy and retention in care among adults living with HIV in Tanzania.

    PubMed

    McCoy, Sandra I; Fahey, Carolyn; Rao, Aarthi; Kapologwe, Ntuli; Njau, Prosper F; Bautista-Arredondo, Sergio

    2017-01-01

    Interventions incorporating constructs from behavioral economics and psychology have the potential to enhance HIV 'treatment as prevention' (TasP) strategies. To test this hypothesis, we evaluated an intervention to improve antiretroviral therapy (ART) adherence based on the concepts of social norms and priming. We used tools from marketing research and patient-centered design to develop a combination intervention that included visual feedback about clinic-level retention in care, a self-relevant prime, and useful take-home items with the priming image. The intervention was implemented at two HIV primary clinics in Shinyanga, Tanzania in 2-week intervals for six months. We conducted a quasi-experimental pilot study with a random sample of exposed and unexposed adult patients living with HIV infection (PLHIV) to compare retention and the proportion of patients with medication possession ratio (MPR) ≥95% after six months. Intervention acceptability was determined with a convenience sample of 405 PLHIV at baseline (n = 189) and endline (n = 216). Medical records were reviewed for 438 PLHIV (320 intervention, 118 standard of care). In adjusted analyses, PLHIV exposed to the intervention were significantly more likely to be in care after 6 months (87% vs. 79%, adjusted odds ratio (ORa) = 1.73, 95% CI: 1.08, 2.78, p<0.05) and were more likely to achieve MPR≥95% (70% vs. 59%, OR = 1.51, 95% CI: 0.96, 2.37, p = 0.07). The intervention was associated with increases in staff support of treatment goals (100% vs. 95%, p = 0.01) and life goals (66% vs. 50%, p<0.01), the perceived likelihood of other patients' adherence (54% vs. 32%, p<0.01), support from other patients (71% vs. 60%, p = 0.03), and being very satisfied with care (53% vs. 35%, p<0.01). This novel intervention has the potential to improve the clinic experience, short-term retention in care, and ART adherence. Future studies are needed to expand the generalizability of the approach and evaluate effectiveness on

  12. Longitudinal Changes in Emerging Adults' Attachment Preferences for Their Mother, Father, Friends, and Romantic Partner: Focusing on the Start and End of Romantic Relationships