Barreiro, Pablo; Fernández-Montero, José Vicente; de Mendoza, Carmen; Labarga, Pablo; Soriano, Vincent
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.
Routman, Justin S.; Willig, James H.; Westfall, Andrew O.; Abroms, Sarah R.; Varshney, Mohit; Adusumilli, Sunil; Allison, Jeroan J.; Savage, Karen G.; Saag, Michael S.; Mugavero, Michael J.
Summary The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited. The present study found similar first year virologic and CD4 outcomes among antiretroviral-naïve patients treated through routine care vs. those participating in clinical trials. Background The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited due to study eligibility criteria and volunteer bias. While well chronicled in many conditions, the efficacy vs. effectiveness of antiretroviral therapy (ART) remains understudied. Methods A retrospective study of the UAB 1917 Clinic Cohort evaluated naïve patients starting ART between 1/1/00–12/31/06. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virologic failure (VF=VL>50 copies/mL) and change from baseline CD4 count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. Results Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials vs. 449 (79%) receiving ART via routine care. ART receipt through routine care was not associated with VF at either 6 (OR=1.00;95%CI=0.54–1.86) or 12 (OR=1.56;95%CI=0.80–3.05) months in primary analyses. No significant differences in CD4 count responses at 6 and 12 months were observed. Conclusions Though marked differences in efficacy vs. effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients initiating antiretroviral therapy for HIV. PMID:20067423
Background Although severe oral opportunistic infections decreased with the implementation of highly active antiretroviral therapy, periodontitis is still a commonly described problem in patients infected with human immunodeficiency virus (HIV). The objective of the present investigation was to determine possible differences in periodontal parameters between antiretroviral treated and untreated patients. Methods The study population comprised 80 patients infected with HIV divided into two groups. The first group was receiving antiretroviral therapy while the second group was therapy naive. The following parameters were examined: probing pocket depth, gingival recession, clinical attachment level, papilla bleeding score, periodontal screening index and the index for decayed, missed and filled teeth. A questionnaire concerning oral hygiene, dental care and smoking habits was filled out by the patients. Results There were no significant differences regarding the periodontal parameters between the groups except in the clinical marker for inflammation, the papilla bleeding score, which was twice as high (P < 0.0001) in the antiretroviral untreated group (0.58 ± 0.40 versus 1.02 ± 0.59). The participants of this investigation generally showed a prevalence of periodontitis comparable to that in healthy subjects. The results of the questionnaire were comparable between the two groups. Conclusion There is no indication for advanced periodontal damage in HIV-infected versus non-infected patients in comparable age groups. Due to their immunodeficiency, HIV-infected patients should be monitored closely to prevent irreversible periodontal damage. Periodontal monitoring and early therapy is recommended independent of an indication for highly active antiretroviral therapy. PMID:22472296
Sashindran, V.K.; Chauhan, Rajeev
HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID:26900224
Mondy, Kristin; Tebas, Pablo
The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.
Mugavero, Michael J.; May, Margaret; Ribaudo, Heather J.; Gulick, Roy M.; Riddler, Sharon A.; Haubrich, Richard; Napravnik, Sonia; Abgrall, Sophie; Phillips, Andrew; Harris, Ross; Gill, M. John; de Wolf, Frank; Hogg, Robert; Günthard, Huldrych F.; Chêne, Geneviève; D'Arminio Monforte, Antonella; Guest, Jodie L.; Smith, Colette; Murillas, Javier; Berenguer, Juan; Wyen, Christoph; Domingo, Pere; Kitahata, Mari M.; Sterne, Jonathan A. C.; Saag, Michael S.
Background The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites. Methods Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/ml) at 24- and 48-weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by 3rd drug [Abacavir (ABC), Efavirenz (EFV), and Lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death. Results Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR=0.53, 95% CI 0.36–0.79) and ART-CC (0.46, 0.37–0.57). Virologic superiority of EFV (vs. ABC) appeared comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% CI 0.54–1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs 0.87, 0.45–1.69). Conclusions Between ART regimen virologic efficacy of 3rd drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials appear generalizable to the routine care setting of ART-CC clinical cohorts. PMID:21857357
Olender, Susan A; Taylor, Barbara S; Wong, Marcia; Wilkin, Timothy J
The 2015 Conference on Retroviruses and Opportunistic Infections included new and exciting advances in the realm of antiretroviral therapy. The Temprano trial demonstrated benefits from early antiretroviral therapy and isoniazid preventive therapy. Important data on investigational antiretroviral drugs were presented, including tenofovir alafenamide fumarate and BMS-955176, an HIV-1 maturation inhibitor. Novel data on the HIV care continuum from resource-rich and -limited settings highlighted persistent sex- and race-related disparities in care engagement, and the crucial need to bring HIV testing and care into the community to improve engagement across the care continuum. Life expectancy data from resource-limited settings reveal dramatic improvements across sub-Saharan Africa, although people with HIV still live 5 years to 10 years less than those without HIV, and new cost-effectiveness research revealed that the price of antiretroviral therapy itself remains a key driver of cost and cost-effectiveness calculations. Results from the PROMISE trial showed reduced rates of mother-to-child transmission among women who received antiretroviral therapy with 3 drugs compared with women who received zidovudine monotherapy, supporting current World Health Organization guidelines.
Shepherd, Bryan E; Liu, Qi; Mercaldo, Nathaniel; Jenkins, Cathy A; Lau, Bryan; Cole, Stephen R; Saag, Michael S; Sterling, Timothy R
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.
Rutishauser, Rachel; Hartogensis, Wendy; Deguit, Christian D; Krone, Melissa; Hoh, Rebecca; Hecht, Rick; Pilcher, Christopher D; Bacchetti, Peter; Deeks, Steven G; Hunt, Peter W; McCune, Joseph M
In untreated HIV infection, CD8+ T cell exhaustion (i.e., decreased proliferative and effector capacity) is associated with high levels of expression of co-inhibitory receptors, including PD-1, TIGIT, CD160, and 2B4. This is evident for both HIV-specific and non-HIV-specific CD8+ T cells. Antiretroviral therapy (ART) initiated during chronic infection decreases but may not completely normalize the expression of such "exhaustion markers." Compared to initiation of ART later in the course of disease, initiation soon after infection reduces some parameters of chronic inflammation and adaptive immune dysfunction. However, it is not known if Early ART (e.g., initiated within the first six months after HIV infection) versus Delayed ART (e.g., initiated during chronic infection) preferentially reduces expression of exhaustion markers. We evaluated exhaustion marker expression on subsets of circulating effector and memory CD8+ T cells at longitudinal pre- and post-ART (two and five years on ART) time points from n=19 (Early ART) and n=23 (Delayed ART) individuals. Prior to ART, TIGIT and CD160 were expressed on a statistically significantly higher proportion of effector and transitional memory cells from individuals in the Delayed ART group: the timing of ART initiation, however, did not consistently affect the expression of the exhaustion markers once viral suppression was achieved. Understanding which factors do and do not regulate aspects of CD8+ T cell exhaustion, including the expression of exhaustion markers, is critical to inform the rational design of CD8+ T cell-based therapies to treat HIV, for which CD8+ T cell exhaustion remains an important barrier to efficacy.
Duber, Herbert C; Roberts, D Allen; Ikilezi, Gloria; Fullman, Nancy; Gasasira, Anne; Gakidou, Emmanuela; Haakenstad, Annie; J Levine, Aubrey; Achan, Jane
Increased demand for antiretroviral therapy (ART) services combined with plateaued levels of development assistance for HIV/AIDS requires that national ART programmes monitor programme effectiveness. In this pilot study, we compared commonly utilised performance metrics of 12- and 24-month retention with rates of viral load (VL) suppression at 15 health facilities in Uganda. Retrospective chart review from which 12- and 24-month retention rates were estimated, and parallel HIV RNA VL testing on consecutive adult patients who presented to clinics and had been on ART for a minimum of six months. Rates of VL suppression were then calculated at each facility and compared to retention rates to assess the correlation between performance metrics. Multilevel logistic regression models predicting VL suppression and 12- and 24-month retention were constructed to estimate facility effects. We collected VL samples from 2961 patients and found that 88% had a VL ≤1000 copies/ml. Facility rates of VL suppression varied between 77% and 96%. When controlling for patient mix, a significant variation in facility performance persisted. Retention rates at 12 and 24 months were 91% and 79%, respectively, with a comparable facility-level variation. However, neither 12-month (ρ = 0.16) nor 24-month (ρ = -0.19) retention rates were correlated with facility rates of VL suppression. Retaining patients in care and suppressing VL are both critical outcomes. Given the lack of correlation noted in this study, the utilisation of VL monitoring may be necessary to truly assess the effectiveness of health facilities delivering ART services. © 2016 John Wiley & Sons Ltd.
Auld, Andrew F; Shiraishi, Ray W; Mbofana, Francisco; Couto, Aleny; Fetogang, Ernest Benny; El-Halabi, Shenaaz; Lebelonyane, Refeletswe; Pilatwe, Pilatwe Tlhagiso; Hamunime, Ndapewa; Okello, Velephi; Mutasa-Apollo, Tsitsi; Mugurungi, Owen; Murungu, Joseph; Dzangare, Janet; Kwesigabo, Gideon; Wabwire-Mangen, Fred; Mulenga, Modest; Hachizovu, Sebastian; Ettiegne-Traore, Virginie; Mohamed, Fayama; Bashorun, Adebobola; Nhan, Do Thi; Hai, Nguyen Huu; Quang, Tran Huu; Van Onacker, Joelle Deas; Francois, Kesner; Robin, Ermane G; Desforges, Gracia; Farahani, Mansour; Kamiru, Harrison; Nuwagaba-Biribonwoha, Harriet; Ehrenkranz, Peter; Denison, Julie A; Koole, Olivier; Tsui, Sharon; Torpey, Kwasi; Mukadi, Ya Diul; van Praag, Eric; Menten, Joris; Mastro, Timothy D; Hamilton, Carol Dukes; Abiri, Oseni Omomo; Griswold, Mark; Pierre, Edna; Xavier, Carla; Alfredo, Charity; Jobarteh, Kebba; Letebele, Mpho; Agolory, Simon; Baughman, Andrew L; Mutandi, Gram; Preko, Peter; Ryan, Caroline; Ao, Trong; Gonese, Elizabeth; Herman-Roloff, Amy; Ekra, Kunomboa A; Kouakou, Joseph S; Odafe, Solomon; Onotu, Dennis; Dalhatu, Ibrahim; Debem, Henry H; Nguyen, Duc B; Yen, Le Ngoc; Abdul-Quader, Abu S; Pelletier, Valerie; Williams, Seymour G; Behel, Stephanie; Bicego, George; Swaminathan, Mahesh; Dokubo, E Kainne; Adjorlolo-Johnson, Georgette; Marlink, Richard; Lowrance, David; Spira, Thomas; Colebunders, Robert; Bangsberg, David; Zee, Aaron; Kaplan, Jonathan; Ellerbrock, Tedd V
Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.
Scarsi, Kimberly K; Eisen, Geoffrey; Darin, Kristin M; Meloni, Seema T; Rawizza, Holly E; Tchetgen Tchetgen, Eric J; Agbaji, Oche O; Onwujekwe, Daniel I; Gashau, Wadzani; Nkado, Reuben; Okonkwo, Prosper; Murphy, Robert L; Kanki, Phyllis J
Despite sparse efficacy data, tenofovir-emtricitabine or tenofovir-lamivudine plus nevirapine is used in many resource-constrained settings. This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir-emtricitabine or lamivudine (tenofovir group) or zidovudine-lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03-1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40-.63) and increasing age (HR, 0.98; 95% CI, .97-.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. Compared with zidovudine-lamivudine, the use of tenofovir-lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.
Scarsi, Kimberly K.; Eisen, Geoffrey; Darin, Kristin M.; Meloni, Seema T.; Rawizza, Holly E.; Tchetgen Tchetgen, Eric J.; Agbaji, Oche O.; Onwujekwe, Daniel I.; Gashau, Wadzani; Nkado, Reuben; Okonkwo, Prosper; Murphy, Robert L.; Kanki, Phyllis J.
Background. Despite sparse efficacy data, tenofovir–emtricitabine or tenofovir–lamivudine plus nevirapine is used in many resource-constrained settings. Methods. This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir–emtricitabine or lamivudine (tenofovir group) or zidovudine–lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. Results. A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21–1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03–1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40–.63) and increasing age (HR, 0.98; 95% CI, .97–.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. Conclusions. Compared with zidovudine–lamivudine, the use of tenofovir–lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection. PMID:26561532
Nachega, Jean B.; Hislop, Michael; Nguyen, Hoang; Dowdy, David W.; Chaisson, Richard E.; Regensberg, Leon; Cotton, Mark; Maartens, Gary
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
Koethe, John R.; Jenkins, Cathy A.; Petucci, Christopher; Culver, Jeffrey; Shepherd, Bryan E.; Sterling, Timothy R.
Abstract In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART. We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50 copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism. HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P < 0.05 for both) compared with men but had similar CD4+ count (median 701 cells/μL), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3 kg/m2). However, women had higher insulin sensitivity compared with men (P < 0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P < 0.01 for all), and lower C3 and C5 acylcarnitines (P < 0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite
Koethe, John R; Jenkins, Cathy A; Petucci, Christopher; Culver, Jeffrey; Shepherd, Bryan E; Sterling, Timothy R
In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50 copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P < 0.05 for both) compared with men but had similar CD4+ count (median 701 cells/μL), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3 kg/m). However, women had higher insulin sensitivity compared with men (P < 0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P < 0.01 for all), and lower C3 and C5 acylcarnitines (P < 0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite levels did not
Taylor, Barbara S; Shalev, Noga; Wilkin, Timothy J
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.
The XVI International AIDS Conference (AIDS 2006), organized by the International AIDS Society (IAS), took place August 12-18 in Toronto, Canada. It was attended by over 26,000 participants from more than 170 countries and featured more than 4,500 abstracts as well as an array of community and cultural activities. The theme of the meeting was "Time to deliver", emphasizing the continued need and urgency in bringing effective HIV prevention and treatment strategies to those living with and affected by HIV/AIDS. The meeting's agenda was broad and included policy and programmatic topics as well as scientific research. This report focuses on reports presented at the conference that directly deal with antiretroviral therapy. This is primarily because of the nature of the venue where it is intended to be published (Drug News & Perspectives) as well as the expertise of the author. It is not a lack of recognition of the other equally important topics and discussions that took place at AIDS 2006. The author is solely responsible for the selection of topics and presentations to be included in this report.
Dragovic, Gordana; Smith, Colette J; Jevtovic, Djordje; Dimitrijevic, Bozana; Kusic, Jovana; Youle, Mike; Johnson, Margaret A
The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p < 0.0001). The most frequently prescribed antiretrovirals were zidovudine with lamivudine (149; 25 %) and efavirenz [329, 55 %] at HCB and emtricitabine with tenofovir (899; 51 %) and efavirenz [681, 39 %] at RFH. At HCB, a median of 2 CD4 count measurements in the first year of cART were taken, compared to 5 at RFH (p < 0.0001). Median (IQR) CD4 cell increase after 12 months was +211 (+86, +359) and +212 (+105, +318) respectively. 287 (48 %) individuals from HCB and 1452 (82 %) from RFH had an available viral load measurement, of which 271 (94 %) and 1280 (88 %) were <400 copies/mL (p < 0.0001). After 36 months, comparable percentages had made at least one antiretroviral switch (77 % HCB vs. 78 % RFH; p = 0.23). However, switches for toxicity/patient choice were more common at RFH. After 12 and 36 months of cART 3 % and 8 % of individuals died at HCB, versus 2 % and 4 % at RFH (p < 0.0001). In middle
Bisson, Gregory P; Gross, Robert; Bellamy, Scarlett; Chittams, Jesse; Hislop, Michael; Regensberg, Leon; Frank, Ian; Maartens, Gary; Nachega, Jean B
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
Morris, Jennifer L.; Kraus, Donna M.
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
Lesho, Emil P; Gey, Daniela C
Antiretroviral regimens are complicated and difficult for patients to follow, and they can have serious side effects, such as osteonecrosis and bone demineralization. Protease inhibitor therapy has been associated with hyperlipidemia, hyperglycemia, gastrointestinal symptoms, and body-fat distribution abnormalities. Nonnucleoside reverse transcriptase inhibitors can cause rashes and hepatotoxicity, and nucleoside reverse transcriptase inhibitors can cause lactic acidosis, hypersensitivity reactions, neuropathies, pancreatitis, anemia, and neutropenia. Malabsorption can occur if antiretroviral agents are taken improperly with regard to meals or if they are taken with certain other drugs or herbal remedies. Some commonly prescribed drugs can cause dangerous drug toxicities if they are taken by patients who are also taking certain antiretroviral medications. Suboptimal exposure to antiretrovirals because of noncompliance or malabsorption can result in viral resistance and loss of future treatment options.
Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo
For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.
Silva, Ana Cristina Araújo Lemos; Rodrigues, Blenda Sousa Carli; Micheletti, Adilha Misson Rua; Tostes, Sebastião; Meneses, Antonio Carlos Oliveira; Silva-Vergara, Mário Leon; Adad, Sheila Jorge
A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.
Silva, Ana Cristina Araújo Lemos; Rodrigues, Blenda Sousa Carli; Micheletti, Adilha Misson Rua; Tostes, Sebastião; Meneses, Antonio Carlos Oliveira; Silva-Vergara, Mário Leon; Adad, Sheila Jorge
A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989–2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies. PMID:22461978
Background Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Methods Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. Results In adjusted analyses, ART-naïve (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. Conclusions In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman’s health. PMID:24593018
Huntington, Susie; Thorne, Claire; Anderson, Jane; Newell, Marie-Louise; Taylor, Graham P; Pillay, Deenan; Hill, Teresa; Tookey, Pat; Sabin, Caroline
Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. In adjusted analyses, ART-naïve (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman's health.
Background Few studies have compared the impact of different antiretroviral regimens on residual immune activation and inflammation with discordant results. Aim of the study was to investigate the impact of various antiretroviral regimens on markers of immune activation and inflammation during the first two years of effective therapy. Methods We studied HIV-infected antiretroviral-naïve patients who began cART with either abacavir/lamivudine or tenofovir/emtricitabine, combined with ritonavir-boosted lopinavir (LPV/r), atazanavir (ATV/r) or efavirenz (EFV). All the patients had a virological response within 6 months, which was maintained for 2 years with no change in their ART regimen. C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), monokine induced by interferon-γ (MIG) and interferon-γ-inducible protein-10 (IP-10) were measured in stored plasma obtained at cART initiation and 24 months later. Mean changes from baseline were analyzed on loge-transformed values and multivariable linear regression models were used to study the effect of the treatment components, after adjusting for factors that might have influenced the choice of ART regimen or biomarker levels. Differences were expressed as the mean fold change percentage difference (Δ). Results Seventy-eight patients (91% males) with a median age of 43 years met the inclusion criteria. Their median baseline CD4 cell count was 315/mm3 and HIV-1 RNA level 4.6 log10 copies/ml. During the 2-years study period, IL-6, IP-10 and MIG levels fell significantly, while hs-CRP and sCD14 levels remained stable. IP-10 and MIG levels declined significantly less strongly with ATV/r than with EFV (IP-10Δ -57%, p = 0.011; MIGΔ -136%, p = 0.007), while no difference was noted between LPV/r and EFV. The decline in IL-6 did not differ significantly across the different treatment components. Conclusions After the first 2 years of successful cART, IL-6, IP-10 and MIG fell markedly while hs
Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J
The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa.
Kanters, Steve; Vitoria, Marco; Doherty, Meg; Socias, Maria Eugenia; Ford, Nathan; Forrest, Jamie I; Popoff, Evan; Bansback, Nick; Nsanzimana, Sabin; Thorlund, Kristian; Mills, Edward J
New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART regimens for HIV in ART-naive patients. For this systematic review and network meta-analysis, we searched for randomised clinical trials published up to July 5, 2015, comparing recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. We extracted data on trial and patient characteristics, and the following primary outcomes: viral suppression, mortality, AIDS defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events. We synthesised data using network meta-analyses in a Bayesian framework and included older treatments, such as indinavir, to serve as connecting nodes. We defined network nodes in terms of specific antivirals rather than specific ART regimens. We categorised backbone regimens and adjusted for them through group-specific meta-regression. We used the GRADE framework to interpret the strength of inference. We identified 5865 citations through database searches and other sources, of which, 126 articles related to 71 unique trials were included in the network analysis, including 34 032 patients randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the odds ratio (OR) for viral suppression was 1·87 (95% credible interval [CrI] 1·34-2·64) with dolutegravir and 1·40 (1·02-1·96) with raltegravir; with respect to viral suppression, low-dose efavirenz was similar to all other treatments. Both low-dose efavirenz and integrase strand transfer inhibitors tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz. The most protective effect relative to efavirenz in network meta-analyses was that of dolutegravir (OR 0·26, 95% CrI 0·14-0·47), followed by low-dose efavirenz (0·39
Sanjeeva, G N; Sukanya, V; Pavithra, H B; Dodderi, S K; Rewari, B B; Govindaraj, M; Shivananda, S; Premalatha, R
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.
Laws, M Barton; Wilson, Ira B; Bowser, Diana M; Kerr, Sarah E
OBJECTIVE To describe how people with HIV understand and experience the problem of adhering to antiretroviral medication regimens. DESIGN We performed a qualitative study based on interviews with HIV-infected patients, including 46 clients of AIDS service organizations, who were sampled according to age, ethnicity, and injection drug use history, and a convenience sample of 15 patients. Interviews were conducted in English or Spanish and were audiotaped and transcribed. PARTICIPANTS Of 52 respondents who had prescriptions for antiretroviral therapy, 25 were randomly selected for in-depth analysis. Of these, 5 reported having an AIDS diagnosis, 15 reported symptoms they attributed to HIV, and 5 reported having no symptoms of HIV disease. MEASUREMENTS AND MAIN RESULTS Investigators prepared structured abstracts of interviews to extract adherence-related data. One investigator compared the abstracts with the original transcripts to confirm the interpretations, and used the abstracts to organize and classify the findings. Most subjects (84%) reported recent nonadherent behavior, including ceasing treatment, medication “holidays,” sleeping through doses, forgetting doses, skipping doses due to side effects, and following highly asymmetric schedules. Initially, most reported that they were not significantly nonadherent, and many did not consider their behavior nonadherent. Only a minority clearly understood the possible consequences of missing doses. Most said they had not discussed their nonadherence with their physicians. CONCLUSIONS Many people rationalize their difficulty in adhering to HIV treatment by deciding that the standard of adherence they can readily achieve is appropriate. Physicians should inquire about adherence-related behavior in specific detail, and ensure that patients understand the consequences of not meeting an appropriate standard. PMID:11119181
Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K.
Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID:26831415
ALCZUK, Silvia de Souza Dantas; BONFIM-MENDONÇA, Patrícia de Souza; ROCHA-BRISCHILIARI, Sheila Cristina; SHINOBU-MESQUITA, Cristiane Suemi; MARTINS, Helen Priscilla Rodrigues; GIMENES, Fabrícia; de ABREU, André Luelsdorf Pimenta; CARVALHO, Maria Dalva de Barros; PELLOSO, Sandra Marisa; SVIDZINSKI, Terezinha Inez Estivalet; CONSOLARO, Marcia Edilaine Lopes
Vulvovaginal candidiasis (VVC) in HIV-infected women contributed to the impairment of their quality of life. The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) use on the vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women. This cross-sectional study included 178 HIV-infected (HIV group) and 200 HIV-uninfected women (control) that were studied at the Specialized Assistance Service (SAE) for sexually transmitted diseases (STD)/AIDS of the city of Maringá, Brazil, from April 1 to October 30, 2011. The yeasts were isolated and identified by phenotypic and molecular methods. The in vitro antifungal susceptibility to fluconazole, itraconazole, nystatin and amphotericin B was tested by the reference microdilution method. Higher frequencies of total vaginal Candida spp. isolation were found in the HIV-infected group than in the control group. However, both groups showed a similar frequency of colonization and VVC. Although C. albicans was the most frequent and sensitive to azolics and polyenes in both HIV-infected and uninfected women, the emerging resistance of C. glabrata to amphotericin B in the HIV-infected women was observed. Although higher frequency of vaginal Candida spp. isolation had been observed in the HIV-infected than in HIV-uninfected women, colonization and VVC showed similar frequency in both groups, indicating that HAART appears to protect against vaginal colonization and VVC. PMID:25923898
Piacenti, Frank J
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
Rachlis, A R; Zarowny, D P
OBJECTIVE: To develop guidelines for health care providers and their HIV-positive patients on the clinical use of antiretroviral agents for HIV infection. OPTIONS: Recommendations published in 1996 by an international panel. OUTCOMES: Improvement in clinical outcomes or in surrogate markers of disease activity. EVIDENCE AND VALUES: The Canadian HIV Trials Network held a workshop on Oct. 19-20, 1996, to develop Canadian guidelines that incorporate information from recent basic and clinical research. RECOMMENDATIONS: Recommendations for the use of antiretroviral drugs in HIV infection are provided for initial therapy, continuing therapy, primary infection, vertical transmission, pediatric therapy and postexposure prophylaxis. VALIDATION: The guidelines are based on consensus of the participants attending the workshop: Canadian investigators, clinicians and invited representatives from the community, government and the pharmaceutical industry. They are subject to review and updating as new information on clinical benefits is published. SPONSORS: The workshop was organized by the National Centre of the Canadian HIV Trials Network. Unrestricted educational grants were provided by 8 pharmaceutical companies. Additional support was provided from the National AIDS Strategy of Health Canada. PMID:9627563
Chung, Michael H.; McKenzie, Kevin P.; De Vuyst, Hugo; Richardson, Barbra A.; Rana, Farzana; Pamnani, Ritesh; Njoroge, Julia W.; Nyongesa-Malava, Evans; Sakr, Samah R.; John-Stewart, Grace C.; Mugo, Nelly R.
Background A rigorous comparison of cervical cancer screening methods utilizing data on immune status, antiretroviral therapy (ART) and colposcopy-directed biopsy has not been performed among HIV-positive women. Methods Between June and November 2009, 500 HIV-positive women were enrolled at an HIV treatment clinic in Nairobi, Kenya, and underwent Papanicolau (Pap) smear, visual inspection with acetic acid (VIA), human papillomavirus (HPV) and colposcopy-directed biopsy (gold standard). Positive Pap smear (ASCUS+, LSIL+, HSIL+), VIA, HPV and their combinations were compared with CIN2/3+. Sensitivity, specificity and AUC (sensitivity and 1–specificity) were compared using pairwise tests and multivariate logistic regression models that included age, CD4+ cell count and ART duration. Results Of 500 enrolled, 498 samples were collected. On histology, there were 172 (35%) normal, 186 (37%) CIN1, 66 (13%) CIN2, 47 (9%) CIN3 and 27 (5%) indeterminate. Pap (ASCUS+) was the most sensitive screening method (92.7%), combination of both Pap (HSIL+) and VIA positive was the most specific (99.1%) and Pap (HSIL+) had the highest AUC (0.85). In multivariate analyses, CD4+ cell count of 350 cells/μl or less was associated with decreased HPV specificity (P = 0.002); ART duration of less than 2 years was associated with decreased HPV (P = 0.01) and VIA (P = 0.03) specificity; and age less than 40 years was associated with increased VIA sensitivity (P < 0.001) and decreased HPV specificity (P = 0.005). Conclusion Pap smear is a robust test among HIV-positive women regardless of immune status or ART duration. Results should be cautiously interpreted when using HPV among those younger, immunosuppressed or on ART less than 2 years, and when using VIA among those aged 40 years or more. PMID:23842133
Chung, Michael H; McKenzie, Kevin P; De Vuyst, Hugo; Richardson, Barbra A; Rana, Farzana; Pamnani, Ritesh; Njoroge, Julia W; Nyongesa-Malava, Evans; Sakr, Samah R; John-Stewart, Grace C; Mugo, Nelly R
A rigorous comparison of cervical cancer screening methods utilizing data on immune status, antiretroviral therapy (ART) and colposcopy-directed biopsy has not been performed among HIV-positive women. Between June and November 2009, 500 HIV-positive women were enrolled at an HIV treatment clinic in Nairobi, Kenya, and underwent Papanicolau (Pap) smear, visual inspection with acetic acid (VIA), human papillomavirus (HPV) and colposcopy-directed biopsy (gold standard). Positive Pap smear (ASCUS+, LSIL+, HSIL+), VIA, HPV and their combinations were compared with CIN2/3+. Sensitivity, specificity and AUC (sensitivity and 1-specificity) were compared using pairwise tests and multivariate logistic regression models that included age, CD4⁺ cell count and ART duration. Of 500 enrolled, 498 samples were collected. On histology, there were 172 (35%) normal, 186 (37%) CIN1, 66 (13%) CIN2, 47 (9%) CIN3 and 27 (5%) indeterminate. Pap (ASCUS+) was the most sensitive screening method (92.7%), combination of both Pap (HSIL+) and VIA positive was the most specific (99.1%) and Pap (HSIL+) had the highest AUC (0.85). In multivariate analyses, CD4⁺ cell count of 350 cells/μl or less was associated with decreased HPV specificity (P = 0.002); ART duration of less than 2 years was associated with decreased HPV (P = 0.01) and VIA (P = 0.03) specificity; and age less than 40 years was associated with increased VIA sensitivity (P < 0.001) and decreased HPV specificity (P = 0.005). Pap smear is a robust test among HIV-positive women regardless of immune status or ART duration. Results should be cautiously interpreted when using HPV among those younger, immunosuppressed or on ART less than 2 years, and when using VIA among those aged 40 years or more.
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
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.
Abdool Karim, Salim S; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M; Friedland, Gerald; Abdool Karim, Quarraisha
We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved. We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here. At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006). Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS
Jones, Joyce; Taylor, Barbara S; Tieu, Hong-Van; Wilkin, Timothy J
The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind. Innovative strategies to improve outcomes include 2-way text messaging, home-based HIV testing, peer navigation, and New York City's realignment of services into comprehensive sexual health programs. A high prevalence of resistance was documented in low- and middle-income settings and policy considerations were modeled to address increasing resistance rates. Novel resistance mutations to integrase strand transfer inhibitors and nucleoside analogue reserve transcriptase inhibitors were identified, but the clinical implications are unclear and require further investigation. Several studies provided insights on dosing and safety of antiretroviral therapy to prevent mother-to-child transmission through pharmacokinetic analysis. A special session devoted to Zika virus included a study of its effects on the central nervous system and a promising animal study of a Zika vaccine.
Money, Deborah M; Wagner, Emily C; Maan, Evelyn J; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E; Forbes, John C; Burdge, David R; Albert, Arianne Y K; Lohn, Zoe; Côté, Hélène C F
Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30-40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety
Money, Deborah M.; Wagner, Emily C.; Maan, Evelyn J.; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E.; Forbes, John C.; Burdge, David R.; Albert, Arianne Y. K.; Lohn, Zoe; Côté, Hélène C. F.
Introduction Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. Methods This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30–40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Results Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). Conclusions In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is
Hainaut, M; Verscheure, V; Ducarme, M; Schandené, L; Levy, J; Mascart, F
The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
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
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
Chan, C K; Wong, K H; Leung, C C; Tam, C M; Chan, K C W; Pang, K W; Chan, W K; Mak, I K Y
To evaluate the optimal timing for initiating antiretroviral therapy in patients with human immunodeficiency virus (HIV)-associated tuberculosis in Hong Kong. Historical cohort. SETTING. Tuberculosis and Chest Service and Special Preventive Programme, Public Health Service Branch, Centre for Health Protection, Department of Health, Hong Kong. Consecutive patients with HIV-associated tuberculosis in a territory-wide TB-HIV registry encountered from 1996 to 2009. Of the 260 antiretroviral therapy-naïve patients with HIV-associated tuberculosis, 32 (12%) had antiretroviral therapy initiated within 2 months after starting anti-tuberculosis treatment (early antiretroviral therapy). Early antiretroviral therapy was associated with a more favourable outcome (cure or treatment completion without relapse) at 24 months (91% vs 67%; P=0.007) than those with antiretroviral therapy started later or not initiated, and remained an independent predictor of a favourable outcome after adjustment for potential confounders. Adverse effects from anti-tuberculosis drugs tended to occur more frequently in patients with early antiretroviral therapy (13/32 or 41%) compared with the remainder (59/228 or 26%; P=0.08). A significantly higher proportion of patients in the former group experienced immune reconstitution inflammatory syndrome than in the latter group (7/32 or 22% vs 9/228 or 4%; P<0.001). There was no death attributable to immune reconstitution inflammatory syndrome. Early initiation of antiretroviral therapy is associated with more favourable tuberculosis treatment outcomes in patients with HIV-associated tuberculosis with a low CD4 count (<200/µL). Drug co-toxicity and immune reconstitution inflammatory syndrome that may be increased by earlier initiation of antiretroviral therapy does not undermine tuberculosis treatment outcomes to a significant extent.
Ahmed, A A; Latoundji, S
A cross-sectional survey was conducted among 112 HIV positive patients who had received antiretroviral therapy for >3 months to assess the efficacy of treatment (viral load <400 copies/mL). The median age at enrolment was 36 years, 90% of patients were at the AIDS stage and median CD4 rate was 118/mm3. Patients received a combined treatment of 2 NRTI +1 NNRTI (51%), 3 NRTI (45%) and 2 NRTI+1 PI (4%). Virological efficacy was seen in 74% of the patients, irrespective of the prescribed protocol and the initial clinical and immunological profile. Mean improvements measured were 20% on the Karnofsky index (KI), 2.1 kg/m2 in body mass index and 82 cells/mm in CD4. The prevalence of side effects was 84%. The predictors for treatment success were quality of care and KI > 70%.
Nabi, Rafiq; Moldoveanu, Zina; Wei, Qing; Golub, Elizabeth T; Durkin, Helen G; Greenblatt, Ruth M; Herold, Betsy C; Nowicki, Marek J; Kassaye, Seble; Cho, Michael W; Pinter, Abraham; Landay, Alan L; Mestecky, Jiri; Kozlowski, Pamela A
Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1), a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of HIV-specific Ig
Nabi, Rafiq; Moldoveanu, Zina; Wei, Qing; Golub, Elizabeth T.; Durkin, Helen G.; Greenblatt, Ruth M.; Herold, Betsy C.; Nowicki, Marek J.; Kassaye, Seble; Cho, Michael W.; Pinter, Abraham; Landay, Alan L.; Mestecky, Jiri
Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1), a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of HIV-specific Ig
Kanters, Steve; Socias, Maria Eugenia; Paton, Nicholas I; Vitoria, Marco; Doherty, Meg; Ayers, Dieter; Popoff, Evan; Chan, Keith; Cooper, David A; Wiens, Matthew O; Calmy, Alexandra; Ford, Nathan; Nsanzimana, Sabin; Mills, Edward J
Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed. In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3-4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models. We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88-1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did
Johnston, Stephen S; Juday, Timothy; Esker, Stephen; Espindle, Derek; Chu, Bong-Chul; Hebden, Tony; Uy, Jonathan
This is the first study to compare the incidence and health care costs of medically attended adverse effects in atazanavir- and darunavir-based antiretroviral therapy (ART) among U.S. Medicaid patients receiving routine HIV care. This was a retrospective study using Medicaid administrative health care claims from 15 states. Subjects were HIV patients aged 18 to 64 years initiating atazanavir- or darunavir-based ART from January 1, 2003, to July 1, 2010, with continuous enrollment for 6 months before (baseline) and 6 months after (evaluation period) ART initiation and 1 or more evaluation period medical claim. Outcomes were incidence and health care costs of the following medically attended (International Classification of Diseases, Ninth Revision, Clinical Modification-coded or treated) adverse effects during the evaluation period: gastrointestinal, lipid abnormalities, diabetes/hyperglycemia, rash, and jaundice. All-cause health care costs were also determined. Patients treated with atazanavir and darunavir were propensity score matched (ratio = 3:1) by using demographic and clinical covariates. Multivariable models adjusted for covariates lacking postmatch statistical balance. Propensity-matched study sample included 1848 atazanavir- and 616 darunavir-treated patients (mean age 41 years, 50% women, 69% black). Multivariable-adjusted hazard ratios (HRs) (for darunavir, reference = atazanavir) and per-patient-per-month health care cost differences (darunavir minus atazanavir) were as follows: gastrointestinal, HR = 1.25 (P = 0.04), $43 (P = 0.13); lipid abnormalities, HR = 1.38 (P = 0.07), $3 (P = 0.88); diabetes/hyperglycemia, HR = 0.84 (P = 0.55), $13 (P = 0.69); and rash, HR = 1.11 (P = 0.23), $0 (P = 0.76); all-cause health care costs were $1086 (P<0.001). Too few instances of jaundice (11 in atazanavir and 1 in darunavir) occurred to support multivariable modeling. Medication tolerability can be critical to the success or failure of ART. Compared with
PATEL, Rena C.; ONONO, Maricianah; GANDHI, Monica; BLAT, Cinthia; HAGEY, Jill; SHADE, Starley B.; VITTINGHOFF, Eric; BUKUSI, Elizabeth A.; NEWMANN, Sara J.; COHEN, Craig R.
SUMMARY Background Given recent concerns of efavirenz reducing the efficacy of contraceptive implants, we sought to determine if pregnancy rates differ among HIV-positive women using various contraceptive methods and efavirenz- or nevirapine-based antiretroviral therapy (ART) regimens. Methods We conducted a retrospective cohort analysis of HIV-positive women aged 15–45 years enrolled in HIV care facilities in western Kenya from January 2011 to December 2013. Pregnancy was diagnosed clinically and the primary exposure was a combination of contraceptive method and ART regimen. We used Poisson models, adjusting for repeated measures, as well as demographic, behavioral and clinical factors, to compare pregnancy rates among women on different contraceptive/ART combinations. Findings 24,560 women contributed 37,635 years of follow-up with 3,337 incident pregnancies. Among women using implants, adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 1·1 (95% CI 0·72–1·5) and 3·3 (95% CI 1·8–4·8) per 100 women-years (w-y), respectively (adjusted incidence rate ratio (aIRR) 3·0, 95% CI 1·3–4·6). Among women using depomedroxyprogesterone acetate (DMPA), adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 4·5 (95% CI 3·7–5·2) and 5·4 (95% CI 4·0–6·8) per 100 w-y, respectively (aIRR 1·2, 95% CI 0·91–1·5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, experienced 3·1–4·1 higher rates of pregnancy than women using implants, with 1·6–2·8 higher rates specifically among women using efavirenz-based ART. Interpretation While HIV-positive women using implants on efavirenz-based ART faced three times higher risk of contraceptive failure than those on nevirapine-based ART, these women still experienced lower contraceptive failure rates than women on all other contraceptive methods, except for intrauterine devices and permanent methods
Koenig, Serena P; Riviere, Cynthia; Leger, Paul; Severe, Patrice; Atwood, Sidney; Fitzgerald, Daniel W; Pape, Jean W; Schackman, Bruce R
We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART) to patients with AIDS in Haiti. We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.
Borges, Álvaro H
To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer risk. The relationship between cART exposure and cancer risk is complex and nuanced. It is an intriguing fact that, whether initiated during severe immunosuppression or not, cART reduces risk of Kaposi sarcoma and NHL. Further research should identify mediators of the benefit of immediate cART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.
Jevtović, Dj; Ranin, J; Salemović, D; Brmbolić, B; Zerjav, S
The unique nature of the replication cycle of the retroviruses, including HIV, offera number of possible targets for chemotherapeutic agents. These are RNA viruses which have the capacity to make DNA copies through their characteristic enzyme, reverse transcriptase, encoded in the pole region of the viral genoma. Reverse transcription is an attractive target for therapeutic intervention as this event is uniquelly associated with retroviruses. Dideoxynucleoside analogues can compete with endogenous nucleosides that are the natural substrate for reverse transcriptase or may be incorporated intro the growing chain of proviral DNA and terminate elongation. Reverse transcriptase inhibition is the principal mechanism of action of zidovudine (AZT) and related nucleosides, dideoxyinosine (ddl) and dideoxycitidine (ddC), which all attach to reverse transcriptase to the same site. This review will discuss current approaches to the antiretroviral therapy in AIDS patients. Several well controlled clinical trials have established both the efficacy and toxicity of AZT in patients with AIDS and severe ARC and it was shown that this drug decreased the incidence and severity of opportunistic infections, with the highly significant reduction in early mortality. The efficacy of newer reverse transcriptase-inhibiting nucleoside derivatives will be discussed too, as well as the issue of combination therapies.
Cornell, Morna; McIntyre, James; Myer, Landon
Most antiretroviral therapy (ART)-related policies remain blind to men's treatment needs. Global and national programmes need to address this blindness urgently, to ensure equitable access to ART in Africa.
Richter, Donna L; Sowell, Richard L; Pluto, Delores M
To examine attitudes and beliefs of African American women of childbearing age, living with HIV, about pregnancy and antiretroviral therapy. Focus groups were conducted using an exploratory design with a convenience sample of HIV-infected women in 2 southeastern cities. Thirty-three African American women of childbearing age participated in 5 focus groups. Attitudes and beliefs about antiretroviral therapy were related to the women's willingness to comply with treatment. The challenge for health care providers is to counter women's willingness to "play the odds" of having a noninfected baby without taking antiretrovirals.
Lodi, Sara; Phillips, Andrew; Logan, Roger; Olson, Ashley; Costagliola, Dominique; Abgrall, Sophie; van Sighem, Ard; Reiss, Peter; Miró, José M; Ferrer, Elena; Justice, Amy; Gandhi, Neel; Bucher, Heiner C; Furrer, Hansjakob; Moreno, Santiago; Monge, Susana; Touloumi, Giota; Pantazis, Nikos; Sterne, Jonathan; Young, Jessica G; Meyer, Laurence; Seng, Rémonie; Dabis, Francois; Vandehende, Marie-Anne; Pérez-Hoyos, Santiago; Jarrín, Inma; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A
Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL. We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have
French, Martyn A; Price, Patricia; Stone, Shelley F
Suppression of HIV replication by highly active antiretroviral therapy (HAART) often restores protective pathogen-specific immune responses, but in some patients the restored immune response is immunopathological and causes disease [immune restoration disease (IRD)]. Infections by mycobacteria, cryptococci, herpesviruses, hepatitis B and C virus, and JC virus are the most common pathogens associated with infectious IRD. Sarcoid IRD and autoimmune IRD occur less commonly. Infectious IRD presenting during the first 3 months of therapy appears to reflect an immune response against an active (often quiescent) infection by opportunistic pathogens whereas late IRD may result from an immune response against the antigens of non-viable pathogens. Data on the immunopathogenesis of IRD is limited but it suggests that immunopathogenic mechanisms are determined by the pathogen. For example, mycobacterial IRD is associated with delayed-type hypersensitivity responses to mycobacterial antigens whereas there is evidence of a CD8 T-cell response in herpesvirus IRD. Furthermore, the association of different cytokine gene polymorphisms with mycobacterial or herpesvirus IRD provides evidence of different pathogenic mechanisms as well as indicating a genetic susceptibility to IRD. Differentiation of IRD from an opportunistic infection is important because IRD indicates a successful, albeit undesirable, effect of HAART. It is also important to differentiate IRD from drug toxicity to avoid unnecessary cessation of HAART. The management of IRD often requires the use of anti-microbial and/or anti-inflammatory therapy. Investigation of strategies to prevent IRD is a priority, particularly in developing countries, and requires the development of risk assessment methods and diagnostic criteria.
Midde, Narasimha M.; Patters, Benjamin J.; Rao, PSS; Cory, Theodore J.; Kumar, Santosh
Introduction Highly Active Antiretroviral Therapy (HAART) has tremendously improved the life expectancy of the HIV-infected population over the past three decades. Protease inhibitors have been one of the major classes of drugs in HAART regimens that are effective in treating HIV. However, the emergence of resistance and cross-resistance against protease inhibitors encourages researchers to develop new PIs with broad-spectrum activity, as well as novel means of enhancing the efficacy of existing PIs. Areas covered In this article we discuss recent advances in HIV protease inhibitor (PI) development, focusing on both investigational and experimental agents. We also include a section on pharmacokinetic booster drugs for improved bioavailability of protease inhibitors. Further, we discuss novel drug delivery systems using a variety of nanocarriers for the delivery of PIs across the blood-brain barrier to treat the HIV in the brain. Expert opinion We discuss our opinion on the promises and challenges on the development of novel investigational and experimental PIs that are less toxic and more effective in combating drug-resistance. Further, we discuss the future of novel nanocarriers that have been developed to deliver PIs to the brain cells. Although these are promising findings, many challenges need to be overcome prior to making them a viable option. PMID:27415449
Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W
CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.
Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M
Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142
Sevelius, Jae M; Carrico, Adam; Johnson, Mallory O
Despite disproportionate rates of HIV among transgender women and evidence that medication adherence is necessary for treatment success and increased likelihood of survival, there has been little investigation into antiretroviral therapy (ART) adherence issues among transgender women. This study examined rates of self-reported ART adherence among transgender women on ART (n = 35) and well-established correlates of nonadherence, including depression, adherence self-efficacy, patient perceptions of interactions with their providers, and perceived adverse side effects of ART compared to other respondents (n = 2,770). Transgender women on ART were less likely to report 90% adherence rates or higher and reported less confidence in their abilities to integrate treatment regimens into their daily lives. When transgender women were compared to other respondents, regardless of the current medication regimen, they reported significantly fewer positive interactions with their health care providers. Training for providers and integration of hormone therapy into HIV care is recommended.
Martinez-Picado, Javier; Deeks, Steven G.
Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619
Leroy, Valeriane; Malateste, Karen; Rabie, Helena; Lumbiganon, Pagakrong; Ayaya, Samuel; Dicko, Fatoumata; Davies, Mary-Ann; Kariminia, Azar; Wools-Kaloustian, Kara; Aka, Edmond; Phiri, Samuel; Aurpibul, Linda; Yiannoutsos, Constantin; Signaté-Sy, Haby; Mofenson, Lynne; Dabis, François
Background We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods HIV-infected children (positive PCR <18 months or positive serology ≥18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). Findings Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. Conclusion Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level. PMID:23187940
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
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
Myung, Patricia; Pugatch, David; Brady, Mark F.; Many, Phok; Harwell, Joseph I.; Lurie, Mark; Tucker, John
Antiretroviral medications are becoming available for HIV-infected children in resource-limited settings. Maryknoll, an international Catholic charity, provided directly observed antiretroviral therapy to HIV-infected children in Phnom Penh, Cambodia. Child care workers administered generic antiretroviral drugs twice daily to children, ensuring adherence. Treatment began with 117 late-stage HIV-infected children; 22 died of AIDS during the first 6 months. The rest were treated for at least 6 months and showed CD4 count increases comparable to those achieved in US and European children. Staffing cost for this program was approximately US $5 per child per month, or 15% more than the price of the medications. Drug toxicities were uncommon and easily managed. Directly observed antiretroviral therapy appears to be a promising, low-cost strategy for ensuring adherent treatment for HIV-infected children in a resource-limited setting. PMID:17463375
de Oliveira, Regina Célia; de Andrade Moraes, Danielle Chianca; Santos, Cleytiane Stephany Silva; da Silva Monteiro, Gicely Regina Sobral; da Rocha Cabral, Juliana; Beltrão, Roberta Andrade; da Silva, Calos Roberto Lyra
Objective To identify the elite of authors about the subject adherence to antiretroviral therapy; to identify the journals turned to publishing articles about adherence to antiretroviral therapy; and to identify and analyze the most commonly used words in abstracts of articles about adherence to antiretroviral therapy. Method A bibliometric study conducted through the Scopus base. We used articles published between 1996 and 2014, after application of the eligibility criteria, there were composed the sample with 24 articles. The data were analyzed descriptively. Were used the laws of bibliometric (Lotka, Bradford and Zipf) and the conceptual cloud map of words, through the program Cmap tools. Results Lotka’s Law identified the 5 authors more productive (46% of the total published). Bradford is impaired in this study. Concerning Zipf, 3 zones were determined, 31.47% of the words with in the first zone, 26.46% in the second and 42.06% in the third. In the conceptual map, the words/factors that positively and negatively influence adherence were emphasized, among them the need for more research in the health services. Conclusion There are few publications about the accession to antiretroviral therapy, and the scientific production is in the process of maturation. One can infer that the theme researched is not yet an obsolete topic. It should be noted that the Bibliometric was a relevant statistic tool to generate information about the publications about the antiretroviral therapy. PMID:28979571
Wyatt, Christina M; Kitch, Douglas; Gupta, Samir K; Tierney, Camlin; Daar, Eric S; Sax, Paul E; Ha, Belinda; Melbourne, Kathleen; McComsey, Grace A
Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria. Methods We examined changes in urine protein:creatinine (UPCR) and albumin:creatinine (UACR) ratios in 245 ART-naïve participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n=124 or TDF/emtricitabine, TDF/FTC, n=121) with open-label protease inhibitor (PI) atazanavir/ritonavir (ATV/r) or non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). Results At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥ 200 mg/g) and 11% had clinically significant albuminuria (UACR ≥ 30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold-change in UPCR (p=0.011) and UACR (p=0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold-change in UPCR (p=0.23) or UACR (p=0.88), and no significant interactions between NRTI and NNRTI/PI components. Conclusion In this pre-specified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings. PMID:25117929
Nakaharai, Kazuhiko; Miyajima, Makiko; Kobayashi, Hiroaki; Shimizu, Akihiro; Hosaka, Yumiko; Horino, Tetsuya; Hori, Seiji
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.
Chao, Linda L.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Rothlind, Johannes C.; Flenniken, Derek L.; Lindgren, Joselyn A.; Weiner, Michael W.
The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance. PMID:14600507
Gardner, Edward M.; Maravi, Moises E.; Rietmeijer, Cornelis; Davidson, Arthur J.; Burman, William J.
Background The association between antiretroviral adherence, healthcare utilization and medical costs has not been well studied. Objective To examine the relationship of adherence to antiretroviral medications to healthcare utilization and healthcare costs. Methods A retrospective cohort study was conducted using data from 325 previously antiretroviral medication-naive HIV-infected individuals initiating first antiretroviral therapy from 1997 through 2003. The setting was an inner-city safety net hospital and HIV clinic in the US. Adherence was assessed using pharmacy refill data. The average wholesale price was used for prescription costs. Healthcare utilization data and medical costs were obtained from the hospital billing database, and differences according to quartile of adherence were compared using analysis of variance (ANOVA). Multivariate logistic regression was used to assess predictors of higher annual medical costs. Sensitivity analyses were used to examine alternative antiretroviral pricing schemes. The perspective was that of the healthcare provider, and costs were in year 2005 values. Results In 325 patients followed for a mean (± SD) 3.2 (1.9) years, better adherence was associated with lower healthcare utilization but higher total medical costs. Annual non-antiretroviral medical costs were $US7612 in the highest adherence quartile versus $US10 190 in the lowest adherence quartile. However, antiretroviral costs were significantly higher in the highest adherence quartile ($US17 513 vs $US8690), and therefore the total annual medical costs were also significantly higher in the highest versus lowest adherence quartile ($US25 125 vs $US18 880). In multivariate analysis, for every 10% increase in adherence, the odds of having annual medical costs in the highest versus lowest quartile increased by 87% (odds ratio 1.87; 95% CI 1.45, 2.40). In sensitivity analyses, very low antiretroviral prices (as seen in resource-limited settings) inverted this
Gardner, Edward M; Maravi, Moises E; Rietmeijer, Cornelis; Davidson, Arthur J; Burman, William J
The association between antiretroviral adherence, healthcare utilization and medical costs has not been well studied. To examine the relationship of adherence to antiretroviral medications to healthcare utilization and healthcare costs. A retrospective cohort study was conducted using data from 325 previously antiretroviral medication-naive HIV-infected individuals initiating first antiretroviral therapy from 1997 through 2003. The setting was an inner-city safety net hospital and HIV clinic in the US. Adherence was assessed using pharmacy refill data. The average wholesale price was used for prescription costs. Healthcare utilization data and medical costs were obtained from the hospital billing database, and differences according to quartile of adherence were compared using analysis of variance (ANOVA). Multivariate logistic regression was used to assess predictors of higher annual medical costs. Sensitivity analyses were used to examine alternative antiretroviral pricing schemes. The perspective was that of the healthcare provider, and costs were in year 2005 values. In 325 patients followed for a mean (+/- SD) 3.2 (1.9) years, better adherence was associated with lower healthcare utilization but higher total medical costs. Annual non-antiretroviral medical costs were $US 7,612 in the highest adherence quartile versus $US 10,190 in the lowest adherence quartile. However, antiretroviral costs were significantly higher in the highest adherence quartile ($US 17,513 vs $US 8,690), and therefore the total annual medical costs were also significantly higher in the highest versus lowest adherence quartile ($US 25,125 vs $US 18,880). In multivariate analysis, for every 10% increase in adherence, the odds of having annual medical costs in the highest versus lowest quartile increased by 87% (odds ratio 1.87; 95% CI 1.45, 2.40). In sensitivity analyses, very low antiretroviral prices (as seen in resource-limited settings) inverted this relationship - excellent adherence
Osime, Odaburhine E; Ese-Onakewhor, Joseph U; Kolade, Samson O
To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). The mean ± standard error of mean (SEM) of PFC was 4.02±0.13 g/l and ELT from the test subjects was 378±15 mins was significantly higher (p<0.05) compared with the control subjects (PFC 3.46±0.12 g/l and ELT 267±9.0 mins). The PCV or hematocrit values in the test subject was 29.1±0.38%, which was significantly lower (p<0.05) compared with the control subject (31.3±0.43%). The PV in the test subject was 1.76±0.02 mPa/s, while the control subjects was higher (1.73±0.02 mPa/s). This increase was not statistically significant (p>0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia.
dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello
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
Hegazi, A; Bailey, R L; Ahadzie, B; Alabi, A; Peterson, K
We examined the relationship of patients' literacy and education to antiretroviral therapy (ART) adherence in an urban treatment centre in The Gambia. Information on education and literacy systematically collected before ART initiation was compared against selected adherence outcomes. Formally educated patients were significantly more likely to achieve virological suppression at both six and 12 months (87% vs. 67%, OR=3.13, P=0.03; 88% vs. 63%, OR=4.49, P=0.007, respectively). Literate patients had similar benefit at 12 months (OR=3.39 P=0.03), with improved virological outcomes associated with degree of literacy (P=0.003). A trend towards similar results was seen at 6 months for Koranically educated patients; however, this was no longer apparent at 12 months. No significant correlation was seen between socio-demographic characteristics and missed appointments. Our study suggests that literacy, formal education and possibly Koranic education may impact favourably on adherence to ART.
Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.
Baillargeon, Jacques; Giordano, Thomas P; Rich, Josiah D; Wu, Z Helen; Wells, Katherine; Pollock, Brad H; Paar, David P
Interruption of antiretroviral therapy (ART) during the first weeks after release from prison may increase risk for adverse clinical outcomes, transmission of human immunodeficiency virus (HIV), and drug-resistant HIV reservoirs in the community. The extent to which HIV-infected inmates experience ART interruption following release from prison is unknown. To determine the proportion of inmates who filled an ART prescription within 60 days after release from prison and to examine predictors of this outcome. Retrospective cohort study of all 2115 HIV-infected inmates released from the Texas Department of Criminal Justice prison system between January 2004 and December 2007 and who were receiving ART before release. Proportion of inmates who filled an ART prescription within 10, 30, and 60 days of release from prison. Among the entire study cohort (N = 2115), an initial prescription for ART was filled by 115 (5.4%) inmates within 10 days of release (95% confidence interval [CI], 4.5%-6.5%), by 375 (17.7%) within 30 days (95% CI, 16.2%-19.4%), and by 634 (30.0%) within 60 days (95% CI, 28.1%-32.0%). In a multivariate analysis of predictors (including sex, age, race/ethnicity, viral load, duration of ART, year of discharge, duration of incarceration, parole, and AIDS Drug Assistance Program application assistance), Hispanic and African American inmates were less likely to fill a prescription within 10 days (adjusted estimated risk ratio [RR], 0.4 [95% CI, 0.2-0.8] and 0.4 [95% CI, 0.3-0.7], respectively) and 30 days (adjusted estimated RR, 0.7 [95% CI, 0.5-0.9] and 0.7 [95% CI, 0.5-0.9]). Inmates with an undetectable viral load were more likely to fill a prescription within 10 days (adjusted estimated RR, 1.8 [95% CI, 1.2-2.7]), 30 days (1.5 [95% CI, 1.2-1.8]), and 60 days (1.3 [95% CI, 1.1-1.5]). Inmates released on parole were more likely to fill a prescription within 30 days (adjusted estimated RR, 1.3 [95% CI, 1.1-1.6]) and 60 days (1.5 [95% CI, 1.4-1.7]). Inmates
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.
Gross, Robert; Bellamy, Scarlett L; Chapman, Jennifer; Han, Xiaoyan; O'Duor, Jacqueline; Palmer, Steven C; Houts, Peter S; Coyne, James C; Strom, Brian L
Adherence to antiretroviral therapy is critical to successful treatment of human immunodeficiency virus (HIV). Few interventions have been demonstrated to improve both adherence and virologic outcomes. We sought to determine whether an intervention derived from problem solving theory, Managed Problem Solving (MAPS), would improve antiretroviral outcomes. We conducted a randomized investigator blind trial of MAPS compared with usual care in HIV-1 infected individuals at 3 HIV clinics in Philadelphia, Pennsylvania. Eligible patients had plasma HIV-1 viral loads greater than 1000 copies/mL and were initiating or changing therapy. Managed Problem Solving consists of 4 in-person and 12 telephone-based meetings with a trained interventionist, then monthly follow-up calls for a year. Primary outcome was medication adherence measured using electronic monitors, summarized as fraction of doses taken quarterly over 1 year. Secondary outcome was undetectable HIV viral load over 1 year. We assessed 218 for eligibility, with 190 eligible and 180 enrolled, 91 randomized to MAPS and 89 to usual care. Fifty-six participants were lost to follow-up: 33 in the MAPS group and 23 in usual care group. In primary intention-to-treat analyses, the odds of being in a higher adherence category was 1.78 (95% CI,1.07-2.96) times greater for MAPS than usual care. In secondary analyses, the odds of an undetectable viral load was 1.48 (95% CI, 0.94-2.31) times greater for MAPS than usual care. In as-treated analyses, the effect of MAPS was stronger for both outcomes. There was neither a difference by prior treatment status nor change in effect over time. Managed Problem Solving is an effective antiretroviral adherence intervention over the first year with a new regimen. It was equally effective at improving adherence in treatment experienced and naïve patients and did not lose effect over time. Implementation of MAPS should be strongly considered where resources are available. clinicaltrials
Ramos-Sanchez, Eduardo Milton; Goto, Hiro; Rivero, Dolores Helena Rodriguez Ferreira; Mauad, Thais; de Souza, Fernando Nogueira; Monteiro, Andrea Moreira; Gidlund, Magnus
Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs. PMID:25075786
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
Ford, Nathan; Wilson, David; Costa Chaves, Gabriela; Lotrowska, Michel; Kijtiwatchakul, Kannikar
ANTIRETROVIRAL ROLLOUT IN BRAZIL AND THAILAND: Brazil and Thailand are among few developing countries to achieve universal access to antiretroviral therapy. Three factors were critical to this success: legislation for free access to treatment; public sector capacity to manufacture medicines; and strong civil society action to support government initiatives to improve access. LOCAL PRODUCTION OF AFFORDABLE, NON-PATENTED DRUGS: Many older antiretroviral drugs are not patented in either country and affordable generic versions are manufactured by local pharmaceutical institutes. Developing countries were not required to grant patents on medicines until 2005, but under US government threats of trade sanctions, Thailand and Brazil began doing so at least ten years prior to this date. Brazil has used price negotiations with multi-national pharmaceutical companies to lower the price of newer patented antiretrovirals. However, the prices obtained by this approach remain unaffordable. Thailand recently employed compulsory licensing for two antiretrovirals, obtaining substantial price reductions, both for generic and brand products. Following Thailand's example, Brazil has issued its first compulsory license. Middle-income countries are unable to pay the high prices of multinational pharmaceutical companies. By relying on negotiations with companies, Brazil pays up to four times more for some drugs compared with prices available internationally. Compulsory licensing has brought treatment with newer antiretrovirals within reach in Thailand, but has resulted in pressure from industry and the US government. An informed and engaged civil society is essential to support governments in putting health before trade.
Leporrier, Jérémie; Delbos, Valérie; Unal, Guillemette; Honoré, Patricia; Etienne, Manuel; Bouchaud, Olivier; Caron, François
Background. Despite antiretroviral therapy, it is generally believed that the risk for pneumococcal infections (PnIs) is high among patients infected with human immunodeficiency virus (HIV). However, most studies in this field have been conducted before 2010, and the proportion of virologically suppressed patients has drastically increased in these latter years thanks to larger indications and more effective antiretroviral regimens. This study aimed to re-evaluate the current risk of PnI among adult patients infected with HIV. Methods. The incidence of PnI was evaluated between 1996 and 2014 in 2 French regional hospitals. The 80 most recent cases of PnI (2000–2014) were retrospectively compared with 160 controls (HIV patients without PnI) to analyze the residual risk factors of PnI. Results. Among a mean annual follow-up cohort of 1616 patients, 116 PnIs were observed over 18 years. The risk factors of PnI among patients infected with HIV were an uncontrolled HIV infection or “classic” risk factors of PnI shared by the general population such as addiction, renal or respiratory insufficiency, or hepatitis B or C coinfection. Pneumococcal vaccination coverage was low and poorly targeted, because only 5% of the cases had been previously vaccinated. The incidence of invasive PnIs among HIV patients with a nonvirologically suppressed infection or comorbidities was 12 times higher than that reported in the general population at the country level (107 vs 9/100000 patients), whereas the incidence among virologically suppressed HIV patients without comorbidities was lower (7.6/100000 patients). Conclusions. Human immunodeficiency virus infection no longer per se seems to be a significant risk factor for PnI, suggesting a step-down from a systematic to an “at-risk patient” targeted pneumococcal vaccination strategy. PMID:28018929
Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta
Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a research area with great growth potential which may be useful to guide the rational use of antiretrovirals.
Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta
Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982
Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.
Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681
Mandas, Antonella; Iorio, Eugenio Luigi; Congiu, Maria Gabriella; Balestrieri, Cinzia; Mereu, Antonello; Cau, Daniela; Dessì, Sandra; Curreli, Nicoletta
It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART) is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated), and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence) have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence). Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants). Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress. PMID:19884983
Patrikar, Seema; Shankar, Subramanian; Kotwal, Atul; Basannar, D R; Bhatti, Vijay; Verma, Rajesh; Mukherji, Sandip
As HIV steps into the third decade, there are more number of patients living on lifelong (antiretroviral therapy) ART and facing the threat of drug resistance with subsequent treatment failure. The aim of this study was to determine predictors of first-line ART failure with the objectives to estimate the burden of 2nd line ART. A retrospective 5-year cohort of HIV patients who were initiated on first line ART in 2008-09 was studied. Patients were followed from the time of ART initiation. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate probabilities and predictors of first line ART failure. Of the total of 195 patients initiated on first line ART, 15 patients were switched to second line ART yielding 7.69% failure rate. During the 7178 person-years of follow-up, the incidence of first line ART failure was 2.09 per 1000 person-years. The Kaplan-Meier survival analysis gave a mean survival time of 55.6 months. BMI, CD4 count at ART initiation and presence of opportunistic infections were significant predictors of first line ART failure. The burden of second line ART patients by the end of 5 years of first line ART is expected to be 151 patients. Though the first line ART failure is quite low in this study, we still need to be vigilant for lower BMI, low baseline CD4 count and occurrence of opportunistic infections to efficiently manage failures on first line ART.
Ostrop, N J; Hallett, K A; Gill, M J
To measure patient adherence to antiretroviral therapy over a two-year period and to identify factors impacting adherence. In a regional HIV treatment center, 100 consecutive patients starting any new antiretroviral agent were enrolled in this study, which consisted of a one-year retrospective data review and a one-year prospective component. The tools used for evaluating adherence were the monthly prescription refill data and a patient questionnaire. Data analyzed included overall adherence, adherence to individual antiretrovirals, and change in adherence over time, as well as factors reported as influencing adherence. Greater than 80% adherence in taking prescribed doses was seen in 75% of patients during the retrospective phase of the study; adherence increased to 84% in the prospective phase. Throughout the prospective phase of the study, monthly median adherence rates were 98-100%. Suboptimal adherence secondary to pill fatigue or number of daily pills did not occur. Reported nonadherence to dietary restrictions varied among drugs. The primary cause given for poor adherence was difficulty remembering followed by inconvenient dosing schedule and difficulty scheduling administration times around meals. At least one adherence tool was used by 61% of patients. A diagnosis of AIDS was associated with lower adherence in our patient population (p = 0.039); substance abuse and psychiatric history had no influence. Adherence to antiretroviral treatment regimens did not diminish over the two years studied. Several patients with poor adherence were identified, emphasizing the importance of addressing this issue both prior to and throughout treatment. A personalized approach by healthcare providers can optimize patient adherence to antiretroviral therapy by providing careful drug selection in addition to routine follow-up and the provision of information, feedback, and reminder systems.
Fasinu, Pius S; Gurley, Bill J; Walker, Larry A
For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy).
Sedaghat, Ahmad R; Wilke, Claus O
More and more antiretroviral therapies are being developed for treatment of HIV infection. The in-vivo efficacy of these drugs is commonly predicted based on in-vitro measures of antiviral effect. One primary in-vitro measure is the IC50, the amount of drug required for 50% inhibition of viral replication. We have previously shown that HIV life-cycle kinetics impact clinically observed HIV viral dynamics. Here we present a mathematical model of how they affect the pharmacodynamics of antiretroviral drugs. We find that experimentally measured antiretroviral IC50s are determined by three factors: (i) intrinsic drug properties (e.g. drug-target binding), (ii) kinetics of the HIV life cycle, and (iii) kinetics of drug-inhibited infected cells. Our model predicts that the IC50 is a declining function of the duration of the drug-susceptible stage in the host cell. We combine our model with known viral life-cycle kinetics to derive a measure of intrinsic properties, reflecting drug action, for known antiretroviral drugs from previously measured IC50s. We show that this measure of intrinsic drug property correlates very well with in vitro-measured antiviral activity, whereas experimentally measured IC50 does not. Our results have implications for understanding pharmacodynamics of and improving activity of antiretroviral drugs. Our findings predict that drug activity can be improved through co-administration of synergistic drugs that delay the viral life cycle but are not inhibitory by themselves. Moreover, our results may easily extend to treatment of other pathogens.
Bobkova, M R
The lecture is devoted to the analysis of the state-of-the-art of the impact of genetic diversity of human immunodeficiency (HIV) viruses on the pattern of infection and the efficiency of antiretroviral therapy (ART). It provides brief information on the origin and evolution of HIV and on the current classification of their genetic variants. The molecular epidemiological situation of HIV infection in Russia and nearby states and the major molecular HIV variants that are dominant in these countries, as well as their origin and prevalence trends are characterized. How the diversity of HIV can affect the efficiency of diagnosis, the transmission of the virus, and the pattern of HIV pathogenesis are briefly reviewed. The comparative data available in the world's scientific literature on these topics are given. More detailed attention is given to the possible causes of varying therapeutic effects against different HIV subtypes, as well as to the specific features of the formation and phenotyping manifestation of ART drug resistance mutations. There is evidence for the necessity of forming a unified follow-up system for treated HIV-infected patients during ART scaling, including in an effort to evaluate the impact of the specific features of the HIV genome on the efficiency of treatment regimens used in Russia.
Barrueco, N; Castillo, I; Ais, A; Martínez, C; Sanjurjo, M
To present a pharmaceutical care program for pediatric patients receiving antiretroviral therapy. In order to establish the pharmaceutical care procedure, papers published up to 2004 on the pharmaceutical care provided to patients receiving antiretroviral therapy were reviewed through a search in Medline and the journal Farmacia Hospitalaria. In addition, bibliographic references that can be systematically used to analyze the pharmacotherapy of each patient have been selected. The pharmaceutical care procedure is divided in three stages (data collection, analysis of the pharmacotherapeutic profile and resolution of the drug-related problems identified) that take place through a semi-structured type of interview. In order to systematize the role of the pharmacist, a table with information on antiretroviral drugs used in Pediatrics was created, as well as an information three-page leaflet and a data collection form. The program includes the goals of the pharmaceutical care process as defined in the recommendations of GESIDA-SEFH-National AIDS Plan 2004 and systematizes the proposed intervention strategies, in an attempt to provide the patient and the caregiver with the information required for an optimum management, in the most comprehensive way and tailored to their individual characteristics.
Hobbs, Charlotte V.; Gabriel, Erin E.; Kamthunzi, Portia; Tegha, Gerald; Tauzie, Jean; Petzold, Elizabeth; Barlow-Mosha, Linda; Chi, Benjamin H.; Li, Yonghua; Ilmet, Tiina; Kirmse, Brian; Neal, Jillian; Parikh, Sunil; Deygoo, Nagamah; Jean Philippe, Patrick; Mofenson, Lynne; Prescott, William; Chen, Jingyang; Musoke, Philippa; Palumbo, Paul; Duffy, Patrick E.; Borkowsky, William
Background HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed. Methods Thirty-one children from Malawi aged 4–62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor. Results We found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment and LPV-rtv based ART were used concurrently and when accounting for a LPV-rtv and antimalarial treatment interaction (adjusted HR 0.39; 95% CI (0.17,0.89); p = 0.03). Conclusions LPV-rtv in combination with malaria treatment was associated with lower risk of recurrent positive BS, but not CCM, in HIV-infected children. Larger, randomized studies are needed to confirm these findings which may permit ART optimization for malaria-endemic settings. Trial Registration ClinicalTrials.gov NCT00719602 PMID:27936233
Schackman, Bruce R.; Goldie, Sue J.; Weinstein, Milton C.; Losina, Elena; Zhang, Hong; Freedberg, Kenneth A.
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
Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio
The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral
Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G
Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.
Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.
LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438
Mulubwa, Chama; Mweemba, Oliver; Katayamoyo, Patrick; Halwindi, Hikabasa
About 30% of the patients initiated on antiretroviral therapy in Zambia default treatment. Some of these patients later restart treatment; however, the characteristics of these patients have not been well described and documented. The aim of this study was to describe and document the socio-demographic and clinical characteristics of patients who default and restart antiretroviral therapy, and to determine the socio-demographic characteristics associated with CD4 count response at 6 and 24 months of restarting antiretroviral therapy. A longitudinal retrospective analysis was performed on data from 535 adult patients restarting antiretroviral therapy in 2009 and 2010 at five antiretroviral therapy centres in Copperbelt and Central provinces of Zambia. To determine the association between the socio-demographic characteristics and CD4 cell count, quantile regression models were used. Older age above 45 years was associated with a significantly lower CD4 cell response by 38.1 cells/mm(3) (95% Confidence interval [CI]: -109.4 to -0.2) compared to the younger age (15-29 years). Patients in formal employment (Adjusted Coefficient [AC] 29.5, 95% CI: 22.8 to 81.1) and self-employment (AC 48.1, 95% CI: 18.6 to 77.4) gained significantly higher CD4 cells than those unemployed. In addition, baseline CD4 count, type of treatment, WHO staging, total duration on treatment and duration lost to follow-up were found to be strong predictors of CD4 cell count at 6 and 24 months after restarting antiretroviral therapy treatment. Age and occupation were the only socio-demographic characteristics predicting CD4 count in the patients at 6 months after restarting antiretroviral therapy after adjusting for other confounding clinical variables.
Integrating Cervical Cancer Screening with HIV Care in Cameroon: Comparative Risk Analysis of Cervical Disease in HIV-Infected Women Receiving Antiretroviral Therapy to Women in the General Population
Bekolo, Cavin Epie; O’Bryan, Gillian; Tchago, François Edmond; Nangue, Charlette; Bekoule, Patrick Sylvestre; Kollo, Basile
Background While the effect of highly active antiretroviral therapy (HAART) on natural history of cervical lesions remains controversial, resource limited countries need to understand the relevance of their own data to their settings. We compared the risk of cervical disease in HAART-experienced women with that in women in the general population of Cameroon. Methods A retrospective cross sectional survey of women aged 35 years and above, attending a voluntary screening campaign for cervical cancer at the Nkongsamba Regional Hospital in Cameroon between February and May 2014. Squamous intraepithelial lesions (SIL) were determined by Pap smear. Multiple logistic regression was used to compare the odds of SIL in women on HAART to women from the community with unknown HIV status. Results Included were 302 women of whom 131(43.4%) were HIV-infected and receiving HAART on the site while 171 (56.6%) were women from the community. Cervical disease was observed in 51(16.9%) persons of whom 15 (11.5%) cases in the HAART group and 36 (21.1%) cases in the general group (p = 0.027). After controlling for age and other covariates, women in the HAART group had a 67% reduction in the odds of cervical lesions compared with the community group [adjusted odd ratio (aOR) = 0.33, 95%CI: 0.15–0.73, p = 0.006). Conclusion HIV-infected women receiving HAART have a lower risk of cancer than women in the general population. This finding may not be attributed to HAART alone but to all the health benefits derived from receiving a comprehensive HIV care. PMID:26866371
Floyd, Sian; Marston, Milly; Baisley, Kathy; Wringe, Alison; Herbst, Kobus; Chihana, Menard; Kasamba, Ivan; Bärnighausen, Till; Urassa, Mark; French, Neil; Todd, Jim; Zaba, Basia
Objective To provide a broad and up-to-date picture of the effect of antiretroviral therapy (ART) provision on population-level mortality in Southern and East Africa. Methods Data on all-cause, AIDS and non-AIDS mortality among 15–59 year olds were analysed from demographic surveillance sites (DSS) in Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and the Africa Centre (South Africa), using Poisson regression. Trends over time from up to 5 years prior to ART roll-out, to 4–6 years afterwards, are presented, overall and by age and sex. For Masaka and Kisesa, trends are analysed separately for HIV-negative and HIV-positive individuals. For Karonga and the Africa Centre, trends in AIDS and non-AIDS mortality are analysed using verbal autopsy data. Results For all-cause mortality, overall rate ratios (RRs) comparing the period 2–6 years following ART roll-out with the pre-ART period were 0.58 (5.9 vs. 10.2 deaths per 1000 person-years) in Karonga, 0.79 (7.2 vs. 9.1 deaths per 1000 person-years) in Kisesa, 0.61 (6.7 compared with 11.0 deaths per 1000 person-years) in Masaka and 0.79 (14.8 compared with 18.6 deaths per 1000 person-years) in the Africa Centre DSS. The mortality decline was seen only in HIV-positive individuals/AIDS mortality, with no decline in HIV-negative individuals/non-AIDS mortality. Less difference was seen in Kisesa where ART uptake was lower. Conclusions Falls in all-cause mortality are consistent with ART uptake. The largest falls occurred where ART provision has been decentralised or available locally, suggesting that this is important. PMID:22943383
Paydary, Koosha; Khaghani, Parisa; Emamzadeh-Fard, Sahra; Alinaghi, Seyed Ahmad Seyed; Baesi, Kazem
After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint. PMID:23835806
Garrett, Nigel; Norman, Emily; Leask, Kerry; Naicker, Nivashnee; Asari, Villeshni; Majola, Nelisile; Karim, Quarraisha Abdool; Karim, Salim S Abdool
WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272-1095) by 2015 (p < 0.001). Median viral load at ART initiation decreased over this period from 5.2 (IQR 4.6-5.6) to 4.1 (IQR 3.4-4.6) log copies/ml (p = 0.004). Virological suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.
Collazos, Julio; Asensi, Víctor; Cartón, José Antonio
The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.
French, Clare E.; Thorne, Claire; Tariq, Shema; Cortina-Borja, Mario; Tookey, Pat A.
During their second pregnancy with diagnosed HIV (n = 1177), two-fifths of women in the UK/Ireland not on antiretroviral therapy (ART) at conception had an immunological indication for treatment (CD4+ <350 cells/μl), of whom nearly half had CD4+ at least 350 cells/μl in their previous pregnancy. Those initiating ART during pregnancy had a 4.3-fold increased odds of detectable viral load at delivery compared with those conceiving on treatment, suggesting that continuation of ART after pregnancy may be beneficial for many women. PMID:24685820
Takuva, Simbarashe; Evans, Denise; Zuma, Khangelani; Okello, Velephi; Louwagie, Goedele
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.
Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia
SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.
Risa, Kathleen J; Nepon, Lisa; Justis, Janice C; Panwalker, Anand; Berman, Stephen M; Cinti, Sandro; Wagener, Marilyn M; Singh, Nina
The extent of use of alternative therapies, psychosocial and disease-specific variables predictive of alternative therapy use, and factors motivating the use of alternative therapies in HIV-infected patients receiving highly active antiretroviral therapy (HAART) have not been well defined. Types of alternative therapies used, demographic and medical data, coping (Billing and Moos inventory of coping with illness styles), social support (Irwing and Sarason questionnaire), sense of personal control (Pearlin's Mastery scale), quality of life (Medical Outcome Study scale), health beliefs, and adherence rate were prospectively assessed in 118 HIV-infected patients receiving HAART. Of 38% (45/118) of the patients who used alternative therapies, 56% (25/45) began using alternative therapies since the initiation of HAART. While Caucasian patients were more likely to use alternative therapies than all other patients (P = 0.015), new users of alternative therapies were more likely to be African-American (P = 0.022). Alternative therapy users reported less satisfaction with their emotional support (P = 0.027), and had greater psychological distress (P = 0.048), but were more likely to utilize problem-focused coping (P = 0.015). Patients who used alternative therapies were less likely to believe that HAART was beneficial (P = 0.06). Physicians were unaware of patients' alternative therapy use in 40% (18/45) of all patients who used alternative therapies, in 67% of herbal therapy users, and in 100% of dietary supplement users. Adherence to antiretroviral therapy, CD4 count, and HIV-RNA level were neither predictive nor affected by alternative therapy use. Despite scepticism about the benefits of HAART, resort to alternative therapies did not undermine adherence with antiretroviral therapy. Although able actively to cope with their illness, users of alternative therapies had greater psychological distress and were less satisfied with their emotional support. Interventions aimed
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
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
Collins, Sean E; Grant, Philip M; Shafer, Robert W
HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression.
Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda; Neuhaus, Jacquie; El-Sadr, Wafaa; Tracy, Russell; Kuller, Lewis; Shlipak, Michael; Angus, Brian; Klinker, Harting; Ross, Michael
Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.
Mocroft, A; Wyatt, C; Szczech, L; Neuhaus, J; El-Sadr, W; Tracy, R; Kuller, L; Shlipak, M; Angus, B; Klinker, H; Ross, M
Background Cystatin C has been proposed as an alternative marker of renal function. We sought to determine if participants randomized to episodic use of antiretroviral therapy guided by CD4+ count (drug conservation; DC) had altered cystatin C levels compared to those randomised to continuous antiretroviral therapy (viral suppression; VS) in the Strategies for Management of Antiretroviral Therapy Trial, and to identify factors associated with increased cystatin C. Methods Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the DC and VS groups respectively. Logistic regression was used to model the odds of ≥ 0.15 mg/dl increase in cystatin C (1 standard deviation [SD]) in the first month after randomisation, adjusting for demographic and clinical characteristics. Results At randomisation, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the DC and VS arms respectively (p=0.29). In the first month after randomisation, 21.8% and 10.6% had ≥0.15 mg/dl increase in cystatin C in the DC and VS arm respectively (p=0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomisation. After adjustment, participants in the VS arm had significantly reduced odds of ≥0.15 mg/dl increase in cystatin C in the first month (OR 0.42; 95% CI 0.23–0.74, p=0.0023). Conclusions These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function. PMID:19050388
Moreno, Santiago; López Aldeguer, Jose; Arribas, José Ramón; Domingo, Pere; Iribarren, Jose Antonio; Ribera, Esteban; Rivero, Antonio; Pulido, Federico
The introduction of combination antiretroviral therapy (cART) has substantially modified the natural history of HIV infection. At the beginning of the cART era the objective was focused on HIV-1-associated mortality and morbidity, but as this objective was accomplished other issues emerged, including toxicity, resistance and compliance with treatment. Moreover, the participation of other disease mechanisms, such as proinflammatory activity, in the so-called non-AIDS events is becoming increasingly important. To overcome these issues, therapeutic options have dramatically expanded, which has made the management of HIV-1-infected patients increasingly complex. The intense changes seen raise the question of what will be the future of HIV infection and its treatment. A projection into the future may help to reflect on current limitations, needs and research priorities, to optimize patient care. To debate on this topic a group of 38 experts has initiated The HIV 2020 Project, with the aim of reflecting on the future of HIV infection and identifying the needs that should be the attention of research in different areas. This document summarizes the group's conclusions on the future of antiretroviral treatment, presented as 20 relevant questions. Each question includes the current status of the topic and our vision for the future.
Idoko, J A; Agbaji, O; Agaba, P; Akolo, C; Inuwa, B; Hassan, Zuweira; Akintunde, L; Badung, B; Muazu, M; Danang, M; Imade, G; Sankale, J Louis; Kanki, Phyllis
This study examines the use of various direct observation therapy-HAART treatment support modalities in Jos, Nigeria. A 12-month observational study enrolling 175 antiretroviral naïve patients into four arms of direct observation therapy-HAART (highly active antiretroviral therapy); daily observed therapy (DOT), twice weekly observed therapy (TWOT), weekly observed therapy (WOT) and self-administered therapy (SAT), examined community treatment support using family and community members. Treatment outcomes were much better in the treatment-supported groups compared with the control self-therapy group. CD4 cell increases were 218/microL (DOT), 267/microL (TWOT), 205/microL (WOT) versus 224/microL (SAT), whereas plasma HIV-1 RNA reached undetectable levels (<400 copies/mL) in 91%, 88%, 84% versus 79% of patients in the DOT, TWOT, WOT versus SAT groups, respectively, at 48 weeks. We, therefore, strongly support the use of treatment support in our settings.
Ezechi, L O; Musa, Z A; Otobo, V O; Idigbe, I E; Ezechi, O C
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.
Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.
Tiruneh, Yordanos M.; Wilson, Ira B.
This study assessed adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Ethiopia and explored the sociocultural context in which they relate to their regimen requirements. Data were collected through semi-structured in-depth interviews with 105 patients on ART and observations held at the study clinic. We analyzed data using both qualitative and quantitative methods. Our findings indicate that study participants are highly adherent to dose but less adherent to dose schedule. Strict dose time instructions were reported as stressful and unrealistic. The discrepancy between adherence to dose and dose schedule could be explained by time perception, difficulty with the strictness of medication regimens, or beliefs about dose timing adherence. Care providers should acknowledge the complexities of medication practices and engage in shared decision-making to incorporate patients’ perspectives and identify effective interventions. PMID:26873491
Chetty, Verusia; Maharaj, Sonil S
After antiretroviral therapy (ART) became available in South Africa, persons living with HIV (PLWH) began to survive, but they often experienced disability as a result of their illness and treatments. Management of HIV is more often successful with a holistic approach including medicine, rehabilitation, and social care. There is limited literature on collaborations between nurses and allied health professionals in the rehabilitation of PLWH, with no documentation of partnerships between nurses and physiotherapists in high-HIV burdened countries. We investigated the collaboration between nurses and physiotherapists in the rehabilitation of PLWH. We conducted two focus groups with experienced nurses at two residential facilities for PLWH in KwaZulu-Natal, South Africa, using Van Manen's pedagogy on interpretive phenomenology as the conceptual framework. Three barriers to collaboration were found: role governance, environmental structure, and organizational variance. Education and in-service programs and workshops were suggested to curb the divide.
KANTOR, RAMI; ZIJENAH, LYNN S.; SHAFER, ROBERT W.; MUTETWA, SOLOMON; JOHNSTON, ELIZABETH; LLOYD, ROBERT; VON LIEVEN, ANDREA; ISRAELSKI, DENNIS; KATZENSTEIN, DAVID A.
HIV-1 drug resistance mutations have been identified and characterized mostly in subtype B HIV-1 infection. The extent to which antiretroviral drugs select for drug resistance mutations in non-subtype B HIV-1 is not known. We obtained HIV-1 reverse transcriptase (RT) and protease sequences from 21 Zimbabwean patients failing antiretroviral drug therapy. We compared these sequences with 56 published RT and protease subtype C sequences from untreated patients, 990 RT and 1140 protease subtype B sequences from treated patients, and 340 RT and 907 protease subtype B sequences from untreated patients and identified four mutation categories of subtype C HIV-1. Seventeen of the 21 patients (81%) had known drug resistance mutations. Mutations at 15 RT and 11 protease positions were more common in subtype C isolates than in subtype B isolates. HIV-1 subtype C-infected individuals receiving antiretroviral therapy develop many of the known subtype B drug resistance mutations. Comparison of subtype C RT and protease sequences with a large database of subtype B sequences identified subtype C-specific polymorphisms and candidate drug resistance mutations. PMID:12512512
May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC
The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235
Cesar, Carina; Shepherd, Bryan E; Jenkins, Cathy A; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C; Cahn, Pedro
Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001). Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.
May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D'Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan A C
The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70,000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).
Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro
Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931
Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.
Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ≤ 1.3 × 109/l), anemia (hemoglobin ≤ 10 g/dl), and thrombocytopenia (platelets ≤ 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784
Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B
Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. The frequencies of neutropenia (absolute neutrophil count ≤1.3×10⁹/l), anemia (hemoglobin ≤10g/dl), and thrombocytopenia (platelets ≤125×10⁹/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Parikh, Sunil; Fehintola, Fatai; Huang, Liusheng; Olson, Alexander; Adedeji, Waheed A; Darin, Kristin M; Morse, Gene D; Murphy, Robert L; Taiwo, Babafemi O; Akinyinka, Olusegun O; Adewole, Isaac F; Aweeka, Francesca T; Scarsi, Kimberly K
Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.
Summary Background Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. Methods The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude death rates were also calculated. Findings 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude death rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than men. Patients with presumed transmission via injecting drug use had lower life expectancies than those from other transmission groups (32·6 [1·1] years vs 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 counts than in those with higher baseline counts
Behrens, G M; Meyer, D; Stoll, M; Schmidt, R E
Effective antiretroviral therapy leads to rapid decrease in plasma HIV-1 RNA, frequently followed by an increase in CD4 T-helper cell counts. The improvement of immune function during highly active antiretroviral therapy has important impact on natural history of AIDS-related opportunistic disorders. Here we describe cases of unusual clinical inflammatory syndromes in CMV retinitis, hepatitis C, and atypical mycobacteriosis in HIV-1 infected patients associated with the initiation of antiretroviral therapy. Pathogenetic implications and therapeutic management of these new immunopathologic syndromes are discussed.
Thompson, George R.; Patel, Payal K.; Kirkpatrick, William R.; Westbrook, Steven D.; Berg, Deborah; Erlandsen, Josh; Redding, Spencer W.; Patterson, Thomas F.
Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida spp. may also cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of oropharyngeal candidiasis but few studies have evaluated the current impact of ART on the epidemiology of oropharyngeal candidiasis and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied and symptomatic infection occurred in a third. In addition, resistant yeasts were still common occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, oropharyngeal candidasis remains a significant infection in advanced AIDS even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in oropharyngeal candidiasis are important in managing patients with this infection and are the focus of this review. PMID:20156694
Githinji, Leah Nyawira; Gray, Diane M; Hlengwa, Sipho; Myer, Landon; Zar, Heather J
Lung disease is a common cause of mortality and morbidity in HIV-infected adolescents, but there is limited information on the spectrum of lung function impairment in adolescents on antiretroviral therapy. To investigate lung function in HIV-infected adolescents on antiretroviral therapy in the Cape Town Adolescent Antiretroviral Cohort (Cape Town, South Africa). A total of 515 South African adolescents, aged 9-14 years, stable on antiretroviral therapy for at least 6 months, underwent baseline lung function testing. Measures included spirometry, nitrogen multiple-breath washout, forced oscillation technique, 6-minute walk test, single-breath carbon monoxide diffusion testing, and bronchodilator response testing. A comparator group of 110 age- and ethnicity-matched HIV-uninfected adolescents was also tested. For the HIV-infected adolescents (mean [SD] age 12 [1.6] years, 52% male), the median (interquartile range) duration of antiretroviral therapy was 7.6 (4.6-9.2) years. The median (interquartile range) nadir CD4 was 510.5 (274-903) cells/mm(3). HIV-infected adolescents had significantly lower FEV1, FVC, FEV1/FVC, diffusing capacity of carbon monoxide, respiratory system compliance, and functional residual capacity than HIV-uninfected adolescents (P < 0.05 for all associations). HIV-infected adolescents had higher airway resistance and lung clearance index than HIV-uninfected adolescents (P < 0.05 for all associations). Although generally small in magnitude, these differences remained significant after adjusting for age, sex, and height. In addition, age, sex, height, and history of past lower respiratory tract infection or pulmonary tuberculosis were associated with reduced lung function. Perinatally infected South African HIV-infected adolescents on antiretroviral therapy have lower lung function than uninfected adolescents. Prior lower respiratory tract infection or pulmonary tuberculosis is associated with lower lung function.
Dash, Prasanta K; Gendelman, Howard E; Roy, Upal; Balkundi, Shantanu; Alnouti, Yazen; Mosley, Rodney L; Gelbard, Harris A; McMillan, Joellyn; Gorantla, Santhi; Poluektova, Larisa Y
Long-acting nanoformulated antiretroviral therapy (nanoART) with improved pharmacokinetics, biodistribution and limited systemic toxicities will likely improve drug adherence and access to viral reservoirs. Atazanavir and ritonavir crystalline nanoART were formulated in a poloxamer-188 excipient by high-pressure homogenization. These formulations were evaluated for antiretroviral and neuroprotective activities in humanized NOD/scid-IL-2Rgc (NSG) mice. NanoART-treated NSG mice were evaluated for drug biodistribution, pharmacodynamics and toxicity. CD34 human hematopoietic stem cells were transplanted at birth in replicate NSG mice. The mice were infected with HIV-1ADA at 5 months of age. Eight weeks later, the infected animals were treated with weekly subcutaneous injections of nanoformulated ATV and RTV. Peripheral viral load, CD4 T-cell counts and lymphoid and brain histopathology and immunohistochemistry tests were performed. NanoART treatments by once-a-week injections reduced viral loads more than 1000-fold and protected CD4 T-cell populations. This paralleled high ART levels in liver, spleen and blood that were in or around the human minimal effective dose concentration without notable toxicities. Importantly, examination of infected brain subregions showed that nanoART elicited neuroprotective responses with detectable increases in microtubule-associated protein-2, synaptophysin and neurofilament expression when compared to untreated virus-infected animals. Therapeutic interruptions produced profound viral rebounds. Long-acting nanoART has translational potential with sustained and targeted efficacy and with limited systemic toxicities. Such success in drug delivery and distribution could improve drug adherence and reduce viral resistance in infected people.
Jiamsakul, Awachana; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Li, Patrick CK; Phanuphak, Praphan; Sirisanthana, Thira; Sungkanuparph, Somnuek; Kantipong, Pacharee; Lee, Christopher KC; Mustafa, Mahiran; Merati, Tuti; Kamarulzaman, Adeeba; Singtoroj, Thida; Law, Matthew
Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow-up time started from ART initiation and was censored at 24 months, loss to follow-up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence
Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T
We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.
Peluso, Michael J; Spudich, Serena
The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.
Marsit, Carmen J; Brummel, Sean S; Kacanek, Deborah; Seage, George R; Spector, Stephen A; Armstrong, David A; Lester, Barry M; Rich, Kenneth
The use of combination antiretroviral therapy (cART) to prevent HIV mother-to-child transmission during pregnancy and delivery is generally considered safe. However, vigilant assessment of potential risks of these agents remains warranted. Epigenetic changes including DNA methylation are considered potential mechanisms linking the in utero environment with long-term health outcomes. Few studies have examined the epigenetic effects of prenatal exposure to pharmaceutical agents, including antiretroviral therapies, on children. In this study, we examined the methylation status of the LINE-1 and ALU-Yb8 repetitive elements as markers of global DNA methylation alteration in peripheral blood mononuclear cells obtained from newborns participating in the Pediatric HIV/AIDS Cohort Study SMARTT cohort of HIV-exposed, cART-exposed uninfected infants compared to a historical cohort of HIV-exposed, antiretroviral-unexposed infants from the Women and Infants Transmission Study Cohort. In linear regression models controlling for potential confounders, we found the adjusted mean difference of AluYb8 methylation of the cART-exposed compared to the -unexposed was -0.568 (95% CI: -1.023, -0.149) and for LINE-1 methylation was -1.359 (95% CI: -1.860, -0.857). Among those exposed to cART, subjects treated with atazanavir (ATV), compared to those on other treatments, had less AluYb8 methylation (-0.524, 95% CI: -0.025, -1.024). Overall, these results suggest a small but statistically significant reduction in the methylation of these repetitive elements in an HIV-exposed, cART-exposed cohort compared to an HIV-exposed, cART-unexposed historic cohort. The potential long-term implications of these differences are worthy of further examination.
Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello
to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. 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. 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. 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. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral
Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M
Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. Results The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated
Fowler, M.G.; Qin, M.; Fiscus, S.A.; Currier, J.S.; Flynn, P.M.; Chipato, T.; McIntyre, J.; Gnanashanmugam, D.; Siberry, G.K.; Coletti, A.S.; Taha, T.E.; Klingman, K.L.; Martinson, F.E.; Owor, M.; Violari, A.; Moodley, D.; Theron, G.B.; Bhosale, R.; Bobat, R.; Chi, B.H.; Strehlau, R.; Mlay, P.; Loftis, A.J.; Browning, R.; Fenton, T.; Purdue, L.; Basar, M.; Shapiro, D.E.; Mofenson, L.M.
BACKGROUND Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum “tail” of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, −1.3 percentage points; repeated confidence interval, −2.1 to −0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was
P.N., Suparna; Achappa, Basavaprabhu; B., Unnikrishnan; Madi, Deepak; Chowta, Mukta N.; Ramapuram, John T; Rao, Satish; Mahalingam, Soundarya
Background and Objective: The recognition and the assessment of the carotid intimal thickness helps in predicting the risk of the cardiovascular events in Human Immunodeficiency Virus (HIV) infected patients who are on Antiretroviral Therapy (ART). The objective of this study was to assess and compare the carotid intimal thickness in HIV positive individuals who were on antiretroviral therapy with HIV positive individuals who were not on anti-retroviral therapy. Subjects and Methods: All the HIV positive individuals who were 20 years old and above, who had been diagnosed by the National AIDS Control Organization (NACO) guidelines were included in the study. The HIV positive individuals who were diagnosed with diabetes mellitus and hypertension were excluded from the study. The study subjects were divided into 2 groups i.e. HIV patients who were on anti-retroviral therapy and HIV patients who were not on anti-retroviral therapy. The patients had to be on anti-retroviral therapy for a minimum of 6 months for them to be included in the first group. The data was collected by using a semi structured, pre-tested proforma, which included the demographic details, the duration of the HIV infection, details of the antiretroviral treatment, a history of smoking/ alcohol consumption and details on the assessments of the metabolic syndrome. Results: A total of 42 patients were included in the study. Among them, 28 were males (66.7%) and 14 were females (33.3%). Twenty six patients were on ART and the remaining patients were treatment naive. There were significant differences with regards to their age and the duration of the HIV infection, which was longer in the patients who were on ART (p= 0.049, p=0.003 respectively). The Body Mass Index (BMI), the waist: hip ratio, the mid-arm circumference, the waist circumference, the skin fold thickness and the carotid intimal-media thickness were higher in the HIV patients who were on ART as compared to those in the treatment naive
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
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.
Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J
Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.
Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias
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
Bahamondes M, Laura; Villar Z, M José; Orellana C, Carolina; González R, Jimena; Montenegro U, Cristian
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).
Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun
Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.
Cribbs, Sushma K; Fontenot, Andrew P
Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV.
The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health. PMID:21958478
Tsertsvadze, Tengiz; Chkhartishvili, Nikoloz; Sharvadze, Lali; Dvali, Natia; Chokoshvili, Otar; Gabunia, Pati; Abutidze, Akaki; Nelson, Kenrad; DeHovitz, Jack; del Rio, Carlos
Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm3. During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216 cell/mm3 and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV. PMID:21490781
Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E
Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection. PMID:25174930
Kahn, James G; Marseille, Elliot A; Bennett, Rod; Williams, Brian G; Granich, Reuben
Recent empirical studies and analyses have heightened interest in the use of expanded antiretroviral therapy (ART) for prevention of HIV transmission. However, ART is expensive, approximately $600 per person per year, raising issues of the cost and cost-effectiveness of ambitious ART expansion. The goal of this review is to equip the reader with the conceptual tools and substantive background needed to understand and evaluate the policy and programmatic implications of cost-effectiveness assessments of ART for prevention. We provide this review in six sections. We start by introducing and explaining basic concepts of health economics as they relate to this issue, including resources, costs, health metrics (such as Disability-Adjusted Life Years), and different types of economic analysis. We then review research on the cost and cost-effectiveness of ART as treatment, and on the cost-effectiveness of traditional HIV prevention. We describe critical issues in the epidemic impact of ART, such as suppression of transmission and the role of the acute phase of infection. We then present a conceptual model for conducting and interpreting cost-effectiveness analyses of ART as prevention, and review the existing preliminary estimates in this area. We end with a discussion of future directions for programmatic demonstrations and evaluation. PMID:21999776
Carlucci, James G.; Kamanga, Aniset; Sheneberger, Robb; Shepherd, Bryan E.; Jenkins, Cathy A.; Spurrier, John; Vermund, Sten H.
Background/Objective Antiretroviral therapy (ART) adherence levels of ≥95% optimize outcomes and minimize HIV drug resistance. As such, identifying barriers to adherence is essential. We sought to assess travel to point-of-care for ART as a potential barrier to adherence in rural Zambia, within the context of patient demographics, perceived stigma, and selected clinical indices. Methods We studied 424 patients receiving ART from the Macha Mission Hospital (MMH). Interviews ascertained age, gender, education, perceived stigma, nearest rural health facility (RHF), and mode/cost/time of transport for each study participant. Motorcycle odometer and global positioning system way-points measured distance from the MMH to each of the RHFs, estimating patients’ home-to-MMH travel distances. Body mass index, World Health Organization HIV/AIDS stage, and pill counts were assessed from review of patients’ medical and pharmacy records. Results At least 95% adherence was documented for 83.7% of the patients in their first months of ART. Travel-related factors did not predict adherence. Adherence was higher for those on ART for a longer time (odds ratio = 1.04 per day; P = 0.002). Conclusions Patients in rural Zambia can achieve adherence rates compatible with good clinical outcomes despite long travel distances. The MMH was able to provide quality HIV/AIDS care by implementing programmatic features selecting for a highly adherent population in this resource-limited setting. PMID:18209678
Vigano, Selena; Negron, Jordi; Ouyang, Zhengyu; Rosenberg, Eric S.; Walker, Bruce D.; Lichterfeld, Mathias
ABSTRACT HIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-specific CD8 T cells with stem cell-like properties, termed T memory stem cells (TSCM cells), is enriched in patients receiving suppressive antiretroviral therapy compared with their levels in untreated progressors or controllers. In addition, a prolonged duration of antiretroviral therapy was associated with a progressive increase in the relative proportions of these stem cell-like HIV-1-specific CD8 T cells. Interestingly, the proportions of HIV-1-specific CD8 TSCM cells and total HIV-1-specific CD8 TSCM cells were associated with the CD4 T cell counts during treatment with antiretroviral therapy but not with CD4 T cell counts, viral loads, or immune activation parameters in untreated patients, including controllers. HIV-1-specific CD8 TSCM cells had increased abilities to secrete interleukin-2 in response to viral antigen, while secretion of gamma interferon (IFN-γ) was more limited in comparison to alternative HIV-1-specific CD8 T cell subsets; however, only proportions of IFN-γ-secreting HIV-1-specific CD8 TSCM cells were associated with CD4 T cell counts during antiretroviral therapy. Together, these data suggest that HIV-1-specific CD8 TSCM cells represent a long-lasting component of the cellular immune response to HIV-1 that persists in an antigen-independent fashion during antiretroviral therapy but seems unable to survive and expand under conditions of ongoing viral replication during untreated infection. IMPORTANCE Memory CD8 T cells that imitate the functional properties of stem cells to maintain lifelong cellular immunity have been hypothesized for many years, but only recently have such cells, termed T memory stem cells (TSCM cells), been
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.
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
The Antiretroviral Cohort Collaboration (ART-CC); Mugavero, Michael J.; May, Margaret; Harris, Ross; Saag, Michael S.; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F.; Dabis, Francois; Hogg, Robert; De Wolf, Frank; Fatkenheuer, Gerd; John Gill, M.; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M.; Staszewski, Schlomo; Sterne, Jonathan A. C.
Objective To determine if differences in short-term virologic failure among commonly used ART regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Design Observational cohort study of patients initiating ART between January 2000 and December 2005. Setting The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. Subjects, participants A total of 13,546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz (EFV), nevirapine (NVP), lopinavir/ritonavir (LPV/r), nelfinavir (NFV), or abacavir (ABC) as third drugs in combination with a zidovudine and lamivudine NRTI backbone. Main outcome measures Short-term (24-week) virologic failure (>500 copies/mL) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Results Compared with EFV as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; NVP (adjusted odds ratio=1.87, 95%CI=1.58,2.22), LPV/r (1.32, 95%CI=1.12–1.57), NFV (3.20, 95%CI=2.74,3.74), and ABC (2.13, 95%CI=1.82,2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with NVP (adjusted hazard ratio for composite outcome measure 1.27, 95%CI=1.04,1.56) and ABC (1.22, 95%CI=1.00,1.48). Conclusions Among antiretroviral-naïve patients initiating therapy, between-ART regimen differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication. PMID:19005271
Papot, Emmanuelle; Landman, Roland; Louni, Françoise; Charpentier, Charlotte; Peytavin, Gilles; Certain, Agnès; Fradet, Clémence; Castro, Daniela R; Preau, Marie; Goujard, Cécile; Yeni, Patrick; Yazdanpanah, Yazdan
In this study, we first assessed costs associated with the use of antiretroviral therapy (ART) in an infectious diseases University Hospital Clinic; second, we evaluated characteristics associated with these costs and finally simulated the impact on the overall ART budget of switching first-line and second-line regimens to less-costly regimens (as effective and well tolerated). Cohort analysis including persons living with HIV (PLHIV) aged at least 18 years on ART to estimate ART costs during 2014. The current study was conducted in the Bichat-Claude Bernard University Hospital Clinic in Paris, France, where 4501 PLHIV consulted in 2014. We used the medical database Nadis to describe patients' ART, characteristics and estimated costs. When assessing the budgetary impact of potential switches, we considered patients' history of failure, CD4 cell count, plasma viral load, resistance mutations, hepatitis B surface antigen or HLAB5701 profile. A total of 4238 of 4501 patients were on ART (94%). The total annual cost of ART prescribed was estimated at &OV0556;48 280 200 in 2014; first/second (simplification)-line regimens represented 25% (1076/4238) of the treated PLHIV and 23% (&OV0556;11 209 000) of the annual cost. For these PLHIV, we considered switches from the most common ART regimens (protease inhibitor boosted by ritonavir or nonnucleoside reverse transcriptase inhibitor + two nucleoside reverse transcriptase inhibitors) to less-expensive regimens. We found savings ranging from &OV0556;36 100 to 1472 600/year. Savings were the highest when we considered switching to generic-based regimens or from protease inhibitor-based triple therapy to protease inhibitor monotherapy. Costs associated with ART prescriptions are very high. Switches to generic-based regimens are associated with large savings. However, those targeting protease inhibitor regimens are also associated with substantial savings and should be considered.
Nolan, David; Mallal, Simon
Lipoatrophy is perhaps the most visibly recognisable component of antiretroviral-therapy-associated lipodystrophy due to the rarity of this form of body composition change in the general population. In this respect, it is apparent that lipoatrophy represents a form of drug toxicity specifically involving the subcutaneous fat tissue, resulting in pathological fat loss that preferentially affects the limbs and face. It is now clear that the choice and duration of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy (stavudine > zidovudine) is the dominant risk factor for clinical lipoatrophy, as well as for the pathological changes to adipose tissue that underlie the clinical syndrome. Host factors have also emerged as important modulators of lipoatrophy severity in patients receiving these NRTI drugs, including age, racial origin, and severity of immune deficiency. On the other hand, the use of selected HIV protease inhibitor drugs is more closely associated with metabolic complications such as dyslipidemia and insulin resistance and has not been convincingly linked to lipoatrophy. This review examines the clinical and pathological manifestations of lipoatrophy, and also presents information regarding the safety profile of alternative NRTI drugs, such as tenofovir and abacavir, that have not been associated with lipoatrophy risk. With increasing knowledge of lipoatrophy pathogenesis, it is likely that moderate and severe forms of this complication can now be considered a preventable complication of HIV treatment. However, it is also important to recognise that there is an ongoing burden of disease in patients who have been affected by lipoatrophy over the past six years, and that therapeutic management of established lipoatrophy will remain a challenge into the future.
Ngatchou, William; Lemogoum, Daniel; Ndobo, Pierre; Yiagnigni, Euloge; Tiogou, Emiline; Nga, Elisabeth; Kouanfack, Charles; Nde, Francis; Degaute, Jean-Paul; van de Borne, Philippe; Leeman, Marc
HIV infection increases cardiovascular risk and highly active antiretroviral therapy may further augment it. We hypothesized that an increase in large artery stiffness may be a mechanism of enhanced cardiovascular risk in treated HIV-infected (HIV-T) patients. Pulse wave velocity (PWV) and augmentation index (AI) were measured in 108 Cameroonian untreated HIV-infected (HIV-UT) patients and in 130 HIV-T patients. Brachial and aortic systolic blood pressure (BP), diastolic BP, and pulse pressure were higher in HIV-T patients than in HIV-UT patients (all, P < 0.01). PWV was comparable in HIV-T and HIV-UT patients (7.2 ± 1.5 vs. 7.46 ± 2.2 m/s, respectively, P = 0.3), whereas AI was higher in HIV-T patients than in HIV-UT patients (7.9 ± 5 vs. 5.76 ± 4%, respectively, P = 0.003). AI was associated independently with age, brachial systolic BP, brachial diastolic BP, and height in HIV patients (R = 0.75, P < 0.01). This study shows that pulse pressure and AI were increased in HIV-T patients, compared with matched HIV-UT patients, suggesting that highly active antiretroviral therapy could increase cardiovascular risk. However, PWV was not accelerated in HIV-T patients.
Cohen, Myron S; Chen, Ying Q; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; Santos, Breno R; Mayer, Kenneth H; Hoffman, Irving F; Eshleman, Susan H; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David D; Essex, Max; Hudelson, Sarah E; Redd, Andrew D; Fleming, Thomas R
An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. The early initiation of ART led to a sustained decrease in genetically linked HIV-1
Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H.S.; Godbole, Sheela V.; Chariyalertsak, Suwat; Santos, Breno R.; Mayer, Kenneth H.; Hoffman, Irving F.; Eshleman, Susan H.; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C.; Makhema, Joseph; Mills, Lisa A.; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E.; Nielsen-Saines, Karin; Celentano, David D.; Essex, Max; Hudelson, Sarah E.; Redd, Andrew D.; Fleming, Thomas R.
BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1– negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained
Lipshultz, Steven E; Williams, Paige L; Zeldow, Bret; Wilkinson, James D; Rich, Kenneth C; van Dyke, Russell B; Seage, George R; Dooley, Laurie B; Kaltman, Jonathan R; Siberry, George K; Mofenson, Lynne M; Shearer, William T; Colan, Steven D
We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs. There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores. There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.
Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.
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
Dworkin, Mark S; Douglas, G W; Sabitha Rani, G P; Chakraborty, Apurba
We assessed the barriers and facilitators to highly active antiretroviral therapy adherence and determined their prevalence among HIV/AIDS patients in Hyderabad, India. We conducted a cross-sectional study among HIV-infected adults prescribed highly active antiretroviral therapy and receiving care from nine clinics. Depression was screened using Patient Health Questionnaire 9 and facilitators of HIV medication adherence were assessed using an 11-item scale which yielded a total positive attitude to disease score. Prevalence ratios of non-adherence between different categories of potential risk factors were calculated. We compared mean 'facilitators to adherence' scores between the adherent and non-adherent population. Multivariable Poisson regression with robust variance was used to identify independent risk factors. Among the 211 respondents, nearly 20% were non-adherent, approximately 8% had either moderately severe or severe depression and mean score for combined facilitators to medication adherence was 33.35 (±7.88) out of a possible 44 points. Factors significantly associated with non-adherence included older age, female sex worker, moderate-to-severe depression and the combined facilitators to medication adherence score. These data from a broad range of clinical settings in Hyderabad reveal that key groups to focus on for adherence intervention are female sex workers, older persons and those with depression.
Sherman, Kenneth E; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T; Rouster, Susan D; Castro, Mario; Feinberg, Judith; Sterling, Richard K; Goodman, Zachary; Aronow, Bruce J; Perelson, Alan S
The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients co-infected with HIV. Co-infection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV co-infected patients into a cART initiation trial and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in increased HCV replication and increased alanine aminotransferase (ALT) in a subset of patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in co-infected patients who underwent successful cART. The effective suppression of HIV by cART initiated a cascade of early and late events in treated patients. Early events involving down-regulation of interferon-stimulated genes may have led to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declined to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV co-infection.
Torres, Jaime R; Torres-Viera, Maria A; Schupbach, Jorg; Rangel, Hector R; Pujol, Flor H
HIV-2 infection was documented for the first time in Venezuela, in a heterosexual couple. Two identical subtype A viral strains exhibiting multiple resistance mutations to antiretroviral drugs were identified. One of the patients suffered from progressive non-immune thrombocytopenia and extranodal NK/T-cell type lymphoma, an association not previously described for HIV-2. His hematological condition promptly improved after onset of an effective antiretroviral therapy.
Jequicene, Tito; Blevins, Meridith; José, Eurico; Lankford, Julie R; Wester, C William; Fuchs, Martina C; Vermund, Sten H
Abstract Problem Despite seven years of investment from the President's Emergency Plan For AIDS Relief (PEPFAR), the expansion of human immunodeficiency virus (HIV)-related services continues to challenge Mozambique’s health-care infrastructure, especially in the country’s rural regions. Approach In 2012, as part of a national acceleration plan for HIV care and treatment, Namacurra district employed a mobile clinic strategy to provide temporary manpower and physical space to expand services at four rural peripheral clinics. This paper describes the strategy deployed, the uptake of services and the key lessons learnt in the first 18 months of implementation. Local setting In 2012, Namacurra´s adult population was estimated to be 125 425, and of those 15 803 were estimated to be HIV infected. Although there is consistent government support of antiretroviral therapy (ART) programmes, national coverage remains low, with less than 15% of those eligible having received ART by December 2012. Relevant changes Between April 2012 and September 2013, Namacurra district enrolled 4832 new patients into HIV care and treatment. By using the mobile clinic strategy for ART expansion, the district was able to expand provision of ART from two to six (of a desired seven) clinics by September 2013. Lessons learnt Mobile clinic strategies could rapidly expand HIV care and treatment in under-funded settings in ways that both build local capacity and are sustainable for local health systems. The clinics best serve as a transition to improved capacity at fixed-site services. PMID:25378759
Teeraananchai, Sirinya; Chaivooth, Suchada; Kerr, Stephen J; Bhakeecheep, Sorakij; Avihingsanon, Anchalee; Teeraratkul, Achara; Sirinirund, Petchsri; Law, Matthew G; Ruxrungtham, Kiat
Access to combination antiretroviral therapy (cART) has decreased mortality in HIV-positive people. We aimed to estimate the expected additional years of life in HIV-positive Thai people after starting cART through the National AIDS Program (NAP), administered by the Thai National Health Security Office (NHSO). The NHSO database collects characteristics of all Thai HIV-infected patients through the National AIDS Program, including linkage with the National Death Registry for vital status. This study included patients aged ≥15 years at cART initiation between 2008 and 2014. The abridged life table method was used to construct life tables stratified by sex and baseline CD4(+) T-cell count. Life expectancy was defined as the additional years of life from age at starting cART. 201,688 eligible patients were included in analyses, contributing 618,837 person-years of follow-up. Median CD4(+) T-cell count was 109 cells/mm(3) and median age 37 years. The overall life expectancy after cART initiation at age 20 was 25.4 (95% CI, 25.3, 25.6) years and 20.6 (95% CI, 20.5, 20.7) at age 35 years. Life expectancy at baseline CD4(+) T-cell count ≥350 cells/mm(3) was 51.9 (95% CI, 51.0, 52.9) years for age 20 years and 43.2 (95% CI, 42.4, 44.1) years for age 35 years, close to life expectancy in the general Thai population. Increasing life expectancy with higher baseline CD4(+) T-cell counts supports the guideline recommendations to start cART irrespective of CD4(+) T-cell count. These results are beneficial to forecast the treatment cost and develop health policies for people living with HIV in Thailand and Asia.
Alpert, Michael; Wickersham, Jeffrey A.; Vázquez, Mariana; Altice, Frederick L.
Purpose While Argentina has significantly improved access to HIV care and antiretroviral therapy (ART) for both the general population and prisoners, the prevalence of alcohol use disorders (AUDs) among HIV-infected prisoners and their relationship to accessing ART in Argentina is currently unknown. This study aims to characterize the substance abuse patterns of HIV-infected prisoners in Argentina and to assess the independent correlates of receipt of pre-incarceration ART. Design/methodology/approach An anonymous, cross-sectional survey of 100 HIV-infected federal prisoners was conducted in the Buenos Aires municipality from July–December 2010. AUDs were assessed using the AUDIT scale. Findings A majority (63 per cent) of participants met criteria for AUDs, 45 per cent of subjects were diagnosed with HIV in prison and one-quarter had initiated ART during the current incarceration. In addition, over one-third (35 per cent) of participants did not receive ART during the pre-incarceration period despite receiving it upon incarceration. This correlated significantly with the presence of having an AUD (AOR 0.20, 95 per cent CI 0.06–0.74, p = 0.016). Practical implications AUDs are prevalent among HIV-infected prisoners in Argentina and are significantly related to negative secondary HIV prevention and treatment outcomes. While Argentina has provided an exemplary model of HIV-related health care reform within its prisons, future efforts to provide screening and treatment for AUDs are needed to improve the health of the nation’s incarcerated population. Originality/value This paper is the first to describe pre-incarceration drug and alcohol use disorders and issues related to access to ART among prisoners in Argentina. PMID:24772187
Alpert, Michael; Wickersham, Jeffrey A; Vázquez, Mariana; Altice, Frederick L
While Argentina has significantly improved access to HIV care and antiretroviral therapy (ART) for both the general population and prisoners, the prevalence of alcohol use disorders (AUDs) among HIV-infected prisoners and their relationship to accessing ART in Argentina is currently unknown. This study aims to characterize the substance abuse patterns of HIV-infected prisoners in Argentina and to assess the independent correlates of receipt of pre-incarceration ART. An anonymous, cross-sectional survey of 100 HIV-infected federal prisoners was conducted in the Buenos Aires municipality from July-December 2010. AUDs were assessed using the AUDIT scale. A majority (63 per cent) of participants met criteria for AUDs, 45 per cent of subjects were diagnosed with HIV in prison and one-quarter had initiated ART during the current incarceration. In addition, over one-third (35 per cent) of participants did not receive ART during the pre-incarceration period despite receiving it upon incarceration. This correlated significantly with the presence of having an AUD (AOR 0.20, 95 per cent CI 0.06-0.74, p = 0.016). AUDs are prevalent among HIV-infected prisoners in Argentina and are significantly related to negative secondary HIV prevention and treatment outcomes. While Argentina has provided an exemplary model of HIV-related health care reform within its prisons, future efforts to provide screening and treatment for AUDs are needed to improve the health of the nation’s incarcerated population. This paper is the first to describe pre-incarceration drug and alcohol use disorders and issues related to access to ART among prisoners in Argentina.
Yilmaz, Aylin; Yiannoutsos, Constantin T; Fuchs, Dietmar; Price, Richard W; Crozier, Kathryn; Hagberg, Lars; Spudich, Serena; Gisslén, Magnus
Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.
Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008
Background Poor adherence to antiretroviral therapy negatively affects the suppression of viral replication. It increases risks of drug resistance, treatment failure, Acquired Immuno Deficiency Syndrome (AIDS)-related morbidity and mortality among children. This study assessed the level of adherence to antiretroviral therapy and its associated factors among children at hospitals in South Wollo Zone, Northeast Ethiopia. Methods An institution-based cross-sectional study was conducted among Human Immunodeficiency Virus (HIV)-infected children in April 2013. A total of 464 children who were taking Antiretroviral Therapy (ART) in the hospitals were included. Data were collected using pretested and structured questionnaires using a face-to-face interview method. Descriptive and summary statistics were employed. Bivariate and multiple logistic regressions were computed. Odds ratios and their 95% confidence intervals were computed to determine the level of significance. Results Of the 464 study samples, 440 children with their caregivers were included in the final analysis. A total of 78.6% of the caregivers reported that their children were adherent to antiretroviral therapy in the month prior to the interview. Caregivers' knowledge about antiretroviral treatment [AOR = 2.72(95% CI: 1.82, 5.39)], no current substance use of the caregivers [Adjusted Odds Ratio (AOR) = 2.21(95% Confidence Interval (CI): 1.34, 7.13)], proximity to the health care facility [AOR = 2.31(95% CI: 1.94, 4.63)], if the child knows HIV-positive status [AOR = 3.47(95% CI: 2.10, 6.81)] and caregiver’s educational status [AOR = 0.59(95% CI: 0.21, 0.82)] were significantly and independently associated with adherence of children to antiretroviral therapy. Conclusion Adherence of antiretroviral therapy in this study was comparable to other studies conducted in developing countries. Caregiver’s knowledge about antiretroviral therapy, no current use of substances, close proximity to
Winston, Alan; Arenas-Pinto, Alejandro; Stöhr, Wolfgang; Fisher, Martin; Orkin, Chloe M.; Aderogba, Kazeem; De Burgh-Thomas, Andrew; O'Farrell, Nigel; Lacey, Charles JN.; Leen, Clifford; Dunn, David; Paton, Nicholas I.
Objective To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. Design We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. Main outcome measure NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. Results Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was −0.5 (−1.2/−0) overall, and −0.3 (−0.7/0.1) and −1.4 (−2/−0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). Conclusions In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. Trial registry ClinicalTrials.gov, NCT01230580 PMID:23646111
Healey, Letha M.; Hahn, Barbara K.; Rehm, Catherine A.; Adelsberger, Joseph; Qin, Jing; Follmann, Dean A.; Tavel, Jorge; Kovacs, Joseph A.; Sereti, Irini
Background Intermittent administration of interleukin-2 (IL-2) to human immunodeficiency virus (HlV)-infected patients on antiretroviral therapy (ART) is capable of inducing significant increases in CD4 T cell counts as a result of increased T cell survival and decreased cell turnover. However, its role in the setting of ART interruptions (STI) is less well characterized. We sought to compare the effect of continuous (C) versus intermittent (P) ART on CD4 responses in patients undergoing IL-2 therapy. Methods CD4 cell responses were compared in 25 patients who underwent IL-2 therapy during periods of continuous ART (n = 90 cycles) as well as during STI (n = 45 cycles). During STI, patients resumed ART for only 10 days surrounding each IL-2 cycle. Results C cycles resulted in a significantly greater CD4 gain than P cycles (Δ156 cells/μL, 95% CI = 68–243). In multivariate analyses, baseline CD4/CD25 expression and treatment arm remained strong predictors of CD4 gain while CD8/CD38+, CD8/DR+, and CD4 Ki67+ phenotype were not predictive. Conclusions Continuous ART was associated with a statistically significantly greater CD4 cell response to IL-2 therapy than was intermittent ART. These observations may have important implications for the appropriate integration of IL-2 therapy into STI strategies. PMID:18597618
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.
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$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. Conclusions In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival
Venkatesh, Kartik K.
As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682
Sax, Paul E; Sypek, Alexis; Berkowitz, Bethany K; Morris, Bethany L; Losina, Elena; Paltiel, A David; Kelly, Kathleen A; Seage, George R; Walensky, Rochelle P; Weinstein, Milton C; Eron, Joseph; Freedberg, Kenneth A
We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.
GARDNER, EDWARD M.; BURMAN, WILLIAM J.; MARAVI, MOISES E.; DAVIDSON, ARTHUR J.
There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, −43% per year), followed by patients with intermediate regimen duration (16 to <28 months, −19% per year), and then patients with longer regimens (≥28 months, −5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed. PMID:16987049
HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/μL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients.
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
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
Corless, Inge B; Hoyt, Alex J; Tyer-Viola, Lynda; Sefcik, Elizabeth; Kemppainen, Jeanne; Holzemer, William L; Eller, Lucille Sanzero; Nokes, Kathleen; Phillips, J Craig; Dawson-Rose, Carol; Rivero-Mendez, Marta; Iipinge, Scholastika; Chaiphibalsarisdi, Puangtip; Portillo, Carmen J; Chen, Wei-Ti; Webel, Allison R; Brion, John; Johnson, Mallory O; Voss, Joachim; Hamilton, Mary Jane; Sullivan, Kathleen M; Kirksey, Kenn M; Nicholas, Patrice K
Medication adherence is the "Plus" in the global challenge to have 90% of HIV-infected individuals tested, 90% of those who are HIV positive treated, and 90% of those treated achieve an undetectable viral load. The latter indicates viral suppression, the goal for clinicians treating people living with HIV (PLWH). The comparative importance of different psychosocial scales in predicting the level of antiretroviral adherence, however, has been little studied. Using data from a cross-sectional study of medication adherence with an international convenience sample of 1811 PLWH, we categorized respondent medication adherence as None (0%), Low (1-60%), Moderate (61-94%), and High (95-100%) adherence based on self-report. The survey contained 13 psychosocial scales/indices, all of which were correlated with one another (p < 0.05 or less) and had differing degrees of association with the levels of adherence. Controlling for the influence of race, gender, education, and ability to pay for care, all scales/indices were associated with adherence, with the exception of Berger's perceived stigma scale. Using forward selection stepwise regression, we found that adherence self-efficacy, depression, stressful life events, and perceived stigma were significant predictors of medication adherence. Among the demographic variables entered into the model, nonwhite race was associated with double the odds of being in the None rather than in the High adherence category, suggesting these individuals may require additional support. In addition, asking about self-efficacy, depression, stigma, and stressful life events also will be beneficial in identifying patients requiring greater adherence support. This support is essential to medication adherence, the Plus to 90-90-90.
Warszawski, Josiane; Tubiana, Roland; Le Chenadec, Jerome; Blanche, Stephane; Teglas, Jean-Paul; Dollfus, Catherine; Faye, Albert; Burgard, Marianne; Rouzioux, Christine; Mandelbrot, Laurent
To identify factors associated with mother-to-child HIV-1 transmission (MTCT) from mothers receiving antenatal antiretroviral therapy. The French Perinatal Cohort (EPF), a multicenter prospective cohort of HIV-infected pregnant women and their children. Univariate analysis and logistic regression, with child HIV status as dependent variable, were conducted among 5271 mothers who received antiretroviral therapy during pregnancy, delivered between 1997 and 2004 and did not breastfeed. The MTCT rate was 1.3% [67/5271; 95% confidence interval (CI), 1.0-1.6]. It was as low as 0.4% (5/1338; 95% CI, 0.1-0.9) in term births with maternal HIV-1 RNA level at delivery below 50 copies/ml. MTCT increased with viral load, short duration of antiretroviral therapy, female gender and severe premature delivery: 6.6% before 33 weeks versus 1.2% at 37 weeks or more (P < 0.001). The type of antiretroviral therapy was not associated with transmission. Intrapartum therapy was associated with four-fold lower MTCT (P = 0.04) in case of virological failure (> 10 000 copies/ml). Elective cesarean section tended to be inversely associated with MTCT in the overall population, but not in mothers who delivered at term with viral load < 400 copies/ml [odds ratio (OR), 0.83; 95% CI, 0.29-2.39; P = 0.37]. Among them, only duration of antenatal therapy was associated with transmission (OR by week, 0.94; 95% CI, 0.90-0.99; P = 0.03). Low maternal plasma viral load is the key factor for preventing MTCT. Benefits in terms of MTCT reduction may be expected from early antiretroviral prophylaxis. The potential toxicity of prolonged antiretroviral use in pregnancy should be evaluated.
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
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.
Cifuentes M, Daniel; Blanco L, Sergio; Ramírez F, Camila
High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.
Chauriye, Verónica; Monsalve, Ximena
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.
Rodríguez, Mónica; Flores, Paúl; Ahumada, Víctor; Vázquez-Vázquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo
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
Ramos, Alberto Novaes; Matida, Luiza Harunari; Hearst, Norman; Heukelbach, Jorg
We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges.
Lessells, Richard J; Avalos, Ava; de Oliveira, Tulio
Tremendous progress has been made with the scale-up of antiretroviral therapy in Africa, with an estimated seven million people now receiving antiretroviral therapy in the region. The long-term success of antiretroviral therapy programs depends on appropriate strategies to deal with potential threats, one of which is the emergence and spread of antiretroviral drug resistance. Whilst public health surveillance forms the mainstay of the World Health Organization approach to antiretroviral drug resistance, there is likely to be increasing demand for access to drug resistance testing as programs mature and as HIV clinical management becomes more complex. African-owned research initiatives have helped to develop affordable resistance testing appropriate for use in the region, and have developed delivery models for resistance testing at different levels of the public health system. Some upper-middle-income countries such as Botswana and South Africa have introduced drug resistance testing for selected patient groups to guide clinical management. The scale-up of resistance testing will require substantial expansion of clinical and laboratory capacity in the region, but the expertise and resources exist in Africa to support this. The long-term population health impact and cost-effectiveness of resistance testing in the region will also require further investigation.
Doerfler, R Eric; Goodfellow, Linda
No study has tested the effectiveness of individualized cognitive behavioral therapy (CBT) interventions to reduce persistent nausea, pain, anxiety, and fatigue in patients on continuous antiretroviral therapy (ART). Our objective was to determine if CBT could reduce nausea, pain, anxiety, and fatigue in patients with HIV on ART. Men ages 40 to 56 years on ART (n = 18) at a suburban HIV clinic were randomly assigned to a control group or the CBT intervention. Usual adherence education and side-effect management were provided to both groups. Symptoms, health perception, medication adherence, and side-effect-reducing medication use were measured at four time points over 3 months. Participants in the intervention group rated usual fatigue and worst fatigue at 60 days, and nausea duration at 90 days significantly lower than controls (p < .05). Brief CBT training may reduce fatigue and nausea in patients with HIV undergoing ART.
Low, Andrea J.; Mburu, Gitau; Welton, Nicky J.; May, Margaret T.; Davies, Charlotte F.; French, Clare; Turner, Katy M.; Looker, Katharine J.; Christensen, Hannah; McLean, Susie; Rhodes, Tim; Platt, Lucy; Hickman, Matthew; Guise, Andy; Vickerman, Peter
Background. Human immunodeficiency virus (HIV)–infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. Methods. We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I2 statistic. Results. We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32–2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17–2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41–3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63–.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21–1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65–1.25). Conclusions. These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID. PMID:27343545
Rostova, N B; Ivanova, E S; Ivanova, Yu N
The aim of the study was medico-social characteristic of HIV-infected patients receiving antiretroviral therapy in 2006-2012 based on the logical and comparative analysis of medical cards with the use of systemic informational approach. The study yielded the medico-social characteristic of HIV-infected patients suggesting the presence of concomitant disorders requiring prescription of several medications to be used either simultaneously or alternatively (in case of poor efficiency or side effects of primary treatment). The data obtained indicate the necessity of optimization of the choice and prescription of pharmacotherapy taking account of its effects and safety based on the analysis of the potential and cost-effectiveness of different therapeutic modalities. The results of the study can be used to develop organizational measures for the improvement of public drug supply.
Keiser, Olivia; Spycher, Ben; Rauch, Andri; Calmy, Alexandra; Cavassini, Matthias; Glass, Tracy R; Nicca, Dunja; Ledergerber, Bruno; Egger, Matthias
An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions.
Baranov, Victoria; Bennett, Daniel; Kohler, Hans-Peter
To reduce the burden of the HIV/AIDS epidemic, international donors recently began providing free antiretroviral therapy (ART) in parts of Sub-Saharan Africa. ART dramatically prolongs life and reduces infectiousness for people with HIV. This paper shows that ART availability increases work time for HIV-negative people without caretaker obligations, who do not directly benefit from the medicine. A difference-in-difference design compares people living near and far from ART, before and after treatment becomes available. Next we explore the possible reasons for this pattern. Although we cannot pinpoint the mechanism, we find that ART availability substantially reduces subjective mortality risk and improves mental health. These results show an undocumented economic consequence of the HIV/AIDS epidemic and an important externality of medical innovation. They also provide the first evidence of a link between the disease environment and mental health.
Baranov, Victoria; Bennett, Daniel; Kohler, Hans-Peter
To reduce the burden of the HIV/AIDS epidemic, international donors recently began providing free antiretroviral therapy (ART) in parts of Sub-Saharan Africa. ART dramatically prolongs life and reduces infectiousness for people with HIV. This paper shows that ART availability increases work time for HIV-negative people without caretaker obligations, who do not directly benefit from the medicine. A difference-in-difference design compares people living near and far from ART, before and after treatment becomes available. Next we explore the possible reasons for this pattern. Although we cannot pinpoint the mechanism, we find that ART availability substantially reduces subjective mortality risk and improves mental health. These results show an undocumented economic consequence of the HIV/AIDS epidemic and an important externality of medical innovation. They also provide the first evidence of a link between the disease environment and mental health. PMID:26516983
Galli, Massimo; Cozzi-Lepri, Alessandro; Ridolfo, Aana Lisa; Gervasoni, Cristina; Ravasio, Laura; Corsico, Laura; Gianelli, Erika; Vaccarezza, Mauro; Vullo, Vincenzo; Cargnel, Antonietta; Minoli, Lorenzo; Coronado, Olga; Giacometti, Andrea; Antinori, Andrea; Antonucci, Giorgio; D'Arminio Monforte, Antonella; Moroni, Mauro
Adipose tissue alterations (ATAs) are a frequent untoward effect of antiretroviral therapy, the causes of which remain incompletely explained. To assess the incidence of ATAs and to identify the associated risk factors in patients infected with human immunodeficiency virus type 1 starting their first-line antiretroviral treatment. In a multicenter investigation designed to study issues related to the treatment of patients starting antiretroviral therapy, physicians were requested to assess the presence of ATAs at enrollment and every 6 months thereafter. The ATAs were considered altogether and grouped as fat loss (lipoatrophy), adipose tissue accumulation (lipohypertrophy), and combined forms. A total of 655 patients were followed up for a median of 86 weeks; 128 patients (19.6%) were diagnosed as having at least 1 morphologic alteration during the study. Female gender and positivity for hepatitis C virus were independently linked to an increased risk of developing morphologic alterations. Age was another independent correlate of risk of developing ATAs. To have been infected through drug injection was a correlate of reduced risk of ATAs. Stavudine exposure was predictive at borderline statistical significance of lipoatrophy (but not of the other forms), and indinavir exposure was associated with a significantly higher risk of developing combined forms. Patients who started therapy with 2 nucleoside reverse transcriptase inhibitors and subsequently added a protease inhibitor during the follow-up had a significantly higher risk of having ATAs compared with patients who continued taking 2 nucleoside reverse transcriptase inhibitors up to the end of follow-up. Different types of ATAs might derive from distinct pathways and multifactorial causes. Adipose tissue alterations are a frequent and relatively early finding during first-line antiretroviral therapy.
Cortes, Claudia P.; Wehbe, Firas H.; McGowan, Catherine C.; Shepherd, Bryan E.; Duda, Stephany N.; Jenkins, Cathy A.; Gonzalez, Elsa; Carriquiry, Gabriela; Schechter, Mauro; Padgett, Denis; Cesar, Carina; Madero, Juan Sierra; Pape, Jean W.; Masys, Daniel R.; Sterling, Timothy R.
Background Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. Methods We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. Results Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007). Conclusions The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated. PMID:24066096
Schwartz, Sheree R; Kumwenda, Newton; Kumwenda, Johnstone; Chen, Shu; Mofenson, Lynne M; Taylor, Allan W; Fowler, Mary Glenn; Taha, Taha E
Highly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi. The post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately post-partum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status. Overall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naïve with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naïve mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naïve mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality. HIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes. Clinical Trials Registration This study is registered at http://clinicaltrials.gov/ under trial number NCT00115648.
Islam, S; Oon, V; Thomas, P
This retrospective cohort study was conducted at Newham University Hospital, London to investigate maternal outcome of planned vaginal delivery as well as rate of maternal-to-child transmission. Between June 2004 and June 2006, 23 (16%) women of 144 HIV-infected pregnant women opted for planned vaginal delivery. Offer of vaginal delivery was based on maternal HIV RNA count <50 cells/ml around 36 weeks' gestation. All women received antiretroviral therapy. Fifteen (65%) women achieved vaginal delivery. Babies were followed up over 18 months. All babies had antiretroviral prophylaxis. No babies were breast-fed. There was no report of maternal-to-child transmission in any of these babies. Our study suggests that planned vaginal delivery could be safe with antiretroviral therapy in pregnancy, optimal intrapartum care, viral load of <1000 copies/ml at delivery, retroviral prophylaxis for babies and avoidance of breast-feeding.
Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang
Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging. PMID:27889708
Kouéta, F; Yé, D; Zoungrana, A; Sacko, A; Ouédraogo-Traoré, R; Kafando, E; Ouédraogo, S
Approximately one-fourth of the estimated 10,000 HIV-infected children in Burkina Faso are undergoing antiretroviral (ARV) therapy. At the Charles de Gaulle Pediatric Hospital Center in Ouagadougou, Burkina Faso, Support for ARV therapy began in July 2003 and a total of 250 children were undergoing treatment in late 2007. The purpose of this retrospective case-control study conducted over a period of 54 months from July 2003 to December 2007 was to investigate cases involving failure of first-line ARV therapy in particular with regard to cause. All patients (n = 32) showing poor virological, immunological, and/or clinical response to ARV therapy were considered as failures and thus included in the case group. The control group (n = 160) consisted of patients with good responses to treatment. Cases and controls were compared using the Chi-square test and odds ratio (OR) technique with a confidence interval at 95%. The failure rate was 12.8%. Failure was significantly correlated with low socioeconomic level (OR = 3), orphan status (OR = 4), age over 10 years (OR = 5), male gender (OR = 3), baseline viral load > or = 1,000,000 copies/mL (OR = 9), and poor compliance (OR = 37). Mortality in children who failed to respond to first-line ARV therapy was 25% due to the unavailability of a national second-line ARV therapy program. This study underlines the need for patient education to promote compliance and for creation of reference centers to prescribe ARV therapy to HIV-infected children including second-line ARV and genotyping.
Shlay, Judith C.; Sharma, Shweta; MS, Grace Peng; Gibert, Cynthia L.; Grunfeld, Carl
Objectives To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). Methods In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ART assessed were: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine (ddI), and abacavir (ABC). Skinfolds and circumferences were measured at baseline and every 4 months. Mid-arm, mid-thigh and waist subcutaneous tissue areas (STAs) and non-subcutaneous tissue areas (NSTAs) were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. Results D4T and ZDV use were associated with losses in STA and skinfold thickness. 3TC use was associated with gains in all STAs and skinfold thickness, while ABC use was associated with an increase in waist STA. Indinavir was associated with gains in waist STA, while indinavir, efavirenz and nevirapine were associated with increases in upper back skinfolds. D4T use was also associated with increases in all NSTAs; 3TC use was associated with the greatest increase in waist NSTA. Conclusions In this prospective non-randomized evaluation, the NRTIs d4T and ZDV were associated with decreases in STAs, while 3TC use was associated with increased STAs and waist NSTA. PMID:19412117
Gantt, Soren; Cattamanchi, Ashok; Krantz, Elizabeth; Magaret, Amalia; Selke, Stacy; Kuntz, Steven R; Huang, Meei-Li; Corey, Lawrence; Wald, Anna; Casper, Corey
Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS. Copyright © 2014 Elsevier B.V. All rights reserved.
Gantt, Soren; Cattamanchi, Ashok; Krantz, Elizabeth; Magaret, Amalia; Selke, Stacy; Kuntz, Steven R.; Huang, Meei-Li; Corey, Lawrence; Wald, Anna; Casper, Corey
Background Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. Objective To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. Study design Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. Results HHV-8 DNA was detected in 3,016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1 to 0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4 to 1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). Conclusions HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS. PMID:24698158
Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.
Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000
Rehman, Andrea M; Woodd, Susannah; Chisenga, Molly; Siame, Joshua; Sampson, Gemma; PrayGod, George; Koethe, John R; Kelly, Paul; Filteau, Suzanne
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.
LARSON, Bruce. A.; FOX, Matthew P.; BII, Margaret; ROSEN, Sydney; ROHR, Julia; SHAFFER, Douglas; SAWE, Fredrick; WASUNNA, Monique; SIMON, Jonathon L.
Objective To estimate the impact of antiretroviral therapy (ART) on labor productivity and income using detailed employment data from two large tea plantations in western Kenya for HIV-infected tea pluckers who initiated ART. Design Longitudinal study using primary data on key employment outcomes for a group of HIV-infected workers receiving anti-retroviral therapy (ART) and workers in the general workforce. Methods We used nearest-neighbor matching methods to estimate the impacts of HIV/AIDS and ART among 237 HIV-positive pluckers on ART (index group) over a four year period (2 years pre- and post-ART) on four monthly employment outcomes—days plucking tea, total kilograms harvested, total days working, and total labor income. Outcomes for the index group were compared to those for a matched reference group from the general workforce. Results We observed a rapid deterioration in all four outcomes for HIV-infected subjects in the period before ART initiation and then a rapid improvement after treatment initiation. By 18–24 months after treatment initiation, the index group harvested 8% (males) and 19% (females) less tea than reference subjects. The index group earned 6% (males) and 9% (females) less income from labor than reference subjects. Women’s income would have dropped further if they had not been able to offset their decline in tea plucking by spending more time on non-plucking assignments. Conclusions HIV-infected workers experienced long-term income reductions before and after initiating ART. The implications of such long-term impacts in low-income countries have not been adequately addressed. PMID:23014516
Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.
The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888
Pineles, Stacy L; Demer, Joseph L; Holland, Gary N; Ransome, Susan S; Bonelli, Laura; Velez, Federico G
On rare occasions, patients infected with human immunodeficiency virus (HIV) can develop a disorder similar to chronic progressive external ophthalmoplegia (CPEO) while undergoing long-term treatment with antiretroviral therapy. Orbital imaging may help explain the pathogenesis of this abnormality. In this case series, 5 adult patients who presented with a CPEO-like disorder after more than 10 years of antiretroviral therapy and who underwent T1-weighted high-resolution magnetic resonance imaging (MRI) of the orbits and brain were retrospectively identified. Patients also were screened for acetylcholine receptor antibody levels. All patients had bilateral external ophthalmoplegia and blepharoptosis. Acetylcholine receptor antibody titers were not increased. Brain MRI was unremarkable. Orbital MRI showed patchy bright signal inside the extraocular muscles that had conserved volume. Patients with HIV under long-term antiretroviral therapy may develop functional abnormalities of extraocular muscles that are structurally normal in size, that is, changes are similar to those observed in the orbital MRIs of patients with CPEO. This constellation of signs and symptoms suggests a possible role of HIV disease or antiretroviral therapy in the CPEO-like syndrome observed in some HIV-infected individuals. Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.
Mirochnick, Mark; Thomas, Timothy; Capparelli, Edmund; Zeh, Clement; Holland, Diane; Masaba, Rose; Odhiambo, Prisca; Fowler, Mary Glenn; Weidle, Paul J; Thigpen, Michael C
There are limited data describing the concentrations of zidovudine, lamivudine, and nevirapine in nursing infants as a result of transfer via breast milk. The Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal, intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and nevirapine from 34 weeks of gestation to 6 months postpartum. In a pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood spots were collected for drug assay on the day of delivery and at 2, 6, 14, and 24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The median concentrations in breast milk of zidovudine, lamivudine, and nevirapine during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml, respectively. Zidovudine was not detectable in any infant plasma samples obtained after the day of delivery, while the median concentrations in infant plasma samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine, respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations. The extent and effect of infant drug exposure via breast milk must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.
Martinez, Valrie; Ta, Thi Dieu Ngan; Mokhtari, Zahra; Guiguet, Marguerite; Miailhes, Patrick; Valantin, Marc-Antoine; Charlotte, Frderic; Bertheau, Philippe; Molina, Jean-Michel; Katlama, Christine; Caumes, Eric
In HIV and hepatitis C virus (HCV) coinfected patients, the role of antiretroviral therapy (ART) on hepatic steatosis (HS) remains controversial. HIV/HCV coinfected patients receiving ART and previously untreated for HCV who underwent a liver biopsy were included. Cumulative duration of exposure to each antiretroviral was recorded up to liver biopsy date. Logistic regression analyses evaluated factors associated with steatosis and its severity. 184 patients were included: median age 41 years, 84% male, 89% Caucasian, 61% with a past history of intravenous drug use. HCV genotypes were 1 (55%), 2 (6%), 3 (26%), and 4 (13%). Median HCV-RNA was 6.18 log10 IU/ml. HIV-RNA was undetectable (<400 copies/ml) in 67% of patients. Median CD4 count was 321/mm3. All patients had been exposed to nucleoside reverse transcriptase inhibitors (median cumulative exposure 56 months); 126 received protease inhibitors (23 months), and 79 non-nucleoside reverse transcriptase inhibitors (16 months). HS was observed in 102 patients (55%): 41% grade 1; 5% grade 2, and 9% grade 3. In multivariate analysis, HCV genotype 3 and HCV viral load were moderately associated with mild steatosis but strongly with grade 2-3 steatosis. After adjustment for the period of biopsy, no association was detected between HS and exposure to any antiretroviral class or drug, or duration of ART globally or comparing genotype 3 to others. Among our ART-treated HIV-HCV cohort predominantly infected with genotype 1, 55% of patients had HS which was associated with HCV-related factors, but not ART class or duration of exposure.
Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho
To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The "Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral" (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test.
Wilson, Ira B.; Laws, M. Barton; Safren, Steven A.; Lee, Yoojin; Lu, Minyi; Coady, William; Skolnik, Paul R.; Rogers, William H.
Background Physicians' limited knowledge of patients' antiretroviral adherence may reduce their ability to perform effective adherence counseling. Methods We conducted a randomized, cross-over study of an intervention to improve physicians' knowledge of patients' antiretroviral adherence. The intervention was a report given to the physician prior to a routine office visit that included data on: MEMS and self-reported data on antiretroviral adherence, patients' beliefs about antiretroviral therapy, reasons for missed doses, alcohol and drug use, and depression. We audio-recorded one intervention and one control visit for each patient to analyze differences in adherence related dialogue. Results 156 patients were randomized, and 106 completed all 5 study visits. Paired audio-recorded visits were available for 58 patients. Using a linear regression model that adjusted for site and baseline MEMS adherence, adherence following intervention visits did not differ significantly from control visits (2.0% higher, p=0.31, 95% CI -1.95% – 5.9%). There was a trend toward more total adherence-related utterances (median of 76 vs. 49.5, p=0.07) and a significant increase in utterances about the current regimen (median of 51.5 vs. 32.5, p=0.0002) in intervention compared with control visits. However less than 10% of adherence-related utterances were classified as “problem solving” in content, and one third of physicians' problem solving utterances were directive in nature. Conclusions Receipt of a detailed report prior to clinic visits containing data about adherence and other factors did not improve patients' antiretroviral adherence. Analyses of patient-provide dialogue suggests that providers who care for persons with HIV may benefit from training in adherence counseling techniques. PMID:20048680
Peterson, Kevin; Jallow, Sabelle; Rowland-Jones, Sarah L.; de Silva, Thushan I.
HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations. PMID:21490779
Dhakal, Ishwori; Casper, Corey; Noy, Ariela; Palefsky, Joel M.; Haigentz, Missak; Krown, Susan E.; Ambinder, Richard F.; Mitsuyasu, Ronald T.
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
Lodi, Sara; Sharma, Shweta; Lundgren, Jens D; Phillips, Andrew N; Cole, Stephen R; Logan, Roger; Agan, Brian K; Babiker, Abdel; Klinker, Hartwig; Chu, Haitao; Law, Matthew; Neaton, James D; Hernán, Miguel A
The Strategic Timing of AntiRetroviral Treatment (START) trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier than the protocol specified. To supplement the published intention-to-treat (ITT) effect estimates, here we estimate the per-protocol effect of immediate versus deferred ART initiation in START. The START trial randomized 4685 HIV-positive participants with CD4 cell counts more than 500 cells/μl to start ART immediately after randomization (immediate initiation group) or to wait until the CD4 cell count dropped below 350 cells/μl or an AIDS diagnosis (deferred initiation group). We used the parametric g-formula to estimate and compare the cumulative 5-year risk of the composite clinical outcome in the immediate initiation group, and deferred initiation groups had all the trial participants adhered to the protocol. We estimated that the 5-year risk of the composite outcome would have been 3.2% under immediate ART initiation and 7.0% under deferred initiation. The difference of 3.8% (95% confidence interval 1.5, 6.5) was larger than the ITT effect estimate of 3.1%, corresponding to a difference in effect estimates of 0.72% (-0.35, 2.35). The ITT effect estimate may underestimate the benefit of immediate ART initiation by 23%. This estimate can be used by patients and policy-makers who need to understand the full extent of the benefit of changes in ART initiation policies.
Lorio, Marco A.; Morris, Michele I.; Abbo, Lilian M.; Simkins, Jacques; Guerra, Giselle; Roth, David; Kupin, Warren L.; Mattiazzi, Adela; Ciancio, Gaetano; Chen, Linda J.; Burke, George W.; Figueiro, Jose M.; Ruiz, Phillip; Camargo, Jose F.
Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients. PMID:28299182
Rosa, Rossana; Suarez, Jose F; Lorio, Marco A; Morris, Michele I; Abbo, Lilian M; Simkins, Jacques; Guerra, Giselle; Roth, David; Kupin, Warren L; Mattiazzi, Adela; Ciancio, Gaetano; Chen, Linda J; Burke, George W; Figueiro, Jose M; Ruiz, Phillip; Camargo, Jose F
Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV (+) kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV (-) to HIV (+) adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV (+) kidney transplant recipients.
Cain, Lauren E; Saag, Michael S; Petersen, Maya; May, Margaret T; Ingle, Suzanne M; Logan, Roger; Robins, James M; Abgrall, Sophie; Shepherd, Bryan E; Deeks, Steven G; John Gill, M; Touloumi, Giota; Vourli, Georgia; Dabis, François; Vandenhende, Marie-Anne; Reiss, Peter; van Sighem, Ard; Samji, Hasina; Hogg, Robert S; Rybniker, Jan; Sabin, Caroline A; Jose, Sophie; Del Amo, Julia; Moreno, Santiago; Rodríguez, Benigno; Cozzi-Lepri, Alessandro; Boswell, Stephen L; Stephan, Christoph; Pérez-Hoyos, Santiago; Jarrin, Inma; Guest, Jodie L; D'Arminio Monforte, Antonella; Antinori, Andrea; Moore, Richard; Campbell, Colin Nj; Casabona, Jordi; Meyer, Laurence; Seng, Rémonie; Phillips, Andrew N; Bucher, Heiner C; Egger, Matthias; Mugavero, Michael J; Haubrich, Richard; Geng, Elvin H; Olson, Ashley; Eron, Joseph J; Napravnik, Sonia; Kitahata, Mari M; Van Rompaey, Stephen E; Teira, Ramón; Justice, Amy C; Tate, Janet P; Costagliola, Dominique; Sterne, Jonathan Ac; Hernán, Miguel A
When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting. Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.
Sax, Paul E.; Sypek, Alexis; Berkowitz, Bethany K.; Morris, Bethany L.; Losina, Elena; Paltiel, A. David; Kelly, Kathleen A.; Seage, George R.; Walensky, Rochelle P.; Weinstein, Milton C.; Eron, Joseph; Freedberg, Kenneth A.
Background We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV. PMID:25397616
Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat
We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients.
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
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
Jordan, Rachel; Gold, Lisa; Cummins, Carole; Hyde, Chris
Objective To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy. Design Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment. Participants Patients with any stage of HIV infection who had not received antiretroviral therapy. Main outcome measures Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers). Search strategy Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001. Results 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality. Conclusions Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs. What is already known on this topicTriple combination antiretroviral therapy is accepted by clinicians and patients as the usual treatment for HIV and has evolved through an incremental strategy in the numbers of drugs combinedGuidance on treatment, however, has predominantly been based on early reports of researchThere are no published analyses that assess the effectiveness of the increasing numbers of drugs used in combinationWhat this study addsThe results of
Gadwalkar, Srikant R; Deepa, D V; Katageri, Anand; Murthy, P Rama; Dhar, Ravi
Persons with HIV infection frequently present with anaemia from different causes, including use of antiretroviral therapy (typically zidovudine), iron deficiency, vitamin B12 deficiency, opportunistic infections (such as mycobacterial and fungal infections), chronic disease, AIDS-associated malignancies, autoimmune haemolysis, and direct effects of HIV infection itself. Persistent infection with Parvovirus B19 (B19) is an important treatable cause of anaemia in HIV-infected patients. We present a case of anaemia in HIV positive patient who did not respond to change of drug therapy and nutritional supplements. Bone marrow biopsy suggested parvo virus infection. Chronic anaemia due to Parvo virus B19 infection is a treatable cause. Human Parvo virus B19 infection is a diagnosis of exclusion in patients who are started on antiretroviral therapy develop anaemia and later not responding to empirical management. Chronic anaemia requiring recurrent transfusions in HIV positive patient Parvo virus infection should be suspected and evaluated.
Robbins, Gregory K.; Testa, Marcia A.; Su, Max; Safren, Steven A.; Morse, Gene; Lammert, Sara; Shafer, Robert W.; Reynolds, Nancy R.; Chesney, Margaret A.
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
Tshikung, Olivier Nawej; Calmy, Alexandra
In 2015, the publication of important studies allowed the development of new guidelines, notably by WHO and the European AIDS ClinicalSociety (EACS), for HIV preventive treatment (pre-exposure prophylaxis), as well as for the start of antiretroviral treatment. The START and TEMPRANO studies have extended the treatment to all HIV-infected patients, irrespective of the level of immunosuppression and therefore the CD4 count. In addition, innovative screening methods, such as self-tests, are now available in all French pharmacies since 15 September 2015. The latest developments in 2015 concerning the prevention, screening, and treatment of HIV are discussed in this article and will certainly have an impact on the care of patients in Switzerland.
de Boer, Mark G J; van den Berk, Guido E L; van Holten, Natasja; Oryszcyn, Josephine E; Dorama, Willemien; Moha, Daoud Ait; Brinkman, Kees
Dolutegravir (DGV) is one of the preferred antiretroviral agents in first-line combination antiretroviral therapy (cART). Though considered to be a well tolerated drug, we aimed to determine the actual rate, timing and detailed motivation of stopping DGV in a real-life clinical setting. A cohort study including all patients who started DGV in two HIV treatment centers in The Netherlands. All cART-naïve and cART-experienced patients who had started DGV were identified from the institutional HIV databases. Clinical data, including motivation and timing of discontinuation of DGV, were extracted from the patient files. Factors that potentially influenced discontinuation of DGV were compared between patients who stopped or continued DGV by multivariate and Kaplan-Meier analyses. In total, 556 patients were included, of whom 102 (18.4%) were cART-naïve at initiation of DGV. Median follow-up time was 225 days. Overall, in 85 patients (15.3%), DGV was stopped. In 76 patients (13.7%), this was due to intolerability. Insomnia and sleep disturbance (5.6%), gastrointestinal complaints (4.3%) and neuropsychiatric symptoms such as anxiety, psychosis and depression (4.3%) were the predominant reasons for switching DGV. In regimens that included abacavir, DGV was switched more frequently (adjusted relative risk 1.92, 95% confidence interval 1.09-3.38, P log-rank 0.01). No virologic failures were observed. A relatively high rate of preliminary discontinuation of DGV due to intolerability was detected in our patient population. In particular, DGV was stopped more frequently if the regimen included abacavir. Multiple factors may explain these unexpected postmarketing observations, which warrant further investigation.
Wongcharoen, Wanwarang; Suaklin, Somkhuan; Tantisirivit, Nualnit; Phrommintikul, Arintaya; Chattipakorn, Nipon
A higher prevalence of QT prolongation has been reported among human immunodeficiency virus (HIV)-infected patients. Previous studies have demonstrated that QT dispersion is a better predictor of serious ventricular tachyarrhythmia and cardiac mortality than corrected QT (QTc) interval. However, data of QT dispersion in HIV-infected patients receiving a combined antiretroviral therapy (cART) is limited. We sought to assess QTc interval and QT dispersion in HIV-infected patients receiving cART. The association between QT parameters and heart rate variability (HRV) was also examined. Ninety-one HIV-infected patients receiving cART (male = 33, mean age = 44 ± 10 years) and 70 HIV-seronegative subjects (male = 25, mean age = 44 ± 8 years) were enrolled in the study. In a resting 12-lead electrocardiogram, QT interval was measured by the tangent method in all leads with well-defined T waves. The QT dispersion was defined as the difference between maximum and minimum QTc intervals in any of 12 leads. The baseline characteristics were not different between the two groups. We demonstrated the significantly longer mean QTc interval (420 ± 21 vs. 409 ± 21 ms, P < 0.001), and greater QT dispersion in HIV-infected group compared to the control group (85 ± 29 vs. 55 ± 23 ms, P < 0.001). Among the HIV-infected patients, those who had lower CD4 lymphocyte count (<350 cells/mm(3)) tended to have greater QT dispersion (92 ± 28 vs. 81 ± 29 ms, P = 0.098). There were no associations between QT parameters and either HRV or cART regimens. HIV-infected patients receiving cART were associated with prolonged QTc interval and increased QT dispersion, independent of autonomic dysfunction and antiretroviral drugs, which may have led to the potentially higher risk of ventricular arrhythmia and cardiac mortality. © 2014 Wiley Periodicals, Inc.
Beckham, Sarah W; Beyrer, Chris; Luckow, Peter; Doherty, Meg; Negussie, Eyerusalem K; Baral, Stefan D
significantly greater hazards of all-cause mortality compared with women while on antiretroviral therapy in LMIC. This effect persists over time on treatment. The clinical and population-level prevention benefits of antiretroviral therapy will only be realized if programmes can improve male engagement, diagnosis, earlier initiation of therapy, clinical outcomes and can support long-term adherence and retention. PMID:27834182
Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M
In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m(2) and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to
Ramadhani, Habib O.; Bartlett, John A.; Thielman, Nathan M.; Pence, Brian W.; Kimani, Stephen M.; Maro, Venance P.; Mwako, Mtumwa S.; Masaki, Lazaro J.; Mmbando, Calvin E.; Minja, Mary G.; Lirhunde, Eileen S.; Miller, William C.
Background Adherence to first-line antiretroviral therapy (ART) may be an important indicator of adherence to second-line ART. Evaluating this relationship may be critical to identify patients at high risk for second-line failure, thereby exhausting their treatment options, and to intervene and improve patient outcomes. Methods Adolescents and adults (n = 436) receiving second-line ART were administered standardized questionnaires that captured demographic characteristics and assessed adherence. Optimal and suboptimal cumulative adherence were defined as percentage adherence of ≥90% and <90%, respectively. Bivariable and multivariable binomial regression models were used to assess the prevalence of suboptimal adherence percentage by preswitch adherence status. Results A total of 134 of 436 (30.7%) participants reported suboptimal adherence to second-line ART. Among 322 participants who had suboptimal adherence to first-line ART, 117 (36.3%) had suboptimal adherence to second-line ART compared with 17 of 114 (14.9%) who had optimal adherence to first-line ART. Participants who had suboptimal adherence to first-line ART were more likely to have suboptimal adherence to second-line ART (adjusted prevalence ratio, 2.4; 95% confidence interval, 1.5–3.9). Conclusions Adherence to first-line ART is an important predictor of adherence to second-line ART. Targeted interventions should be evaluated in patients with suboptimal adherence before switching into second-line therapy to improve their outcomes. PMID:25734147
Ramadhani, Habib O; Bartlett, John A; Thielman, Nathan M; Pence, Brian W; Kimani, Stephen M; Maro, Venance P; Mwako, Mtumwa S; Masaki, Lazaro J; Mmbando, Calvin E; Minja, Mary G; Lirhunde, Eileen S; Miller, William C
Adherence to first-line antiretroviral therapy (ART) may be an important indicator of adherence to second-line ART. Evaluating this relationship may be critical to identify patients at high risk for second-line failure, thereby exhausting their treatment options, and to intervene and improve patient outcomes. Adolescents and adults (n = 436) receiving second-line ART were administered standardized questionnaires that captured demographic characteristics and assessed adherence. Optimal and suboptimal cumulative adherence were defined as percentage adherence of ≥90% and <90%, respectively. Bivariable and multivariable binomial regression models were used to assess the prevalence of suboptimal adherence percentage by preswitch adherence status. A total of 134 of 436 (30.7%) participants reported suboptimal adherence to second-line ART. Among 322 participants who had suboptimal adherence to first-line ART, 117 (36.3%) had suboptimal adherence to second-line ART compared with 17 of 114 (14.9%) who had optimal adherence to first-line ART. Participants who had suboptimal adherence to first-line ART were more likely to have suboptimal adherence to second-line ART (adjusted prevalence ratio, 2.4; 95% confidence interval, 1.5-3.9). Adherence to first-line ART is an important predictor of adherence to second-line ART. Targeted interventions should be evaluated in patients with suboptimal adherence before switching into second-line therapy to improve their outcomes.
Lin, Chunqing; Cao, Xiaobin; Li, Li
Background Using methadone maintenance therapy (MMT) clinics to deliver antiretroviral therapy (ART) is an effective strategy to promote treatment initiation and adherence for HIV-positive drug users. This paper describes the implementation barriers perceived by service providers for an intervention pilot designed to integrate ART services in MMT clinics. Methods The study was conducted in six MMT clinics in Sichuan province, China. Two service providers selected from each of the six clinics underwent training in administering ART. The trained providers delivered ART-related services in their clinics. A focus group was conducted among the service providers to assess their experiences and perceived challenges in delivering integrated services. Results Barriers at policy, institutional, provider, and client levels were identified. Policy level barriers included household registration restrictions and a lack of insurance coverage for testing expenses. Inefficient coordination between treatment sites and MMT clinics was an obstacle at the institutional level. Insufficient training and added workload were barriers at the provider level. Finally, conflict with daily dosing habits was identified as the primary reason that clients did not accept ART. Conclusion Although integrating ART into MMT clinics is beneficial, multilevel barriers to implementation need to be addressed. This study documents the need for treatment transferability and insurance coverage, protection of client confidentiality, proper provider training, coordination with treatment sites, and individualized ART service for MMT clients. PMID:24939555
Gandhi, Monica; Ameli, Niloufar; Bacchetti, Peter; Anastos, Kathryn; Gange, Stephen J; Minkoff, Howard; Young, Mary; Milam, Joel; Cohen, Mardge H; Sharp, Gerald B; Huang, Yong; Greenblatt, Ruth M
Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral
Gosselin, Annie; Wiche Salinas, Tomas Raul; Planas, Delphine; Wacleche, Vanessa S.; Zhang, Yuwei; Fromentin, Rémi; Chomont, Nicolas; Cohen, Éric A.; Shacklett, Barbara; Mehraj, Vikram; Ghali, Maged P.; Routy, Jean-Pierre; Ancuta, Petronela
Objectives: The objective of this article is to investigate the contribution of colon and blood CD4+ T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies and blood samples (n = 13) as well as leukapheresis (n = 20) were collected from chronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4+ T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA−), central memory (TCM; CD45RA−CCR7+), effector (TEM/TM; CD45RA−CCR7−), Th17 (CCR6+CCR4+), Th1Th17 (CCR6+CXCR3+), Th1 (CCR6−CXCR3+), and Th2 (CCR6−CCR4+). Methods: We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV DNA quantification, ELISA and flow cytometry for HIV p24 quantification. HIV reactivation was induced by TCR triggering in the presence/absence of all-trans retinoic acid. Results: Compared with blood, the frequency of CCR6+ TM was higher in the colon. In both colon and blood compartments, CCR6+ TM were significantly enriched in HIV DNA when compared with their CCR6− counterparts (n = 13). In blood, integrated HIV DNA levels were significantly enriched in CCR6+ versus CCR6− TCM of four of five individuals and CCR6+ versus CCR6− TEM of three of five individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV DNA despite their reduced frequency compared with Th2, which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6+ versus CCR6− TM, TCM, and TEM. Conclusion: CCR6 is a marker for colon and blood CD4+ T cells enriched for replication-competent HIV DNA. Novel eradication strategies should target HIV persistence in CCR6+CD4+ T cells from various anatomic sites. PMID:27835617
Inzaule, Seth C; Ondoa, Pascale; Peter, Trevor; Mugyenyi, Peter N; Stevens, Wendy S; de Wit, Tobias F Rinke; Hamers, Raph L
Increased provision of antiretroviral therapy in sub-Saharan Africa has led to a growing number of patients with therapy failure and acquired drug-resistant HIV, driving the demand for more costly further lines of antiretroviral therapy. In conjunction with accelerated access to viral load monitoring, feasible and affordable technologies to detect drug-resistant HIV could help maximise the durability and rational use of available drug regimens. Potential low-cost technologies include in-house Sanger and next-generation sequencing in centralised laboratories, and point mutation assays and genotype-free systems that predict response to antiretroviral therapy at point-of-care. Strengthening of centralised high-throughput laboratories, including efficient systems for sample referral and results delivery, will increase economies-of-scale while reducing costs. Access barriers can be mitigated by standardisation of in-house assays into commercial kits, use of polyvalent instruments, and adopting price-reducing strategies. A stepwise rollout approach should improve feasibility, prioritising WHO-recommended population-based surveillance and management of complex patient categories, such as patients failing protease inhibitor-based antiretroviral therapy. Implementation research, adaptations of existing WHO guidance, and political commitment, will be key to support the appropriate investments and policy changes. In this Personal View, we discuss the potential role of HIV drug resistance testing for population-based surveillance and individual patient management in sub-Saharan Africa. We review the strengths and challenges of promising low-cost technologies and how they can be implemented. Copyright © 2016 Elsevier Ltd. All rights reserved.
Olisah, V O; Baiyewu, O; Sheikh, T L
To determine the prevalence of depressive disorder in patients with HIV/AIDS receiving HAART; to determine the effect of depressive disorder on adherence to antiretroviral therapy; and to determine the significance of the association. The study was conducted amongst outpatients of Ahmadu Bello University Teaching Hospital, Zaria. A sociodemographic and drug adherence questionnaire was administered. The Centre for Epidemiological Studies Depression Scale (CES-D) was used to screen for depressive symptoms while the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to confirm the diagnosis of depressive disorder. A total of 310 patients with HIV/AIDS receiving HAART participated in the study. 68.4% were female and the mean age was 35.5 (± 8.97 years). 37.4% had secondary education, while 27.1% had tertiary education. Sixty-six participants (21.3%) had significant depressive symptoms while 14.2% met ICD-10 diagnostic criteria for depressive disorder. Overall, 73% of participants had good adherence to HAART. 63.6% of participants with depressive disorder had poor adherence to HAART compared to 21.1% of participants without depressive disorder (p<0.05). Depressive disorder in patients with HIV/AIDS is associated with poor adherence to antiretroviral medication. Early identification and treatment of depression in such patients may improve antiretroviral medication adherence and treatment outcomes.
Manguro, Griffins O.; Masese, Linnet N.; Deya, Ruth W.; Magaret, Amalia; Wald, Anna; McClelland, R. Scott; Graham, Susan M.
Objectives Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. PMID:27683204
Charalambous, S; Grant, A D; Day, J H; Pemba, L; Chaisson, R E; Kruger, P; Martin, D; Wood, R; Brink, B; Churchyard, G J
Ways to expand access to antiretroviral treatment (ART) in low income settings are being sought. We describe an HIV care programme including ART in an industrial setting in South Africa. The programme uses guidelines derived from local and international best practice. The training component aims to build capacity among health care staff. Nurses and doctors are supported by experienced HIV clinicians through telephone consultation and site visits. Patients undergo a three-stage counselling procedure prior to starting ART. Drug regimens and monitoring are standardised and prophylaxis against opportunistic infections (isoniazid and cotrimoxazole) is offered routinely. Laboratory and pharmacy services, using named-patient dispensing, are centralized. The programme is designed to ensure that data on clinical and economic outcomes will be available for programme evaluation. Between November 2002-December 2004, ART delivery has been established at 70 ART workplace ART sites. The sites range from 200 to 12000 employees, and from small occupational health clinics and general practitioner rooms to larger hospital clinics. During this period, 2456 patients began ART. Of those on treatment for at least three months, 1728 (78%) have been retained on the programme and only 38 (1.7%) patients have failed the first-line ART regimen. This model for delivery of ART is feasible and successful in an industrial setting. The model may be generalizable to other employment health services in settings of high HIV prevalence, and as a model for implementing ART in other types of health-care settings.
Dalessandro, Margherita; Conti, Chiara M; Gambi, Francesco; Falasca, Katia; Doyle, Robert; Conti, Pio; Caciagli, Francesco; Fulcheri, Mario; Vecchiet, Jacopo
Several strategies have been introduced to manage nonadherence to highly active antiretroviral therapy (HAART). Treatment with antidepressants may improve self-reported adherence. In this brief report, a small sample of HIV-depressed patients (n = 9) were treated for a 6-month period with antidepressants improving self-reported adherence based on the HAART scale (poor, good, satisfactory, and optimal). Before the antidepressant treatment, adherence was reported as "good" by 3 patients and "satisfactory" by 6 patients. After antidepressant therapy, adherence to antiretroviral regimes was statistically higher in HIV-depressed on treatment than in HIV-depressed patients not treated with antidepressants (P < 0.0001). We used chi2 test with a significance level at P < 0.05. Treating depression in HIV-infected patients may serve to improve adherence to HAART.
Li, Nan; Sando, Mary Mwanyika; Spiegelman, Donna; Hertzmark, Ellen; Liu, Enju; Sando, David; Machumi, Lameck; Chalamilla, Guerino; Fawzi, Wafaie
Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy.
Paul, Simon; Bogdanov, Mikhail B; Matson, Wayne R; Metakis, Linda; Jacobs, Jonathan; Beal, M Flint
Mitochondrial toxicity of nucleoside analogues has been proposed to be the etiology of a range of side-effects from antiretroviral therapy of HIV infection. In this study, urinary 8-hydroxy-2'-deoxyguanosine (8OH2'dG), a metabolite of oxidized DNA, was measured to determine if antiretroviral therapy leads to oxidative damage to DNA. A cross-sectional study was carried out measuring urinary 8OH2'dG in three groups of HIV-infected patients: (1) antiretroviral medication naïve, (2) patients on antiretroviral medications without lipodystrophy and (3) patients on antiretroviral medications with lipodystrophy. Twenty-five patients were enrolled in each group. The mean spot urinary 8OH2'dG measurements per mg creatinine for the three groups were: antiretroviral naïve 4.27 +/- 0.61 (ng 8OH2'dG/mg creatinine +/- SEM), on antiretroviral medications without lipodystrophy 2.88 +/- 0.26, and on antiretroviral medications with lipodystrophy 3.27 +/- 0.30. The differences between the means of the three groups is not statistically significant (p = 0.055), and these results are not significantly different from reported values for healthy controls [A carbon column-based liquid chromatography electrochemical approach to routine 8-hydroxy-2-deoxyguanosine measurements in urine and other biologic matrices: a one-year evaluation of methods. Free Radical Biology and Medicine 27 (1999) 647-666].
Ehrhard, Simone; Wernli, Marion; Dürmüller, Ursula; Battegay, Manuel; Gudat, Fred; Erb, Peter
Human immunodeficiency virus infection leads to T-cell exhaustion and involution of lymphoid tissue. Recently, the programmed death-1 pathway was found to be crucial for virus-specific T-cell exhaustion during human immunodeficiency virus infection. Programmed death-1 expression was elevated on human immunodeficiency virus-specific peripheral blood CD8+ and CD4+ T cells and correlated with disease severity. During human immunodeficiency infection, lymphoid tissue acts as a major viral reservoir and is an important site for viral replication, but it is also essential for regulatory processes important for immune recovery. We compared programmed death-1 expression in 2 consecutive inguinal lymph nodes of 14 patients, excised before antiretroviral therapy (antiretroviral therapy as of 1997-1999) and 16 to 20 months under antiretroviral therapy. In analogy to lymph nodes of human immunodeficiency virus-negative individuals, in all treated patients, the germinal center area decreased, whereas the number of germinal centers did not significantly change. Programmed death-1 expression was mostly found in germinal centers. The absolute extent of programmed death 1 expression per section was not significantly altered after antiretroviral therapy resulting in a significant-relative increase of programmed death 1 per shrunken germinal center. In colocalization studies, CD45R0+ cells that include helper/inducer T cells strongly expressed programmed death-1 before and during therapy, whereas CD8+ T cells, fewer in numbers, showed a weak expression for programmed death-1. Thus, although antiretroviral therapy seems to reduce the number of programmed death-1-positive CD8+ T lymphocytes within germinal centers, it does not down-regulate programmed death-1 expression on the helper/inducer T-cell subset that may remain exhausted and therefore unable to trigger immune recovery.
Bamba, Sanata; Lortholary, Olivier; Sawadogo, Adrien; Millogo, Athanase; Guiguemdé, Robert T; Bretagne, Stéphane
Cryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso.
Cheron, Julian; Wyndham-Thomas, Chloé; Sadeghi, Niloufar; Naeije, Gilles
When secondary causes are excluded, mechanisms underlying central nervous system angiitis (ACNS) in human immunodeficiency virus (HIV)-infected patients are still not understood and optimal treatment remains undefined. We report here a patient with an untreated HIV infection who presented multiple ischemic strokes probably due to HIV-ACNS. ACNS signs on vessel-wall imaging magnetic resonance monitoring retracted with combined antiretroviral therapy without adjunct immunosuppressive drugs. PMID:28348548
Mavhandu-Mudzusi, A H; Sandy, P T; Hettema, A
Swaziland has the highest HIV prevalence globally. It faces a critical shortage of health workers for addressing the HIV pandemic. To curb this human resource challenge, Swaziland adopted a nurse-driven model for antiretroviral therapy delivery in line with the recommendations of the World Health Organization on task shifting. The study explored the perceptions of registered nurses on the nurse-led antiretroviral therapy initiation programme in the Hhohho region of Swaziland (NARTIS). The study utilized a phenomenological design, specifically a phenomenographic design. The study was conducted in ten health facilities in the Hhohho region of Swaziland. These facilities comprised eight clinics, a hospital and a health centre. These were registered nurses, trained and certified in the nurse-led antiretroviral therapy initiation programme. The nurses also had experience of working in a nurse-led antiretroviral therapy initiation programme. Eighteen (18) nurses were purposively selected and recruited to participate in the study. Data were collected through open and deep individual interviews guided by a semi-structured interview schedule. The audio-recorded interviews were transcribed and analysed thematically using Sjöström and Dahlgren's approach to data analysis. Three major themes emerged from the study data: nurses' emotional reactions to the implementation of the NARTIS programme, and influences and overcoming barriers to the programme. The study findings have generated insights into this program which is useful for the provision of care to people living with HIV/AIDS in Swaziland. But nurses need support to ensure effective implementation. The study findings have implications for both the practice of the NARTIS programme and health policy development. The development of a health policy that alleviates the barriers to the NARTIS programme can enhance nurses' role and make care provision to people living with HIV/AIDS more effective. © 2017 International Council
Choi, Ju-yeon; Kwon, Oh-Kyung; Choi, Byeong-Sun; Kee, Mee-Kyung; Park, Mina; Kim, Sung Soon
Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20 types of antiretroviral drugs are used in the treatment of human immunodeficiency virus-infected/acquired immune deficiency syndrome patients in South Korea. Despite the rapid development of various antiretroviral drugs, many drug-resistant variants have been reported after initiating HAART, and the efficiency of HAART is limited by these variants. To investigate and estimate the annual antiretroviral drug resistance and prevalence of antiretroviral multi-class drug resistance in Korean patients with experience of treatment. The amplified HIV-1 pol gene in 535 patients requested for genotypic drug resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and Prevention was sequenced and analyzed annually and totally. The prevalence of antiretroviral drug resistance was estimated based on "SIR" interpretation of the Stanford sequence database. Of viruses derived from 787 specimens, 380 samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3% for PI. The percent of annual drug resistance showed similar pattern and slightly declined except 2004 and 2005. The prevalence of multi-class drug resistance against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI, 10.4%; and NRTI/NNRTI, 21.5%. About 50% and less than 10% of patients infected with HIV-1 have multidrug and multiclass resistance linked to 16 antiretroviral drugs, respectively. The significance of this study lies in its larger-scale examination of the prevalence of drug-resistant variants and multidrug resistance in HAART-experienced patients in South Korea. Copyright © 2014 Elsevier B.V. All rights reserved.
Cole, Stephen R.; Greenland, Sander; Brown, Todd T.; Chmiel, Joan S.; Kingsley, Lawrence; Detels, Roger
Human immunodeficiency virus (HIV) researchers often use calendar periods as an imperfect proxy for highly active antiretroviral therapy (HAART) when estimating the effect of HAART on HIV disease progression. The authors report on 614 HIV-positive homosexual men followed from 1984 to 2007 in 4 US cities. During 5,321 person-years, 268 of 614 men incurred acquired immunodeficiency syndrome, 49 died, and 90 were lost to follow-up. Comparing the pre-HAART calendar period (<1996) with the HAART calendar period (≥1996) resulted in a naive rate ratio of 3.62 (95% confidence limits: 2.67, 4.92). However, this estimate is likely biased because of misclassification of HAART use by calendar period. Simple calendar period approaches may circumvent confounding by indication at the cost of inducing exposure misclassification. To correct this misclassification, the authors propose an instrumental-variable estimator analogous to ones previously used for noncompliance corrections in randomized clinical trials. When the pre-HAART calendar period was compared with the HAART calendar period, the instrumental-variable rate ratio was 5.02 (95% confidence limits: 3.45, 7.31), 39% higher than the naive result. Weighting by the inverse probability of calendar period given age at seroconversion, race/ethnicity, and time since seroconversion did not appreciably alter the results. These methods may help resolve discrepancies between observational and randomized evidence. PMID:19318615
Hermans, Sabine M; van Leth, Frank; Kiragga, Agnes N; Hoepelman, Andy I M; Lange, Joep M A; Manabe, Yukari C
To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution. © 2012 Blackwell Publishing Ltd.
Cain, Lauren E; Cole, Stephen R; Greenland, Sander; Brown, Todd T; Chmiel, Joan S; Kingsley, Lawrence; Detels, Roger
Human immunodeficiency virus (HIV) researchers often use calendar periods as an imperfect proxy for highly active antiretroviral therapy (HAART) when estimating the effect of HAART on HIV disease progression. The authors report on 614 HIV-positive homosexual men followed from 1984 to 2007 in 4 US cities. During 5,321 person-years, 268 of 614 men incurred acquired immunodeficiency syndrome, 49 died, and 90 were lost to follow-up. Comparing the pre-HAART calendar period (<1996) with the HAART calendar period (>or=1996) resulted in a naive rate ratio of 3.62 (95% confidence limits: 2.67, 4.92). However, this estimate is likely biased because of misclassification of HAART use by calendar period. Simple calendar period approaches may circumvent confounding by indication at the cost of inducing exposure misclassification. To correct this misclassification, the authors propose an instrumental-variable estimator analogous to ones previously used for noncompliance corrections in randomized clinical trials. When the pre-HAART calendar period was compared with the HAART calendar period, the instrumental-variable rate ratio was 5.02 (95% confidence limits: 3.45, 7.31), 39% higher than the naive result. Weighting by the inverse probability of calendar period given age at seroconversion, race/ethnicity, and time since seroconversion did not appreciably alter the results. These methods may help resolve discrepancies between observational and randomized evidence.
Itinoseki Kaio, Daniella J Itinoseki; Rondó, Patricia Helen C; Luzia, Liania Alves; Souza, José Maria P; Firmino, Aline Vale; Santos, Sigrid Sousa
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.
Brewinski, Margaret; Megazzini, Karen; Freimanis Hance, Laura; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa
In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3–5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9–6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART. PMID:20889625
Brewinski, Margaret; Megazzini, Karen; Hance, Laura Freimanis; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa; Hazra, Rohan
In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.
Wyatt, Christina M.; Klotman, Paul E.; D’Agati, Vivette D.
The classic kidney disease of Human Immunodeficiency Virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which demonstrates collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy, in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes ACE inhibitors or angiotensin receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression. PMID:19013322
Sainz, Talía; Álvarez-Fuente, María; Fernández-Jiménez, Rodrigo; González-Tomé, María Isabel; de José, María Isabel; Ramos, José Tomás; Navarro, María Luisa; Martínez, Jorge; García-Hortelano, Milagros; Medrano, Constancio; Muñoz-Fernández, María Ángeles; Mellado, María José
Previous studies have demonstrated increased risk of adverse cardiac outcomes in adults with HIV infection. However, few studies have addressed this problem in vertically HIV-infected children and adolescents, and the long-term cardiac health of this unique population in the antiretroviral therapy era is still unknown. Ventricular function was evaluated cross-sectionally in a group of HIV-infected children and adolescents and healthy controls, using conventional echocardiography along with tissue Doppler imaging and strain analysis by speckle tracking. Simultaneously, measurements of carotid intima-media thickness were performed. A total of 64 cases and 58 controls were included, mean age was 13.6 ± 5.4 years and 64% were females. All but 2 patients were on antiretroviral treatment, and 64% had undetectable viral load. HIV-infected patients showed higher intima-media thickness (0.425 ± 0.019 vs. 0.415 ± 0.019 mm, P = 0.003). Statistically significant differences were found between groups in ejection fraction and fractional shortening (66.1% and 36.2% in the HIV-infected group vs. 71.5% and 40.8% in the control group, respectively, P = 0.001), although individual values fell within or near normal ranges. There were no significant differences in diastolic function, tissue Doppler imaging or cardiac strain (longitudinal and rotational) between both groups. No associations were identified between echocardiographic parameters and current CD4+ T-lymphocyte counts, CD4+ T-lymphocyte nadir, HIV viral load, duration or type of antiretroviral treatment regimens. In a context of highly effective antiretroviral treatment, no differences were found regarding cardiac abnormalities using conventional and advanced ultrasound imaging techniques in this cohort of vertically HIV-infected children and adolescents, when compared with healthy controls.
Onwumeh, Jennifer; Okwundu, Charles I; Kredo, Tamara
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
Krentz, Hartmut B; Gill, M John
Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.
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.
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
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
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
Gillard, Baiba K.; Raya, Joe L.; Ruiz-Esponda, Raul; Iyer, Dinakar; Coraza, Ivonne; Balasubramanyam, Ashok; Pownall, Henry J.
Objective HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high density lipoprotein-cholesterol (HDL-C). In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL-C concentrations and raised plasma HDL-C and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Approach and Results Hypolipidemic therapy reduced the TG contents of LDL and HDL. At baseline, HIV/ART low density lipoproteins (LDL) were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester (CE)-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very low density lipoproteins, LDL and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[3H]CE uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-CE uptake than did NL plasma (p<0.001). Conclusion Compared to NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. Based on this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities and/or hepatic CE uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness. PMID:23640486
Baghirath, P V; Krishna, A B; Gannepalli, A; Ali, M M
To assess and compare the oral manifestations of HIV-infected paediatric patients undergoing ART (anti-retroviral therapy) and those not undergoing ART. A cross-sectional study was conducted amongst the 5-12 years old, HIV positive children (receiving and not receiving ART) registered at Nireekshana ART centre, Hyderabad and HIV negative children enrolled in a nearby school. HIV-related oral lesions were diagnosed according to WHO criteria. Information on age, gender, place of residence (urban/rural), socio-economic status, duration of HIV infection, duration of ART therapy, use of traditional medicine, presence of HIV-related systemic disease was recorded. CD4+ cell count was also determined for each subject. Chi-square test, stepwise multiple linear and logistic regression were used for statistical analysis. For all tests, confidence interval and p value were set at 95 % and p ≤ 0.05, respectively. Twelve percent and 21.3 % of the study participants were on short-term and long-term ART (Group I), respectively. A greater proportion of HIV patients receiving treatment had CD4+ cell counts of more than 750 cells/mm(3). Nearly 81.3 % of HIV patients receiving long-term therapy did not have any oral lesions. Around half of the participants not receiving treatment suffered from HIV-related oral lesions. The best predictors for presence of oral lesions were socio-economic status, group (ART treatment), duration of HIV infection and CD4+ cell count. The results of the present study demonstrated that ART proved to be effective in reducing the prevalence of HIV-related oral lesions.
Pérez-Valero, Ignacio; González-Baeza, Alicia; Estébanez, Miriam; Montes-Ramírez, María L.; Bayón, Carmen; Pulido, Federico; Bernardino, José I.; Zamora, Francisco X.; Monge, Susana; Gaya, Francisco; Lagarde, María; Rubio, Rafael; Hernando, Asunción; Arnalich, Francisco; Arribas, José R.
Background In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. Methods In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. Results Of the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15). Conclusions Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART. PMID:23936029
Puthanakit, Thanyawee; Vonthanak, Saphonn; Ananworanich, Jintanat; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; Vibol, Ung; Kerr, Stephen J.; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Ngo-Giang-Huong, Nicole; Chettra, Kea; Cheunyam, Theshinee; Suwarnlerk, Tulathip; Ubolyam, Sasiwimol; Shearer, William T.; Paul, Robert; Mofenson, Lynne M.; Fox, Lawrence; Law, Matthew G.; Cooper, David A.; Phanuphak, Praphan; Vun, Mean Chhi; Ruxrungtham, Kiat
Summary Background The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival. Methods In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1–12 years who were infected with HIV and had CD4 percentages of 15–24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091. Findings Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6·4 years (IQR 3·9–8·4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16–22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98·7% (95% CI 94·7–99·7; 148 of 150 patients) compared with 97·9% (93·7–99·3; 146 of 149 patients) in the early treatment group (p=0·6). Interpretation AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or
Puthanakit, Thanyawee; Saphonn, Vonthanak; Ananworanich, Jintanat; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; Vibol, Ung; Kerr, Stephen J; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Ngo-Giang-Huong, Nicole; Chettra, Kea; Cheunyam, Theshinee; Suwarnlerk, Tulathip; Ubolyam, Sasiwimol; Shearer, William T; Paul, Robert; Mofenson, Lynne M; Fox, Lawrence; Law, Matthew G; Cooper, David A; Phanuphak, Praphan; Vun, Mean Chhi; Ruxrungtham, Kiat
The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival. In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1-12 years who were infected with HIV and had CD4 percentages of 15-24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091. Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6·4 years (IQR 3·9-8·4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16-22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98·7% (95% CI 94·7-99·7; 148 of 150 patients) compared with 97·9% (93·7-99·3; 146 of 149 patients) in the early treatment group (p=0·6). AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question
Eckard, Allison Ross; Jiang, Ying; Debanne, Sara M.; Funderburg, Nicholas T.; McComsey, Grace A.
Background. Human immunodeficiency virus (HIV)–infected individuals are at increased risk of cardiovascular disease (CVD) due in part to inflammation. Statins decrease inflammation in the general population, but their effect during HIV infection is largely unknown. Methods. This is an ongoing randomized, double-blinded, placebo-controlled trial to evaluate the effect of statin therapy on inflammatory markers during HIV infection. Subjects received rosuvastatin 10 mg daily or placebo for 24 weeks. Subjects were receiving stable (>12 weeks) antiretroviral therapy and had a low-density lipoprotein (LDL) cholesterol level of ≤130 mg/dL and evidence of heightened immune activation or inflammation. This was a prespecified interim analysis. Results. A total of 147 subjects were enrolled (78% were male, 70% were black, and the median age was 47 years). By 24 weeks, LDL cholesterol levels had decreased in the statin group, compared with an increase in the placebo group (−28% vs +3.8%; P < .01). A 10% reduction in the lipoprotein-associated phospholipase A2 (Lp-PLA2) level was seen in the statin group, compared with a 2% reduction in the placebo group (P < .01). In multivariable regression, receipt of statin treatment and having a nadir CD4+ T-cell count of ≤100 cell/µL were the only statistically significant predictors of a decrease in Lp-PLA2 level. Markers of systemic inflammation did not change significantly between groups. Conclusions. Twenty-four weeks of rosuvastatin therapy significantly decreased the level of Lp-PLA2, a vascular-specific, inflammatory enzyme that predicts cardiovascular events in the general population. Statins may hold promise as a means of attenuating CVD risk in HIV-infected individuals by decreasing Lp-PLA2 levels. PMID:24415784
Larson, Elysia; Bendavid, Eran; Tuoane-Nkhasi, Maletela; Mbengashe, Thobile; Goldman, Thurma; Wilson, Melinda; Klausner, Jeffrey D
Our aim was to describe the association between increasing access to antiretroviral therapy and all-cause mortality in South Africa from 2005 to 2009. We undertook a longitudinal, population-level study, using antiretroviral monitoring data reported by PEPFAR implementing partners and province-level and national all-cause mortality records from Statistics South Africa (provider of official South African government statistics) to analyse the association between antiretroviral therapy and mortality. Using mixed effects models with a random intercept for province, we estimated the contemporaneous and lagging association between antiretroviral therapy and all-cause mortality in South Africa. We also conducted subgroup analyses and estimated the number of deaths averted. For each 100 HIV-infected individuals on antiretroviral therapy reported by PEPFAR implementing partners in South African treatment programmes, there was an associated 2.9 fewer deaths that year (95% CI: 1.5, 4.2) and 6.3 fewer deaths the following year (95% CI: 4.6, 8.0). The associated decrease in mortality the year after treatment reporting was seen in both adults and children, and men and women. Treatment provided from 2005 to 2008 was associated with 28,305 deaths averted from 2006 to 2009. The scale-up of antiretroviral therapy in South Africa was associated with a significant reduction in national all-cause mortality.
Ojeh, Victor B.; Naima, Nasir; Abah, Isaac O.; Falang, Kakjing D.; Lucy, Ogwuche; London, Ibrahim; Dady, Christiana; Agaba, Patricia; Agbaji, Oche
Objectives: We describe the frequency and types of drug therapy problems (DTPs), and interventions carried out to resolve them, among a cohort of HIV-infected patients on ART in Jos, Nigeria. Methods: A prospective pharmacists’ intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH). Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. Results: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions) were made to resolve DTPs in 401 (4.3%) patients with a mean age of 41 (SD=10) years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%), unnecessary drug (n=55, 13.1%) and wrong drug indication (n=55, 13.1%). Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%), rectification of incomplete prescriptions (n=85, 20.2%), change of drug or dosage (n=67, 16.0%), and discontinuation of the offending drug (n=59, 14.0%). A total of 389 (93%) out of 420 of the recommendations were accepted. In all, 50.4% (212) of the problematic prescriptions were changed and dispensed, 22.2% (89) were clarified and dispensed, while wrong identities were corrected in 11.7% (49). However, 7.5% (30) prescriptions were dispensed as prescribed, 5.2% (21) were not dispensed, and 3% (12) were unresolved. Conclusion: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors. PMID:26131046
Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew
Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197
Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris
Introduction Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm
Duarte, Horacio A.; Harris, D. Robert; Tassiopoulos, Katherine; Leister, Erin; Negrini, Silvia Fabiana Biason de Moura; Ferreira, Flavia Faleiro; Cruz, Maria Leticia Santos; Pinto, Jorge; Allison, Susannah; Hazra, Rohan
Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of HIV-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with HIV viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8–9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population. PMID:25743569
Masiá, Mar; Padilla, Sergio; Barber, Xavier; Sanchis, Marina; Terol, Gertrudis; Lidón, Fernando; Gutiérrez, Félix
Abstract Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1–2) per patient, of 29 (14–58) months duration, and 4 (3–7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (−0.0352–0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], −0.0912 [−0.1604 to −0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher
Rudin, C; Spaenhauer, A; Keiser, O; Rickenbach, M; Kind, C; Aebi-Popp, K; Brinkhof, M W G
There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women. The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity. We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS). Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85-3.6] and 2.5 (95% CI 1.4-4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy. Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women. © 2010 British HIV Association.
Al-Khindi, Timour; Zakzanis, Konstantine K; van Gorp, Wilfred G
The development of antiretroviral therapy (ART) has dramatically improved survival for those living with human immunodeficiency virus (HIV), but whether ART improves cognitive functioning remains unclear. The aim of the present review was to examine systematically the extent to which ART improves cognition among individuals with HIV using meta-analytic methods. Twenty-three studies were included in the quantitative review. ART was associated with modest improvements in attention (mean d = .17; p < .001; 95% confidence interval [CI], .09/.25), executive function (mean d = .18; p < .001; 95% CI, .10/.26), and motor function (mean d = .24; p < .001; 95% CI, .16/.32). ART did not improve language, verbal memory, visual memory or visuospatial function. The extent to which cognition improved was correlated with the change in CD4 cell count following ART, suggesting a link between cognitive outcome and immune system integrity. Together, the present findings indicate that the neuropsychological test performance of most HIV patients taking ART is comparable to those not taking ART. Development of pharmaceutical treatments and rehabilitation strategies that target the cognitive effects of HIV infection is needed.
Cardenas, VA; Meyerhoff, DJ; Studholme, C; Kornak, J; Rothlind, J; Lampiris, H; Neuhaus, J; Grant, RM; Chao, LL; Truran, D; Weiner, MW
Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus–positive (HIV+) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV− controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P < .05) greater rates of white matter volume loss than HIV− control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals—even in the presence of viral suppression in the periphery—are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered. PMID:19499454
Ananworanich, Jintanat; Dubé, Karine; Chomont, Nicolas
The long-lived viral reservoir is a major obstacle to achieving a cure for HIV. Therapeutic strategies, such as early antiretroviral therapy (ART), may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal. HIV persistence is established early in acute HIV infection (AHI) with infection in long-lived memory CD4⁺ T cells. Studies conducted in nonhuman primates have suggested that this could occur as early as 3 days postinfection; however, the timing in humans is uncertain. ART during AHI significantly restricts the HIV reservoirs as compared with later treatment. Early ART, particularly prior to the detection of HIV immunoglobulin M, may also reduce the contribution of the long-lived central memory CD4⁺ T cells to the total HIV reservoir, a profile observed in individuals who naturally control HIV without ART. It is clear that early ART has a greater impact in limiting the HIV reservoirs than later treatment. However, latently infected long-lived memory CD4⁺ T cells persist in most early treated individuals. Therefore, additional interventions will likely be required to eliminate all cells capable of producing replication-competent virus but treatment in AHI may be the critical first step in containing the HIV reservoirs.
Houston, Eric; McKirnan, David J; Cervone, Daniel; Johnson, Matthew S; Sandfort, Theo G M
Using multidimensional scaling (MDS) analysis, this study examined how patient conceptualisations of treatment motivation compare with theoretically based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n=39) rated for similarity between all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivations often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivations. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence.
Lawler, Kathy; Jeremiah, Kealeboga; Mosepele, Mosepele; Ratcliffe, Sarah J.; Cherry, Catherine; Seloilwe, Esther; Steenhoff, Andrew P.
Objective To explore the prevalence and features of HIV-associated neurocognitive disorders (HANDS) in Botswana, a sub-Saharan country at the center of the HIV epidemic. Design and Methods A cross sectional study of 60 HIV-positive individuals, all receiving highly active antiretroviral therapy (HAART), and 80 demographically matched HIV-seronegative control subjects. We administered a comprehensive neuropsychological test battery and structured psychiatric interview. The lowest 10th percentile of results achieved by control subjects was used to define the lower limit of normal performance on cognitive measures. Subjects who scored abnormal on three or more measures were classified as cognitively impaired. To determine the clinical significance of any cognitive impairment, we assessed medication adherence, employment, and independence in activities of daily living (ADL). Results HIV+ subjects were impaired for all cognitive-motor ability areas compared with matched, uninfected control subjects. Thirty seven percent of HIV+ patients met criteria for cognitive impairment. Conclusion These findings indicate that neurocognitive impairment is likely to be an important feature of HIV infection in resource-limited countries; underscoring the need to develop effective treatments for subjects with, or at risk of developing, cognitive impairment. PMID:21365002
Houston, Eric; McKirnan, David J.; Cervone, Daniel; Johnson, Matthew S.; Sandfort, Theo G.M.
Using multidimensional scaling analysis (MDS), this study examined how patient conceptualisations of treatment motivation compare with theoretically-based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n = 39) rated for similarity all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach, and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivation often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively-valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivation. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence. PMID:21942538
Ananworanich, Jintanat; Dubé, Karine; Chomont, Nicolas
Purpose of review The long-lived viral reservoir is a major obstacle to achieving a cure for HIV. Therapeutic strategies, such as early antiretroviral therapy (ART), may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal. Recent findings HIV persistence is established early in acute HIV infection (AHI) with infection in long-lived memory CD4+ T cells. Studies conducted in nonhuman primates have suggested that this could occur as early as 3 days postinfection; however, the timing in humans is uncertain. ART during AHI significantly restricts the HIV reservoirs as compared with later treatment. Early ART, particularly prior to the detection of HIV immunoglobulin M, may also reduce the contribution of the long-lived central memory CD4+ T cells to the total HIV reservoir, a profile observed in individuals who naturally control HIV without ART. Summary It is clear that early ART has a greater impact in limiting the HIV reservoirs than later treatment. However, latently infected long-lived memory CD4+ T cells persist in most early treated individuals. Therefore, additional interventions will likely be required to eliminate all cells capable of producing replication-competent virus but treatment in AHI may be the critical first step in containing the HIV reservoirs. PMID:25415421
Martinez, Homero; Palar, Kartika; Linnemayr, Sebastian; Smith, Alexandria; Derose, Kathryn Pitkin; Ramírez, Blanca; Farías, Hugo; Wagner, Glenn
Food insecurity and malnutrition negatively affect adherence to antiretroviral therapy (ART) and are associated with poor HIV clinical outcomes. We examined the effect of providing household food assistance and nutrition education on ART adherence. A 12-month prospective clinical trial compared the effect of a monthly household food basket (FB) plus nutrition education (NE) versus NE alone on ART adherence on 400 HIV patients at four clinics in Honduras. Participants had been receiving ART for an average of 3.7 years and were selected because they had suboptimal adherence. Primary outcome measures were missed clinic appointments, delayed prescription refills, and self-reported missed doses of ART. These three adherence measures improved for both groups over 12 months (p < 0.01), mostly within 6 months. On-time prescription refills improved for the FB plus NE group by 19.6 % more than the group receiving NE alone after 6 months (p < 0.01), with no further change at 12 months. Change in missed appointments and self-reported missed ART doses did not significantly differ by intervention group.
Crowell, Trevor A; Hatano, Hiroyu
Elite controllers naturally suppress HIV viraemia below the level of detection using standard methods, but demonstrate persistent inflammation and low-level viraemia that is detectable via ultrasensitive assays. These factors may contribute to an increased risk of non-AIDS-related morbidity and mortality among elite controllers. Data suggest that cardiovascular disease may be of particular concern in elite controllers, as evidenced by an increased burden of subclinical cardiovascular disease upon radiographic screening and an elevated rate of hospitalisations for cardiovascular disease as compared to non-controllers who are treated with antiretroviral therapy (ART). Widespread use of ART among non-controllers has led to significant declines in morbidity and mortality, but guidelines are generally silent on the role of ART in the care of elite controllers. Multiple small studies have demonstrated that laboratory markers of inflammation, immune activation and HIV burden improve after initiation of ART in elite controllers. Clinicians must consider these potential benefits of ART when deciding whether to initiate treatment in asymptomatic elite controllers.
McCoy, Katryna; Waldrop-Valverde, Drenna; Balderson, Benjamin H.; Mahoney, Christine; Catz, Sheryl
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
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.
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
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
Wyatt, Christina M.; Morgello, Susan; Katz-Malamed, Rebecca; Wei, Catherine; Klotman, Mary E.; Klotman, Paul E.; D’Agati, Vivette D.
With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications. PMID:19052538
Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood
Background: The introduction of antiretroviral therapy has caused a remarkable decrease in the occurrence of diseases and mortality among HIV-positive patients, while this success has not been achieved among injection addicts due to a low adherence to antiretroviral medicine. This study aims at clarifying the important factors affecting adherence to treatment in addicts suffering from HIV. Materials and Methods: In this qualitative research, data were gathered through in-depth interviews and field notes, and were interpreted through content analysis in the form of constant comparison. The participants were 16 drug addicts living with HIV/AIDS. Most of them had records of imprisonment and were receiving Highly Active Antiretroviral Therapy (HAART) drug treatments in the AIDS center of Imam Khomeini Hospital complex, affiliated to Tehran University of Medical Sciences. Sampling was started in a purposive method and was continued until data were saturated. Results: Four main categories including psychological reactions, contradictory beliefs, perceived support, and individual and environmental barriers were extracted from the data, each having some sub-categories. Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments. PMID:26985220
Dore, G J; Correll, P K; Li, Y; Kaldor, J M; Cooper, D A; Brew, B J
To determine the protective efficacy of highly active antiretroviral therapy (HAART) against AIDS dementia complex (ADC) relative to other initial AIDS-defining illnesses (ADIs), Australian AIDS notification data over recent years were examined. All initial ADIs in Australia over the period 1992-1997 were included. Three initial ADI groups were established: ADC; other predominantly central nervous system (CNS) ADIs (toxoplasmosis and cryptococcosis); and non-CNS ADIs. For each ADI grouping, the proportion of total ADls, and median CD4 cell count in the pre-HAART era (1992-1995) were compared with the HAART era (1996 and 1997). Initial ADls peaked in Australia in 1994 (n = 1049), with a gradual decline to 1996 (n = 722), and a marked decline in 1997 (n = 367). ADC constituted 4.4% of initial ADIs over the period 1992-1995, but increased after the introduction of HAART to 6.0% in 1996 and 6.5% in 1997 (P = 0.02). In contrast, the proportion of other CNS ADIs (1992-1995, 8.1%; 1996, 6.0%; 1997, 8.2%; P = 0.41) was stable over the period 1992-1997. The median CD4 cell count at ADC diagnosis increased from 70/mm3 in 1992-1995 to 120/mm3 in 1996 and 170/mm3 in 1997 (P = 0.04). Although the median CD4 cell count also increased significantly over this period for both other CNS ADIs (40-60/mm3; P = 0.02), and non-CNS ADIs (60-70/mm3; P = 0.02), the increase was small. A proportional increase in ADC compared with other ADIs and a marked increase in the median CD4 cell count at ADC diagnosis have occurred since the introduction of HAART in Australia. These changes suggest that HAART has a lesser impact on ADC than on other ADIs, with the poor CNS penetration of many antiretroviral agents a possible explanation.
Youn, Bora; Shireman, Theresa I; Lee, Yoojin; Galárraga, Omar; Rana, Aadia I; Justice, Amy C; Wilson, Ira B
Whether the rate of HIV antiretroviral therapy (ART) persistence has improved over time in the United States is unknown. We examined ART persistence trends between 2001 and 2010, using non-HIV medications as a comparator. We conducted a retrospective cohort study using Medicaid claims. We defined persistence as the duration of treatment from the first to the last fill date before a 90-day permissible gap and used Kaplan-Meier curves and Cox proportional hazard models to assess crude and adjusted nonpersistence. The secular trends of ART persistence in 43 598 HIV patients were compared with the secular trends of persistence with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB), statins, and metformin in non-HIV-infected patients and subgroups of HIV patients who started these control medications while using ART. Median time to ART nonpersistence increased from 23.9 months in 2001-2003 to 35.4 months in 2004-2006 and was not reached for those starting ART in 2007-2010. In adjusted models, ART initiators in 2007-2010 had 11% decreased hazard of nonpersistence compared with those who initiated in 2001-2003 (P < 0.001). For non-HIV patients initiating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), statins, and metformin, the hazard ratios for nonpersistence comparing 2007-2010 to 2001-2003 were 1.07, 0.94, and 1.02, respectively (all P < 0.001). For HIV patients initiating the three control medications, the hazard ratios of nonpersistence comparing 2007-2010 to 2001-2003 were 0.71, 0.65, and 0.63, respectively (all P < 0.001). Persistence with ART improved between 2001 and 2010. Persistence with control medications improved at a higher rate among HIV patients using ART than HIV-negative controls.
Chiegil, Robert J; Zungu, Lindiwe I; Jooste, Karien
This paper describes perceptions of the end users on quality of antiretroviral therapy (ART) in public health facilities in Nigeria. Health care services in Nigeria face challenges of meeting end users' requirements and expectations for quality ART service provision. A qualitative design was followed. Unstructured focus group discussions were conducted with end users (n = 64) in six locations across the six geopolitical zones of Nigeria. The findings indicate that end users were satisfied with uninterrupted antiretroviral drug supplies, courtesy treatment, volunteerism of support group members and quality counselling services. End users expect effective collaboration between healthcare providers and support group members, to enhance the quality of life of people living with HIV. A best practice guideline for the provision of end user focused ART service provision was developed for nurse managers. © 2013 John Wiley & Sons Ltd.
Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.
Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730
Ranieri, Roberto; Sommella, Jvana; D'Angelo, Cinzia; Nigro, Francesco; Poccobelli, Michelangelo; Lari, Cesare; Di Benedetto, Domenica; D'Arminio Monforte, Antonella
In HIV-positive patients detention often represents a unique opportunity for health care. HIV-positive inmates enjoy the same rights as non-restricted people, as established under national and international legislation, declarations and guidelines. Antiretroviral therapy in restricted men shows some peculiarities such as the voluntary non-taking of drugs to worsen the health status or obtain legal benefits and the high frequency of concomitant psychiatric treatment. On the other hand, patient compliance may be considerably improved by adopting DOT strategy. Aiming to define the choices of first and subsequent lines of therapy with respect to the patient's epidemiological characteristics and other ongoing treatments in two major correctional facilities in Milan (Opera and San Vittore, harbouring about 2500 inmates), we collected punctual data (March 6, 2014) drawn from the single patient forms of therapy. Our results show the same prevalence of HIV infection in both facilities (3%), AIDS and viral hepatitis coinfection cases being more frequent in Opera. Both in Opera and San Vittore we found a high adherence to antiretroviral therapy (high CD4 count average and high percentage of HIV-RNA suppressed). The first and subsequent choice of main lines was TDF+FTC+RTV+ATV. The choice of efavirenz (EFV) as the third drug was often excluded due to its neuropsychiatric implications. The most common cause of drug change was toxicity followed by simplification and then by virological failure. Finally we showed a high frequency of concomitant psychiatric therapy (77% in Opera, 67% in San Vittore), noting the hypothetical interactions with antiretroviral drugs.
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.
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
Mpondo, Bonaventura C T; Kalluvya, Samuel E; Peck, Robert N; Kabangila, Rodrick; Kidenya, Benson R; Ephraim, Lucheri; Fitzgerald, Daniel W; Downs, Jennifer A
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.
Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David
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.
Puttkammer, Nancy H.; Zeliadt, Steven B.; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Coq, Nancy Rachel Labbé; Raphael, Nernst Atwood; Sherr, Kenneth; Tegger, Mary; Yuhas, Krista; Barnhart, Scott
Objective To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005–2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. Methods This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. Results Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8–18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54–2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. Conclusions The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; “bridging services” for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti. PMID:25563149
Beck, Eduard J; Vitoria, Marco; Mandalia, Sundhiya; Crowley, Siobhan; Gilks, Charles F; Souteyrand, Yves
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.
Ferreros, Inmaculada; Hurtado, Isabel; del Amo, Julia; Muga, Roberto; del Romero, Jorge; García, Patricia; Alastrué, Ignacio; Belda, Josefina; Guevara, Marcela; Pérez, Santiago
Several observational studies support the protective effect of combined antiretroviral therapy (cART) on time to first AIDS-defining event, but the effect on multiple AIDS defining illnesses remains unclear.The aim of this study is to analyse whether the protective effect of cART persists beyond the first AIDS-defining illness. A total of 1938 subjects from GEMES seroconverter cohort have been included. To analyse cART effectiveness, calendar time has been divided into three periods according to antiretroviral availability. A population-averaged proportional hazard model with staggered entries that counted the gap time, and had event-specific baseline risks, was fitted. During follow-up, 1524 (78.6%), 259 (13.4%), 83 (4.3%) and 72 (3.7%) subjects incurred 0, 1, 2, and 3 or more AIDS-defining illnesses, respectively. After adjustment for sex, age at seroconversion and exposure category, the Relative Risk (RR) of AIDS in the cART period was 0.38 (95%CI 0.30-0.48) compared with the 1992-95 period. The RR of the first, second and third AIDS-defining illness in the cART period were 0.40 (95% CI: 0.32-0.50), 0.27 (95% CI: 0.15-0.50) and 0.41 (95% CI: 0.18-0.96) respectively, relative to the reference calendar period when we allowed the odds ratios to vary by the number of prior AIDS-defining events. The relative risk of AIDS, taking all events into account, was 0.32 (95% CI: 0.25-0.40). Intravenous drug users have a higher risk of developing a first episode of AIDS than homosexuals, RR: 2.14 (95% CI: 1.48-3.10). Results indicate that the relative effect of cART appears to be both protective and stable over multiple AIDS-defining illnesses. Analysis of multiple AIDS-defining illnesses improves the precision of the estimated relative risk. Copyright © 2010 Elsevier España, S.L. All rights reserved.
Di Biagio, Antonio; Cozzi-Lepri, Alessandro; Angarano, Gioacchino; Gori, Andrea; Quirino, Tiziana; De Luca, Andrea; Costantini, Andrea; Mussini, Cristina; Rizzardini, Giuliano; Castagna, Antonella; Antinori, Andrea; d'Arminio Monforte, Antonella
Background: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan–Meier analysis was used for the outcome discontinuation of ≥1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4+ cell (P = 0.011), and higher lymphocyte T CD8+ cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity. PMID:26871881
Rebick, Gabriel W; Franke, Molly F; Teng, Jessica E; Gregory Jerome, J; Ivers, Louise C
Food rations are increasingly offered as part of HIV programs in resource-poor settings, often targeted solely to those with under-nutrition by low body mass index (BMI). This practice does not consider food insecurity, another important risk factor for poor outcomes in people living with HIV/AIDS (PLWH). We analyzed factors associated with low BMI and severe food insecurity in 523 PLWH receiving antiretroviral therapy in rural Haiti using logistic regression. Food insecurity was present in 89 % of individuals. Among those with severe food insecurity, 86 % had a BMI ≥ 18.5 kg/m(2). Severe food insecurity was associated with illiteracy [adjusted odds ratio (AOR) 1.79, p = 0.005], having no income (AOR 1.58, p = 0.04), and poverty (p < 0.001). Compared with those with little to no food insecurity, individuals with severe food insecurity had a less diverse diet. We found that food insecurity was highly prevalent in PLWH receiving antiretroviral therapy in rural Haiti. Using BMI as a sole criterion for food supplementation in HIV programs can exclude highly vulnerable individuals who may benefit from such support.
Yang, Jing; Geng, Wenqing; Zhang, Min; Han, Xiaoxu; Shang, Hong
Sixteen original recombinant pseudoviruses were generated by cloning the reverse transcriptase and protease genes of human immunodeficiency virus (HIV)-1 from patients into a plasmid vector (pNL4-3-ΔE-EGFP). By site-directed mutagenesis two restriction endonuclease sites, ApaI and AgeI, were inserted into pNL4-3-ΔE-EGFP. Phenotypic susceptibility of recombinant pseudoviruses to five different classes of antiretroviral drugs was determined using a luciferase reporter assay system. The results were subjected to comparative analyses to detect genotype-phenotype associations. Among 16 strains tested, 12 strains had a discordant genotype-phenotype resistance pattern to at least one drug. In five strains resistance to two, in two strains to three, and in one strain resistance to four drugs was detected. HIV resistance genotyping could predict the phenotype for nevirapine and azidothymidine. For lamivudine, 2'-3'-didehydro-2'-3'dideoxythymidine and didanosine, phenotypic resistance testing was necessary. The study showed that in patients who experienced long-term highly active antiretroviral therapy and virological failure, there is some discordance between genotypic and phenotypic HIV drug resistance. To address the issue of limited resources in China, genotypic and phenotypic resistance testing should be done for different drugs in order to guide clinical therapy more effectively.
Hampanda, Karen M; Abuogi, Lisa L; Ahmed, Yusuf
HIV-positive women's adherence to antiretrovirals is critical for prevention of mother-to-child transmission. We aimed to establish if mothers taking triple lifelong antiretroviral therapy report higher adherence compared to mothers taking short-course prophylaxis under Option A in Lusaka, Zambia. In this clinic-based cross-sectional study, we interviewed 320 HIV-positive mothers at a large public health facility in Lusaka in 2014. Participants reported adherence using a visual analog scale. Multiple logistic regression models were used to determine the adjusted odds of adherence by mother's prescribed regimen. Women taking lifelong triple antiretroviral therapy report higher adjusted odds of adherence during pregnancy, postpartum, and to giving the infant prophylaxis compared to women to women taking short-course prophylaxis. Women on lifelong therapy may have better adherence compared to women on short course prophylaxis because they knew their positive status for longer or were symptomatic with HIV-related disease. The lifelong therapy regimen may be easier for women to follow, particularly because they are required to give the infant prophylaxis for a shorter duration of time. Our results indicate that lifelong triple antiretroviral therapy has the potential to promote better drug adherence during and after pregnancy among women living with HIV in sub-Saharan Africa, compared to short-course antiretroviral regimens.
Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C.; Richman, Douglas D.; Smith, Davey M.
Abstract We investigated the pol genotype in two phylogenetically and epidemiologically linked partners, who were both experiencing persistent low-level viremia during antiretroviral therapy. In one partner we identified a new residue insertion between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding region (HXB2 numbering). We then investigated the potential impact of identified mutations in RT and antiretroviral binding affinity using a novel computational approach. PMID:24020934
Chaillon, Antoine; Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C; Richman, Douglas D; Smith, Davey M
We investigated the pol genotype in two phylogenetically and epidemiologically linked partners, who were both experiencing persistent low-level viremia during antiretroviral therapy. In one partner we identified a new residue insertion between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding region (HXB2 numbering). We then investigated the potential impact of identified mutations in RT and antiretroviral binding affinity using a novel computational approach.
Edwards, Jessie K.; Cole, Stephen R.; Westreich, Daniel; Moore, Richard; Mathews, Christopher; Geng, Elvin; Eron, Joseph J.; Mugavero, Michael J.
Missing outcome data due to loss to follow-up occurs frequently in clinical cohort studies of HIV-infected patients. Censoring patients when they become lost can produce inaccurate results if the risk of the outcome among the censored patients differs from the risk of the outcome among patients remaining under observation. We examine whether patients who are considered lost to follow up are at increased risk of mortality compared to those who remain under observation. Patients from the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who newly initiated combination antiretroviral therapy between January 1, 1998 and December 31, 2009 and survived for at least one year were included in the study. Mortality information was available for all participants regardless of continued observation in the CNICS. We compare mortality between patients retained in the cohort and those lost-to-clinic, as commonly defined by a 12-month gap in care. Patients who were considered lost-to-clinic had modestly elevated mortality compared to patients who remained under observation after 5 years (risk ratio (RR): 1.2; 95% CI: 0.9, 1.5). Results were similar after redefining loss-to-clinic as 6 months (RR: 1.0; 95% CI: 0.8, 1.3) or 18 months (RR: 1.2; 95% CI: 0.8, 1.6) without a documented clinic visit. The small increase in mortality associated with becoming lost to clinic suggests that these patients were not lost to care, rather they likely transitioned to care at a facility outside the study. The modestly higher mortality among patients who were lost-to-clinic implies that when we necessarily censor these patients in studies of time-varying exposures, we are likely to incur at most a modest selection bias. PMID:25010739
Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho
Objectives To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. Method This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The “Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral” (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Results Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. Conclusion A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test. PMID:27695297
Nanfack, Aubin J; Redd, Andrew D; Bimela, Jude S; Ncham, Genesis; Achem, Emmanuel; Banin, Andrew N; Kirkpatrick, Allison R; Porcella, Stephen F; Agyingi, Lucy A; Meli, Josephine; Colizzi, Vittorio; Nádas, Arthur; Gorny, Miroslaw K; Nyambi, Phillipe N; Quinn, Thomas C; Duerr, Ralf
The global intensification of antiretroviral therapy (ART) can lead to increased rates of HIV drug resistance (HIVDR) mutations in treated and also in ART-naive patients. ART-naive HIV-1-infected patients from Cameroon were subjected to a multimethod HIVDR analysis using amplification-refractory mutation system (ARMS)-PCR, Sanger sequencing, and longitudinal next-generation sequencing (NGS) to determine their profiles for the mutations K103N, Y181C, K65R, M184V, and T215F/Y. We processed 66 ART-naive HIV-1-positive patients with highly diverse subtypes that underlined the predominance of CRF02_AG and the increasing rate of F2 and other recombinant forms in Cameroon. We compared three resistance testing methods for 5 major mutation sites. Using Sanger sequencing, the overall prevalence of HIVDR mutations was 7.6% (5/66) and included all studied mutations except K65R. Comparing ARMS-PCR with Sanger sequencing as a reference, we obtained a sensitivity of 100% (5/5) and a specificity of 95% (58/61), caused by three false-positive calls with ARMS-PCR. For 32/66 samples, we obtained NGS data and we observed two additional mismatches made up of minority variants (7% and 18%) that might not be clinically relevant. Longitudinal NGS analyses revealed changes in HIVDR mutations in all five positive subjects that could not be attributed to treatment. In one of these cases, superinfection led to the temporary masking of a resistant virus. HIVDR mutations can be sensitively detected by ARMS-PCR and sequencing methods with comparable performances. Longitudinal changes in HIVDR mutations have to be considered even in the absence of treatment. Copyright © 2017 American Society for Microbiology.
Patel, Rena; Kassaye, Seble; Gore-Felton, Cheryl; Wyshak, Grace; Kadzirange, Gerard; Woelk, Godfrey; Katzenstein, David
Little is known about the psychosocial impact of antiretroviral therapy (ART) among women in sub-Saharan Africa. Therefore, we conducted a cross-sectional study in Zimbabwe to assess the impact of ART on HIV-positive women's health-related quality of life, using the Medical Outcomes Study-HIV Quality of Life (QOL) questionnaire. Additionally, we assessed socio-demographics, reproductive and sexual health, HIV-related history, disclosure, social stigma, self-esteem, and depression. Structured interviews were conducted with 200 HIV-positive women and categorized into three groups by treatment: (1) Group 1 (n=31) did not meet clinical or laboratory criteria to begin treatment; (2) Group 2 (n=73) was eligible to begin treatment but awaiting initiation of treatment; and (3) Group 3 (n=96) was on ART for a median of 13 months. The women had similar socio-demographic characteristics but varied significantly in clinical characteristics. Women on ART reported fewer AIDS-related symptoms in the last week and year and had higher current and lower baseline CD4 counts compared to women not on ART. On most QOL domains women on ART reported higher mean scores as compared to women not on ART (p<0.01). Additionally, women on ART reported less depression compared to women not on ART (p<0.001). Between the two groups of women not on ART, unexpectedly, there were no significant differences in their scores for QOL or depression. Thus, Zimbabwean women living with HIV experience better overall QOL and lower depression on ART. Altogether, our findings suggest that ART delivery in resource-poor communities can enhance overall QOL as well as psychosocial functioning, which has wide-ranging public health implications.
González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo
The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.
Lazarus, Jeffrey V; Safreed-Harmon, Kelly; Nicholson, Joey; Jaffar, Shabbar
In response to the lack of evidence-based guidance for how to continue scaling up antiretroviral therapy (ART) in ways that make optimal use of limited resources, to assess comparative studies of ART service delivery models implemented in sub-Saharan Africa. A systematic literature search and analysis of studies that compared two or more methods of ART service delivery using either CD4 count or viral load as a primary outcome. Most studies identified in this review were small and non-randomised, with low statistical power. Four of the 30 articles identified by this review conclude that nurse management of ART compares favourably to physician management. Seven provide evidence of the viability of managing ART at lower levels within the health system, and one indicates that vertical and integrated ART programmes can achieve similar outcomes. Five articles show that community/home-based ART management can be as effective as facility-based ART management. Five of seven articles investigating community support link it to better clinical outcomes. The results of four studies suggest that directly observed therapy may not be an important component of ART programmes. Given that the scale-up of antiretroviral therapy represents the most sweeping change in healthcare delivery in sub-Saharan Africa in recent years, it is surprising to not find more evidence from comparative studies to inform implementation strategies. The studies reported on a wide range of service delivery models, making it difficult to draw conclusions about some models. The strongest evidence was related to the feasibility of decentralisation and task-shifting, both of which appear to be effective strategies. © 2014 John Wiley & Sons Ltd.
Bader, J; Schöni-Affolter, F; Böni, J; Gorgievski-Hrisoho, M; Martinetti, G; Battegay, M; Klimkait, T
A significant percentage of patients infected with HIV-1 experience only suboptimal CD4 cell recovery while treated with combination therapy (cART). It is still unclear whether viral properties such as cell tropism play a major role in this incomplete immune response. This study therefore intended to follow the tropism evolution of the HIV-1 envelope during periods of suppressive cART. Viruses from two distinct patient groups, one with good and another one with poor CD4 recovery after 5 years of suppressive cART, were genotypically analysed for viral tropism at baseline and at the end of the study period. Patients with CCR5-tropic CC-motif chemokine receptor 5 viruses at baseline tended to maintain this tropism to the study end. Patients who had a CXCR4-tropic CXC-motif chemokine receptor 4 virus at baseline were overrepresented in the poor CD4 recovery group. Overall, however, the majority of patients presented with CCR5-tropic viruses at follow-up. Our data lend support to the hypothesis that tropism determination can be used as a parameter for disease progression even if analysed long before the establishment of a poorer immune response. Moreover, the lasting predominating CCR5-tropism during periods of full viral control suggests the involvement of cellular mechanisms that preferentially reduce CXCR4-tropic viruses during cART. © 2016 British HIV Association.
Charalambous, Salome; Grant, Alison D; Innes, Craig; Hoffmann, Christopher J; Dowdeswell, Rob; Pienaar, Jan; Fielding, Katherine L; Churchyard, Gavin J
To describe the association between isoniazid preventive therapy (IPT) and mortality among individuals starting antiretroviral therapy (ART) in a workplace programme in South Africa where tuberculosis (TB) incidence is very high. ART-naive individuals starting ART from January 2004 to December 2007 were followed for up to 12 months. Deaths were ascertained from clinic and human resource data. The association between IPT and mortality was assessed using Cox regression. A total of 3270 individuals were included (median age 45; 93% men; median baseline CD4 cell count 155 cells/μl (interquartile range 87-221); and 45% with WHO stage 3/4]. Nine hundred twenty-two (28%) individuals started IPT either prior to or within 3 months of starting ART. Individuals who started IPT tended to have less advanced HIV disease at ART initiation. Two hundred fifty-nine (7.9%) deaths were observed with overall mortality rate 8.9 per 100 person-years [95% confidence interval (CI) 7.9-10.6]. The unadjusted mortality rate was lower among those who received IPT compared with those who did not [3.7/100 vs. 11.1/100 person-years, respectively, hazard ratio 0.34 (95% CI 0.24-0.49)]; this association remained after adjustment for age, baseline CD4 cell count, baseline WHO stage, year of ART start, and individual company (hazard ratio 0.51, 95% CI 0.32-0.80). In sensitivity analyses restricted to those with no previous history of TB (n = 3036) or with no TB symptoms at ART initiation (n = 2251), IPT remained associated with reduced mortality [adjusted hazard ratios 0.51 (95% CI 0.32-0.81) and 0.48 (95% CI 0.24-0.96), respectively]. Mortality was lower among individuals receiving IPT with or prior to ART start. These results support routine use of IPT in conjunction with ART.
Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D
Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740
Olalla, Julián; Urdiales, Daniel; Pombo, Marta; del Arco, Alfonso; de la Torre, Javier; Prada, José Luis
Pulmonary arterial hypertension (PAH) is a serious disorder, more prevalent in patients infected with human immunodeficiency virus (HIV). It is not entirely clear what role is played by highly active antiretroviral therapy (HAART) in PAH development or course. Our aim was to describe PAH prevalence in a series of HIV-infected patients and identify possible links with cumulative and current use of different antiretrovirals. Cross-sectional study of a cohort of HIV-infected patients attending a hospital in southern Spain. Demographic data, data on HIV infection status and on cumulative and recent antiretroviral treatment were recorded. Transthoracic echocardiography was performed in all study participants. PAH was defined as pulmonary artery systolic pressure of 36mmHg or more. A total of 400 patients participated in the study; 178 presented with tricuspid regurgitation and 22 of these presented with PAH (5.5%). No differences were encountered in age, sex, CD4 lymphocytes, proportion of naive patients or patients with AIDS. No differences were encountered in cumulative use of antiretrovirals. However, recent use of lamivudine was associated with a greater presence of PAH, whereas recent use of tenofovir and emtricitabine was associated with a lower presence of PAH. Logistic regression analysis was performed including the use of lamivudine, emtricitabine and tenofovir. Only recent use of tenofovir was associated with a lower presence of PAH (odds ratio 0.31; 95% confidence interval: 0.17-0.84). PAH prevalence in our study was similar to others series. Current use of tenofovir may be associated with lower PAH prevalence. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.
Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496
Sailasuta, Napapon; Ananworanich, Jintanat; Lerdlum, Sukalaya; Sithinamsuwan, Pasiri; Fletcher, James LK; Tipsuk, Somporn; Pothisri, Mantana; Jadwattanakul, Tanate; Jirajariyavej, Supunnee; Chalermchai, Thep; Catella, Stephanie; Busovaca, Edgar; Desai, Akash; Paul, Robert; Valcour, Victor
Objective Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. Methods We used single voxel proton magnetic resonance spectroscopy (MRS) in four brain regions to measure changes in neuronal and glia biomarkers in cART-naïve subjects before (n=59, 27 with HAND) and after 12 months of cART. Results At baseline we observed elevated total choline (CHO) in the basal ganglia (BG, p=0.002) and in the posterior cingulate gyrus (PCG, p=0.022) associated with HIV-infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, p=0.040). N-acetylaspartate (NAA) was elevated in the BG (p=0.047). Using a mixed model approach among all HIV-infected individuals at 6 months, we observed decreased NAA in FWM (p =0.031), decreased creatine (CR) in PCG (p=0.026) and increased MI in FGM (p=0.023). At 12 months, we observed an increase in BG MI (p=0.038) and in FGM (p=0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (p=0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared to those without HAND exhibited elevated CHO in the PCG (p=0.018) and decreased GLU in both FWM (p=0.027) and BG (p=0.013). Conclusions cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART. PMID:26258565
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.
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
Takarinda, K. C.; Owiti, P.; Mutasa-Apollo, T.; Mugurungi, O.; Buruwe, L.; Reid, A. J.
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
Babiloni, Claudio; Pennica, Alfredo; Vecchio, Fabrizio; Onorati, Paolo; Muratori, Chiara; Ferracuti, Stefano; Roma, Paolo; Donato, Nicole; Noce, Giuseppe; Del Percio, Claudio; Bonacci, Cristiano; Di Campli, Francesco; Gianserra, Laura; Teti, Elisabetta; Aceti, Antonio; Soricelli, Andrea; Viscione, Magdalena; Rossini, Paolo M; Andreoni, Massimo
We tested the hypothesis that 5months of combined anti-retroviral therapy (cART) affect cortical sources of resting state cortical electroencephalographic (EEG) rhythms in naïve HIV subjects. Eyes-closed resting state EEG data were recorded at baseline (i.e. pre-treatment; T0), T1 (after 4weeks of cART), T2 (after 8weeks of cART), and T5 (after 5months of cART) in 38 naïve HIV subjects. EEG data were also recorded in 40 age-matched cognitively normal subjects for control purposes. EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), and beta 2 (20-30Hz). Cortical EEG sources were estimated by LORETA software. Compared to the control group, the HIV group at T0 showed greater delta sources and lower widespread alpha sources. cART induced a global improvement of biological (viral load, CD4 count) and EEG (delta, alpha) markers, remarkable even after 4weeks. Compared to HIV Responders (>100cells/μl at 5-month follow up), the HIV Mild Responders (<100cells/μl) showed greater parietal delta sources at baseline and lower occipital alpha sources at 5-month follow up. In naïve HIV subjects, 5months of successful cART affect brain synchronization mechanisms at the basis of the generation of delta and alpha rhythms. The present EEG markers may be useful secondary neurophysiological end points for pharmacological clinical trials in naïve HIV subjects. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Velasco, Cesar; Pérez, Inaki; Podzamczer, Daniel; Llibre, Josep Maria; Domingo, Pere; González-García, Juan; Puig, Inma; Ayala, Pilar; Martín, Mayte; Trilla, Antoni; Lázaro, Pablo; Gatell, Josep Maria
The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Kumar, Vikram; Doros, Gheorghe; Farmer, Eric; Drainoni, Mari-Lynn; Rybin, Denis; Myung, Dan; Jackson, Jonathan; Backman, Elke; Stanic, Anela; Skolnik, Paul R.
Abstract Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue. PMID:21323532
Introduction The global scale-up of antiretroviral therapy (ART) for HIV patients has led to concerns regarding inequities in utilization of ART services in resource-limited contexts. In this paper, we describe regional and sex differentials in the distribution of ART among adult HIV patients in Ghana. We highlight the need for interventions to address the gender-based and geographic inequities related to the utilization of ART services in Ghana. Methods We reviewed National AIDS/STIs Control Program’s ART service provision records from January 2003 through December 2010, extracting data on adults aged 15+ who initiated ART in Ghana over a period of eight years. Data on the number of patients on treatment, year of enrollment, sex, and region were obtained and compared. Results The number of HIV patients receiving ART in Ghana increased more than 200-fold from 197 in 2003, to over 45,000 in 2010. However, for each of six continuous years (2005-2010) males comprised approximately one-third of adults newly enrolled on ART. As ART coverage has expanded in Ghana, the proportion of males receiving ART declined from 41.7% in 2004 to 30.1% in 2008 and to 27.6% in 2010. Also, there is disproportionate regional ART utilization across the country. Some regions report ART enrollment lower than their percent share of number of HIV infected persons in the country. Conclusions Attention to the comparatively fewer males initiating ART, as well as disproportionate regional ART utilization is urgently needed. All forms of gender-based inequities in relation to HIV care must be addressed in order for Ghana to realize successful outcomes at the population level. Policy makers in Ghana and elsewhere need to understand how gender-based health inequities in relation to HIV care affect both men and women and begin to design appropriate interventions. PMID:23072340
Rappold, Michaela; Rieger, Armin; Steuer, Andrea; Geit, Maria; Sarcletti, Mario; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Leierer, Gisela; Ledergerber, Bruno; Zangerle, Robert
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.
Gutiérrez, Carolina; Serrano-Villar, Sergio; Madrid-Elena, Nadia; Pérez-Elías, Maria J; Martín, Maria Elena; Barbas, Coral; Ruipérez, Javier; Muñoz, Eduardo; Muñoz-Fernández, Maria Angeles; Castor, Trevor; Moreno, Santiago
The protein kinase C (PKC) agonist bryostatin-1 has shown significant ex-vivo potency to revert HIV-1 latency, compared with other latency reversing agents (LRA). The safety of this candidate LRA remains to be proven in treated HIV-1-infected patients. In this pilot, double-blind phase I clinical-trial (NCT 02269605), we included aviraemic HIV-1-infected patients on triple antiretroviral therapy to evaluate the effects of two different single doses of bryostatin-1 (10 or 20 μg/m) compared with placebo. Twelve patients were included, four in each arm. Bryostatin-1 was well tolerated in all participants. Two patients in the 20 μg/m arm developed grade 1 headache and myalgia. No detectable increases of cell-associated unspliced (CA-US) HIV-1-RNA were observed in any study arm, nor differences in HIV-1 mRNA dynamics between arms (P = 0.44). The frequency of samples with low-level viraemia did not differ between arms and low-level viraemia did not correlate with CA-US HIV-1-RNA levels (P = 0.676). No changes were detected on protein kinase C (PKC) activity and in biomarkers of inflammation (sCD14 and interleukin-6) in any study arm. After the single dose of bryostatin-1, plasma concentrations were under detection limits in all the patients in the 10 μg/m arm, and below 50 pg/ml (0.05 nmol/l) in those in the 20 μg/m arm. Bryostatin-1 was safe at the single doses administered. However, the drug did not show any effect on PKC activity or on the transcription of latent HIV, probably due to low plasma concentrations. This study will inform next trials aimed at assessing higher doses, multiple dosing schedules or combination studies with synergistic drugs.
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
Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy
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
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
Heaton, R.K.; Clifford, D.B.; Franklin, D.R.; Woods, S.P.; Ake, C.; Vaida, F.; Ellis, R.J.; Letendre, S.L.; Marcotte, T.D.; Atkinson, J.H.; Rivera-Mindt, M.; Vigil, O.R.; Taylor, M.J.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T.L.; Wong, J.; Grant, I.
Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. GLOSSARY ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CHARTER = CNS HIV Antiretroviral Therapy Effects Research; CIDI = Composite International Diagnostic Interview; CLIA = Clinical Laboratory Improvement Amendments; CPE = CNS penetration effectiveness; HAD = HIV-associated dementia; HAND = HIV
To determine current evidence about the use of complementary and alternative medicine in the context of highly active antiretroviral therapy. The following objectives included identifying the risks and benefits of using complementary and alternative medicine when living with the human immunodeficiency virus (HIV) and taking such medications. In Canada and the USA, HIV/AIDS service organisations recognise that people affected or infected by HIV are increasingly choosing to use complementary and alternative medicine to cope with this disease. These same organisations advocate for increased access to complementary and alternative medicine and more information about the safe use of complementary and alternative medicine to make informed decisions. Based on the increased integral use of complementary and alternative medicine and conventional medicine in Canada and the USA, the literature review was limited to these two countries. Systematic review. Available full-text abstracts published in English from 2000-2009 were retrieved by electronic searches of selected databases, including the websites of Health Canada and American National Center for Complementary and Alternate Medicine (NCCAM). Forty studies were examined and were categorised by referring to the NCCAM (2007) four types of complementary and alternative medicine. Insufficient evidence exists to support the use of a particular complementary and alternate therapy to enhance the management of HIV disease. Decisions about using complementary and alternative medicine in conjunction with highly active antiretroviral therapy are often poorly informed. Safety risks and potential drug interactions are frequently ignored as people who use highly active antiretroviral therapy prefer to focus on the physical and mental benefits of using selected complementary and alternate therapies to promote their quality of life. As life expectancy increases, from the use of highly active antiretroviral therapy, it is important for
Klein, Marina B; Althoff, Keri N; Jing, Yuezhou; Lau, Bryan; Kitahata, Mari; Lo Re, Vincent; Kirk, Gregory D; Hull, Mark; Kim, H Nina; Sebastiani, Giada; Moodie, Erica E M; Silverberg, Michael J; Sterling, Timothy R; Thorne, Jennifer E; Cescon, Angela; Napravnik, Sonia; Eron, Joe; Gill, M John; Justice, Amy; Peters, Marion G; Goedert, James J; Mayor, Angel; Thio, Chloe L; Cachay, Edward R; Moore, Richard
Human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown. Twelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996-2000), middle (2001-2005), and modern (2006-2010) eras. Among 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61-1.47) for HCV, 0.95 (.40-2.26) for HBV, and 1.52 (.46-5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy. Despite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
Brogan, Anita J; Smets, Erik; Mauskopf, Josephine A; Manuel, Sarah A L; Adriaenssen, Ines
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
Chakravarty, Jaya; Tiwary, Narendra K.; Prasad, Shashi Ranjan; Shukla, Saurabh; Tiwari, Anurag; Mishra, Rabindra Nath; Sundar, Shyam
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
Imai, Kazuo; Misawa, Kazuhisa; Matsumura, Takahiro; Fujikura, Yuji; Mikita, Kei; Tokoro, Masaharu; Maeda, Takuya; Kawana, Akihiko
We herein describe a case of progressive human immunodeficiency virus (HIV)-associated cholangiopathy despite normalization of laboratory parameters, which had indicated liver dysfunction, after the initiation of combined anti-retroviral therapy (cART). HIV-associated cholangiopathy remains important as a differential diagnosis of bile duct disorders, although it is considered to be a rare disease in the era of cART. Magnetic resonance cholangiopancreatography could thus be a powerful tool for the diagnosis and follow-up of this disease. PMID:27725553
Manzar, Md Dilshad; Sony, Peter; Salahuddin, Mohammed; Kumalo, Abera; Geneto, Mathewos; Pandi-Perumal, Seithikurippu R; Moscovitch, Adam; BaHammam, Ahmed S
Human immunodeficiency virus (HIV) infection, and the anti-retroviral therapy (ART) associated complications necessitate that the medical care system keeps evolving for proper management of this group of patients. Electrolyte imbalance and sleep problems are common in patients on ART. Both of these conditions are associated with increased morbidity (such as acute kidney injury, chronic kidney disease, low CD4 count, non-adherence and depression) and mortality. Therefore, screening for both sleep problems and electrolytes imbalance may help to decrease the risk of complications in patients on ART.
Manzar, Md Dilshad; Sony, Peter; Salahuddin, Mohammed; Kumalo, Abera; Geneto, Mathewos; Pandi-Perumal, Seithikurippu R; Moscovitch, Adam; BaHammam, Ahmed S
Human immunodeficiency virus (HIV) infection, and the anti-retroviral therapy (ART) associated complications necessitate that the medical care system keeps evolving for proper management of this group of patients. Electrolyte imbalance and sleep problems are common in patients on ART. Both of these conditions are associated with increased morbidity (such as acute kidney injury, chronic kidney disease, low CD4 count, non-adherence and depression) and mortality. Therefore, screening for both sleep problems and electrolytes imbalance may help to decrease the risk of complications in patients on ART. PMID:28966741
Hosseinipour, Mina C; Schechter, Mauro
Due to the rapid expansion of first-line antiretroviral therapy in resource-limited settings (RLS), increasing numbers of people are living with HIV for prolonged periods of time. Treatment programs must now decide how to balance monitoring costs necessary to maximize health benefits for those already on treatment with the continued demand to initiate more patients on first-line treatment. We review currently available evidence related to monitoring strategies in RLS and discuss their implications on timing of switching to second-line treatment, development of HIV resistance, and clinical outcome.
Mok, Hoi Ping; Hart, Elizabeth; Venkatesan, Pradhib
Immune reconstitution inflammatory syndrome is a recognized complication after the initiation of combination antiretroviral therapy (cART). We report a patient who developed life-threatening pulmonary immune reconstitution inflammatory syndrome (IRIS) three days after initiation of cART. We reviewed published cases of IRIS after Pneumocystis pneumonia (PCP), in particular the time from initiation of cART to IRIS event. The median duration from the initiation of cART to the onset of IRIS was 15 days in the 33 patients reviewed. This report alerts clinicians to the rapidity of the development of pulmonary IRIS following PCP after the initiation of cART.
Ogarkov, O B; Ebers, A; Zhdanova, S; Moiseeva, E; Koshcheyev, M E; Zorkaltseva, E; Shugaeva, S; Vitko, S; Lyles, G; Houpt, E R; Heysell, S K
A bundle of initiatives to integrate human immunodeficiency virus (HIV) and tuberculosis (TB) services was assessed for the impact on antiretroviral therapy (ART) initiation at a TB referral hospital in Irkutsk, Russian Federation, from February 2014 to December 2015. The ART initiation rates in 166 ART-naïve patients undergoing anti-tuberculosis treatment (34.1% with multidrug or extensively drug-resistant TB) increased significantly from 14 (17%) pre-intervention to 44 (54%) post-intervention (P < 0.001). A survey of TB hospital staff identified administrative prioritisation as the most important initiative for increasing ART initiation.
Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo
Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.
Ogarkov, O. B.; Ebers, A.; Zhdanova, S.; Moiseeva, E.; Koshcheyev, M. E.; Zorkaltseva, E.; Shugaeva, S.; Vitko, S.; Lyles, G.; Houpt, E. R.
A bundle of initiatives to integrate human immunodeficiency virus (HIV) and tuberculosis (TB) services was assessed for the impact on antiretroviral therapy (ART) initiation at a TB referral hospital in Irkutsk, Russian Federation, from February 2014 to December 2015. The ART initiation rates in 166 ART-naïve patients undergoing anti-tuberculosis treatment (34.1% with multidrug or extensively drug-resistant TB) increased significantly from 14 (17%) pre-intervention to 44 (54%) post-intervention (P < 0.001). A survey of TB hospital staff identified administrative prioritisation as the most important initiative for increasing ART initiation. PMID:28123963
Bhattacharya, Sangeeta Das; Arya, Bikas K.
This article reviews a case of a child with perinatal HIV followed for 30 months during a prospective cohort study on pneumonia prevention in HIV-infected children. The point of this case report is to illustrate how delayed access to antiretroviral therapy (ART) in HIV-infected children impacts immunization response and growth. Given the WHO's early release guideline changes on ART recommendations and the expected full revised guidelines coming out this year, this article is a timely discussion on the need for access to ART for HIV infected Indian children regardless of CD4 count.
Montagnier, Luc; Aïssa, Jamal; Lavallée, Claude; Mbamy, Mireille; Varon, Joseph; Chenal, Henri
Electromagnetic signals of low frequency have been shown to be durably produced in aqueous dilutions of the Human Imunodeficiency Virus DNA. In vivo, HIV DNA signals are detected only in patients previously treated by antiretroviral therapy and having no detectable viral RNA copies in their blood. We suggest that the treatment of AIDS patients pushes the virus towards a new mode of replication implying only DNA, thus forming a reservoir insensitive to retroviral inhibitors. Implications for new approaches aimed at eradicating HIV infection are discussed.
Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M
Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients.
Gendelman, Howard E.; Gelbard, Harris A.
Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025
Antoniou, Tony; Szadkowski, Leah; Walmsley, Sharon; Cooper, Curtis; Burchell, Ann N; Bayoumi, Ahmed M; Montaner, Julio S G; Loutfy, Mona; Klein, Marina B; Machouf, Nima; Tsoukas, Christos; Wong, Alexander; Hogg, Robert S; Raboud, Janet
Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking. We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason). Additional endpoints included virologic failure, discontinuation due to virologic failure, discontinuation for other reasons, and virologic suppression. We studied 222 patients treated with darunavir/ritonavir and 1791 patients treated with atazanavir/ritonavir. Following multivariable adjustment, there was no difference between darunavir/ritonavir and atazanavir-ritonavir in the risk of regimen failure (adjusted hazard ratio 0.76, 95% CI 0.56 to 1.03) Darunavir/ritonavir-treated patients were at lower risk of virologic failure relative to atazanavir/ritonavir treated patients (aHR 0.50, 95% CI 0.28 to 0.91), findings driven largely by high rates of virologic failure among atazanavir/ritonavir-treated patients in the province of British Columbia. Of 108 discontinuations due to virologic failure, all occurred in patients starting atazanavir/ritonavir. There was no difference between regimens in time to discontinuation for reasons other than virologic failure (aHR 0.93; 95% CI 0.65 to 1.33) or virologic suppression (aHR 0.99, 95% CI 0.82 to 1.21). The risk of regimen failure was similar between patients treated with darunavir/ritonavir and atazanavir/ritonavir. Although darunavir/ritonavir was associated with a lower risk of virologic failure relative to atazanavir/ritonavir, this difference varied substantially by Canadian province and likely reflects regional variation in prescribing practices and patient
Nabeta, Henry W; Okia, Richard; Rhein, Joshua; Lukande, Robert
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
Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita
A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501
Kantor, Rami; Katzenstein, David A; Efron, Brad; Carvalho, Ana Patricia; Wynhoven, Brian; Cane, Patricia; Clarke, John; Sirivichayakul, Sunee; Soares, Marcelo A; Snoeck, Joke; Pillay, Candice; Rudich, Hagit; Rodrigues, Rosangela; Holguin, Africa; Ariyoshi, Koya; Bouzas, Maria Belen; Cahn, Pedro; Sugiura, Wataru; Soriano, Vincent; Brigido, Luis F; Grossman, Zehava; Morris, Lynn; Vandamme, Anne-Mieke; Tanuri, Amilcar; Phanuphak, Praphan; Weber, Jonathan N; Pillay, Deenan; Harrigan, P. Richard; Camacho, Ricardo; Schapiro, Jonathan M; Shafer, Robert W
Background The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. Methods and Findings To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Conclusion Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. PMID:15839752
Cribbs, Sushma K; Tse, Caroline; Andrews, Joel; Shenvi, Neeta; Martin, Greg S
Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to affect outcomes. We hypothesized that HIV-infected patients with severe sepsis would have worse outcomes compared with their HIV-uninfected counterparts in a large safety-net hospital where access to healthcare is low and delivery of critical care is delayed. Secondary analysis of an ongoing prospective observational study between 2006 and 2010. Three adult ICUs (medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital, Atlanta, GA. Adult patients with severe sepsis in the ICU. Baseline patient characteristics and clinical outcomes were collected. HIV-infected and HIV-uninfected patients with sepsis were compared using t tests, chi-square tests, and logistic regression; p values less than 0.05 indicated significance. Of 1,095 patients with severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200. HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01). HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of mortality by multivariate regression modeling after adjusting for age, history of pneumonia, history of hospital-acquired infection, and history of sepsis. HIV-infected patients with severe sepsis continue to suffer worse outcomes compared with HIV-uninfected patients in a large urban safety-net hospital caring for patients with limited access to medical care. Further studies need to be done to investigate the effect of socioeconomic status and mitigate healthcare disparities among critically ill HIV-infected patients.
Badri, Motasim; Maartens, Gary; Mandalia, Sundhiya; Bekker, Linda-Gail; Penrod, John R; Platt, Robert W; Wood, Robin; Beck, Eduard J
Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19) for the HAART group versus 3.73 (95% CI: 3.55-3.97) for the No-ART group, and 8.71 (95% CI: 8.40-9.03) versus 4.35 (95% CI: 4.12-5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52) for the HAART versus 15.36 (95% CI: 13.97-16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49) compared with 6.60 (95% CI: 5.69-7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and
Meyer-Rath, Gesine; Brennan, Alana T; Fox, Matthew P; Modisenyane, Tebogo; Tshabangu, Nkeko; Mohapi, Lerato; Rosen, Sydney; Martinson, Neil
Few studies have compared hospitalisations before and after antiretroviral therapy (ART) initiation in the same patients. We analysed the cost of hospitalisations among 3,906 adult patients in two South African hospitals, 30% of whom initiated ART. Hospitalisations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count <100 cells/mm3 when compared to 200–350 cells/mm3 in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95% confidence interval, CI, 85–158) for patients on ART and USD 72 (95% CI, 56–89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalisation before and immediately after ART initiation. PMID:23187948
Dryden-Peterson, Scott; Jayeoba, Oluwemimo; Hughes, Michael D.; Jibril, Haruna; Keapoletswe, Koona; Tlale, Josephine; Modise, Taolo A.; Asmelash, Aida; Moyo, Sikhulile; van Widenfelt, Erik; Makhema, Joseph; Essex, Max; Shapiro, Roger L.; Lockman, Shahin
Few studies have compared the programmatic effectiveness of the recommended strategies of antenatal highly-active antiretroviral therapy (HAART) and zidovudine for prevention of mother-to-child transmission (MTCT). We prospectively followed infants (93% formula-fed) whose mothers who took either HAART (258 infants) or zidovudine (170 infants) during pregnancy in the Botswana national program. Overall, 10 infants (2.5%) acquired HIV— 9 infants in the zidovudine group (5.5%, 95%CI 2.6-10.2%) and 1 infant in the HAART group (0.4%, 95%CI 0.0-2.2%). Maternal HAART was associated with decreased MTCT (P=0.001) and improved HIV-free survival (P=0.040) compared with zidovudine (with or without single-dose nevirapine) in a programmatic setting. PMID:21792062
Wandeler, Gilles; Gsponer, Thomas; Bihl, Florian; Bernasconi, Enos; Cavassini, Matthias; Kovari, Helen; Schmid, Patrick; Battegay, Manuel; Calmy, Alexandra; Egger, Matthias; Furrer, Hansjakob; Rauch, Andri
Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study. CD4 cell recovery during ART was significantly impaired in hepatitis B surface antigen-positive patients and in those with anti-hepatitis B core antigen alone compared with HBV-uninfected patients, despite similar virological efficacy of ART. CD4 increase in patients with resolved HBV infection was similar to that in HBV-uninfected individuals.
Ferro, Enrico G.; Culbert, Gabriel J.; Wickersham, Jeffrey A.; Marcus, Ruthanne; Steffen, Alana D.; Pauls, Heather A.; Westergaard, Ryan P.; Lee, Christopher K.; Kamarulzaman, Adeeba
Abstract Background. Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods. Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. Results. The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8–36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5–5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44–.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34–.57) were significantly less likely to have ART deferred. Conclusions. Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence
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
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
Bazin, Gabriela Ricordi; Gaspar, Mariza Curto Saavedra; Silva, Nicole Carvalho Xavier Micheloni da; Mendes, Carolina da Costa; Oliveira, Cora Pichler de; Bastos, Leonardo Soares; Cardoso, Claudete Aparecida Araújo
This study aims to evaluate antiretroviral therapy in children and adolescents with AIDS. We selected 247 abstracts published from 1983 to 2013, collected from the PubMed and LILACS databases. Sixty-nine articles were selected. Attention to research in the pediatric age bracket in 30 years of the epidemic is explained by the age group's immunological characteristics, since AIDS progresses faster in children than in adults. Recent studies focus on the initiation of highly active antiretroviral therapy before the onset of symptoms. Early introduction of combination antiretroviral therapy has been implemented effectively and safely in populations with limited resources, leading to significantly improved survival. The current challenge is to manage a chronic disease with acute complications. New studies should focus on population specificities and identify the individual needs of pediatric patients.
Shah, Ira; Gupta, Shradha; Shah, Dhaval M; Dhabe, Harshal; Lala, Mamatha
There are several studies on renal manifestations in human immunodeficiency virus (HIV) infected children from American and African regions, but similar studies from India are lacking. A cross-sectional study was carried out in 28 HIV infected antiretroviral therapy (ART) naïve children coming to the pediatric HIV clinic. Demographic data of the children, clinical presentations including blood pressure, detailed laboratory investigations (serum creatinine, glomerular filtration rate), urine analysis (urine morphology, urine albumin, pus cells, and red blood cells), and CD4 counts were collected. Of the 28 children, 15 (53.6%) had renal manifestations with a male to female ratio of 1:1.5. The most common renal manifestation in our study was abnormal glomerular filtration rate (GFR) in 11 (44.0%) of 25 children. This was followed by pus cells in urine in 6 (21.4%) of the 28 children while 3 (10.7%) of them had proteinuria. The mean age of children with renal manifestations was 5.04±2.75 years as compared to those without renal manifestations who had a mean age of 7.38±2.95 years (P=0.0390). CDC class and sex were not associated with renal manifestations. Our study suggests that reduced GFR is the common renal manifestation, particularly in younger children. Other renal manifestations are related to proteinuria. The lack of correlation of CDC classification with renal manifestations mandates screening of children with HIV for renal disease. A more detailed study of renal manifestations in HIV-infected children is needed.
McNairy, Margaret L; Joseph, Patrice; Unterbrink, Michelle; Galbaud, Stanislas; Mathon, Jean-Edouard; Rivera, Vanessa; Jannat-Khah, Deanna; Reif, Lindsey; Koenig, Serena P; Domercant, Jean Wysler; Johnson, Warren; Fitzgerald, Daniel W; Pape, Jean W
We report patient outcomes after antiretroviral therapy (ART) initiation in a network of HIV facilities in Haiti, including temporal trends and differences across clinics, during the expansion of HIV services in the country. We assessed outcomes at 12 months after ART initiation (baseline) using routinely collected data on adults (≥15 years) in 11 HIV facilities from July 2007-December 2013. Outcomes include death (ascertained from medical records), lost to follow-up (LTF) defined as no visit > 365 days from ART initiation, and retention defined as being alive and attending care ≥ 365 days from ART initiation. Outcomes were compared across calendar year of ART initiation and across facilities. Risk factors for death and LTF were assessed using Cox proportional hazards and competing risk regression models. Cumulatively, 9,718 adults initiated ART with median age 37 years (IQR 30-46). Median CD4 count was 254 cells/uL (IQR 139-350). Twelve months after ART initiation, 4.4% (95% CI 4.0-4.8) of patients died, 21.7% (95% CI 20.9-22.6) were LTF, and 73.9% (95% CI 73.0-74.8) were retained in care. Twelve-month mortality decreased from 13.8% among adults who started ART in 2007 to 4.4% in 2013 (p<0.001). Twelve-month LTF after ART start was 29.2% in 2007, 18.7% in 2008, and increased to 30.1% in 2013 (p<0.001). Overall, twelve-month retention after ART start did not change over time but varied widely across facilities from 61.1% to 86.5%. Expansion of HIV services across Haiti has been successful with increasing numbers of patients initiating ART and decreasing twelve-month mortality rates. However, overall retention has not improved, despite differences across facilities, suggesting additional strategies to improve engagement in care are needed.
Blaser, Nello; Bertisch, Barbara; Kouyos, Roger D; Calmy, Alexandra; Bucher, Heiner C; Cavassini, Matthias; Estill, Janne; Keiser, Olivia; Egger, Matthias
The incidence of anal cancer is high in HIV-positive MSM. We modeled the impact of screening strategies and combination antiretroviral therapy (cART) coverage on anal cancer incidence in Switzerland. Individual-based, dynamic simulation model parameterized with Swiss HIV Cohort Study and literature data. We assumed all men to be human papillomavirus infected. CD4 cell count trajectories were the main predictors of anal cancer. From 2016 we modeled cART coverage either as below 100% (corresponding to 2010-2015) or as 100%, and the following four screening strategies: no screening, yearly anal cytology (Papanicolaou smears), yearly anoscopy and targeted anoscopy 5 years after CD4 count dropped below 200 cells/μl. Median nadir CD4 cell count of 6411 MSM increased from 229 cells/μl during 1980-1989 to 394 cells/μl during 2010-2015; cART coverage increased from 0 to 83.4%. Modeled anal cancer incidence peaked at 81.7/100 000 in 2009, plateaued 2010-2015 and will decrease to 58.7 by 2030 with stable cART coverage, and to 52.0 with 100% cART coverage. With yearly cytology, incidence declined to 38.2/100 000 by 2030, with yearly anoscopy to 32.8 and with CD4 cell count guided anoscopy to 51.3. The numbers needed to screen over 15 years to prevent one anal cancer case were 384 for yearly cytology, 313 for yearly anoscopy and 242 for CD4 cell count-dependent screening. Yearly screening of HIV-positive MSM may reduce anal cancer incidence substantially, with a number needed to screen that is comparable with other screening interventions to prevent cancer.
Mangona, Lucília; Daca, Timóteo; Tchonga, Francisco; Bule, Odete; Bhatt, Nilesh; Jani, Ilesh; Damasceno, Albertino; Prista, António
The aim of this study was to evaluate and compare the effect of two types of exercises interventions on the regularity and health-related physical fitness in HIV-infected individuals who use antiretroviral therapy (ART). A total of 53 HIV+ African women (mean age=39.5±8.4 years) on ART participated in the study. Subjects were randomly divided into 3 groups, namely, formal exercise (FEG), playful exercise (PEG) and control (CG). During 12 weeks, the exercise groups underwent a program of 1-hour duration with a frequency of 3 times a week. The FEG performed a protocol that included 20 minutes of exercise, cycling at 60 % of V̇O2peak, increasing to 75 % and 85 % in the 4th and 8th weeks, respectively, and a muscular endurance circuit consisted of 6 exercises at 15 repetitions per minute (RM). The PEG followed a program consisting of active games. Before and after the intervention the participants were submitted to a clinical evaluation including immunological parameters (CD4+), cardiovascular risk factors, physical fitness and anthropometry. Comparison of somatic variables before and after the program showed no exercise effect. Immunological and cardiovascular variables were also independent of the exercise group. The main effect was found in cardiorespiratory fitness: exercise groups increased significantly in V̇O2peak (FEG=14.7 %; PEG=11.1 %) with no significant differences in CG. The percentage of high attendance was identical between the two groups. It was concluded that there is no contraindication for exercise in this type of population and the beneficial effect was mainly in cardiorespiratory fitness, regardless of the type of exercise performed.
Mangona, Lucília; Daca, Timóteo; Tchonga, Francisco; Bule, Odete; Bhatt, Nilesh; Jani, Ilesh; Damasceno, Albertino; Prista, António
The aim of this study was to evaluate and compare the effect of two types of exercises interventions on the regularity and health-related physical fitness in HIV-infected individuals who use antiretroviral therapy (ART). A total of 53 HIV+ African women (mean age=39.5±8.4 years) on ART participated in the study. Subjects were randomly divided into 3 groups, namely, formal exercise (FEG), playful exercise (PEG) and control (CG). During 12 weeks, the exercise groups underwent a program of 1-hour duration with a frequency of 3 times a week. The FEG performed a protocol that included 20 minutes of exercise, cycling at 60 % of V̇O2peak, increasing to 75 % and 85 % in the 4th and 8th weeks, respectively, and a muscular endurance circuit consisted of 6 exercises at 15 repetitions per minute (RM). The PEG followed a program consisting of active games. Before and after the intervention the participants were submitted to a clinical evaluation including immunological parameters (CD4+), cardiovascular risk factors, physical fitness and anthropometry. Comparison of somatic variables before and after the program showed no exercise effect. Immunological and cardiovascular variables were also independent of the exercise group. The main effect was found in cardiorespiratory fitness: exercise groups increased significantly in V̇O2peak (FEG=14.7 %; PEG=11.1 %) with no significant differences in CG. The percentage of high attendance was identical between the two groups. It was concluded that there is no contraindication for exercise in this type of population and the beneficial effect was mainly in cardiorespiratory fitness, regardless of the type of exercise performed. PMID:26587077
Wandeler, Gilles; Gerber, Florian; Rohr, Julia; Chi, Benjamin H; Orrell, Catherine; Chimbetete, Cleophas; Prozesky, Hans; Boulle, Andrew; Hoffmann, Christopher J; Gsponer, Thomas; Fox, Matthew P; Zwahlen, Marcel; Egger, Matthias
There is debate over using tenofovir or zidovudine alongside lamivudine in second-line antiretroviral therapy (ART) following stavudine failure. We analysed outcomes in cohorts from South Africa, Zambia and Zimbabwe Patients aged ≥16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programmes in southern Africa were included. We estimated the causal effect of receiving tenofovir or zidovudine on mortality and virological failure using Cox proportional hazards marginal structural models. Its parameters were estimated using inverse probability of treatment weights. Baseline characteristics were age, sex, calendar year and country. CD4(+) T-cell count, creatinine and haemoglobin levels were included as time-dependent confounders. A total of 1,256 patients on second-line ART, including 958 on tenofovir, were analysed. Patients on tenofovir were more likely to have switched to second-line ART in recent years, spent more time on first-line ART (33 versus 24 months) and had lower CD4(+) T-cell counts (172 versus 341 cells/μl) at initiation of second-line ART. The adjusted hazard ratio comparing tenofovir with zidovudine was 1.00 (95% CI 0.59, 1.68) for virological failure and 1.40 (0.57, 3.41) for death. We did not find any difference in treatment outcomes between patients on tenofovir or zidovudine; however, the precision of our estimates was limited. There is an urgent need for randomized trials to inform second-line ART strategies in resource-limited settings.
Warshaw, Meredith G.; Miller, William C.; Castro, Hannah; Fiscus, Susan A.; Harper, Lynda M.; Harrison, Linda J.; Klein, Nigel J.; Lewis, Joanna; Melvin, Ann J.; Tudor-Williams, Gareth; McKinney, Ross E.
BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization “mild” immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with “severe” immunosuppression, more children with “mild” immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or “advanced” immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with “mild” immunosuppression at any age or “advanced” immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks. PMID:25266426
Kore, Idil; Ananworanich, Jintanat; Valcour, Victor; Fletcher, James LK; Chalermchai, Thep; Paul, Robert; Reynolds, Jesse; Tipsuk, Somporn; Ubolyam, Sasiwimol; Rattanamanee, Somprartthana; Jagodzinski, Linda; Kim, Jerome; Spudich, Serena
OBJECTIVE To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART). DESIGN Prospective study of Thai AHI participants examined at 3 and 6 months following initiation of cART. METHODS 36 AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test (GP), Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A (TM). Raw scores were standardized to 251 age-and-education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared to that of controls at 6 months. Analyses included multivariable regression, non-parametric repeated measures ANOVA, and Mann-Whitney U test. RESULTS Baseline NP scores for the AHI group were within normal range (Z scores range: −0.26 to −0.13). NP performance improved on CT1, CT2, and TM in the initial 3 months (ps <0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (p=0.018). Participants that performed >1 standard deviation below normative means on >2 tests (n=8) exhibited higher baseline cerebrospinal fluid (CSF) HIV RNA (p=0.047) and had no improvement after cART. CONCLUSIONS Most AHI individuals had normal NP performance and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance which correlated with higher CSF HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals. PMID:26509933
Johnston, Stephen S; Juday, Timothy; Farr, Amanda M; Chu, Bong-Chul; Hebden, Tony
To compare antiretroviral therapy (ART) adherence and persistence and total healthcare expenditures in Medicaid-insured patients with human immunodeficiency virus (HIV) initiating preferred or nonpreferred first-line ART based on March 2012 HHS HIV treatment guidelines. Retrospective observational study using Medicaid administrative healthcare claims from 15 states. Subjects were HIV patients 18 to 64 years who initiated first-line HIV-related ART between January 1, 2007, and September 30, 2011, with continuous enrollment for 6 months prior to and at least 3 months following ART initiation. Patients were classified as having initiated preferred or nonpreferred ART based on March 2012 HHS HIV treatment guidelines. Outcomes were: ART adherence (proportion of days covered dichotomized at ≥80% and ≥95%), time to ART nonpersistence, and per patient per month (PPPM) total healthcare expenditures. Outcomes were evaluated using multivariable regressions. Sample included 1979 patients initiating preferred ART regimens and 1614 patients initiating nonpreferred ART; overall mean age was 41 years; 48% of subjects were female. In the multivariable analyses, patients initiating preferred ART regimens had significantly greater odds of adherence ≥80% (odds ratio [OR], 1.38; 95% CI, 1.07-1.77) and adherence ≥95% (OR, 1.26; 95% CI, 1.05-1.51), and a significantly lower hazard of nonpersistence (HR, 0.48; 95% CI, 0.44-0.52). PPPM total healthcare expenditures were numerically lower for patients initiating preferred ART regimens (-$341; 95% CI, -$888 to $255) but the difference was not deemed significant. This study reinforces the value of HHS recommendations for first-line ART. The potential impact of these findings will grow as more HIV patients become Medicaid-eligible under the Patient Protection and Affordable Care Act.
He, Na; Duan, Song; Ding, Yingying; Rou, Keming; McGoogan, Jennifer M.; Jia, Manhong; Yang, Yuecheng; Wang, Jibao; Montaner, Julio S. G.; Wu, Zunyou
Background Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China's current HIV treatment program prevents new HIV infections among discordant couples in rural China. Methods A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence. Results A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup. Conclusions ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China's HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region. PMID:24236010
Kwong-Leung Yu, Joseph; Tok, Teck-Siang; Tsai, Jih-Jin; Chang, Wu-Shou; Dzimadzi, Rose K.; Yen, Ping-Hsiang; Makombe, Simon D.; Nkhata, Amon; Schouten, Erik J.; Kamoto, Kelita; Harries, Anthony D.
Background Long term retention of patients on antiretroviral therapy (ART) in Africa's rapidly expanding programmes is said to be 60% at 2 years. Many reports from African ART programmes make little mention of patients who are transferred out to another facility, yet Malawi's national figures show a transfer out of 9%. There is no published information about what happens to patients who transfer-out, but this is important because if they transfer-in and stay alive in these other facilities then national retention figures will be better than previously reported. Methodology/Principal Findings Of all patients started on ART over a three year period in Mzuzu Central Hospital, North Region, Malawi, those who transferred out were identified from the ART register and master cards. Clinic staff attempted to trace these patients to determine whether they had transferred in to a new ART facility and their outcome status. There were 805 patients (19% of the total cohort) who transferred out, of whom 737 (92%) were traced as having transferred in to a new ART facility, with a median time of 1.3 months between transferring-out and transferring-in. Survival probability was superior and deaths were lower in the transfer-out patients compared with those who did not transfer. Conclusion/Significance In Mzuzu Central Hospital, patients who transfer-out constitute a large proportion of patients not retained on ART at their original clinic of registration. Good documentation of transfer-outs and transfer-ins are needed to keep track of national outcomes. Furthermore, the current practice of regarding transfer-outs as being double counted in national cohorts and subtracting this number from the total national registrations to get the number of new patients started on ART is correct. PMID:18446230
Cagle, Anthony; McGrath, Christine; Richardson, Barbra A; Donovan, Dennis; Sakr, Sameh; Yatich, Nelly; Ngomoa, Richard; Chepngeno Langat, Agnes; John-Stewart, Grace; Chung, Michael H
Studies on the effects of alcohol use on HIV disease progression have been contradictory, with at least one study finding a positive effect of low alcohol consumption on CD4 count. In addition, most such studies have taken place in the developed West. We investigated the association between alcohol use and immune reconstitution through CD4 count response among HIV-infected individuals on antiretroviral therapy (ART) at an urban sub-Saharan African clinic. This was a retrospective cohort study of treatment-naïve HIV-infected adults initiating ART in Nairobi, Kenya and followed for 12 months between January 2009 and December 2012. At enrollment, a standardized questionnaire was used to collect data on sociodemographic variables and alcohol consumption. CD4 count was measured every six months. Linear regression models assessed the association between CD4 count and alcohol consumption, categorized as abstinent, moderate, or hazardous. Overall, 854 participants were included, 522 of which were women, with 85 (25.6%) men and 50 (9.6%) women reporting any alcohol use, and 8 (2.4%) men and 7 (1.3%) women reporting hazardous drinking. At baseline, alcohol use was associated with higher education and socioeconomic status. Median CD4 count was higher among alcohol users compared to those who abstained at baseline and at 6 and 12 months post-ART initiation, although this was only significant at 6 months. There were no differences in adherence between abstainers and drinkers. While overall alcohol use was significantly associated with higher CD4 counts, moderate and hazardous use treated separately were not. We conclude that, while alcohol use was associated with higher CD4 counts at 12 months post-ART, the mechanism for this association is unclear but may reflect unmeasured socioeconomic or nutritional differences. Additional research is required on the specific drinking patterns of this population and the types of alcoholic beverages consumed to clarify this relationship.
Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315
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
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.
Sun, Yu; Fu, Yajing; Zhang, Zining; Tang, Tian; Liu, Jing; Ding, Haibo; Han, Xiaoxu; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun
Abstract Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function. PMID:28700479
Pyra, Maria; Heffron, Renee; Mugo, Nelly R.; Nanda, Kavita; Thomas, Katherine K.; Celum, Connie; Kourtis, Athena P.; Were, Edwin; Rees, Helen; Bukusi, Elizabeth; Baeten, Jared M.
Objective To assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. Methods Using data from 5,153 HIV-infected women followed prospectively one to three years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral, or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHR) and test interactions between each method and ART use. Results During follow-up, 9% of women ever used implants, 40% used injectables, and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART (aHR 0.06, 95% CI 0.01-0.45) and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed non-statistically significant reduced effectiveness when concurrently using efavirenz. Conclusion Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use. PMID:26544706
Oette, Mark; Kaiser, Rolf; Däumer, Martin; Petch, Ruth; Fätkenheuer, Gerd; Carls, Horst; Rockstroh, Jürgen Kurt; Schmalöer, Dirk; Stechel, Jürgen; Feldt, Torsten; Pfister, Herbert; Häussinger, Dieter
Primary HIV drug resistance has been associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART) in several trials. The aim of the study was to assess the efficacy of first-line HAART guided by resistance testing. In a prospective multicenter study in the state of Nordrhein-Westfalen, Germany, chronically HIV-infected patients underwent genotypic resistance testing and were monitored for 48 weeks after initiation of HAART. Primary drug resistance was found in 30 of 269 patients entering the study between January 2001 and December 2003 [11.2%; 95% confidence interval, 7.4-14.9]. In intent-to-treat analysis, the proportion of patients with viral load below 50 copies/mL after 24 and 48 weeks was 70.0% and 66.7%, respectively, in patients with resistance and 74.1% and 73.6%, respectively, in patients without (P = 0.66 and 0.51). In on-treatment analysis, the proportions were 80.8% and 83.3%, respectively, in patients with resistance and 81.9% and 85.0%, respectively, in patients without (P= 0.79 and 0.77). These results were also valid considering a detection limit of 400 copies/mL. The prevalence of primary drug resistance was 11.2% in chronically HIV-infected patients. HAART guided by resistance testing had similar efficacy in patients with primary drug resistance as compared with patients with wild-type virus. Based on these facts, resistance-adapted first-line HAART is suggested as routine practice.
Matthews, Lynn T.; Ashaba, Scholastic; Tsai, Alexander C.; Kanters, Steve; Robak, Magdalena; Psaros, Christina; Kabakyenga, Jerome; Boum, Yap; Haberer, Jessica E.; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.
Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health. PMID:25436816
Kleinman, Nora J; Manhart, Lisa E; Mohanraj, Rani; Kumar, Shuba; Jeyaseelan, Lakshmanan; Rao, Deepa; Simoni, Jane M
Optimal adherence to antiretroviral therapy (ART) is key to viral suppression, but may be impeded by psychosocial consequences of HIV-infection such as stigma and depression. Measures of adherence in India have been examined in clinic populations, but little is known about the performance of these measures outside clinical settings. We conducted a cross-sectional study of 151 Tamil-speaking people living with HIV/AIDS (PLHA) in India recruited through HIV support networks and compared single item measures from the Adult AIDS Clinical Trial Group (AACTG) scale, a visual analog scale (VAS), and a question on timing of last missed dose. Depression was measured using the Major Depression Inventory (MDI) and HIV-related stigma was measured using an adaptation of the Berger Stigma Scale. Mean age was 35.6 years (SD ± 5.9); 55.6% were male; mean MDI score was 11.9 (SD ± 9.1); and mean stigma score was 67.3 (SD ± 12.0). Self-reported perfect adherence (no missed doses) was 93.3% using the AACTG item, 87.1% using last missed dose, and 83.8% using the VAS. The measures had moderate agreement with each other (kappa 0.45-0.57). Depression was associated with lower adherence irrespective of adherence measure used, and remained significantly associated in multivariable analyses adjusting for age and marital status. Stigma was not associated with adherence irrespective of the measure used. The VAS captured the greatest number of potentially non-adherent individuals and may be useful for identifying PLHA in need of adherence support. Given the consistent and strong association between poorer adherence and depression, programs that jointly address adherence and mental health for PLHA in India may be more effective than programs targeting only one.
Gianella, Sara; Kosakovsky Pond, Sergei L; Oliveira, Michelli F; Scheffler, Konrad; Strain, Matt C; De la Torre, Antonio; Letendre, Scott; Smith, Davey M; Ellis, Ronald J
To design effective eradication strategies, it may be necessary to target HIV reservoirs in anatomic compartments other than blood. This study examined HIV RNA rebound following interruption of antiretroviral therapy (ART) in blood and cerebrospinal fluid (CSF) to determine whether the central nervous system (CNS) might serve as an independent source of resurgent viral replication. Paired blood and CSF samples were collected longitudinally from 14 chronically HIV-infected individuals undergoing ART interruption. HIV env (C2-V3), gag (p24) and pol (reverse transcriptase) were sequenced from cell-free HIV RNA and cell-associated HIV DNA in blood and CSF using the Roche 454 FLX Titanium platform. Comprehensive sequence and phylogenetic analyses were performed to search for evidence of unique or differentially represented viral subpopulations emerging in CSF supernatant as compared with blood plasma. Using a conservative definition of compartmentalization based on four distinct statistical tests, nine participants presented a compartmentalized HIV RNA rebound within the CSF after interruption of ART, even when sampled within 2 weeks from viral rebound. The degree and duration of viral compartmentalization varied considerably between subjects and between time-points within a subject. In 10 cases, we identified viral populations within the CSF supernatant at the first sampled time-point after ART interruption, which were phylogenetically distinct from those present in the paired blood plasma and mostly persisted over time (when longitudinal time-points were available). Our data suggest that an independent source of HIV RNA contributes to viral rebound within the CSF after treatment interruption. The most likely source of compartmentalized HIV RNA is a CNS reservoir that would need to be targeted to achieve complete HIV eradication.
Carlson, Renee Donahue; Rolfes, Melissa A; Birkenkamp, Kate E; Nakasujja, Noeline; Rajasingham, Radha; Meya, David B; Boulware, David R
Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.
Braunstein, Sarah L; Robertson, McKaylee M; Myers, Julie; Nash, Denis
HIV surveillance programs do not typically collect comprehensive data on antiretroviral therapy (ART). We validated a population-based measure of ART initiation that uses HIV viral load (VL) results in the absence of data on ART. We used CD4/VL data reported to NYC HIV Surveillance for persons aged ≥13 years and diagnosed with HIV from 2006 to 2012 to validate estimates of ART initiation date based on 3 ART initiation definitions: (1) ≥1-log decline in copies per milliliter between 2 VLs over 3 months; (2) ≥2-log decline in copies per milliliter between 2 VLs over 3 months; and (3) the earliest of either a ≥1-log decline in VL over 3 months, or a change from detectable VL to undetectable VL (<400 copies/mL) over any interval. We plotted median CD4 counts by quarter before and after ART initiation to compare estimated initiation date with nadir of the CD4 trajectory. A total of 24,348 persons were diagnosed with HIV in NYC from 2006 to 2012. In all, 12,123 persons had probable ART initiation based on ≥2-log decline, 12,719 based on ≥1-log decline, and 14,311 based on ≥1-log decline or detectable-undetectable change. Lowest median CD4 count occurred at the estimated ART initiation date for all 3 definitions. The definition based on a ≥1-log VL decline or a change from detectable to undetectable VL captured more ART initiations and identified earlier initiation dates. Serial VL measures are a valid source for estimating ART initiation. A definition that includes a ≥1-log VL decline or a change from detectable to undetectable VL performed best.
Braunstein, Sarah L.; Robertson, McKaylee M.; Myers, Julie; Nash, Denis
Introduction HIV surveillance programs do not typically collect comprehensive data on antiretroviral therapy (ART). We validated a population-based measure of ART initiation that uses HIV viral load (VL) results in the absence of data on ART. Methods We used CD4/VL data reported to NYC HIV Surveillance for persons aged ≥13 years and diagnosed with HIV from 2006 to 2012 to validate estimates of ART initiation date based on 3 ART initiation definitions: (1) ≥1-log decline in copies per milliliter between 2 VLs over 3 months; (2) ≥2-log decline in copies per milliliter between 2 VLs over 3 months; and (3) the earliest of either a ≥1-log decline in VL over 3 months, or a change from detectable VL to undetectable VL (<400 copies/mL) over any interval. We plotted median CD4 counts by quarter before and after ART initiation to compare estimated initiation date with nadir of the CD4 trajectory. Results A total of 24,348 persons were diagnosed with HIV in NYC from 2006 to 2012. In all, 12,123 persons had probable ART initiation based on ≥2-log decline, 12,719 based on ≥1-log decline, and 14,311 based on ≥1-log decline or detectable–undetectable change. Lowest median CD4 count occurred at the estimated ART initiation date for all 3 definitions. The definition based on a ≥1-log VL decline or a change from detectable to undetectable VL captured more ART initiations and identified earlier initiation dates. Conclusions Serial VL measures are a valid source for estimating ART initiation. A definition that includes a ≥1-log VL decline or a change from detectable to undetectable VL performed best. PMID:27152466
Atukunda, Ruth; Imakit, Richard; Memiah, Peter
There is limited data on the prevalence of depression in HIV and AIDS patients in Sub-Saharan Africa and little resources have been allocated to address this issue. Depression affects patient adherence to treatment and predisposes patients to resistance which poses a public health threat. It also affects quality of life and productivity of patients. From August 2008 to March 2009, 731 patient adherence surveys were administered to assess disease, treatment knowledge and services received. The primary variable of interest was patients’ level of depressive symptoms score, constructed using factor analysis from five survey questions relating to: sadness, need to be alone, hopelessness and confusion and was categorized as no depressive symptoms (score 0), low depressive symptoms (score 1-2), moderate depressive symptoms (score 3-4) and high depressive symptoms (score 5-10). Majority of the patients on highly active antiretroviral therapy (HAART) (59%) were found to have depressive symptoms and this was more among women than men (66% vs 43%). There was some association of depressive symptoms with non-disclosure (70% of those who had not disclosed had depressive symptoms compared to 53% among those who had disclosed). There is a high prevalence of depressive symptoms among adult patients on HAART. There is need for in-depth evaluation to find out the root causes of depressive symptoms among HAART patients in AIDSRelief clinics. There is need to integrate mental health management in HIV care and treatment as well as training the existing health workers on mental health management. PMID:28299108
Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen
Objectives This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. Methods We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. Results During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12–35.16) and older age (AOR, 1.04; 95% CI, 1.00–1.09). The positive association between duration of exposure to ritonavir
Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen
This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16) and older age (AOR, 1.04; 95% CI, 1.00-1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident
Thanawuth, Nattasiri; Rojpibulstit, Malee
The objective of this study was to examine the extent of unprotected sex among patients already established in HIV-medical care and their associated factors. Sexually active patients who were receiving antiretroviral therapy (ART) from five public hospitals in Trang province, Southern Thailand, were interviewed. Of 279 studied patients, 37.3% had unprotected sex in the prior 3 months and 27.2% did not disclose their serostatus to sexual partners. The median duration interquartile range (IQR) of using ART was 47 (27-60) months and 26.7% were non-adherent to ART (i.e., taking less than 95% of the prescribed doses). More than one-third had the perception that ART use would protect against HIV transmission even with unprotected sex. About 36.6% reported that they were unaware of their current CD4 counts and nearly one-third did not receive any safe sex counseling at each medical follow-up. After adjustment for potential confounders, non-adherence to ART and HIV-nondisclosure were strongly associated with an increase in the risk of unprotected sex with the adjusted odds ratio (aOR) of 5.03 (95% CI 2.68-9.44) and 3.89 (95% CI 1.57-9.61), respectively. In contrast, the risk for engaging in unprotected sex was less likely among patients having a negative-serostatus partner (aOR = 0.30; 95% CI 0.12-0.75), a longer duration of the use of ART (aOR = 0.98; 95%CI 0.97-0.99) and an unawareness of their current CD4 levels (aOR = 0.54; 95% CI 0.30-0.99). To maximize the benefits from ART, there should be a bigger emphasis on the "positive prevention" program and more efforts are needed to target the population at risk for unprotected sex. Strategies to encourage adherence to ART and for disclosure of serostatus are also required.
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
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.
Cunha, Maria do Carmo Soares Alves; Siqueira Filho, Aristarco Gonçalves de; Santos, Silvia Reis dos; Abreu, Thalita Fernandes de; Oliveira, Ricardo Hugo S de; Baptista, Denise Marcelino; Dantas, Marylane Christian Feitosa; Carvalho, Márcia Fernanda; Guedes, Luciane Gaspar
To describe the prevalence of cardiac abnormalities in the echocardiogram of children with AIDS followed up in a reference service at 18+/-6 months of AIDS confirmed diagnosis. A cross-section study with a cohort after 18+/-6 months of AIDS diagnosis. The study included a total of 93 children with a confirmed diagnosis of AIDS with vertical transmission, with no malignancies and who underwent echocardiogram (echo) during cardiologic evaluation. Cardiac abnormalities were assessed in patients who were not treated (G1) and patients who were treated (G2) with combination antiretroviral therapy. When diagnosed with AIDS, the children were on average 3.07 years old and 50.50% were female. The combination regimen with antiretroviral agents was used by 47 patients (G2). Cardiac involvement was present in 40 children (43.00%). The presence of left ventricular dysfunction (G1: 39.10%; G2: 10.60%) and the isolated enlargement of left ventricle (G1: 6.60%; G2: 14.90%) were the most frequent findings. We observed a significant association between the groups without and with combination antiretroviral therapy asregards the presence of left ventricular dysfunction (PR= 3.42; [1.41-8.26]; p = 0.02) and malnutrition (PR = 1.79; [1.00-3.20]; p = 0.04). Cardiac involvement was frequent in children with AIDS and left ventricular dysfunction was the most common abnormality on echocardiogram. There was a statistically significant difference between the groups with and without triple combination treatment as regards the presence of left ventricular dysfunction and malnutrition.
Puligujja, Pavan; McMillan, JoEllyn; Kendrick, Lindsey; Li, Tianyuzi; Balkundi, Shantanu; Smith, Nathan; Veerubhotla, Ram S.; Edagwa, Benson J.; Kabanov, Alexander V.; Bronich, Tatiana; Gendelman, Howard E.; Liu, Xin-Ming
Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified atazanavir/ritonavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use. PMID:23680933
Anglemyer, Andrew; Rutherford, George W; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi
Background Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). Objectives To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. Search methods We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Selection criteria Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART Data collection and analysis Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Main results One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350–550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I2=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95%CI 0.17, 0.75] with substantial heterogeneity (I2=62%). We also performed
Musa, Baba Maiyaki; Gebi, Usman; Etiebet, Mary-Ann; Omuh, Helen; Ekedegwa, Patrick; Dakum, Patrick; Blattner, William
Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART) in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males) with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF). Fourty-four percent, 23% and 33% of patients were on TDF, D4T & AZT based regimen, respectively (P=0.66). Increment of >100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF & D4T compared with those in AZT based regimens (ANOVA; P<0.0003). Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P<0.0001). Equally, multivariate logistic regression found age
Rappold, Michaela; Rieger, Armin; Steuer, Andrea; Geit, Maria; Sarcletti, Mario; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Leierer, Gisela; Ledergerber, Bruno; Zangerle, Robert
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
Yanik, Elizabeth L; Napravnik, Sonia; Ryscavage, Patrick; Eron, Joseph J; Koletar, Susan L; Moore, Richard D; Zinski, Anne; Cole, Stephen R; Hunt, Peter; Crane, Heidi M; Kahn, James; Mathews, William C; Mayer, Kenneth H; Taiwo, Babafemi O
We assessed laboratory monitoring after combination antiretroviral therapy initiation among 3678 patients in a large US multisite clinical cohort, censoring participants at last clinic visit, combination antiretroviral therapy change, or 3 years. Median days (interquartile range) to first hematologic, hepatic, renal, and lipid tests were 30 (18-53), 31 (19-56), 33 (20-59), and 350 (96-1106), respectively. At 1 year, approximately 80% received more than 2 hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received 1 or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities.
Martin-Odoom, Alexander; Bonney, Evelyn Yayra; Opoku, Derek Kofi
Patients infected with human immunodeficiency virus (HIV) usually develop some form of ocular complication in the different segments of the eye due to immune deficiency. In Ghana, data regarding ocular complications among HIV/AIDS patients is scarce. This study investigated the occurrence of ocular complications in HIV infected patients undergoing antiretroviral therapy at the Agogo Presbyterian Hospital in the Ashanti Region of Ghana. Blood samples were taken from 100 confirmed HIV infected patients. The CD4 + T cell count and WHO clinical staging were determined. The patients were taken through thorough ophthalmic assessments to determine any ocular complications. Forty-eight patients (48 %) had at least one HIV-related ocular complication. These complications occurred more frequently among those with CD4 counts below 200 cells/μL. Of the participants with HIV-related ocular complications, 11 (23 %) had retinal microvasculopathy, 10 (21 %) showed allergic conjunctivitis, 7 (15 %) had HIV retinopathy and 7 (15 %) had conjunctival carcinoma. All the participants in the study were on first-line antiretroviral therapy; 68 % were females and 72 % were in the Stage 3 of the WHO Clinical Staging of HIV infection. The prevalence of ocular complications in HIV positive persons under treatment in Ghana is high. Lower CD4 + T cell counts coupled with age were predisposing factors to HIV-related ocular complications.
Smith, Daniel Jordan; Mbakwem, Benjamin C
To examine and understand the marital and fertility aspirations and behaviours of individuals receiving antiretroviral therapy (ART) in Nigeria and evaluate the effects on sexual behaviour, disclosure, and adherence. The study used ethnographic methods of participant observation and in-depth interviews of individuals receiving ART through a government-supported programme in southeastern Nigeria. Interviews and observations of individuals on treatment demonstrate that marriage and childbearing are paramount desires for people whose health is restored by ART. The concept of life projects is introduced and combined with the established idea of therapeutic itineraries to show how participation in and adherence to treatment, disclosure of HIV status, and decisions about sexual behaviour cannot be understood in purely biomedical terms. Marital and reproductive aspirations routinely impinge on and often trump clinical and public health priorities. Emblematic case studies are provided to illustrate the social dynamics that motivate and explain behaviour seemingly inimical to individual and public health. Effective antiretroviral programme design and therapy management will require acknowledging and often enabling rather than discouraging the marital and reproductive goals of individuals if issues of disclosure, adherence, and prevention are to be realistically addressed.
Holstad, Marcia McDonnell; DiIorio, Colleen; Magowe, Mabel K M
Women comprise the fastest growing group of persons with AIDS. They are often diagnosed later in the disease, when antiretroviral therapy (ART) is strongly indicated. Antiretroviral therapy has transformed the course of HIV/AIDS to a treatable, chronic illness. This article provides a profile of women with HIV/AIDS and describes ART. Selected research related to adherence and motivation is summarized. Psychosocial and economic concerns specific to women, ART, adherence, and motivation are presented. The article reviews challenges for risk reduction behaviors for HIV+ women, such as sexual activity and substance abuse. The authors discuss the Keeping Health and Active with Risk reduction and Medication Adherence (KHARMA) Project, a research project in progress that was designed to promote adherence to both ART and risk reduction behaviors in HIV+ women. The study includes two groups: a motivational group intervention based on motivational interviewing and a health promotion program control group tailored to the needs of HIV+ women. A description of the tailored intervention and project update is included.
Peyre, Marion; Gauchet, Aurélie; Roustit, Matthieu; Leclercq, Pascale; Epaulard, Olivier
Background: Physician attitude influences the way patients cope with diagnosis and therapy in chronic severe diseases such as cancer. Previous studies showed that such an effect exists in HIV care; it is likely that it begins with the first contact with a physician. Objective: We aimed to explore in HIV-infected persons their perception of the first consultation they had with an HIV specialist (PFC-H), and whether this perception correlates with adherence to antiretroviral therapy. Method: The study was conducted in Grenoble University Hospital, France, a tertiary care center. Every antiretroviral-experienced patient was asked to freely complete a self-reported, anonymous questionnaire concerning retrospective PFC-H, present adherence (Morisky scale), and present perceptions and beliefs about medicine (BMQ scale). Results: One hundred and fifty-one questionnaires were available for evaluation. PFC-H score and adherence were correlated, independently from age, gender, and numbers of pill(s) and of pill intake(s) per day. BMQ score also correlated with adherence; structural equation analysis suggested that the effect of PFC-H on adherence is mediated by positive beliefs. Conclusion: These results suggest that for HIV-infected persons, the perceptions remaining from the first consultation with an HIV specialist physician influence important issues such as adherence and perception about medicine. Physicians must be aware of this potentially long-lasting effect. PMID:27708747
Holmes, Kathleen; Winskell, Kate
The perception in low-resource settings that investment of resources in people living with HIV (PLHIV) is wasted because AIDS is both an incurable and deadly disease is known as resource-based stigma. In this paper, we draw on in-depth interviews (IDI), focus group discussions (FGD), and key informant interviews (KII) with 77 HIV-positive microfinance participants and nongovernmental organization leaders to examine resource-based stigma in the context of increased access to antiretroviral therapy (ART) at an individual, household, and community level in Côte d'Ivoire. The purpose of this exploratory paper is to examine: (1) resource-based stigmatization in the era of ART and (2) the relationship among microfinance, a poverty-reduction intervention, and HIV stigmatization. The frequency with which resource-based stigma was discussed by respondents suggests that it is an important component of HIV-related stigma in this setting. It affected PLHIV's access to material as well as social resources, leading to economic discrimination and social devaluation. Participation in village savings and loans groups, however, mitigated resource-based HIV stigma, suggesting that in the era of increased access to antiretroviral therapy, economic programs should be considered as one possible HIV stigma-reduction intervention.
Zhao, Yan; Shi, Cynthia X.; McGoogan, Jennifer M.; Rou, Keming; Zhang, Fujie; Wu, Zunyou
Aims The objective of this study was to examine factors that predict antiretroviral therapy (ART) access among eligible, HIV-positive methadone maintenance treatment (MMT) clients. We also tested the hypothesis that sustained MMT participation increases the likelihood of accessing ART. Design A nationwide cohort study conducted from March 1, 2004 to December 31, 2011. Setting MMT clients were followed from the time of their enrollment in China's national MMT program until their death or the study end date. Participants Our cohort was composed of 7,111 ART-eligible, HIV-positive MMT clients, 49.2% of whom remained ART-naïve and 50.8% of whom received ART. Measurements Demographic variables, drug use history, MMT program participation, and HIV-related clinical characteristics of study participants who remained naïve to ART and those who accessed ART were compared by univariate and multivariable analysis. Findings Predictors of accessing ART among this cohort included being retained in MMT at the time of first meeting ART eligibility (AOR=1.84, CI: 1.55-2.21, p<0.001) compared to meeting ART eligibility before entering MMT (AOR=0.98, CI:0.80-1.21, p=0.849) or previously entering MMT and dropping out before meeting ART eligibility. Additional predictors were CD4 >200 cells/μL when ART-eligibility requirement was first met (AOR=1.94, CI: 1.73-2.19, p<0.001 compared to CD4=200-350 cells/μL), and being in a stable partner relationship (married/cohabitating: AOR=1.14, CI: 1.01-1.28, p=0.029). Conclusions Retained participation in methadone maintenance treatment (MMT) increases the likelihood that eligible clients will access antiretroviral therapy (ART). These results highlight the potential benefit of co-localization of MMT and ART services in a “one-stop-shop” model. PMID:25533863
Patterson, Sophie; Cescon, Angela; Samji, Hasina; Chan, Keith; Zhang, Wendy; Raboud, Janet; Burchell, Ann N; Cooper, Curtis; Klein, Marina B; Rourke, Sean B; Loutfy, Mona R; Machouf, Nima; Montaner, Julio S G; Tsoukas, Chris; Hogg, Robert S
We sought to evaluate life expectancy and mortality of HIV-positive individuals initiating combination antiretroviral therapy (ART) across Canada, and to consider the potential error introduced by participant loss to follow-up (LTFU). Our study used data from the Canadian Observational Cohort (CANOC) collaboration, including HIV-positive individuals aged ≥18 years who initiated ART on or after January 1, 2000. The CANOC collaboration collates data from eight sites in British Columbia, Ontario, and Quebec. We computed abridged life-tables and remaining life expectancies at age 20 and compared outcomes by calendar period and patient characteristics at treatment initiation. To correct for potential underreporting of mortality due to participant LTFU, we conservatively estimated 30% mortality among participants lost to follow-up. 9997 individuals contributed 49,589 person-years and 830 deaths for a crude mortality rate of 16.7 [standard error (SE) 0.6] per 1000 person-years. When assigning death to 30% of participants lost to follow-up, we estimated 1170 deaths and a mortality rate of 23.6 [SE 0.7] per 1000 person-years. The crude overall life expectancy at age 20 was 45.2 [SE 0.7] and 37.5 [SE 0.6] years after adjusting for LTFU. In the LTFU-adjusted analysis, lower life expectancy at age 20 was observed for women compared to men (32.4 [SE 1.1] vs. 39.2 [SE 0.7] years), for participants with injection drug use (IDU) history compared to those without IDU history (23.9 [SE 1.0] vs. 52.3 [SE 0.8] years), for participants reporting Aboriginal ancestry compared to those with no Aboriginal ancestry (17.7 [SE 1.5] vs. 51.2 [SE 1.0] years), and for participants with CD4 count <350 cells/μL compared to CD4 count ≥350 cells/μL at treatment initiation (36.3 [SE 0.7] vs. 43.5 [SE 1.3] years). Life expectancy at age 20 in the calendar period 2000-2003 was lower than in periods 2004-2007 and 2008-2012 in the LTFU-adjusted analyses (30.8 [SE 0.9] vs. 38.6 [SE 1.0] and 54.2 [SE
McMahon, James H; Jordan, Michael R; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y; Wanke, Christine A; Lewin, Sharon R; Elliott, Julian H
Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤ 6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.
Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang
Abstract A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1–infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1–infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART. PMID:26579828
Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang
A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1-infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1-infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART.
Shi, Binshan; Kitchen, Christina; Weiser, Barbara; Mayers, Douglas; Foley, Brian; Kemal, Kimdar; Anastos, Kathryn; Suchard, Marc; Parker, Monica; Brunner, Cheryl; Burger, Harold
Characterization of residual plasma virus during antiretroviral therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand the evolution of HIV-1 pol and env genes in viremic patients under selective pressure of ART, we performed longitudinal analyses of plasma-derived pol and env sequences from single HIV-1 genomes. We tested the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism), and that recombination played a role in evolution of viral strains. Recombinants were identified by using Bayesian and other computational methods. High-level genotypic resistance was seen in ~70% of X4 and R5 strains during ART. There was no significant association between resistance and tropism. Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution. PMID:20451945
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
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.
Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peñaloza, Cristina; Rugeles, Maria T
Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these
Ghislain, Mathilde; Bastard, Jean-Philippe; Meyer, Laurence; Capeau, Jacqueline; Fellahi, Soraya; Gérard, Laurence; May, Thierry; Simon, Anne; Vigouroux, Corinne; Goujard, Cécile
HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation. Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142). Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07). After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease.
Ghislain, Mathilde; Bastard, Jean-Philippe; Meyer, Laurence; Capeau, Jacqueline; Fellahi, Soraya; Gérard, Laurence; May, Thierry; Simon, Anne; Vigouroux, Corinne; Goujard, Cécile
Objectives HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation. Methods Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142). Results Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07). Conclusion After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease. PMID:26636578
Cerqueira, Daniella Ferraz; Portela, Maristela Barbosa; Pomarico, Luciana; de Araújo Soares, Rosangela Maria; de Souza, Ivete Pomarico Ribeiro; Castro, Glória Fernanda
To evaluate predisposing factors such as orofacial manifestations, immunosuppression status and antiretroviral therapy in relation to oral colonization by Candida spp. in Brazilian HIV-infected children and their uninfected siblings in the era of highly active antiretroviral therapy (HAART). Whole stimulated saliva was collected from 65 HIV-infected children (HIV+) and 40 uninfected siblings (HIV-), followed by assessment of orofacial manifestation, caries indexes and the number of cavitated dentinal carious teeth (CDT). The salivary samples were cultured and the colonies were counted. After which they were identified by sugar assimilation and fermentation (API 20C). Data was analyzed using chi-square, Mann-Whitney, Spearman tests and logistic regression. Regarding positive growth, HIV+ presented 80% (52/65) and HIV- 57.5% (23/40) (P = 0.013). Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). Mean CD4%, immune-status and history of recurrent oral candidiasis (OC) had no influence on Candida isolation. Mixed Candida spp. cultures were observed in HIV+ (40%) and HIV- (52%): C. albicans was more frequently found in both groups, with a higher prevalence in HIV+ (P = 0.05); other non-albicans species were isolated in HIV+ and HIV-. Low prevalence of orofacial manifestations was observed in HIV+ (10.7% of OC). There was an association between means of CDT and Candida growth (P < 0.05) and a positive correlation between number of CDT and Candida cfu-counts in HIV+ and HIV-. Mean CD4% and immune-status had no influence on Candida isolation. Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). The HIV infected children had a significantly higher prevalence of oral Candida spp. compared to their uninfected siblings. Absence of HAART and presence of dentinal carious teeth increased significantly Candida spp. colonization in these children.
Andrade, Regis M; Andrade, Arnaldo F B; Lazaro, Marta A; Vieira, Morgana M M; Barros, Priscila O; Borner, Alice R S; Silva-Filho, Renato G; Santos, Juliana O; Brindeiro, Rodrigo M; Tanuri, Amilcar; Bento, Cleonice A M
The purpose of this study was to evaluate the impact of age on tetanus-specific immune response in successfully highly active antiretroviral therapy-treated AIDS patients, using healthy age-matched individuals as controls. Whole Peripheral blood mononuclear cells or CD8(+) cell-depleted peripheral blood mononuclear cells from previously tetanus toxoid (TT)-immunized individuals were activated with TT plus IL-2, and cell proliferation, cytokine production, and in vitro HIV-1 replication were measured. The in vivo magnitude of the humoral immune response was also assessed by antibody measurements. Our results showed that, compared with other groups, both in vitro TT-specific lymphoproliferation and serum antibody concentration were lower in older AIDS patients. Although the IL-1beta and tumour necrosis factor alpha (TNF-alpha) production were higher in cultures from aged HIV-1-infected patients, a dramatic damage on the interferon gamma (IFN-gamma) release was observed, when compared with younger patients. CD8(+) T lymphocytes depletion reduced IL-1beta and TNF-alpha release in the older groups, however, it did not significantly alter their IFN-gamma production. Furthermore, the neutralization of endogenous IL-10 did not change the IFN-gamma deficiency in older AIDS patients. Finally, the lower cellular immune response in this patient group was not related to in vitro HIV-1 replication. The results suggest that successfully highly active