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  1. Prevalence of Drug Resistance Mutations and HIV Type 1 Subtypes in an HIV Type 1-Infected Cohort in Rural Tanzania

    PubMed Central

    Masimba, Pax; Kituma, Elimsaada; Klimkait, Thomas; Horvath, Edit; Stoeckle, Marcel; Hatz, Christoph; Mossdorf, Erick; Mwaigomole, Emmanuel; Khamis, Salim; Jullu, Boniphace; Abdulla, Salim; Tanner, Marcel

    2013-01-01

    Abstract The development of resistance mutations in drug-targeted HIV-1 genes compromises the success of antiretroviral therapy (ART) programs. Genotyping of these mutations enables adjusted therapeutic decisions both at the individual and population level. We investigated over time the prevalence of HIV-1 primary drug resistance mutations in treatment-naive patients and described the HIV-1 subtype distribution in a cohort in rural Tanzania at the beginning of the ART rollout in 2005–2007 and later in 2009. Viral RNA was analyzed in 387 baseline plasma samples from treatment-naive patients over a period of 5 years. The reverse transcriptase (RT) and protease genes were reversely transcribed, polymerase chain reaction (PCR) amplified, and directly sequenced to identify HIV-1 subtypes and single nucleotide polymorphisms associated with drug resistance (DR-SNPs). The prevalence of major DR-SNPs in 2005–2007 in the RT gene was determined: K103N (5.0%), Y181C (2.5%), M184V (2.5%), and G190A (1.7%), and M41L, K65KR, K70KR, and L74LV (0.8%). In samples from 2009 only K103N (3.3%), M184V, and T215FY (0.8%) were detected. Initial frequencies of subtypes C, A, D, and recombinants were 43%, 32%, 18%, and 7%, respectively. Later similar frequencies were found except for the recombinants, which were found twice as often (15%), highlighting the subtype diversity and a relatively stable subtype frequency in the area. DR-SNPs were found at initiation of the cohort despite very low previous ART use in the area. Statistically, frequencies of major mutations did not change significantly over the studied 5-year interval. These mutations could reflect primary resistances and may indicate a possible risk for treatment failure. PMID:23806135

  2. Prevalence of drug resistance mutations and HIV type 1 subtypes in an HIV type 1-infected cohort in rural Tanzania.

    PubMed

    Masimba, Pax; Kituma, Elimsaada; Klimkait, Thomas; Horvath, Edit; Stoeckle, Marcel; Hatz, Christoph; Mossdorf, Erick; Mwaigomole, Emmanuel; Khamis, Salim; Jullu, Boniphace; Abdulla, Salim; Tanner, Marcel; Felger, Ingrid

    2013-09-01

    The development of resistance mutations in drug-targeted HIV-1 genes compromises the success of antiretroviral therapy (ART) programs. Genotyping of these mutations enables adjusted therapeutic decisions both at the individual and population level. We investigated over time the prevalence of HIV-1 primary drug resistance mutations in treatment-naive patients and described the HIV-1 subtype distribution in a cohort in rural Tanzania at the beginning of the ART rollout in 2005-2007 and later in 2009. Viral RNA was analyzed in 387 baseline plasma samples from treatment-naive patients over a period of 5 years. The reverse transcriptase (RT) and protease genes were reversely transcribed, polymerase chain reaction (PCR) amplified, and directly sequenced to identify HIV-1 subtypes and single nucleotide polymorphisms associated with drug resistance (DR-SNPs). The prevalence of major DR-SNPs in 2005-2007 in the RT gene was determined: K103N (5.0%), Y181C (2.5%), M184V (2.5%), and G190A (1.7%), and M41L, K65KR, K70KR, and L74LV (0.8%). In samples from 2009 only K103N (3.3%), M184V, and T215FY (0.8%) were detected. Initial frequencies of subtypes C, A, D, and recombinants were 43%, 32%, 18%, and 7%, respectively. Later similar frequencies were found except for the recombinants, which were found twice as often (15%), highlighting the subtype diversity and a relatively stable subtype frequency in the area. DR-SNPs were found at initiation of the cohort despite very low previous ART use in the area. Statistically, frequencies of major mutations did not change significantly over the studied 5-year interval. These mutations could reflect primary resistances and may indicate a possible risk for treatment failure. PMID:23806135

  3. The evolving molecular epidemiology of HIV type 1 among injecting drug users (IDUs) in Malaysia.

    PubMed

    Tee, Kok Keng; Saw, Teik Leong; Pon, Chee Keong; Kamarulzaman, Adeeba; Ng, Kee Peng

    2005-12-01

    Earlier studies in the 1990s indicate that human immunodeficiency virus type 1 (HIV-1) subtype B has been the predominant subtype among injecting drug users (IDUs) in Malaysia. More recent studies performed between 2003 and 2004, however, show a high prevalence of unique CRF01_AE/B intersubtype recombinants among IDUs. To determine the subtype distribution among IDUs in Kuala Lumpur prior to the emergence of CRF01_AE/B intersubtype recombinants, the gag-pol or the reverse transcriptase gene was sequenced from IDUs who were diagnosed as HIV positive between 1993 and 2002. Subtype B was present at 50.0% followed by CRF01_AE/B recombinant at 41.7%, with more CRF01_AE/B recombinants detected between 2000 and 2002. All CRF01_AE/B recombinants shared similar recombination patterns. Interestingly, we found that this potential new candidate of circulating recombinant form (CRF) could have emerged as early as the mid-1990s. The results showed evidence of changing HIV-1 molecular epidemiology toward the predominance of CRF01_AE/B intersubtype recombinants among IDUs in Kuala Lumpur. PMID:16379608

  4. Polymeric Nanoparticles Containing Combination Antiretroviral Drugs for HIV Type 1 Treatment

    PubMed Central

    Shibata, Annemarie; McMullen, Emily; Pham, Alex; Belshan, Michael; Sanford, Bridget; Zhou, You; Goede, Michael; Date, Abjijit A.

    2013-01-01

    Abstract The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition of HIV-1 replication. We developed nanoparticles of biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by a high-pressure homogenization method. The method resulted in >79% drug entrapment efficiency for each of the three drugs. The average size of cART NPs was 138.3±55.4 nm as measured by dynamic light scanning, confirmed by scanning electron microscopy (SEM) with an average surface charge of −13.7±4.5. Lissamine-rhodamine-labeled fluorescent PLGA NPs exhibited efficient uptake in nonimmune (HeLa cells) and immune (H9 T cells) cells as measured by confocal microscopy. Cells treated with cART NPs resulted in minimal loss of cell viability over 28 days. Subcellular fractionation studies demonstrated that HIV-1-infected H9 monocytic cells treated with cART NPs contained significantly (p<0.05) higher nuclear, cytoskeleton, and membrane antiretroviral drug levels compared to cells treated with drug solutions alone. Finally, cART NPs efficiently inhibited HIV-1 infection and transduction. The IC50 for each of the three drugs in the cART NPs was <31 nM. These experiments demonstrate the efficacy of a novel PLGA NPs formulation for the delivery of cART to inhibit HIV-1 replication. PMID:23289671

  5. Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

    PubMed Central

    Shafer, Robert W.

    2002-01-01

    There are 16 approved human immunodeficiency virus type 1 (HIV-1) drugs belonging to three mechanistic classes: protease inhibitors, nucleoside and nucleotide reverse transcriptase (RT) inhibitors, and nonnucleoside RT inhibitors. HIV-1 resistance to these drugs is caused by mutations in the protease and RT enzymes, the molecular targets of these drugs. Drug resistance mutations arise most often in treated individuals, resulting from selective drug pressure in the presence of incompletely suppressed virus replication. HIV-1 isolates with drug resistance mutations, however, may also be transmitted to newly infected individuals. Three expert panels have recommended that HIV-1 protease and RT susceptibility testing should be used to help select HIV drug therapy. Although genotypic testing is more complex than typical antimicrobial susceptibility tests, there is a rich literature supporting the prognostic value of HIV-1 protease and RT mutations. This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs. PMID:11932232

  6. Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy.

    PubMed Central

    Balzarini, J; Karlsson, A; Pérez-Pérez, M J; Camarasa, M J; Tarpley, W G; De Clercq, E

    1993-01-01

    Human immunodeficiency virus type 1 (HIV-1)-infected CEM cells were treated by the HIV-1-specific inhibitors bis-heteroarylpiperazine (BHAP), 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)-on e (TIBO) R82913, nevirapine, and the N3-methylthymine derivative of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO-m3T), as single agents or in combination, at escalating concentrations. When used individually, the compounds led to the emergence of drug-resistant virus strains within two to five subcultivations. The resulting strains were designated HIV-1/BHAP, HIV-1/TIBO, HIV-1/Nev, and HIV-1/TSAO-m3T, respectively. The mutant viruses showed the following amino acid substitutions in their reverse transcriptase (RT): Leu-100-->Ile for HIV-1/BHAP; Lys-103-->Asn for HIV-1/TIBO; Val-106-->Ala for HIV-1/Nev; and Glu-138-->Lys for HIV-1/TSAO-m3T. Both the Tyr-181-->Cys and Val-106-->Ala mutations were found in another mutant emerging following treatment with nevirapine at escalating concentrations. The BHAP-resistant virus remained fully sensitive to the inhibitory effects of nevirapine and TSAO-m3T, whereas the TSAO-m3T-resistant virus remained fully sensitive to the inhibitory effects of nevirapine and BHAP. When different pairs of nonnucleoside RT inhibitors (i.e., BHAP plus TSAO-m3T, nevirapine plus TSAO-m3T, TIBO plus TSAO-m3T, nevirapine plus TIBO, and BHAP plus nevirapine) were used, resistant virus emerged as fast as with single-drug therapy. In all cases the Tyr-181-->Cys mutation appeared; the virus showed markedly reduced sensitivity to all HIV-1-specific inhibitors but retained sensitivity to 2',3'-dideoxynucleoside analogs such as zidovudine, ddC, and ddI. Our findings argue against simultaneous combination of two different nonnucleoside RT inhibitors that are unable to inhibit HIV-1 mutant strains containing the Tyr-181-->Cys mutation when administered as single

  7. Short communication: molecular epidemiology of HIV type 1 infection in northern Greece (2009-2010): evidence of a transmission cluster of HIV type 1 subtype A1 drug-resistant strains among men who have sex with men.

    PubMed

    Antoniadou, Zoi-Anna; Kousiappa, Ioanna; Skoura, Lemonia; Pilalas, Dimitris; Metallidis, Simeon; Nicolaidis, Pavlos; Malisiovas, Nicolaos; Kostrikis, Leondios G

    2014-03-01

    A prospective molecular epidemiology study of HIV-1 infection was conducted in newly diagnosed and antiretroviral-naive patients in Northern Greece between 2009 and 2010 using a predefined enrolling strategy. Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 44.9% and 42.9%, respectively, followed by subtype C (3.1%), CRF02_AG (4.1%), CRF04_cpx (2.0%), and subtypes CRF01_01, F1, and G (1.0%). A high rate of clustered transmission of subtype A1-resistant strains to reverse transcriptase (RT) inhibitors was observed among men having sex with men. Indeed, 15 out of 17 study subjects (88.2%) infected with transmitted drug resistance (TDR) strains were implicated in transmission clusters, 10 of whom (66.7%) were men who have sex with men (MSM), and were also infected with subsubtype A1 strains. The main cluster within subtype A1 (I) included eight men reporting having sex with men from Thessaloniki infected with dual-class RT-resistant strains carrying both T215C and Y181C mutations. PMID:24059291

  8. Short Communication: Molecular Epidemiology of HIV Type 1 Infection in Northern Greece (2009–2010): Evidence of a Transmission Cluster of HIV Type 1 Subtype A1 Drug-Resistant Strains Among Men Who Have Sex with Men

    PubMed Central

    Antoniadou, Zoi-Anna; Kousiappa, Ioanna; Skoura, Lemonia; Pilalas, Dimitris; Metallidis, Simeon; Nicolaidis, Pavlos; Malisiovas, Nicolaos

    2014-01-01

    Abstract A prospective molecular epidemiology study of HIV-1 infection was conducted in newly diagnosed and antiretroviral-naive patients in Northern Greece between 2009 and 2010 using a predefined enrolling strategy. Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 44.9% and 42.9%, respectively, followed by subtype C (3.1%), CRF02_AG (4.1%), CRF04_cpx (2.0%), and subtypes CRF01_01, F1, and G (1.0%). A high rate of clustered transmission of subtype A1-resistant strains to reverse transcriptase (RT) inhibitors was observed among men having sex with men. Indeed, 15 out of 17 study subjects (88.2%) infected with transmitted drug resistance (TDR) strains were implicated in transmission clusters, 10 of whom (66.7%) were men who have sex with men (MSM), and were also infected with subsubtype A1 strains. The main cluster within subtype A1 (I) included eight men reporting having sex with men from Thessaloniki infected with dual-class RT-resistant strains carrying both T215C and Y181C mutations. PMID:24059291

  9. Genetic similarity of HIV type 1 subtype E in a recent outbreak among injecting drug users in northern Vietnam to strains in Guangxi Province of southern China.

    PubMed

    Kato, K; Shiino, T; Kusagawa, S; Sato, H; Nohtomi, K; Shibamura, K; Nguyen, T H; Pham, K C; Truong, X L; Mai, H A; Hoang, T L; Bunyaraksyotin, G; Fukushima, Y; Honda, M; Wasi, C; Yamazaki, S; Nagai, Y; Takebe, Y

    1999-09-01

    To investigate the molecular epidemiology of a recent HIV-1 outbreak in northern Vietnam and its relation to the epidemic in surrounding areas, we analyzed 17 HIV-positive blood specimens from 3 heterosexuals, 2 sexually transmitted disease patients, and 12 injecting drug users (IDUs), collected in 4 provinces near Hanoi in 1998. These were compared with the specimens from Ho Chi Minh City (n = 10) and An Giang Province (n = 10) in southern Vietnam and with published sequences from neighboring countries. Genetic subtyping based on the env C2/V3 sequences revealed that HIV-1 subtype E predominated throughout Vietnam in all risk populations; the exception was one typical United States-European-type HIV-1 subtype B detected in a patient in Ho Chi Minh City, the first case of HIV infection identified in Vietnam in 1990. The HIV-1 subtype E sequences identified in 9 of the 12 IDUs from northern provinces were closely related phylogenetically to those in IDUs in nearby Guangxi Province of China, and also shared a common amino acid signature downstream of the env V3 loop region. The low interperson nucleotide diversity among IDUs in northern Vietnam supports the view that HIV-1 subtype E was introduced recently among IDUs in northern Vietnam. These data indicate a linkage between HIV-1 circulating among IDUs in northern Vietnam and southern China, and suggest recent transborder introductions as the likely source of HIV-1 subtype E in northern Vietnam. PMID:10480629

  10. Genetic characterization and transmitted drug resistance of the HIV type 1 epidemic in men who have sex with men in Beijing, China.

    PubMed

    Li, Lin; Han, Na; Lu, Junfeng; Li, Tianyi; Zhong, Xiangfu; Wu, Hao; Rayner, Simon; Chen, Lili; Liu, Yongjian; Wang, Xiaolin; Li, Hanping; Li, Jingyun

    2013-03-01

    A rapid increase in the number of HIV cases in the men who have sex with men (MSM) population has been observed in China; however, little information is available on the genetic characterization of HIV prevalent in this population. In this study, 95 HIV-1-seropositive drug-naive patients from the Beijing MSM population were enrolled. The genetic characterization and transmission of drug resistance of HIV-1 were examined based on full-length gag, pol, and partial env gene sequences. Three subtypes, including CRF01_AE (56.0%), B (30.8%), and CRF07_BC (12.6%), were identified. Close phylogenetic relationships were found among these strains with isolates from other populations in Beijing and MSM isolates from Hebei province, which suggested that the Beijing MSM population might act as a bridge for HIV transmission between MSM and other high-risk populations. Drug-resistant mutations were identified in 5.3% of sampled individuals. Our results provided detailed genetic data and would be helpful for understanding the transmitting pattern of HIV strains between MSM and other populations. PMID:23121221

  11. Distinct HIV Type 1 Strains in Different Risk Groups and the Absence of New Infections by Drug-Resistant Strains in Lithuania

    PubMed Central

    Caplinskas, Saulius; Loukachov, Vladimir V.; Gasich, Elena L.; Gilyazova, Alla V.; Caplinskiene, Irma

    2013-01-01

    Abstract To analyze HIV-1 genotypes in Lithuania and the transmission of drug-resistant viruses, HIV-1 sequences were obtained from 138 individuals, who were diagnosed as HIV-1 infected in 1990–2008 and represented all major risk groups. Subtype A strains, dominating in the former Soviet Union (90% of cases), were found in 60% of individuals, followed by subtype B (22%) and CRF03_AB (12%) strains. The remaining 7% of the strains included variants belonging to subtype C, CRF01_AE, CRF02_AG, more complex recombinant forms, and strains that could not be reliably genotyped. Analysis of virus genotypes per risk group revealed the circulation of distinct HIV-1 strains in different risk groups: subtype A viruses were present in 82% of injecting drug users (IDUs), but less than a half of heterosexually infected individuals and cases with unknown transmission route, and none of men having sex with men (MSM). We observed no mutations causing drug resistance among 27 newly diagnosed HIV-1 cases. PMID:23186249

  12. Phylogenetic analysis of env, gag, and tat genes of HIV type 1 detected among the injecting drug users in West Bengal, India.

    PubMed

    Mullick, Ranajoy; Sengupta, Satarupa; Sarkar, Kamalesh; Saha, M K; Chakrabarti, Sekhar

    2006-12-01

    A recent occurrence of HIV-1 seropositivity among a group of injecting drug users (IDUs) in Darjeeling, a hilly district in northern West Bengal, revealed overall 11.8% HIV seroprevalence. Our study based on env (C2-V3), gag (p24-p7), and tat (exon-1) genomic regions of HIV-1 detected among this population showed that Darjeeling IDU sequences belonged to subtype C. Interestingly, the IDU sequences from Darjeeling were again found to be closer to the C strains from Manipur, a northeastern state in India, which is linked to the Golden Triangle via the Manipur-Myanmar border, rather than the IDU C sequences from Nepal, a neighboring country of India. The outgroup reference strains from different sites of IDU-driven epidemics in the world like Russia, Vietnam, Thailand, and Spain belonged to the nonsubtype C group and formed separate clusters from the subtype C cluster in our analysis. These results indicate a rapid spread of HIV-1 by possible drug trafficking along international boundaries, which might also help in the invasion of HIV-1 among IDUs of Darjeeling through the Manipur-Myanmar border of India. PMID:17209773

  13. Evaluation of two commercial kits for the detection of genotypic drug resistance on a panel of HIV type 1 subtypes A through J.

    PubMed

    Fontaine, E; Riva, C; Peeters, M; Schmit, J C; Delaporte, E; Van Laethem, K; Van Vaerenbergh, K; Snoeck, J; Van Wijngaerden, E; De Clercq, E; Van Ranst, M; Vandamme, A M

    2001-11-01

    We compared the two commercially available sequencing kits for HIV-1 drug resistance testing, the ViroSeq Genotyping System (Applied Biosystems, Foster City, CA, U.S.A.) and the TRUGENE HIV-1 Genotyping Kit (Visible Genetics, Inc., Toronto, Ontario, Canada), with our in-house genotyping system. Fifteen viral isolates from African patients (6 treated and 9 untreated) covering a panel of HIV-1 subtypes A through J and 7 plasma samples from Belgian and African patients (2 treated and 5 untreated) were tested. All the samples could be amplified and sequenced by the three systems; however, for all systems, alternative amplification/sequencing primers had to be used for some samples belonging to subtype B as well as to other subtypes. The consensus sequence was partially derived from only one strand for the in-house system and for the ViroSeq Genotyping System. The TRUGENE HIV-1 Genotyping Kit scored the highest number of ambiguities, followed by the ViroSeq Genotyping System and the in-house system. For 11 samples, these differences in reporting mixtures affected 14 resistance-related positions, which altered the interpretation toward protease inhibitors for 2 samples when using version 1.2 RetroGram software (Virology Networks, Utrecht, The Netherlands). All three systems were able to sequence diluted samples with a viral load down to 10 3 or 10 4 RNA copies/ml. Our data therefore suggest that the performance of amplification and sequencing primers must be improved to allow fast and reliable resistance testing for all HIV-1 subtypes. PMID:11694832

  14. Transmitted Drug Resistance Among Antiretroviral-Naive Patients with Established HIV Type 1 Infection in Santo Domingo, Dominican Republic and Review of the Latin American and Caribbean Literature

    PubMed Central

    Taylor, Barbara S.; Rojas Fermín, Rita A.; Reyes, Emily Virginia; Vaughan, Catherine; José, Lina; Javier, Carmen; Franco Estévez, Ramona; Donastorg Cabral, Yeycy; Batista, Arelis; Lie, Yolanda; Coakley, Eoin; Hammer, Scott M.; Brudney, Karen

    2012-01-01

    Abstract Emergence of HIV resistance is a concerning consequence of global scale-up of antiretroviral therapy (ART). To date, there is no published information about HIV resistance from the Dominican Republic. The study's aim was to determine the prevalence of transmitted drug resistance (TDR) to reverse transcriptase and protease inhibitors in a sample of chronically HIV-1-infected patients in one clinic in Santo Domingo. The data are presented in the context of a review of the TDR literature from Latin America and the Caribbean. Genotype testing was successfully performed on 103 treatment-naive adults planning to initiate antiretroviral therapy; the World Health Organization (WHO) list of surveillance drug resistance mutations (SDRM) was used to determine the presence of TDR mutations. WHO SDRM were identified in eight patients (7.8%); none had received sdNVP. There were no significant differences in epidemiologic or clinical variables between those with or without WHO SDRM. The prevalence of WHO SDRM was 1.0% and 6.8% for nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. No WHO SDRMs for protease inhibitors were identified. Among 12 studies of TDR in the region with a sample size of at least 100 subjects, the reported prevalence of SDRM ranged from 2.8% to 8.1%. The most commonly identified SDRM was K103N. This information adds to our understanding of the epidemiology of TDR in the region and the possible role such mutations could play in undermining first-line treatment. Ongoing surveillance is clearly needed to better understand the TDR phenomenon in the Caribbean. PMID:21851324

  15. (Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes.

    PubMed Central

    Olmsted, R A; Slade, D E; Kopta, L A; Poppe, S M; Poel, T J; Newport, S W; Rank, K B; Biles, C; Morge, R A; Dueweke, T J; Yagi, Y; Romero, D L; Thomas, R C; Sharma, S K; Tarpley, W G

    1996-01-01

    The (alkylamino)piperidine bis(heteroaryl)piperizines (AAP-BHAPs) are a new class of human immunodeficiency virus type 1 (HIV-1)-specific inhibitors which were identified by targeted screening of recombinant reverse transcriptase (RT) enzymes carrying key nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-conferring mutations and NNRTI-resistant variants of HIV-1. Phenotypic profiling of the two most potent AAP-BHAPs, U-95133 and U-104489, against in vitro-selected drug-resistant HIV-1 variants carrying the NNRTI resistance-conferring mutation (Tyr->Cys) at position 181 of the HIV-1 RT revealed submicromolar 90% inhibitory concentration estimates for these compounds. Moreover, U-104489 demonstrated potent activity against BHA-P-resistant HIV-1MF harboring the Pro-236->Leu RT substitution and significantly suppressed the replication of clinical isolates of HIV-1 resistant to both delavirdine (BHAP U-90152T) and zidovudine. Biochemical and phenotypic characterization of AAP-BHAPresistant HIV-1IIIB variants revealed that high-level resistance to the AAP-BHAPs was mediated by a Gly-190->Glu substitution in RT, which had a deleterious effect on the integrity and enzymatic activity of virion-associated RT heterodimers, as well as the replication capacity of these resistant viruses. PMID:8648704

  16. Sex-Based Differences in HIV Type 1 Pathogenesis

    PubMed Central

    Addo, Marylyn M.; Altfeld, Marcus

    2014-01-01

    Human immunodeficiency virus (HIV) remains a global infectious diseases threat that disproportionally affects women. Beyond social and political factors, biological and genetic differences have been identified that lead to differential disease courses and outcomes in men and women. Following HIV type 1 (HIV-1) seroconversion, women have up to 40% lower HIV loads and higher CD4+ T-cell counts than men. However, at the same level of viremia, progression to AIDS is faster in women. After adjustment for viral load, HIV-positive women also display increased levels of generalized immune activation and experience the consequences of elevated inflammatory activity more frequently than men. Part of these observations are linked to sex-based differences in innate immunity, in which the differential ability of plasmacytoid dendritic cells to produce interferon α following stimulation of Toll-like receptor 7 and upregulation of interferon-stimulated genes play a central role. Here, we review the current knowledge and remaining gaps therein regarding sex-based differences in HIV-1 pathogenesis. PMID:24966195

  17. Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.

    PubMed Central

    Boyer, P L; Currens, M J; McMahon, J B; Boyd, M R; Hughes, S H

    1993-01-01

    A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been reported. Several lines of evidence, including the isolation of RT mutants that show cross resistance, suggest that, despite their structural diversity, many of these inhibitors bind to a common site on HIV-1 RT. We have recently reported that, on the basis of analyses of HIV-1/HIV-2 chimeras, the natural product calanolide A may interact with a different site or sites in HIV-1 RT. We have used BspMI cassette mutagenesis to prepare a collection of HIV-1 RT mutants that show resistance to the known members of the general class of nonnucleoside inhibitors. This collection of mutants can be used to determine whether a new drug will show cross resistance with known inhibitors and to define amino acid positions critical for the action of the drugs. The mutants were used to analyze calanolide A, 1H,3H-thiazolo[3,4-a]benzimidazole(4i), and the acyclic nucleoside analog 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. These analyses suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors. However, the drugs respond differently to the panel of drug-resistant HIV-1 RTs, indicating that while the binding sites of the drugs overlap they are not identical. PMID:7680393

  18. Comparative Fitness of Multi-Dideoxynucleoside-Resistant Human Immunodeficiency Virus Type 1 (HIV-1) in an In Vitro Competitive HIV-1 Replication Assay

    PubMed Central

    Kosalaraksa, Pope; Kavlick, Mark F.; Maroun, Victor; Le, Richard; Mitsuya, Hiroaki

    1999-01-01

    We examined whether human immunodeficiency virus type 1 (HIV-1) fitness was altered upon the acquisition of a set or subset of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene, which confers resistance to multiple dideoxynucleosides (MDR), as well as the zidovudine resistance-associated mutation T215Y, using a competitive HIV-1 replication assay in a setting of an HXB2D genetic background. Target H9 cells were exposed to a 50:50 mixture of paired infectious molecular clones, and HIV-1 in the culture supernatant was transmitted to new cultures every 7 to 10 days. The polymerase-encoding region of the virus was sequenced at various time points, and the relative proportion of the two viral populations was determined. In the absence of drugs, the comparative order for replicative fitness was HIV-162/75/77/116/151 > HIV-177/116/151 > HIV-1151 > wild-type HIV-1 (HIV-1wt) > HIV-175/77/116/151 > HIV-1151/215 > HIV-1215. In the presence of zidovudine or didanosine, the order was HIV-162/75/77/116/151 > HIV-177/116/151 > HIV-175/77/116/151 > HIV-1151 > HIV-1215. HIV-1215S(TCC), a putative intermediate infectious clone for HIV-1215, replicated comparably to HIV-1wt, while two putative intermediates for HIV-1151 [HIV-1151L(CTG) and HIV-1151K(AAG)] replicated much less efficiently than HIV-1wt and HIV-1151, suggesting that for HIV-1151 to develop, two base substitutions are likely to occur concurrently or within a short interval. These data may illustrate the molecular basis by which HIV-1151 emerges much less frequently than HIV-1215. The present data also demonstrate that several MDR HIV-1 variants are more fit than HIV-1wt in the absence of drugs and that resistance-associated mutations and drug pressure are critical variates for HIV-1 fitness. PMID:10364282

  19. Performance of the Affymetrix GeneChip HIV PRT 440 Platform for Antiretroviral Drug Resistance Genotyping of Human Immunodeficiency Virus Type 1 Clades and Viral Isolates with Length Polymorphisms

    PubMed Central

    Vahey, Maryanne; Nau, Martin E.; Barrick, Sandra; Cooley, John D.; Sawyer, Robert; Sleeker, Alex A.; Vickerman, Peter; Bloor, Stuart; Larder, Brendan; Michael, Nelson L.; Wegner, Scott A.

    1999-01-01

    The performance of a silica chip-based resequencing method, the Affymetrix HIV PRT 440 assay (hereafter referred to as the Affymetrix assay), was evaluated on a panel of well-characterized nonclade B viral isolates and on isolates exhibiting length polymorphisms. Sequencing of human immunodeficiency virus type 1 (HIV-1) pol cDNAs from clades A, C, D, E, and F resulted in clade-specific regions of base-calling ambiguities in regions not known to be associated with resistance polymorphisms, as well as a small number of spurious resistance polymorphisms. The Affymetrix assay failed to detect the presence of additional serine codons distal to reverse transcriptase (RT) codon 68 that are associated with multinucleoside RT inhibitor resistance. The increasing prevalence of non-clade B HIV-1 strains in the United States and Europe and the identification of clinically relevant pol gene length polymorphisms will impact the generalizability of the Affymetrix assay, emphasizing the need to accommodate this expanding pool of pol genotypes in future assay versions. PMID:10405396

  20. Women, drugs and HIV

    PubMed Central

    Azim, Tasnim; Bontell, Irene; Strathdee, Steffanie A.

    2014-01-01

    Women who inject drugs are among the most vulnerable to HIV through both unsafe injections and unprotected sex. They are also among the most hidden affected populations, as they are more stigmatized than their male counterparts. Many sell sex to finance their own and their partner’s drug habit and often their partner exerts a significant amount of control over their sex work, condom use and injection practices. Women who use drugs all over the world face many different barriers to HIV service access including police harassment, judgmental health personnel and a fear of losing their children. In order to enable these women to access life-saving services including needle-syringe and condom programs, opioid substitution therapy and HIV testing and treatment, it is essential to create a conducive environment and provide tailor-made services that are adapted to their specific needs. In this commentary, we explore the risks and vulnerabilities of women who use drugs as well as the interventions that have been shown to reduce their susceptibility to HIV infection. PMID:25277726

  1. Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates by nonradioisotopic reverse transcriptase-typing assay.

    PubMed Central

    Urabe, T; Sano, K; Nakano, T; Odawara, F; Lee, M H; Otake, T; Okubo, S; Hayami, M; Misaki, H; Baba, M

    1994-01-01

    We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay. Images PMID:7527425

  2. HIV Type 1 Gag as a Target for Antiviral Therapy

    PubMed Central

    2012-01-01

    Abstract The Gag proteins of HIV-1 are central players in virus particle assembly, release, and maturation, and also function in the establishment of a productive infection. Despite their importance throughout the replication cycle, there are currently no approved antiretroviral therapies that target the Gag precursor protein or any of the mature Gag proteins. Recent progress in understanding the structural and cell biology of HIV-1 Gag function has revealed a number of potential Gag-related targets for possible therapeutic intervention. In this review, we summarize our current understanding of HIV-1 Gag and suggest some approaches for the development of novel antiretroviral agents that target Gag. PMID:21848364

  3. Neisseria gonorrhoeae enhances infection of dendritic cells by HIV type 1.

    PubMed

    Zhang, Jizhong; Li, Geling; Bafica, Andre; Pantelic, Milica; Zhang, Pei; Broxmeyer, Hal; Liu, Ying; Wetzler, Lee; He, Johnny J; Chen, Tie

    2005-06-15

    Clinical studies indicate that Neisseria gonorrhoeae (gonococci (GC)) has the capacity to enhance HIV type 1 (HIV-1) infection. We studied whether GC enhances HIV infection of activated dendritic cells (DCs). The results show that GC can dramatically enhance HIV replication in human DCs during coinfection. The GC component responsible for HIV infection enhancement may be peptidoglycan, which activates TLR2. TLR2 involvement is suggested by bacterial lipoprotein, a TLR2-specific inducer, which stimulates a strong enhancement of HIV infection by human DCs. Moreover, participation of TLR2 is further implicated because GC is unable to stimulate expression of HIV in DCs of TLR2-deficient HIV-1-transgenic mice. These results provide one potential mechanism through which GC infection increases HIV replication in patients infected with both GC and HIV. PMID:15944306

  4. In vitro Isolation and Identification of Human Immunodeficiency Virus (HIV) Variants with Reduced Sensitivity to C-2 Symmetrical Inhibitors of HIV Type 1 Protease

    NASA Astrophysics Data System (ADS)

    Otto, M. J.; Garber, S.; Winslow, D. L.; Reid, C. D.; Aldrich, P.; Jadhav, P. K.; Patterson, C. E.; Hodge, C. N.; Cheng, Y.-S. E.

    1993-08-01

    Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi(CHOH)]_2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val -> Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.

  5. Molecular epidemiology of HIV type 1 subtypes in Rwanda.

    PubMed

    Kemal, Kimdar S; Anastos, Kathryn; Weiser, Barbara; Ramirez, Christina M; Shi, Qiuhu; Burger, Harold

    2013-06-01

    HIV-1 infection is characterized by genetic diversity, with multiple subtypes and recombinant variants circulating, particularly in sub-Saharan Africa. During the Rwandan genocide, many women experienced multiple rapes and some became HIV-1 infected. We studied plasma and peripheral blood mononuclear cells (PBMCs) from 30 infected women comprising two exposure groups: those with numerous contacts, raped multiple times, and women with one lifetime sexual partner and no history of rape. Population-based sequences from gag, pol, and env genes were analyzed to determine HIV-1 subtypes and intersubtype recombination. Individual plasma-derived variants from 12 women were also analyzed. Subtype A was found in 24/30 (80%), intersubtype recombination (AC and AD) in 4/30 (13%), and subtypes C and D in 1/30 each. In two subjects, the pattern of HIV-1 recombination differed between plasma and PBMC-derived sequences. Intersubtype recombination was common, although there were no significant differences in subtype or recombination rates between exposure groups. PMID:23458210

  6. Etiologic Agents and Antifungal Susceptibility of Oral Candidosis from Romanian patients with HIV-infection or type 1 diabetes mellitus.

    PubMed

    Minea, Bogdan; Nastasa, Valentin; Kolecka, Anna; Mares, Magdalena; Marangoci, Narcisa; Rosca, Irina; Pinteala, Mariana; Hancianu, Monica; Mares, Mihai

    2016-01-01

    This is the first Romanian investigation of oral candidosis in patients suffering of HIV-infection or type 1 diabetes mellitus (T1DM). Candida albicans was the dominant species in both types of isolates: n = 14 (46.7%) in T1DM, n = 60 (69.8%) in HIV. The most frequent non-albicans Candida spp. were Candida kefyr (n = 6; 20%) in T1DM and Candida dubliniensis (n = 8; 9.3%) in HIV. Resistance to fluconazole was detected only in the HIV non-albicans Candida group (n = 8; 9.3%). All isolates were susceptible to VOR. The experimental drug MXP had MIC values equal or close to the ones of VOR. Echinocandin resistance was more frequent than azole resistance. PMID:27282005

  7. Pin1 liberates the human immunodeficiency virus type-1 (HIV-1): Must we stop it?

    PubMed

    Hou, Hai; Wang, Jing-Zhang; Liu, Bao-Guo; Zhang, Ting

    2015-07-01

    Acquired immune deficiency syndrome (AIDS) is mainly caused by the human immunodeficiency virus type-1 (HIV-1). To our knowledge, this is the first review focusing on the vital role of Pin1 in the infection of HIV-1 and the development of AIDS. We and others have demonstrated that Pin1, the only known cis-to-trans isomerase recognizing the pThr/pSer-Pro motifs in proteins, plays striking roles in several human diseases. Interestingly, recent evidence gradually indicates that Pin1 regulates several key steps of the life cycle of HIV-1, including the uncoating of the HIV-1 core, the reverse transcription of the RNA genome of HIV-1, and the integration of the HIV-1 cDNA into human chromosomes. Whereas inhibiting Pin1 suppresses all of these key steps and attenuates the replication of HIV-1, at the same time different PIN1 gene variants are correlated with the susceptibility to HIV-1 infection. Furthermore, Pin1 potentially promotes HIV-1 infection by activating multiple oncogenes and inactivating multiple tumor suppressors, extending the life span of HIV-infected cells. These descriptions suggest Pin1 as a promising therapeutic target for the prevention of HIV-1 and highlight the possibility of blocking the development of AIDS by Pin1 inhibitors. PMID:25913034

  8. Molecular characterization of HIV type 1 strains from newly diagnosed patients in Cyprus (2007-2009) recovers multiple clades including unique recombinant strains and lack of transmitted drug resistance.

    PubMed

    Kousiappa, Ioanna; Achilleos, Charis; Hezka, Johana; Lazarou, Yiota; Othonos, Katerina; Demetriades, Ioannis; Kostrikis, Leondios G

    2011-11-01

    HIV-1 evolution generates substantial genetic diversity among isolates, the majority of which are represented in areas where multiple strains cocirculate. A heterogeneous genetic HIV-1 pool has been found in Cyprus, directing us to determine the dynamics of the local HIV-1 infection by characterizing strains isolated from 74 subjects during 2007-2009, representing 88% of the known-living HIV-1-infected population, of whom 53 are newly diagnosed therapy-naive patients and 21 are chronic patients, according to the European HIV Resistance guidelines. Near full-length genome sequences were amplified by RT-nested PCR using diluted RNA from all HIV-1 seropositives and sequenced using a newly designed assay. Resistant mutations were not found among the population of the newly diagnosed therapy-naive patients either to protease, reverse transcriptase, or integrase inhibitors. Phylogenetic analyses indicated subtype B as the main subtype (48.6%), followed by subtype A (18.9%), subtype C (10.8%), CRF02_AG (8.1%), CRF11_cpx (2.7%), and (sub)subtype F1 and CRF37_cpx (1.4% each). Six HIV-1 isolates (8.1%) were not classified in any pure (sub)subtype or circulating recombinant form (CRF). Complete phylogenetic and bootscanning analyses revealed that each isolate had a new, unique recombinant pattern and is distinct from all other CRFs or unique recombinant forms (URFs) reported so far. Two of the six isolates have the same mosaic pattern. Analogous to results of the earlier epidemiological studies, this study expands on the HIV-1 sequence database and reveals the high degree of diversity of HIV-1 infection in Cyprus. PMID:21453134

  9. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    NASA Astrophysics Data System (ADS)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    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.

  10. Polyclonal B-cell activation reveals antibodies against human immunodeficiency virus type 1 (HIV-1) in HIV-1-seronegative individuals.

    PubMed Central

    Jehuda-Cohen, T; Slade, B A; Powell, J D; Villinger, F; De, B; Folks, T M; McClure, H M; Sell, K W; Ahmed-Ansari, A

    1990-01-01

    Identification of human immunodeficiency virus type 1 (HIV-1)-infected individuals is of paramount importance for the control of the spread of AIDS worldwide. Currently, the vast majority of screening centers throughout the world rely on serological techniques. As such, clinically asymptomatic but HIV-infected, seronegative individuals are rarely identified. In this report we show that 18% (30/165) of seronegative individuals who were considered to be a unique cohort of patients at high risk for HIV infection had circulating B cells that, upon in vitro polyclonal activation with pokeweed mitogen, produced antibodies reactive with HIV. Furthermore, polymerase chain reaction analysis of DNA obtained from aliquots of the peripheral blood mononuclear cells from these seronegative but pokeweed mitogen assay-positive individuals tested revealed the presence of HIV-specific sequences in a significant number of samples. In addition, depletion of CD8+ T cells from peripheral blood mononuclear cells of HIV-1-seronegative individuals prior to in vitro culture with pokeweed mitogen resulted in increased sensitivity for detecting HIV-reactive antibodies. This assay has obvious epidemiological implications, especially in the case of high-risk groups, and also provides a simple technique to enhance detection of HIV-infected individuals. Of further interest is the determination of the mechanisms related to the lack of HIV-specific antibodies in the serum of these infected individuals. Images PMID:2111024

  11. Persistent HIV Type 1 Seronegative Status Is Associated With Lower CD8+ T-Cell Activation.

    PubMed

    Kuebler, Peter J; Mehrotra, Megha L; Shaw, Brian I; Leadabrand, Kaitlyn S; Milush, Jeffrey M; York, Vanessa A; Defechereux, Patricia; Grant, Robert M; Kallás, Esper G; Nixon, Douglas F

    2016-02-15

    We leveraged data from the Preexposure Prophylaxis Initiative (iPrEx), a global trial of preexposure chemoprophylaxis against human immunodeficiency virus type 1 (HIV-1) infection, to compare T-cell activation between those who remained negative for HIV-1 and those who became infected during the trial. The frequency of CD38(+)HLA-DR(+) CD8(+) T cells was greater in those who seroconverted, relative to the frequency in those who remained uninfected (1.30% vs 0.82%, respectively; P = .005). This translated to an odds ratio of 4.26 (95% confidence interval, 1.54-11.78) for the association between CD8(+) T-cell activation and infection with HIV-1. T-cell activation may be a biomarker for elevated HIV-1 infection risk. PMID:26310308

  12. Seroprevalence of HIV-type 1 in a northern California health plan population: an unlinked survey.

    PubMed Central

    Hiatt, R A; Capell, F J; Ascher, M S

    1992-01-01

    We conducted an unlinked seroprevalence survey for human immunodeficiency virus-type 1 (HIV-1) of 9821 persons who had a routine personal health appraisal examination in 1989 while members of the Kaiser Permanente Medical Care Program in northern California. An outside laboratory performed enzyme immunoassay (EIA) analyses, and the California Viral and Rickettsial Diseases Laboratory confirmed EIA-reactive samples by immunofluorescent assay and Western blot assay. Only 20 specimens (0.2%) were confirmed as positive, and 18 were from men. These data suggest that, at the time of this survey, HIV-1 infection was not widespread in the northern California population represented by this health plan membership. PMID:1546773

  13. 75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... (70 FR 43439), FDA announced the availability of the draft guidance of the same title. FDA received...: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV... Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor...

  14. HIV type 1 Thai subtype E is predominant in South Vietnam.

    PubMed

    Menu, E; Truong, T X; Lafon, M E; Nguyen, T H; Müller-Trutwin, M C; Nguyen, T T; Deslandres, A; Chaouat, G; Duong, Q T; Ha, B K; Fleury, H J; Barré-Sinoussi, F

    1996-05-01

    Samples of peripheral blood mononuclear cells from 50 HIV-1-infected individuals in South Vietnam were analyzed to determine with which HIV-1 subtype the subjects were infected. Participants were from Ho Chi Minh city and five surrounding provinces; 16 samples from female prostitutes, 32 from IV drug users, and one each from a man and woman not in any HIV risk group. 32 individuals were therefore most likely infected by IV drug use and the rest through sexual contacts. PCR amplification and heteroduplex mobility assay found all but one case to be infected with HIV-1 subtype E. The only nonsubtype E infection was HIV-1 subtype B in a woman sexually infected by her seropositive partner who was most likely exposed to the virus in Europe. HIV-1 subtype E strongly predominates in South Vietnam. The homogeneous geographic distribution of subtype E suggests the recent introduction of the virus into the country. A Thai origin can be considered given the genetic relationship between the Thai and Vietnamese subtypes E. It may be assumed that subtype E infections of Vietnamese prostitutes are related to the progressive entry and spread of HIV-1 subtype E from Thailand to Cambodia and then to southern Vietnam. PMID:8743088

  15. In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques

    PubMed Central

    Ambrose, Zandrea; Boltz, Valerie; Palmer, Sarah; Coffin, John M.; Hughes, Stephen H.; KewalRamani, Vineet N.

    2004-01-01

    Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies of NNRTI resistance, we examined whether a SIV that causes immunopathogenesis in pigtail macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIVmne: SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIVmne contains the entire HIV-1 RT coding region. Both mutant viruses grew to high titers in vitro but had reduced fitness relative to wild-type SIVmne. Although the HIV-1 RT was properly processed into p66 and p51 subunits in RT-SHIVmne particles, the RT-SHIVmne virions had lower levels of RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT activity in RT-SHIVmne and SIV-RT-YY particles. HIV-1 and RT-SHIVmne were similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However, SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIVmne. Classical NNRTI resis tance mutations were selected in RT-SHIVmne after in vitro drug treatment and were monitored in a sensitive allele-specific real-time RT-PCR assay. Collectively, these results indicate that RT-SHIVmne may be a useful model in macaques for the preclinical evaluation of NNRTIs and for studies of the development of drug resistance in vivo. PMID:15564466

  16. Unique Thermodynamic Response of Tipranavir to Human Immunodeficiency Virus Type 1 Protease Drug Resistance Mutations

    SciTech Connect

    Muzammil,S.; Armstrong, A.; Kang, L.; Jakalian, A.; Bonneau, P.; Schmelmer, V.; Amzel, L.; Freire, E.

    2007-01-01

    Drug resistance is a major problem affecting the clinical efficacy of antiretroviral agents, including protease inhibitors, in the treatment of infection with human immunodeficiency virus type 1 (HIV-1)/AIDS. Consequently, the elucidation of the mechanisms by which HIV-1 protease inhibitors maintain antiviral activity in the presence of mutations is critical to the development of superior inhibitors. Tipranavir, a nonpeptidic HIV-1 protease inhibitor, has been recently approved for the treatment of HIV infection. Tipranavir inhibits wild-type protease with high potency (K{sub i} = 19 pM) and demonstrates durable efficacy in the treatment of patients infected with HIV-1 strains containing multiple common mutations associated with resistance. The high potency of tipranavir results from a very large favorable entropy change (-T{Delta}S = -14.6 kcal/mol) combined with a favorable, albeit small, enthalpy change ({Delta}H = -0.7 kcal/mol, 25{sup o}C). Characterization of tipranavir binding to wild-type protease, active site mutants I50V and V82F/I84V, the multidrug-resistant mutant L10I/L33I/M46I/I54V/L63I/V82A/I84V/L90M, and the tipranavir in vitro-selected mutant I13V/V32L/L33F/K45I/V82L/I84V was performed by isothermal titration calorimetry and crystallography. Thermodynamically, the good response of tipranavir arises from a unique behavior: it compensates for entropic losses by actual enthalpic gains or by sustaining minimal enthalpic losses when facing the mutants. The net result is a small loss in binding affinity. Structurally, tipranavir establishes a very strong hydrogen bond network with invariant regions of the protease, which is maintained with the mutants, including catalytic Asp25 and the backbone of Asp29, Asp30, Gly48 and Ile50. Moreover, tipranavir forms hydrogen bonds directly to Ile50, while all other inhibitors do so by being mediated by a water molecule.

  17. High Sequence Conservation of Human Immunodeficiency Virus Type 1 Reverse Transcriptase under Drug Pressure despite the Continuous Appearance of Mutations

    PubMed Central

    Ceccherini-Silberstein, Francesca; Gago, Federico; Santoro, Maria; Gori, Caterina; Svicher, Valentina; Rodríguez-Barrios, Fátima; d'Arrigo, Roberta; Ciccozzi, Massimo; Bertoli, Ada; Monforte, Antonella d'Arminio; Balzarini, Jan; Antinori, Andrea; Perno, Carlo-Federico

    2005-01-01

    To define the extent of sequence conservation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) in vivo, the first 320 amino acids of RT obtained from 2,236 plasma-derived samples from a well-defined cohort of 1,704 HIV-1-infected individuals (457 drug naïve and 1,247 drug treated) were analyzed and examined in structural terms. In naïve patients, 233 out of these 320 residues (73%) were conserved (<1% variability). The majority of invariant amino acids clustered into defined regions comprising between 5 and 29 consecutive residues. Of the nine longest invariant regions identified, some contained residues and domains critical for enzyme stability and function. In patients treated with RT inhibitors, despite profound drug pressure and the appearance of mutations primarily associated with resistance, 202 amino acids (63%) remained highly conserved and appeared mostly distributed in regions of variable length. This finding suggests that participation of consecutive residues in structural domains is strictly required for cooperative functions and sustainability of HIV-1 RT activity. Besides confirming the conservation of amino acids that are already known to be important for catalytic activity, stability of the heterodimer interface, and/or primer/template binding, the other 62 new invariable residues are now identified and mapped onto the three-dimensional structure of the enzyme. This new knowledge could be of help in the structure-based design of novel resistance-evading drugs. PMID:16051864

  18. Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

    PubMed

    Prakash, Om; Mason, Andrew; Luftig, Ronald B; Bautista, Abraham P

    2002-07-01

    Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. PMID:12086918

  19. Evaluation of the disinfectant effect of Solprogel against human immunodeficiency virus type 1 (HIV-1).

    PubMed

    Hernández, A; Belda, F J; Domínguez, J; Matas, L; Gimenez, M; Caraballo, M; Ramil, C; Ausina, V

    1996-11-01

    The antiviral activities of sodium dichloroisocyanurate (NaDCC) and a commercial product (Solprogel 2%) against human immunodeficiency virus type 1 (HIV-1) were investigated using a quantitative suspension test method. Solprogel is a compound that contains NaDCC and a biodegradable polymer of acrylic acid. Viral suspensions were prepared containing 3.2 x 10(6) tissue culture infective dose 50 (TCID50) in culture media. Syncytium formation in the MT-2 line and HIV antigen p24 on the supernatant of the cultures were used to determine viral titre. Results indicate that satisfactory disinfection (1000-fold reduction in 5 min) can be achieved using NaDCC and Solprogel at concentrations of 100 and 120 ppm available chlorine, respectively. PMID:8923278

  20. HIV type 1 gag genetic diversity among antenatal clinic attendees in North Rift Valley, Kenya.

    PubMed

    Nyagaka, Benuel; Kiptoo, Michael K; Lihana, Raphael W; Khamadi, Samoel A; Makokha, Ernest P; Kinyua, Joyceline G; Mwangi, Joseph; Osman, Saida; Lagat, Nancy J; Muriuki, Joseph; Okoth, Vincent; Gicheru, Michael; Ng'ang'a, Zipporah; Songok, Elijah M

    2012-05-01

    HIV genetic recombination and high mutation rate increase diversity allowing it to escape from host immune response or antiretroviral drugs. This diversity has enabled specific viral subtypes to be predominant in specific regions. To determine HIV-1 subtypes among seropositive antenatal clinic attendees in Kenya's North Rift Valley, a cross-sectional study was carried out on 116 HIV-1-positive blood samples. Proviral DNA was extracted from peripheral blood mononuclear cells by DNAzol lysis and ethanol precipitation. Polymerase chain reactions using specific primers for HIV-1 gag and population sequencing on resulting amplicons were carried out. Phylogenetic analysis revealed that 81 (70%) were subtype A1, 13 (11%) subtype D, 8 (7%) subtype C, 3 (3%) subtype A2, 1 (1%) subtype G, and 10 showed possible recombinants: 5 (4%) subtype A1D, 4 (3%) subtype A1C, and 1 (1%) subtype A2C. These data support the need to establish circulating subtypes for better evaluation of effective HIV diagnostic and treatment options in Kenya. PMID:21827277

  1. HIV type 1 integrase inhibitors: from basic research to clinical implications.

    PubMed

    Jegede, Oyebisi; Babu, John; Di Santo, Roberto; McColl, Damian J; Weber, Jan; Quiñones-Mateu, Miguel

    2008-01-01

    Similar to other retroviruses, productive infection with HIV-1 requires three key steps in the viral replication: (i) reverse transcription of viral genomic RNA into viral cDNA by the viral reverse transcriptase; (ii) integration of viral cDNA into host cell genome using the viral integrase; and (iii) cleavage of newly synthesized viral polypeptide by the viral protease into individual viral proteins during new virion assembly. Following their discovery, all three viral enzymes were considered as targets for antiretroviral drugs. However, while multiple reverse transcriptase and protease inhibitors have been used for more than 12 years to treat HIV-infected individuals, only recently has the viral integrase enzyme emerged as an alternative, clinically validated target to block HIV-1 replication. Here we review the biology of HIV-1 integration, the mechanisms of action and development of resistance to integrase inhibitors, and the latest data on the most recent clinical trials involving this promising, novel class of antiretroviral drugs. PMID:18820719

  2. Drugs, Alcohol and HIV

    MedlinePlus

    ... Combat Veterans & their Families Readjustment Counseling (Vet Centers) War Related Illness & Injury Study Center Homeless Veterans Returning ... follow these reminders: Never reuse or "share" syringes, water, or drug preparation equipment. Use only syringes obtained ...

  3. Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery

    PubMed Central

    Thomas, Mark P; Potter, Barry VL

    2014-01-01

    Cortisol is synthesized by 11β-hydroxysteroid dehydrogenase type 1, inhibitors of which may treat disease associated with excessive cortisol levels. The crystal structures of 11β-hydroxysteroid dehydrogenase type 1 that have been released may aid drug discovery. The crystal structures have been analyzed in terms of the interactions between the protein and the ligands. Despite a variety of structurally different inhibitors the crystal structures of the proteins are quite similar. However, the differences are significant for drug discovery. The crystal structures can be of use in drug discovery, but care needs to be taken when selecting structures for use in virtual screening and ligand docking. PMID:21446847

  4. HIV infection in females dependent on drugs.

    PubMed

    Wai, B H; Singh, S; Varma, S L

    1996-03-01

    One hundred and seventy-one drug-dependent females in a drug rehabilitation centre were studied to estimate the prevalence of HIV infection among them. Twenty-four (14%) were positive on the Western Blot test. The presence of HIV infection was significantly correlated with syphilis (p < 0.03) and age (p < 0.001); 83% of those who were HIV positive were intravenous drug users. The need for harm reduction programmes to prevent spread of HIV infection among injecting drug users is stressed. PMID:8867206

  5. Demonstration of de novo HIV type 1 production by detection of multiply spliced and unspliced HIV type 1 RNA in paraffin-embedded tonsils.

    PubMed

    Brachtel, Elena F; Mascola, John R; Wear, Douglas J; Ehrenberg, Philip K; Dayhoff, Deborah E; Sanders-Buell, Eric; Michael, Nelson L; Frankel, Sarah Schlesinger

    2002-07-20

    HIV-1 infection of tonsils takes place when virus spreads systemically, and may occur when tonsillar tissue serves as the initial portal of HIV-1 entry. The HIV replication cycle includes the production of regulatory and accessory gene mRNAs, produced by splicing of genomic mRNA, that are hallmarks of de novo virus production. We sought to demonstrate, for the first time, the presence of multiply spliced viral RNA transcripts in archival tissue as a marker for active virus replication. Further, amplified cDNA sequences from unspliced pol gene mRNA were used to define the genetic subtype of HIV-1 within these tissues. RNA was extracted from surgical pathological, formalin-fixed, paraffin-embedded specimens, and RT-PCR was performed with primers for unspliced and multiply spliced HIV-1 transcripts. Amplification products were analyzed by agarose gel electrophoresis and their specificity was confirmed by sequencing and Southern blot hybridization. Unspliced HIV-1 pol transcripts yielded cDNA amplicons of 184 base pairs (bp) that were cloned and sequenced. Phylogenetic analysis revealed these sequences to be of HIV-1 subtype B. Multiply spliced transcripts specific for the tat/rev (173 bp), tat (268 bp), and tat/rev/nef (146 bp) regulatory gene mRNAs could be demonstrated in all cases. These results support the demonstration of active replication of HIV-1 in archival tonsillar tissues previously shown by p24 antigen staining. They also show the feasibility of performing molecular epidemiologic studies on HIV-1 cDNA sequences from archived pathologic specimens. PMID:12167270

  6. Recombinant virus assay: a rapid, phenotypic assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates.

    PubMed Central

    Kellam, P; Larder, B A

    1994-01-01

    Antiviral drug susceptibility assays for clinical human immunodeficiency virus type 1 (HIV-1) isolates are required to monitor the development of drug resistance during clinical trials and antiretroviral drug therapy. First-generation phenotypic assays possess a number of drawbacks, not least the selection of unrepresentative virus populations during cocultivation. Here we describe a rapid phenotypic assay for the assessment of the susceptibility of clinical isolates to reverse transcriptase (RT) inhibitors. This procedure, called the recombinant virus assay, allows the generation of viable virus by homologous recombination of a PCR-derived pool of RT coding sequences into an RT-deleted, noninfectious proviral clone, pHIV delta BstEII. A nested PCR procedure has been optimized to allow the amplification of an RT pool from both uncultured and cocultured infected patient peripheral blood lymphocyte (PBL) DNA for subsequent use in the creation of recombinant viruses. Analysis of two patients during the course of zidovudine therapy showed that this approach produced viruses which accurately exhibited the same genotype and phenotype as that of the original infected PBL DNA. The recombinant virus assay can be performed in approximately 3 weeks without the use of donor PBLs and therefore represents a rapid, nonselective procedure for the assay of clinical isolates. Images PMID:8141575

  7. HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission.

    PubMed

    Collins-Fairclough, Aneisha M; Dennis, Ann M; Nelson, Julie A E; Weir, Sharon S; Figueroa, J Peter

    2015-08-01

    The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs. PMID:26133540

  8. HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission

    PubMed Central

    Dennis, Ann M.; Nelson, Julie A.E.; Weir, Sharon S.; Figueroa, J. Peter

    2015-01-01

    Abstract The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs. PMID:26133540

  9. Recreational drug use in type 1 diabetes: an invisible accomplice to poor glycaemic control?

    PubMed

    Lee, P; Greenfield, J R; Gilbert, K; Campbell, L V

    2012-02-01

    Recreational drug use during 'rave' parties is increasingly popular, but the impact of recreational drug use in type 1 diabetes (T1D) is not known. We determined the self-reported pattern and effects of recreational/illicit drug use in Australians with T1D people by inviting people with T1D to participate in an anonymous online/paper survey of drug use, through national radio broadcast and online/hospital advertising. Of the people with T1D who responded to our survey, more than three quarters reported having used recreational/illicit drug, but few people had informed health professionals about drug use. Drug use was associated with worse glycaemic control and higher risk of diabetic ketoacidosis. Medical awareness of common, currently underreported, drug use in young people with T1D is essential. It offers the possibility of helping such patients improve related suboptimal metabolic control. PMID:22356493

  10. Human Immunodeficiency Virus Type 1 (HIV-1) Tat Induces Nitric-oxide Synthase in Human Astroglia*

    PubMed Central

    Liu, Xiaojuan; Jana, Malabendu; Dasgupta, Subhajit; Koka, Sreenivas; He, Jun; Wood, Charles; Pahan, Kalipada

    2007-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1 tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-κB and C/EBPβ, transcription factors responsible for the induction of iNOS. Activation of NF-κB as well as C/EBPβ by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPβ, and inhibition of RSV-tat-induced production of NO by Δp65, a dominant-negative mutant of p65, and ΔC/EBPβ, a dominant-negative mutant of C/EBPβ, suggest that RSV-tat induces iNOS through the activation of NF-κB and C/EBPβ. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and ΔERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO

  11. Induction of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses in HIV Vaccine Trial Participants Who Subsequently Acquire HIV-1 Infection

    PubMed Central

    Horton, Helen; Havenar-Daughton, Colin; Lee, Deborah; Moore, Erin; Cao, Jianhong; McNevin, John; Andrus, Thomas; Zhu, Haiying; Rubin, Abbe; Zhu, Tuofu; Celum, Connie; McElrath, M. Juliana

    2006-01-01

    Candidate human immunodeficiency virus type 1 (HIV-1) vaccines designed to elicit T-cell immunity in HIV-1-uninfected persons are under investigation in phase I to III clinical trials. Little is known about how these vaccines impact the immunologic response postinfection in persons who break through despite vaccination. Here, we describe the first comprehensive characterization of HIV-specific T-cell immunity in vaccine study participants following breakthrough HIV-1 infection in comparison to 16 nonvaccinated subjects with primary HIV-1 infection. Whereas none of the 16 breakthrough infections possessed vaccine-induced HIV-1-specific T-cell responses preinfection, 85% of vaccinees and 86% of nonvaccinees with primary HIV-1 infection developed HIV-specific T-cell responses postinfection. Breakthrough subjects' T cells recognized 43 unique HIV-1 T-cell epitopes, of which 8 are newly described, and 25% were present in the vaccine. The frequencies of gamma interferon (IFN-γ)-secreting cells recognizing epitopes within gene products that were and were not encoded by the vaccine were not different (P = 0.64), which suggests that responses were not anamnestic. Epitopes within Nef and Gag proteins were the most commonly recognized in both vaccinated and nonvaccinated infected subjects. One individual controlled viral replication without antiretroviral therapy and, notably, mounted a novel HIV-specific HLA-C14-restricted Gag LYNTVATL-specific T-cell response. Longitudinally, HIV-specific T cells in this individual were able to secrete IFN-γ and tumor necrosis factor alpha, as well as proliferate and degranulate in response to their cognate antigenic peptides up to 5 years postinfection. In conclusion, a vaccinee's ability to mount an HIV-specific T-cell response postinfection is not compromised by previous immunization, since the CD8+ T-cell responses postinfection are similar to those seen in vaccine-naïve individuals. Finding an individual who is controlling infection

  12. Alternate approaches for pediatric type 1 diabetes drug development and potential regulatory approval: a perspective.

    PubMed

    Turner, J Rick; Close, Kelly L; Fleming, G Alexander; Wherrett, Diane K; DiMeglio, Linda A

    2015-10-01

    The incidence and prevalence of pediatric type 1 diabetes are increasing globally, including in the U.S. While the increasing number of cases of pediatric diabetes makes expeditious availability of new medical products and therapies for diabetes care essential, there have been many barriers encountered in bringing some drugs and devices to pediatric patients who may benefit. Newer insulins have been studied and approved for use in children. However, hurdles exist in the inclusion of children in studies of therapies aimed at preventing β-cell loss in those with new-onset diabetes and those at risk for type 1 diabetes. This Perspective focuses on potential solutions to the challenges experienced in bringing new drugs for pediatric type 1 diabetes to marketing approval. Given their central importance as the users of medical products, patient perspectives are included along with scientific and regulatory considerations. PMID:26404928

  13. [Research development of HIV drug resistance].

    PubMed

    Zou, Wen; Liu, Ying; Wang, Jian; Gao, Guo-Jian; Dong, Ji-Peng; Xian, Qing-Fei

    2013-08-01

    Highly active antiretroviral combination therapy significantly reduced the mortality, but in the high-speed copying, high genetic variation and drug selection pressure under the effect of the increasingly serious problem of drug resistance greatly weakened the role of HAART inhibit viral replication and reduce antiviral treatment. This paper reports the latest trends in HIV drug-resistance in order to develop anti-HIV drugs in clinical programs, research and development of new guidance anti-HIV-1 strategy to bring guidance. PMID:24228557

  14. Role and modulation of drug transporters in HIV-1 therapy.

    PubMed

    Alam, Camille; Whyte-Allman, Sana-Kay; Omeragic, Amila; Bendayan, Reina

    2016-08-01

    Current treatment of human immunodeficiency virus type-1 (HIV-1) infection involves a combination of antiretroviral drugs (ARVs) that target different stages of the HIV-1 life cycle. This strategy is commonly referred to as highly active antiretroviral therapy (HAART) or combined antiretroviral therapy (cART). Membrane-associated drug transporters expressed ubiquitously in mammalian systems play a crucial role in modulating ARV disposition during HIV-1 infection. Members of the ATP-binding cassette (ABC) and solute carrier (SLC) transporter superfamilies have been shown to interact with ARVs, including those that are used as part of first-line treatment regimens. As a result, the functional expression of drug transporters can influence the distribution of ARVs at specific sites of infection. In addition, pathological factors related to HIV-1 infection and/or ARV therapy itself can alter transporter expression and activity, thus further contributing to changes in ARV disposition and the effectiveness of HAART. This review summarizes current knowledge on the role of drug transporters in regulating ARV transport in the context of HIV-1 infection. PMID:27181050

  15. Drug and Alcohol Use -- A Significant Risk Factor for HIV

    MedlinePlus

    ... A Significant Risk Factor for HIV Drug and Alcohol Use - A Significant Risk Factor for HIV Email ... with HIV currently use drugs or binge on alcohol. Many people are unaware that the increased risk ...

  16. Mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    DOEpatents

    Korber, Bette T.; Fischer, William; Liao, Hua-Xin; Haynes, Barton F.; Letvin, Norman; Hahn; Beatrice H.

    2011-05-31

    The present invention relates to mosaic clade M HIV-1 Env polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  17. Susceptibility Testing by Polymerase Chain Reaction DNA Quantitation: A Method to Measure Drug Resistance of Human Immunodeficiency Virus Type 1 Isolates

    NASA Astrophysics Data System (ADS)

    Eron, Joseph J.; Gorczyca, Paul; Kaplan, Joan C.; D'Aquila, Richard T.

    1992-04-01

    Polymerase chain reaction (PCR) DNA quantitation (PDQ) susceptibility testing rapidly and directly measures nucleoside sensitivity of human immunodeficiency virus type 1 (HIV-1) isolates. PCR is used to quantitate the amount of HIV-1 DNA synthesized after in vitro infection of peripheral blood mononuclear cells. The relative amounts of HIV-1 DNA in cell lysates from cultures maintained at different drug concentrations reflect drug inhibition of virus replication. The results of PDQ susceptibility testing of 2- or 3-day cultures are supported by assays measuring HIV-1 p24 antigen production in supernatants of 7- or 10-day cultures. DNA sequence analyses to identify mutations in the reverse transcriptase gene that cause resistance to 3'-azido-3'-deoxythymidine also support the PDQ results. With the PDQ method, both infectivity titration and susceptibility testing can be performed on supernatants from primary cultures of peripheral blood mononuclear cells. PDQ susceptibility testing should facilitate epidemiologic studies of the clinical significance of drug-resistant HIV-1 isolates.

  18. Near full-length genomic characterization of a HIV type 1 BC recombinant strain from Manipur, India.

    PubMed

    Sarkar, Roni; Sarkar, Kamalesh; Singh, N Brajachand; Singh, Y Manihar; Chakrabarti, Sekhar

    2012-10-01

    Genetic complexity of HIV-1 is brought about by recombination between HIV-1 subtypes which leads to the development of epidemiologically significant founder strains. In the present study, the near full-length genome sequence of an HIV-1 isolate from an injecting drug user of Manipur (India) was determined, which evidenced the presence of a novel HIV-1 BC recombinant strain. Near full-length genome was amplified by polymerase chain reaction using primer walking approach. The recombination break points were detected using bootscan and simplot analyses. This isolate exhibited a mosaic structure consisting of subtype C backbone with subtype B insertions at the upstream of pol gene (3026-3259) and the downstream of env gene which spanned till the nef gene (8183-8961). Phylogenetic relationships determined with neighbor-joining trees, revealed that the subtype C sequences clustered with sequences from Indian subtype C HIV-1 strains, and the subtype B sequences clustered with HIV-1 subtype B strains from Thailand. This finding may create a complex scenario of HIV-1 epidemic among the injecting drug users of Manipur in near future. PMID:22710995

  19. A Case of Primary HIV Type 1 and Cytomegalovirus Coinfection Presenting with Widespread Clinical Disease

    PubMed Central

    Kim, Joseph Y.; Singer, Elyse J.; Bonelli, Laura; Klausner, Jeffrey D.

    2015-01-01

    Coinfection of HIV-1 and cytomegalovirus (CMV) may occur given the shared routes of transmission, and the clinical presentations of each process overlap. We present a case of acute HIV-1 and CMV coinfection presenting with an acute febrile illness complicated by meningitis, hepatitis, and retinopathy. This and other similar cases demonstrate the need to consider CMV coin-fection in acute HIV-1 disease, particularly in situations with significant end-organ damage. PMID:24476962

  20. Nucleic acids encoding mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    DOEpatents

    Korber, Bette T; Fischer, William; Liao, Hua-Xin; Haynes, Barton F; Letvin, Norman; Hahn, Beatrice H

    2015-04-21

    The present invention relates to nucleic acids encoding mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  1. Potent and selective inhibition of human immunodeficiency virus type 1 (HIV-1) by 5-ethyl-6-phenylthiouracil derivatives through their interaction with the HIV-1 reverse transcriptase.

    PubMed Central

    Baba, M; De Clercq, E; Tanaka, H; Ubasawa, M; Takashima, H; Sekiya, K; Nitta, I; Umezu, K; Nakashima, H; Mori, S

    1991-01-01

    In the search for 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine (HEPT) derivatives, we have found several 5-ethyl-6-(phenylthio)uracil analogues to be highly potent and selective inhibitors of human immunodeficiency virus (HIV) type 1. 1-Benzyloxymethyl-5-ethyl-6-phenylthiouracil, the most potent congener of the series, inhibits HIV-1 replication in a variety of cell systems, including peripheral blood lymphocytes, at a concentration of 1.5-7.0 nM, which is lower by a factor of 10(3) than the 50% antivirally effective concentration of the parent compound HEPT. The 5-ethyl-6-(phenylthio)uracil analogues, like HEPT itself, do not inhibit HIV-2 replication but do inhibit replication of 3'-azido-3'-deoxythymidine-resistant mutants of HIV-1. 1-Benzyloxy-methyl-5-ethyl-6-phenylthiouracil and its congeners are targeted at the HIV-1 reverse transcriptase (RT). They do not inhibit HIV-2 RT. They do not need to be metabolized to exert their inhibitory effect on HIV-1 RT. Yet this inhibitory effect is competitive with the natural substrate dTTP. The HEPT derivatives represent a group of RT inhibitors with a unique mode of interaction with HIV-1 RT. PMID:1706522

  2. A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1.

    PubMed

    Thomasy, Sara M; Maggs, David J

    2016-07-01

    Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats. PMID:27091747

  3. Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety considerations and controversy over therapeutic applications.

    PubMed

    Romano, Gaetano; Claudio, Pier Paolo; Tonini, Tiziana; Giordano, Antonio

    2003-01-01

    The latest generation of lentiviral vectors based on HIV-1 is one of the most efficient tools for gene transduction of mammalian cells. However, the possible employment of HIV-based vectors in clinical trials is a very controversial issue, mainly due to safety and ethical concerns. HIV-1 is a lethal pathogenic agent, which induces AIDS. Genetic vectors must derive either from viruses that are not pathogenic in humans, or that eventually just cause mild illnesses. Patients exposed to HIV-based vectors will test seropositive to certain components of HIV-1. In addition, there might be other possible adverse effects in patients that cannot be predicted, as many aspects of the pathogenesis of AIDS have not been completely understood yet. On these grounds, it seems necessary to improve the design of other lentiviral vectors, which derive from viruses that are not pathogenic in humans and are distantly related to primate retroviridae. PMID:14693483

  4. Decreased HIV Type 1 Transcription in CCR5-Δ32 Heterozygotes During Suppressive Antiretroviral Therapy

    PubMed Central

    Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C.; Lada, Steven M.; Yukl, Steven; Cockerham, Leslie R.; Pilcher, Christopher D.; Hecht, Frederick M.; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D.; Deeks, Steven G.; Pillai, Satish K.

    2014-01-01

    Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P = .035), RNA to DNA transcriptional ratios (P = .013), and frequency of detectable HIV 2–long terminal repeat circular DNA (P = .013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2 = 0.136; P = .002). Our findings suggest that curative strategies should further explore manipulation of CCR5. PMID:24935955

  5. HIV Type 1 Transmission Networks Among Men Having Sex with Men and Heterosexuals in Kenya

    PubMed Central

    Faria, Nuno Rodrigues; Hassan, Amin; Hamers, Raph L.; Mutua, Gaudensia; Anzala, Omu; Mandaliya, Kishor; Cane, Patricia; Berkley, James A.; Rinke de Wit, Tobias F.; Wallis, Carole; Graham, Susan M.; Price, Matthew A.; Coutinho, Roel A.; Sanders, Eduard J.

    2014-01-01

    Abstract We performed a molecular phylogenetic study on HIV-1 polymerase sequences of men who have sex with men (MSM) and heterosexual patient samples in Kenya to characterize any observed HIV-1 transmission networks. HIV-1 polymerase sequences were obtained from samples in Nairobi and coastal Kenya from 84 MSM, 226 other men, and 364 women from 2005 to 2010. Using Bayesian phylogenetics, we tested whether sequences clustered by sexual orientation and geographic location. In addition, we used trait diffusion analyses to identify significant epidemiological links and to quantify the number of transmissions between risk groups. Finally, we compared 84 MSM sequences with all HIV-1 sequences available online at GenBank. Significant clustering of sequences from MSM at both coastal Kenya and Nairobi was found, with evidence of HIV-1 transmission between both locations. Although a transmission pair between a coastal MSM and woman was confirmed, no significant HIV-1 transmission was evident between MSM and the comparison population for the predominant subtype A (60%). However, a weak but significant link was evident when studying all subtypes together. GenBank comparison did not reveal other important transmission links. Our data suggest infrequent intermingling of MSM and heterosexual HIV-1 epidemics in Kenya. PMID:23947948

  6. HIV Type 1 transmission networks among men having sex with men and heterosexuals in Kenya.

    PubMed

    Bezemer, Daniela; Faria, Nuno Rodrigues; Hassan, Amin; Hamers, Raph L; Mutua, Gaudensia; Anzala, Omu; Mandaliya, Kishor; Cane, Patricia; Berkley, James A; Rinke de Wit, Tobias F; Wallis, Carole; Graham, Susan M; Price, Matthew A; Coutinho, Roel A; Sanders, Eduard J

    2014-02-01

    We performed a molecular phylogenetic study on HIV-1 polymerase sequences of men who have sex with men (MSM) and heterosexual patient samples in Kenya to characterize any observed HIV-1 transmission networks. HIV-1 polymerase sequences were obtained from samples in Nairobi and coastal Kenya from 84 MSM, 226 other men, and 364 women from 2005 to 2010. Using Bayesian phylogenetics, we tested whether sequences clustered by sexual orientation and geographic location. In addition, we used trait diffusion analyses to identify significant epidemiological links and to quantify the number of transmissions between risk groups. Finally, we compared 84 MSM sequences with all HIV-1 sequences available online at GenBank. Significant clustering of sequences from MSM at both coastal Kenya and Nairobi was found, with evidence of HIV-1 transmission between both locations. Although a transmission pair between a coastal MSM and woman was confirmed, no significant HIV-1 transmission was evident between MSM and the comparison population for the predominant subtype A (60%). However, a weak but significant link was evident when studying all subtypes together. GenBank comparison did not reveal other important transmission links. Our data suggest infrequent intermingling of MSM and heterosexual HIV-1 epidemics in Kenya. PMID:23947948

  7. Non-insulin drugs to treat hyperglycaemia in type 1 diabetes mellitus.

    PubMed

    Frandsen, Christian Seerup; Dejgaard, Thomas Fremming; Madsbad, Sten

    2016-09-01

    Insulin treatment of individuals with type 1 diabetes has shortcomings and many patients do not achieve glycaemic and metabolic targets. Consequently, the focus is on novel non-insulin therapeutic approaches that reduce hyperglycaemia and improve metabolic variables without increasing the risk of hypoglycaemia or other adverse events. Several therapies given in conjunction with insulin have been investigated in clinical trials, including pramlintide, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter inhibitors, metformin, sulfonylureas, and thiazolidinediones. These drugs have pleiotropic effects on glucose metabolism and different actions complementary to those of insulin-this Review reports the effects of these drugs on glycaemic control, glucose variability, hypoglycaemia, insulin requirements, and bodyweight. Existing studies are of short duration with few participants; evidence for the efficacy of concomitant treatments is scarce and largely clinically insignificant. A subgroup of patients with type 1 diabetes for whom non-insulin antidiabetic drugs could significantly benefit glycaemic control cannot yet be defined, but we suggest that obese patients prone to hypoglycaemia and patients with residual β-cell function are populations of interest for future trials. PMID:26969516

  8. Demonstration of Sustained Drug-Resistant Human Immunodeficiency Virus Type 1 Lineages Circulating among Treatment-Naïve Individuals▿ †

    PubMed Central

    Hué, Stéphane; Gifford, Robert J.; Dunn, David; Fernhill, Esther; Pillay, Deenan

    2009-01-01

    Transmission of human immunodeficiency virus (HIV) drug resistance is well-recognized and compromises response to first-line therapy. However, the population dynamics of transmitted resistance remains unclear, although previous models have assumed that such transmission reflects direct infection from treated individuals. We investigated whether population-based phylogenetic analyses would uncover lineages of resistant viruses circulating in untreated individuals. Through the phylogenetic analysis of 14,061 HIV type 1 (HIV-1) pol gene sequences generated in the United Kingdom from both treatment-naïve and -experienced individuals, we identified five treatment-independent viral clusters containing mutations conferring cross-resistance to antiretroviral drugs prescribed today in the United Kingdom. These viral lineages represent sustainable reservoirs of resistance among new HIV infections, independent of treatment. Dated phylogenies reconstructed through Bayesian Markov chain Monte Carlo inference indicated that these reservoirs originated between 1997 and 2003 and have persisted in the HIV-infected population for up to 8 years. Since our cohort does not represent all infected individuals within the United Kingdom, our results are likely to underestimate the number and size of the resistant reservoirs circulating among drug-naïve patients. The existence of sustained reservoirs of resistance in the absence of treatment has the capacity to threaten the long-term efficacy of antiretroviral therapy and suggests there is a limit to the decline of transmitted drug resistance. Given the current decrease in resistance transmitted from treated individuals, a greater proportion of resistance is likely to come from drug-naïve lineages. These findings provide new insights for the planning and management of treatment programs in resource-rich and developing countries. PMID:19158238

  9. Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV).

    PubMed

    Diem, Kurt; Nickle, David C; Motoshige, Alexis; Fox, Alan; Ross, Susan; Mullins, James I; Corey, Lawrence; Coombs, Robert W; Krieger, John N

    2008-04-01

    We present phylogenetic evidence supporting viral compartmentalization between the blood (peripheral blood mononuclear cells or plasma) and multiple genitourinary sites in HIV-infected men. Four of the five subjects evaluated demonstrated compartmentalization of viral sequences between urogenital tract specimens (tissue or fluid) and at least one blood category. HIV sequence migration from blood to urogenital tract was detected in four of five men, with migration from urogenital tract to blood in the fifth, and cross migration between both compartments noted in one man. These observations add 5 additional cases to the 27 total reported cases in which male urogenital tract compartmentalization has been studied, investigate surgical samples/specimens that have not been evaluated previously, and provide further evidence for restricted flow of HIV between the blood and the genital tract. As such, our study findings are important for understanding the long-term response to antiretroviral therapy, the design of vaccines, and the sexual transmission of HIV. PMID:18426336

  10. Performance of an In-House Human Immunodeficiency Virus Type 1 Genotyping System for Assessment of Drug Resistance in Cuba

    PubMed Central

    Alemán, Yoan; Vinken, Lore; Kourí, Vivian; Pérez, Lissette; Álvarez, Alina; Abrahantes, Yeissel; Fonseca, Carlos; Pérez, Jorge; Correa, Consuelo; Soto, Yudira; Schrooten, Yoeri; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2015-01-01

    As commercial human immunodeficiency virus type 1 drug resistance assays are expensive, they are not commonly used in resource-limited settings. Hence, a more affordable in-house procedure was set up taking into account the specific epidemiological and economic circumstances of Cuba. The performance characteristics of the in-house assay were evaluated using clinical samples with various subtypes and resistance patterns. The lower limit of amplification was determined on dilutions series of 20 clinical isolates and ranged from 84 to 529 RNA copies/mL. For the assessment of trueness, 14 clinical samples were analyzed and the ViroSeq HIV-1 Genotyping System v2.0 was used as the reference standard. The mean nucleotide sequence identity between the two assays was 98.7% ± 1.0. Additionally, 99.0% of the amino acids at drug resistance positions were identical. The sensitivity and specificity in detecting drug resistance mutations was respectively 94.1% and 99.5%. Only few discordances in drug resistance interpretation patterns were observed. The repeatability and reproducibility were evaluated using 10 clinical samples with 3 replicates per sample. The in-house test was very precise as nucleotide sequence identity among paired nucleotide sequences ranged from 98.7% to 99.9%. The acceptance criteria were met by the in-house test for all performance characteristics, demonstrating a high degree of accuracy. Subsequently, the applicability in routine clinical practice was evaluated on 380 plasma samples. The amplification success rate was 91% and good quality consensus sequences encoding the entire protease and the first 335 codons in reverse transcriptase could be obtained for 99% of the successful amplicons. The reagent cost per sample using the in-house procedure was around € 80 per genotyping attempt. Overall, the in-house assay provided good results, was feasible with equipment and reagents available in Cuba and was half as expensive as commercial assays. PMID

  11. Nucleic acids encoding modified human immunodeficiency virus type 1 (HIV-1) group M consensus envelope glycoproteins

    DOEpatents

    Haynes, Barton F.; Gao, Feng; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.; Kothe, Denise; Li, Ying Ying; Decker, Julie; Liao, Hua-Xin

    2011-12-06

    The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

  12. Isolation of human immunodeficiency virus type 1 (HIV-1) RNA from feces by a simple method and difference between HIV-1 subpopulations in feces and serum.

    PubMed Central

    van der Hoek, L; Boom, R; Goudsmit, J; Snijders, F; Sol, C J

    1995-01-01

    A simple method for the isolation and subsequent detection of human immunodeficiency virus type 1 (HIV-1) RNA from feces is described. Viral RNA was isolated by the method developed by Boom et al. (R. Boom, C.J.A. Sol, M.M.M. Salimans, C.L. Jansen, P.M.E. Wertheim-van Dillen, and J. van der Noordaa, J. Clin. Microbiol. 28:495-503, 1990), which was adapted for feces. HIV-1 RNA was detected by reverse transcription (RT) followed by a nested PCR encompassing the V3 region. Reconstruction experiments revealed that the efficiencies of the extraction technique and the subsequent RT-PCR were not considerably affected by the varied composition of feces. The method was applied on fecal specimens from 18 HIV-1-infected individuals, among which were samples that had been stored for 9 years. It appeared that HIV-1 RNA was detectable in the feces of 12 persons (67%). Viral RNA was present in the feces of persons who fulfilled the criteria for CDC class II and CDC class III HIV infection as well as in patients who were diagnosed with AIDS (CDC class IV). Direct sequencing of amplimers obtained from paired fecal and serum specimens showed that differences in sequence heterogeneity existed. In one patient a remarkable difference in the HIV-1 sequences between isolates from feces and serum was observed. In conclusion, HIV-1 RNA is frequently present in the feces of HIV-1-infected individuals, and in some cases the HIV-1 subpopulation in feces differs from the HIV-1 subpopulation in serum. PMID:7751361

  13. Increased Frequency of CD49b/LAG-3(+) Type 1 Regulatory T Cells in HIV-Infected Individuals.

    PubMed

    Koch, Kristina; Koch, Nora; Sandaradura de Silva, Ute; Jung, Norma; Schulze zur Wiesch, Julian; Fätkenheuer, Gerd; Hartmann, Pia; Romerio, Fabio; Lehmann, Clara

    2015-12-01

    In HIV-1 infection elevated serum levels of interferon-α (IFN-α) and interleukin-10 (IL-10) are associated with immune hyperactivation and disease progression. Recently, coexpression of CD49b and LAG-3 was shown to identify Type 1 regulatory T (Tr1) cells, which secrete large amounts of the immunosuppressive cytokine IL-10. We analyzed the frequency of CD49b/LAG-3(+) Tr1 cells in the peripheral blood of HIV-infected individuals at different stages of the disease. We found increased levels of CD49b/LAG-3(+) Tr1 cells as well as IL-10 in HIV patients. With disease progression, Tr1 cells negatively correlate with frequency of plasmacytoid dendritic cells (pDCs), the main producers of IFN-α. However, elevated IL-10 levels could not be ascribed to the CD49b/LAG-3(+)Tr1 cell population. Moreover, we showed in vitro that IFN-α leads to an upregulation of IL-10 as well as CD49b/LAG-3(+) Tr1 cell counts in healthy controls, recapitulating effects observed in vivo during HIV infection. Our results suggest that overexpression of IFN-α during HIV infection drives the generation of CD49b/LAG-3(+) Tr1 cells and the immunosuppressive cytokine IL-10. Furthermore, it remains unclear whether elevated IL-10 levels are beneficial or detrimental in regard to disease progression. PMID:26192268

  14. HIV type 1 subtypes among bar and hotel workers in Moshi, Tanzania.

    PubMed

    Kiwelu, Ireen E; Renjifo, Boris; Chaplin, Beth; Sam, Noel; Nkya, Watoky M M M; Shao, John; Kapiga, Saidi; Essex, Max

    2003-01-01

    The HIV-1 prevalence among bar and hotel workers in Tanzania suggests they are a high-risk group for HIV-1 infection. We determined the HIV-1 subtype of 3'-p24/5'-p7 gag and C2-C5 env sequences from 40 individuals representing this population in Moshi. Genetic patterns composed of A(gag)-A(env), C(gag)-C(env), and D(gag)-D(env) were found in 19 (48.0%), 8 (20.0%), and 3 (8.0%) samples, respectively. The remaining 10 samples (25%) had different subtypes in gag and env, indicative of intersubtype recombinants. Among these recombinants, two contained sequences from HIV-1 subsubtype A2, a new genetic variant in Tanzania. Five bar and hotel workers may have been infected with viruses from a common source, based on phylogenetic analysis. The information obtained by surveillance of HIV-1 subtypes in a high-risk population should be useful in the design and evaluation of behavioral, therapeutic, and vaccine trial interventions aimed at reducing HIV-1 transmission. PMID:12596722

  15. Alternating versus continuous drug regimens in combination chemotherapy of human immunodeficiency virus type 1 infection in vitro.

    PubMed Central

    Mazzulli, T; Rusconi, S; Merrill, D P; D'Aquila, R T; Moonis, M; Chou, T C; Hirsch, M S

    1994-01-01

    We compared the in vitro efficacies of two-, three-, and four-drug combinations given continuously or in alternating regimens against a clinical isolate of human immunodeficiency virus type 1. In H9 cells and peripheral blood mononuclear cells, at the drug concentrations used in this study, there was greater suppression of human immunodeficiency virus type 1 infection as the number of drugs in the regimen was increased from one to four simultaneously administered agents. Although alternating drug regimens were effective, they were not better than continuous administration of either single drugs or combinations of agents and were less effective than giving all drugs of an alternating regimen simultaneously. PMID:8031028

  16. Action of anti-HIV drugs and resistance: reverse transcriptase inhibitors and protease inhibitors.

    PubMed

    Imamichi, Tomozumi

    2004-01-01

    Currently, 20 drugs have been approved for Human Immunodeficiency Virus type-1 (HIV-1) clinical therapy. These drugs inhibit HIV-1 reverse transcriptase, protease, or virus entry. Introduction of a combination therapy with reverse transcriptase inhibitors and protease inhibitors has resulted in a drastic decrease in HIV-1 related mortality. Although the combination therapy can suppress viral replication below detection levels in current available assays, low levels of on-going viral replication still persist in some patients. Long-term administration of the combination therapy may increase selective pressure against viruses, and subsequently induce emergence of multiple drug-resistant HIV-1 variants. Attempts have been made to design novel antiretroviral drugs that would be able to suppress replication of the resistant variants. At present, several investigational drugs are being tested in clinical trials. These drugs target not only the resistant variants, but also improvement in oral bioavilability or other viral proteins such as HIV-1 integrase, ribonuclease H, and HIV-1 entry (CD4 attachment inhibitors, chemokine receptors antagonists, and fusion inhibitors). Understanding mechanism(s) of action of the drugs and mechanisms of drug resistance is necessary for successful designs in the next generation of anti-HIV-1 drugs. In this review, the mechanisms of action of reverse transcriptase- and protease-inhibitors, and the mechanism of resistance to these inhibitors, are described. PMID:15579086

  17. Drugs That Fight HIV-1

    MedlinePlus

    ... program of the National Institutes of Health Nucleoside Reverse Transcriptase Inhibitors (NRTIs) NRTIs block reverse transcriptase, an enzyme HIV- ... these products are on last page.) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) NNRTIs bind to and alter reverse transcriptase, ...

  18. Drugs + HIV, Learn the Link

    MedlinePlus Videos and Cool Tools

    ... with HIV is a key predictor of the development of AIDS. Because of their compromised immune system, ... Children, Youth and Families The American Academy of Child & Adolescent Psychiatry (AACAP) The United Negro College Fund, ...

  19. Phylogeographic reconstruction of HIV type 1B in Montenegro and the Balkan region.

    PubMed

    Ciccozzi, Massimo; Lai, Alessia; Ebranati, Erika; Gabanelli, Elena; Galli, Massimo; Mugosa, Boban; Vratnica, Zoran; Vujoševic, Danijela; Lauševic, Dragan; Ciotti, Marco; Cella, Eleonora; Lo Presti, Alessandra; Zehender, Gianguglielmo

    2012-10-01

    Human immunodeficiency virus (HIV) is one of the most genetically variable human viruses as it is characterized by high rates of mutation, viral replication, and recombination. Phylodynamics is a powerful means of describing the behavior of an infection as a combination of evolutionary and ecological processes. Only a few studies of HIV-1 molecular epidemiology have so far been carried out in the Balkans. In this study, we used Bayesian methods to reconstruct the phylogeography and phylodynamics of HIV-1B in Montenegro and some other Balkan countries on the basis of pol gene sequences retrieved from a public database. The phylogenetic analysis showed that 43% of the isolates grouped in accordance with their geographic area, whereas the majority were interspersed in the tree, thus confirming the multiple introductions of HIV-1B in the Balkans. The Bayesian phylogeographic analysis suggested that HIV-1B entered the Balkans in the early 1970s probably through Greece and other Mediterranean tourist/travel destinations (such as Slovenia). Other Balkan countries, such as Bulgaria and Serbia, may have played an important role in spreading the infection to the entire Eastern Mediterranean area, and possibly to Northeast Europe. This suggests that the Balkans may have played a role as a "gateway" between Western and Eastern Europe. PMID:22364163

  20. Breaking the Taboo: Illicit Drug Use among Adolescents with Type 1 Diabetes Mellitus

    PubMed Central

    Hogendorf, Anna M.; Fendler, Wojciech; Sieroslawski, Janusz; Bobeff, Katarzyna; Wegrewicz, Krzysztof; Malewska, Kamila I.; Przudzik, Maciej W.; Szmigiero-Kawko, Malgorzata; Sztangierska, Beata; Mysliwiec, Malgorzata; Szadkowska, Agnieszka; Mlynarski, Wojciech

    2016-01-01

    Background. The aim of the study was to explore the prevalence of illicit drug use in a group of Polish adolescents with type 1 diabetes (DM1) in comparison with a national cohort of their healthy peers. Methods. Two hundred and nine adolescents with DM1, aged 15–18 years, were studied in 2013 with an anonymous questionnaire prepared for the European School Survey Project on Alcohol and Other Drugs (ESPAD). The control group was a representative sample of 12114 students at the same age who took part in ESPAD in 2011. Metabolic control was regarded as good if self-reported HbA1c was <8% or poor if HbA1c was ≥8%. Results. Lifetime prevalence of illicit drug use was lower among adolescents with DM1 than in the control group [58 (28%) versus 5524 (46%), p = 10−5]. Cannabis preparations were the most frequently used substances [38 (18.3%) versus 3976 (33.1%), p = 10−5], followed by tranquilizers, sedatives, and amphetamine. Lifetime and last 12-month use of cannabis were associated with poorer glycemic control (HbA1c ≥ 8%), p < 0.01 and 0.02, respectively. Conclusions. Adolescents with DM1 report using illicit drugs to a lesser extent than their healthy peers. The use of cannabis is associated with a poorer metabolic control in teens with DM1. PMID:26858959

  1. Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase.

    PubMed Central

    Pauwels, R; Andries, K; Debyser, Z; Van Daele, P; Schols, D; Stoffels, P; De Vreese, K; Woestenborghs, R; Vandamme, A M; Janssen, C G

    1993-01-01

    In vitro evaluation of a large chemical library of pharmacologically acceptable prototype compounds in a high-capacity, cellular-based screening system has led to the discovery of another family of human immunodeficiency virus type 1 (HIV-1) inhibitors. Through optimization of a lead compound, several alpha-anilinophenylacetamide (alpha-APA) derivatives have been identified that inhibit the replication of several HIV-1 strains (IIIB/LAI, RF, NDK, MN, HE) in a variety of host cell types at concentrations that are 10,000- to 100,000-fold lower than their cytotoxic concentrations. The IC50 of the alpha-APA derivative R 89439 for HIV-1 cytopathicity in MT-4 cells was 13 nM. The median 90% inhibitory concentration (IC90) in a variety of host cells was 50-100 nM. Although these alpha-APA derivatives are active against a tetrahydroimidazo [4,5,1-jk][1,4]benzodiazepin-2(1H)-thione-(TIBO)-resistant HIV-1 strain, they do not inhibit replication of HIV-2 (strains ROD and EHO) or simian immunodeficiency virus (strains Mac251, mndGB1, and agm3). An HIV-1 strain containing the Tyr181-->Cys mutation in the reverse transcriptase region displayed reduced sensitivity. alpha-APA derivative R 89439 inhibited virion and recombinant reverse transcriptase of HIV-1 but did not inhibit that of HIV-2. Reverse transcriptase inhibition depended upon the template/primer used. The relatively uncomplicated synthesis of R 89439, its potent anti-HIV-1 activity, and its favorable pharmacokinetic profile make R 89439 a good candidate for clinical studies. PMID:7680476

  2. Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase.

    PubMed Central

    Fujihashi, T; Hara, H; Sakata, T; Mori, K; Higuchi, H; Tanaka, A; Kaji, H; Kaji, A

    1995-01-01

    Halogenated gomisin J (a derivative of lignan compound), represented by the bromine derivative 1506 [(6R, 7S, S-biar)-4,9-dibromo-3,10-dihydroxy-1,2,11,12-tetramethoxy-6, 7-dimethyl-5,6,7,8- tetrahydrodibenzo[a,c]cyclo-octene], was found to be a potent inhibitor of the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) on MT-4 human T cells (50% effective dose, 0.1 to 0.5 microM). Gomisin J derivatives were active in preventing p24 production from acutely HIV-1-infected H9 cells. The selective indices (toxic dose/effective dose) of these compounds were as high as > 300 in some systems. 1506 was active against 3'-azido-3'-deoxythymidine-resistant HIV-1 and acted synergistically with AZT and 2',3'-ddC. 1506 inhibited HIV-1 reverse transcriptase (RT) in vitro but not HIV-1 protease. From the time-of-addition experiment, 1506 was found to inhibit the early phase of the HIV life cycle. A 1506-resistant HIV mutant was selected and shown to possess a mutation within the RT-coding region (at position 188 [Tyr to Leu]). The mutant RT expressed in Escherichia coli was resistant to 1506 in the in vitro RT assay. Some of the HIV strains resistant to other nonnucleoside HIV-1 RT inhibitors were also resistant to 1506. Comparison of various gomisin J derivatives with gomisin J showed that iodine, bromine, and chlorine in the fourth and ninth positions increased RT inhibitory activity as well as cytoprotective activity. PMID:8540706

  3. Cell-Associated Transmission of HIV Type 1 and Other Lentiviruses in Small-Animal Models

    PubMed Central

    Moench, Thomas R.

    2014-01-01

    Small-animal models of lentivirus transmission have repeatedly demonstrated transmission by cell-associated virus via vaginal, rectal, and oral routes. The earliest experiments were in the cat/feline immunodeficiency virus model, followed a decade later by successful vaginal transmission of cell-associated human immunodeficiency virus (HIV) in mice bearing transplanted human immune cells. After early unsuccessful attempts at cell-associated transmission in nonhuman primates, renewed investigation in diverse primate models has now confirmed the findings from the cat and humanized mouse models. Improvements in humanized mouse models have made them the preferred small-animal models to study HIV mucosal transmission. They provide complementary systems to nonhuman primate models to aid in the elucidation of the many remaining questions on the mechanism of and means to prevent both cell-associated and cell-free HIV transmission across mucosal barriers. PMID:25414420

  4. Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study

    PubMed Central

    Eron, Joseph J.; Clotet, Bonaventura; Durant, Jacques; Katlama, Christine; Kumar, Princy; Lazzarin, Adriano; Poizot-Martin, Isabelle; Richmond, Gary; Soriano, Vincent; Ait-Khaled, Mounir; Fujiwara, Tamio; Huang, Jenny; Min, Sherene; Vavro, Cindy; Yeo, Jane; Walmsley, Sharon L.; Cox, Joseph; Reynes, Jacques; Morlat, Philippe; Vittecoq, Daniel; Livrozet, Jean-Michel; Fernández, Pompeyo Viciana; Gatell, Jose M.; DeJesus, Edwin; DeVente, Jerome; Lalezari, Jacob P.; McCurdy, Lewis H.; Sloan, Louis A.; Young, Benjamin; LaMarca, Anthony; Hawkins, Trevor

    2013-01-01

    Background. Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1–infected subjects with genotypic evidence of RAL resistance. Methods. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log10 copies/mL from baseline or was <400 copies/mL. Results. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Conclusion. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL. PMID:23225901

  5. A role for RNA helicase A in post-transcriptional regulation of HIV type 1

    PubMed Central

    Li, Junzhou; Tang, Hengli; Mullen, Tina-Marie; Westberg, Christopher; Reddy, Thipparthi R.; Rose, David W.; Wong-Staal, Flossie

    1999-01-01

    Retroviruses must bypass the tight coupling of splicing and nuclear export of mRNA in their replication cycle because unspliced genomic RNA and incompletely spliced mRNA must be exported to the cytoplasm for packaging or translation. This process is mediated by a cis-acting constitutive transport element (CTE) for simple retroviruses and by the trans-acting viral protein Rev in concert with its response element (RRE) for complex retroviruses (e.g., HIV). Recently, we identified RNA helicase A (RHA) as a potential cellular cofactor for CTE. Here, we report that RHA also plays a role in Rev/RRE-mediated gene expression and HIV replication. RHA binds weakly to HIV-1 RRE independently of Rev. Overexpression of RHA, but not of an RHA mutant lacking helicase activity, increased both Rev/RRE- and CTE-dependent gene expression and the levels of unspliced HIV mRNA. Microinjection of antibodies to RHA into nuclei dramatically inhibited both CTE- and Rev-dependent gene expression in human cells. Exogenous RHA cDNA, but not the mutant RHA, rescued this inhibition. We propose that RHA is required to release both CTE- and RRE-containing mRNA from spliceosomes before completion of splicing, thus freeing them for nuclear export. PMID:9892698

  6. Polymorphism, recombination, and mutations in HIV type 1 gag-infecting Peruvian male sex workers.

    PubMed

    Yabar, Carlos Augusto; Salvatierra, Javier; Quijano, Eberth

    2008-11-01

    HIV genetic diversity in female sex workers (FSW) has been previously described in Peru; however this information is not yet available for male sex workers (MSW). Therefore, purified peripheral blood mononuclear cell DNA from 147 HIV-infected subjects identified as MSW and FSW was used to amplify a 460-bp fragment corresponding to the p24-p7 region of the gag gene. The PCR product was digested with restriction enzymes to identify genetic polymorphism. Later, a random group of samples (n = 19) was sequenced to perform phylogenetic analysis, intragenic recombination analysis, and deleterious mutations leading to a nonfunctional protein in conservative regions of the Gag protein. RFLP analysis revealed 11 genetic variants for AluI and five for MspI. A group of nonsex workers (NSW) used for comparison showed different RFLP genetic variant distributions. Of interest, nine cases of mixed genetic variants were observed for MSW, one case for FSW, and none for NSW. Phylogenetic analysis revealed that all HIV-1 species were subtype B. Intragenic recombination analysis showed a B/C recombination case from an FSW (boostrap = 1000; p value < 0.05). Of interest, deleterious mutations were observed in three cases of conservative D2 zinc domains for Gag 3/19 and one case of the high homology region (1/19). This study shows that gag of HIV circulating from MSW has high genetic polymorphism involving deleterious mutations in conserved domains from the p24-p7 gag region. PMID:19000025

  7. Sexual role and transmission of HIV Type 1 among men who have sex with men, in Peru.

    PubMed

    Goodreau, Steven M; Goicochea, L Pedro; Sanchez, Jorge

    2005-02-01

    In Latin America, men who have sex with men (MSM) have traditionally practiced role segregation--that is, the adoption of a fixed role (insertive or receptive) rather than a versatile role (both practices) during anal sex. Previous modeling has shown that role segregation may yield a lower incidence of human immunodeficiency virus (HIV) type 1 infection, compared with role versatility; however, the modeling assumed no risk of acquiring HIV-1 during insertive sex, which is now recognized as unlikely. We reexamine the issue by use of a deterministic model incorporating bidirectional transmission and data from a cohort study of MSM in Lima, Peru, to demonstrate the potential effects of role segregation on the trajectory of the HIV-1 epidemic. In Lima, 67% of MSM reported segregated roles in their recent male partnerships. A population of MSM with identical contact rates but complete role versatility would have twice the prevalence of HIV-1 infection throughout the epidemic's first 3 decades. Preferential mixing among versatile MSM does not change overall prevalence but affects which individuals become infected. PMID:15627225

  8. Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes.

    PubMed

    Pang, Dimeng; Irvine, Katharine M; Mehdi, Ahmed M; Thomas, Helen E; Harris, Mark; Hamilton-Williams, Emma E; Thomas, Ranjeny

    2015-08-01

    In the NOD mouse model of type 1 diabetes (T1D), genetically identical mice in the same environment develop diabetes at different rates. Similar heterogeneity in the rate of progression to T1D exists in humans, but the underlying mechanisms are unclear. Here, we aimed to discover peripheral blood (PB) genes in NOD mice predicting insulitis severity and rate of progression to diabetes. We then wished to use these genes to mine existing databases to identify drugs effective in diabetes. In a longitudinal study, we analyzed gene expression in PB samples from NOD.CD45.2 mice at 10 weeks of age, then scored pancreatic insulitis at 14 weeks or determined age of diabetes onset. In a multilinear regression model, Tnf and Tgfb mRNA expression in PB predicted insulitis score (R (2)=0.56, P=0.01). Expression of these genes did not predict age of diabetes onset. However, by expression-profiling PB genes in 10-week-old NOD.CD45.2 mice, we found a signature of upregulated genes that predicted delayed or no diabetes. Major associated pathways included chromatin organization, cellular protein location and regulation of nitrogen compounds and RNA. In a clinical cohort, three of these genes were differentially expressed between first-degree relatives, T1D patients and controls. Bioinformatic analysis of differentially expressed genes in NOD.CD45.2 PB identified drugs that are predicted to delay or prevent diabetes. Of these drugs, 11 overlapped with drugs predicted to induce a human 'non-progressor' expression profile. These data demonstrate that disease heterogeneity in diabetes-prone mice can be exploited to mine novel clinical T1D biomarkers and drug targets. PMID:26366287

  9. Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes

    PubMed Central

    Pang, Dimeng; Irvine, Katharine M; Mehdi, Ahmed M; Thomas, Helen E; Harris, Mark; Hamilton-Williams, Emma E; Thomas, Ranjeny

    2015-01-01

    In the NOD mouse model of type 1 diabetes (T1D), genetically identical mice in the same environment develop diabetes at different rates. Similar heterogeneity in the rate of progression to T1D exists in humans, but the underlying mechanisms are unclear. Here, we aimed to discover peripheral blood (PB) genes in NOD mice predicting insulitis severity and rate of progression to diabetes. We then wished to use these genes to mine existing databases to identify drugs effective in diabetes. In a longitudinal study, we analyzed gene expression in PB samples from NOD.CD45.2 mice at 10 weeks of age, then scored pancreatic insulitis at 14 weeks or determined age of diabetes onset. In a multilinear regression model, Tnf and Tgfb mRNA expression in PB predicted insulitis score (R2=0.56, P=0.01). Expression of these genes did not predict age of diabetes onset. However, by expression-profiling PB genes in 10-week-old NOD.CD45.2 mice, we found a signature of upregulated genes that predicted delayed or no diabetes. Major associated pathways included chromatin organization, cellular protein location and regulation of nitrogen compounds and RNA. In a clinical cohort, three of these genes were differentially expressed between first-degree relatives, T1D patients and controls. Bioinformatic analysis of differentially expressed genes in NOD.CD45.2 PB identified drugs that are predicted to delay or prevent diabetes. Of these drugs, 11 overlapped with drugs predicted to induce a human ‘non-progressor' expression profile. These data demonstrate that disease heterogeneity in diabetes-prone mice can be exploited to mine novel clinical T1D biomarkers and drug targets. PMID:26366287

  10. HIV/STI Risk Behavior of Drug Court Participants

    ERIC Educational Resources Information Center

    Robertson, Angela A.; St. Lawrence, Janet S.; McCluskey, D. Lee

    2012-01-01

    Drug abusing offenders have high rates of HIV and other sexually transmitted infections (STI). To date, the HIV/STI prevention needs of offenders in drug court programs have been ignored. This multi-method study employed interviews to assess drug court professionals' perceptions of the need for an HIV risk reduction intervention to be integrated…

  11. Altered Strand Transfer Activity of a Multi-drug-resistant Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutant with a Dipeptide Fingers Domain Insertion

    PubMed Central

    Nguyen, Laura A.; Daddacha, Waaqo; Rigby, Sean; Bambara, Robert A.; Kim, Baek

    2013-01-01

    Prolonged highly active anti-retroviral therapy (HAART) with multiple nucleoside reverse transcriptase inhibitors (NRTI) for the treatment of human immunodeficiency virus type 1 (HIV-1) infected patients can induce the development of an HIV-1 RT harboring a dipeptide insertion at the RT fingers domain with a background thymidine analog mutation (TAM). This mutation renders viral resistance to multiple NRTIs. We investigated the effect of the dipeptide fingers domain insertion mutation on strand transfer activity using two clinical RT variants isolated during pre- and post-treatment of an infected patient, termed pre-drug RT without the dipeptide insertion and post-drug RT with the Ser-Gly insertion mutation, respectively. First, the post-drug RT displayed elevated strand transfer activity, compared to the pre-drug RT, with two different RNA templates. Second, the post-drug RT exhibited less RNA template degradation than the pre-drug RT, but higher polymerization-dependent RNase H activity. Third, the post-drug RT had a faster association rate for template binding (kon) and lower equilibrium binding constant KD to template, leading to the tighter template binding affinity than the pre-drug RT. The koff rates for pre-drug RT and post-drug RTs were similar. Finally, the removal of the dipeptide insertion from the post-drug RT abolished the elevated strand transfer activity and RNase H activity in addition to the loss of AZT resistance. These biochemical data suggests that the dipeptide insertion mutation elevates strand transfer activity by increasing the interaction of the RT with RNA donor template, promoting cleavage that generates more invasion site for the acceptor template during DNA synthesis. PMID:22100453

  12. The construction and evaluation of SIV/HIV chimeras that express the envelope of European HIV type 1 isolates.

    PubMed

    Ranjbar, S; Jones, S; Stott, E J; Almond, N

    1997-06-10

    The molecular construction of SIV/HIV-1 chimeric viruses (or SHIVs), provides a means of infecting macaques with immunodeficiency viruses that express the envelope protein of HIV-1. However, to date, most SHIVs produced express the envelope of isolates of HIV-1 that have been passaged repeatedly in T cell lines. We have taken SHIV-4 and replaced an NheI-AvrII fragment that encompasses the gp120 region and the extracellular portion of gp41 with the equivalent region of two European isolates of HIV-1 (ACH320.3.1 and HIV-1Han-2). Neither of these viruses had been passaged in T cell lines for prolonged periods prior to molecular cloning. Virus stocks were prepared of both SHIV constructs. In vitro, the relative ability of each clone to replicate in four T cell lines mirrored closely the pattern observed with the parental virus donating the envelope sequences. In vivo, only one of the chimeric viruses was infectious in cynomolgus macaques and its recovery was transient. The factors that affect the replication of SHIVs in vitro and in vivo are discussed. PMID:9171224

  13. Clinical Management of HIV Drug Resistance

    PubMed Central

    Cortez, Karoll J.; Maldarelli, Frank

    2011-01-01

    Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

  14. Phylogenetic Analysis of Near Full-Length HIV Type 1 Genomic Sequences from 21 Korean Individuals

    PubMed Central

    Kim, Jung-Eun; Foley, Brian T.

    2013-01-01

    Abstract The Korean subclade of subtype B (KSB) is the most prevalent HIV-1 strain found in Korea. To date, only two near full-length HIV-1 sequences from Korean patients have been reported. Here, we analyzed a total of 24 near full-length genomes of HIV-1 strains that were isolated from 17 antiretroviral therapy (ART)-naive patients and four ART-exposed patients. Proviral DNA from peripheral blood mononuclear cells was PCR amplified and directly sequenced. Phylogenetic analyses were used to classify viruses from 19 patients as KSB, from one patient as subtype B, from one patient as subtype D, and three viruses from one patient as CRF02_AG. All KSB viruses demonstrated TAAAA instead of TATAA at the TATA box in the LTR. Of the 19 KSB patients, their sequence identities at the nucleotide level ranged from 89.8% to 97.1% from the lowest env gene to the highest pol gene. Other than the CRF02_AG viruses, no recombination events were noted in any of the 19 KSB patients, which is consistent with our previous studies on the pol, vif, and nef genes. Except for one strain, all of the strains were classified as non-syncytium-inducing strains. This is the first report to describe near full-length KSB. PMID:23199052

  15. Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network.

    PubMed

    Holland, C A; Ellenberg, J H; Wilson, C M; Douglas, S D; Futterman, D C; Kingsley, L A; Moscicki, A B

    2000-07-01

    The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network was designed as a study of an adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal of the analysis presented was to examine the relationship of CD4+ T cell counts and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+ subjects who were 13 to 19 years of age were measured at the clinical sites, using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were determined by the NASBA/NucliSens assay at a central laboratory. Past and current treatment with antiretroviral drugs was determined by medical record abstraction and interview data. The slope of the line generated by regressing log10 HIV-1 RNA (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral drug naive was negative and significantly different than zero. A negative association has also been reported for antiretroviral drug-naive, adult males in the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.: Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1 RNA concentrations are correlated with corresponding absolute CD4+ T cell count. The slopes of the lines generated with data from each cohort were different (p = 0.003). In addition to age, there are sex and racial differences in the makeup of the two cohorts. Any or all of these differences may affect the slopes of the lines. PMID:10890357

  16. [Anti-HIV drugs and drug delivery system].

    PubMed

    Obaru, K; Mitsuya, H

    1998-03-01

    A number of candidate drugs for therapy of HIV-1 infection which show significant activity against the virus in vitro were reported; however, many of them have been dropped from drug development due to (i) insufficient intracellular activation in certain human target cells (particularly in case of nucleoside reverse transcriptase inhibitors), (ii) poor pharmacokinetic profiles, or (iii) intolerable in vitro and/or in vivo toxicities. To circumvent some of these problems, certain drug delivery systems have been applied and several candidate drugs including two novel nucleoside reverse transcriptase inhibitors, abacavir and adefovir, have acquired favorable properties in the clinical setting. This paper reviews several avenues for developing prodrugs of anti-HIV-1 agents to overcome their inherent limitations. PMID:9549371

  17. Adhesion and fusion efficiencies of human immunodeficiency virus type 1 (HIV-1) surface proteins

    NASA Astrophysics Data System (ADS)

    Dobrowsky, Terrence M.; Rabi, S. Alireza; Nedellec, Rebecca; Daniels, Brian R.; Mullins, James I.; Mosier, Donald E.; Siliciano, Robert F.; Wirtz, Denis

    2013-10-01

    In about half of patients infected with HIV-1 subtype B, viral populations shift from utilizing the transmembrane protein CCR5 to CXCR4, as well as or instead of CCR5, during late stage progression of the disease. How the relative adhesion efficiency and fusion competency of the viral Env proteins relate to infection during this transition is not well understood. Using a virus-cell fusion assay and live-cell single-molecule force spectroscopy, we compare the entry competency of viral clones to tensile strengths of the individual Env-receptor bonds of Env proteins obtained from a HIV-1 infected patient prior to and during coreceptor switching. The results suggest that the genetic determinants of viral entry were predominantly enriched in the C3, HR1 and CD regions rather than V3. Env proteins can better mediate entry into cells after coreceptor switch; this effective entry capacity does not correlate with the bond strengths between viral Env and cellular receptors.

  18. Nautilus: a bioinformatics package for the analysis of HIV type 1 targeted deep sequencing data.

    PubMed

    Kijak, Gustavo H; Pham, Phuc; Sanders-Buell, Eric; Harbolick, Elizabeth A; Eller, Leigh Anne; Robb, Merlin L; Michael, Nelson L; Kim, Jerome H; Tovanabutra, Sodsai

    2013-10-01

    The advent of next generation sequencing technologies is providing new insight into HIV-1 diversity and evolution, which has created the need for bioinformatics tools that could be applied to the characterization of viral quasispecies. Here we present Nautilus, a bioinformatics package for the analysis of HIV-1 targeted deep sequencing data. The DeepHaplo module determines the nucleotide base frequency and read depth at each position and computes the haplotype frequencies based on the linkage among polymorphisms in the same next generation sequence read. The Motifs module computes the frequency of the variants in the setting of their sequence context and mapping orientation, which allows for the validation of polymorphisms and haplotypes when strand bias is suspected. Both modules are accessed through a user-friendly GUI, which runs on Mac OS X (version 10.7.4 or later), and are based on Python, JAVA, and R scripts. Nautilus is available from www.hivresearch.org/research.php?ServiceID=5&SubServiceID=6 . PMID:23809062

  19. [CYTOKINES DURING THE HUMAN IMMUNODEFICIENCY VIRUS INFECTION TYPE 1(HIV-1)].

    PubMed

    Selimova, L M; Kalnina, L B; Serebrovskaya, L V; Ivanova, L A; Gulyaeva, A N; Nosik, D N

    2016-01-01

    In this work the proinflammatory (IL-1β, IFN-γ, TNF-α, IL-2) and anti-inflammatory (IL-4, IL-10) plasma cytokine levels were evaluated in HIV-infected patients with or without antiretroviral treatment (ART). IFN-γ was detected in 94% samples with and without ART, TNF-α in 88% and IL-2 in 38% samples without ART, as well as in 12% and 30% samples with ART, respectively. Positive correlation was detected between viral RNA and IFN-γ levels (rs = 0.13) and negative correlation (rs = -0.242) in the patients without or with ART. Cosecretion of three cytokines (IFN-γ, TNF-α, IL-2) was detected in 31% samples and two cytokines (IFN-γ, TNF-α) in 35% samples of persons without ART. Cosecretion of three cytokines (IFN-γ, TNF-α, IL-2) was detected in 20% samples with ART; cosecretion of IFN-γ and IL-2 was detected in 10% samples. The higher percentage of the proinflammatory cytokines with cosecretion was detected in plasma HIV-infected patients without ART in the course of 6 and more years, which suggests that their immune system is able to provide disease control. PMID:27145600

  20. HIV, drugs and the legal environment

    PubMed Central

    Strathdee, Steffanie A.; Beletsky, Leo; Kerr, Thomas

    2014-01-01

    A large body of scientific evidence indicates that policies based solely on law enforcement without taking into account public health and human rights considerations increase the health risks of people who inject drugs (PWIDs) and their communities. Although formal laws are an important component of the legal environment supporting harm reduction, it is the enforcement of the law that affects PWIDs' behavior and attitudes most acutely. This commentary focuses primarily on drug policies and policing practices that increase PWIDs' risk of acquiring HIV and viral hepatitis, and avenues for intervention. Policy and legal reforms that promote public health over the criminalization of drug use and PWID are urgently needed. This should include alternative regulatory frameworks for illicit drug possession and use. Changing legal norms and improving law enforcement responses to drug-related harms requires partnerships that are broader than the necessary bridges between criminal justice and public health sectors. HIV prevention efforts must partner with wider initiatives that seek to improve police professionalism, accountability, and transparency and boost the rule of law. Public health and criminal justice professionals can work synergistically to shift the legal environment away from one that exacerbates HIV risks to one that promotes safe and healthy communities. PMID:25265900

  1. Identifying representative drug resistant mutants of HIV

    PubMed Central

    2015-01-01

    Background Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. Results In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. Conclusion This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID:26678327

  2. Types of HIV/AIDS Antiretroviral Drugs

    MedlinePlus

    ... reverse transcriptase (RT) from converting single-stranded HIV RNA into double-stranded HIV DNA―a process called ... RT, interfering with its ability to convert HIV RNA into HIV DNA Integrase Inhibitors block the HIV ...

  3. V3 sequences and paired HIV isolates from 52 non-subtype B HIV type 1-infected patients.

    PubMed

    Monno, Laura; Brindicci, Gaetano; Saracino, Annalisa; Punzi, Grazia; Cibelli, Donatella; Lagioia, Antonella; Angarano, Gioacchino

    2010-03-01

    Viral isolation and V3 sequencing were performed for 52 patients with non-subtype B viruses. The HIV-1 isolation rate was 93%, and 98% of isolates were characterized as NSI. V3 sequences corresponding to NSI isolates were compared to non-subtype B sequences with corresponding SI isolates from the Los Alamos database. The two sequence groups significantly differed in number of sequences with 35 amino acids, net charge, Brigg's coefficient, loss of NGS at positions 6-8, and 11/25 genotype (p < 0.0001). Substantial discrepancies in V3 variability were also observed. Basic amino acids at positions 8, 21, 23, and 24 were more frequent in SI sequences as were uncharged amino acids at positions 5, 6, 7, 8, 12, 13, 25, and 34. When characterizing paired viral isolates and V3 sequences from patients with non-subtype B HIV-1, current V3 sequence-based criteria from subtype B appeared to discriminate well between NSI and SI sequences from non-subtype B patients. PMID:20334572

  4. Systematic identification of synergistic drug pairs targeting HIV.

    PubMed

    Tan, Xu; Hu, Long; Luquette, Lovelace J; Gao, Geng; Liu, Yifang; Qu, Hongjing; Xi, Ruibin; Lu, Zhi John; Park, Peter J; Elledge, Stephen J

    2012-11-01

    The systematic identification of effective drug combinations has been hindered by the unavailability of methods that can explore the large combinatorial search space of drug interactions. Here we present multiplex screening for interacting compounds (MuSIC), which expedites the comprehensive assessment of pairwise compound interactions. We examined ∼500,000 drug pairs from 1,000 US Food and Drug Administration (FDA)-approved or clinically tested drugs and identified drugs that synergize to inhibit HIV replication. Our analysis reveals an enrichment of anti-inflammatory drugs in drug combinations that synergize against HIV. As inflammation accompanies HIV infection, these findings indicate that inhibiting inflammation could curb HIV propagation. Multiple drug pairs identified in this study, including various glucocorticoids and nitazoxanide (NTZ), synergize by targeting different steps in the HIV life cycle. MuSIC can be applied to a wide variety of disease-relevant screens to facilitate efficient identification of compound combinations. PMID:23064238

  5. HIV type 1 pol gene diversity and archived nevirapine resistance mutation in pregnant women in Rwanda.

    PubMed

    Servais, Jean; Lambert, Christine; Karita, Etienne; Vanhove, Dirk; Fischer, Aurelie; Baurith, Therese; Schmit, Jean-Claude; Schneider, François; Hemmer, Robert; Arendt, Vic

    2004-03-01

    This study aimed to find out whether genetic polymorphisms were present in positions potentially affecting susceptibility to antiretrovirals in non-B subtypes from HIV-1-infected patients in Rwanda. Viral pol gene diversity was investigated by direct sequencing in 43 treatment-naive women. In addition, 10 DNA sequences from uncultured peripheral blood mononuclear cells were analyzed 6 weeks after a single dose of nevirapine (prevention of mother-to-child transmission program). Phylogenetic analyses have shown 34 subtype A1, 6 subtype C, and 2 subtype D strains. In addition, an A/C recombinant between the protease (PR) (subtype A1) and the reverse transcriptase (RT) (subtype C) was identified. In the PR coding region, high numbers of polymorphisms were found, including substitutions in secondary PR resistance sites. PR 35D, 36I, and 37N were always present within subtype A as were PR 93L in subtype C strains. PR 10I/V, 20R, 33F, and 77V were found in subtype A whereas PR 36I was highly prevalent in subtype C strains. The A/C recombinant displayed substitutions related to resistance (PR 10, 33, 36 and RT 118). One nevirapine resistance mutation (RT 181Y/C) was found in proviral DNA after 6 weeks. In conclusion, subtypes A and C are predominant in this cohort in Rwanda. Substitutions similar to secondary protease inhibitor resistance mutations are common before treatment whereas major resistance mutation may be archived after a single dose of nevirapine. Accordingly, the hypothesis of a genetic background effect in non-B strains has to be further addressed in programs of introduction of antivirals in Africa. PMID:15117451

  6. Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus.

    PubMed

    de Ronde, A; van Dooren, M; van Der Hoek, L; Bouwhuis, D; de Rooij, E; van Gemen, B; de Boer, R; Goudsmit, J

    2001-01-01

    Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT). Follow-up of the fate of these resistant HIV-1 strains in four newly infected individuals revealed that they were readily replaced by sensitive strains. The RT of the resistant viruses changed at amino acid 215 from tyrosine (Y) to aspartic acid (D) or serine (S), with asparagine (N) as a transient intermediate, indicating the establishment of new wild types. When we introduced these mutations and the original threonine (T)-containing wild type into infectious molecular clones and assessed their competitive advantage in vitro, the order of fitness was in accord with the in vivo observations: 215Y < 215D = 215S = 215T. As detected by real-time nucleic acid sequence-based amplification with two molecular beacons, the addition of AZT or stavudine (d4T) to the viral cultures favored the 215Y mutant in a dose-dependent manner. Our results illustrate that infection with nucleoside analogue-resistant HIV leads in newly infected individuals to mutants that are sensitive to nucleoside analogues, but only a single mutation removed from drug-resistant HIV. Such mutants were shown to be transmissible, stable, and prone to rapid selection for resistance to AZT or d4T as soon as antiretroviral therapy was administered. Monitoring of patients for the presence of new HIV-1 wild types with D, S, or N residues at position 215 may be warranted in order to estimate the threat to long-term efficacy of regimens including nucleoside analogues. PMID:11134272

  7. [Clinical efficacy and tolerance of enfuvirtide (Fuzeon), new antiretroviral inhibitors of intracellular penetration of human immunodeficiency virus (HIV) type 1].

    PubMed

    Raffi, François

    2004-09-01

    The TORO 1 and TORO 2 clinical trials compared the efficacy and safety of enfuvirtide in combination with an optimized background antiretroviral regimen and optimized background regimen alone in HIV-1 infected patients. The patients had had previous treatment with each of the three classes of antiretroviral drugs and had a plasma level of HIV-1 RNA above 5000 copies/ml at baseline. They were randomly assigned in a 2:1 ratio to receive either enfuvirtide (90 mg subcutaneously twice daily) plus a background regimen optimized with the aid of resistance testing, or an optimized antiretroviral regimen alone (control group). Six hundred and sixty-one patients were enrolled in the enfuvirtide arm and 334 in the control group. The median baseline plasma HIV-1 RNA level was 5.2 log10 copies/ml in the enfuvirtide group and 5.1 log10 copies/ml in the control group. Patients had a median of 7 years of previous antiretroviral treatment. The optimized background regimen comprised a mean of 4 antiretroviral drugs in both groups. At week 48, the mean reduction in viral load was -1.48 log10 copies/ml in the enfuvirtide group, and -0.63 log10 copies/ml in the control group (difference = 0.846 log10 copies/ml, IC95%: -1.066; -0.626. p < 0.0001). The mean increase in the CD4+ cell count was significantly greater in the enfuvirtide group (91 cells/mm3) than in the control group (45 cells/mm3). Injection site reactions were the main reported adverse event which occurred in 98% of the enfuvirtide patients. Most had mild to moderate pain or discomfort not requiring analgesic or limiting usual activities. PMID:15742550

  8. Drugs from the sea: a marine sponge-derived compound prevents Type 1 diabetes.

    PubMed

    Van Kaer, L

    2001-11-01

    More than one million Americans have Type 1 diabetes. This disease--also known as autoimmune or juvenile diabetes--strikes children suddenly, makes them dependent on insulin injections for life, and carries the constant threat of devastating complications. While it can and does strike adults, nearly half of all new cases are diagnosed in children. A child is diagnosed with Type 1 diabetes every hour. Type 1 diabetes is caused by the inability of a person"s pancreas to produce sufficient amounts of insulin to control their blood sugar levels and sustain life. While insulin injections allow affected individuals to control their blood sugar and stay alive, it is not a cure nor does it prevent the devastating complications of this disease, which include kidney failure, blindness, amputations, heart attack, and stroke. In Type 1 diabetes, the body"s own immune system goes awry, attacking and destroying insulin-producing cells in the pancreas. PMID:12805764

  9. Current Perspectives on HIV-1 Antiretroviral Drug Resistance

    PubMed Central

    Iyidogan, Pinar; Anderson, Karen S.

    2014-01-01

    Current advancements in antiretroviral therapy (ART) have turned HIV-1 infection into a chronic and manageable disease. However, treatment is only effective until HIV-1 develops resistance against the administered drugs. The most recent antiretroviral drugs have become superior at delaying the evolution of acquired drug resistance. In this review, the viral fitness and its correlation to HIV-1 mutation rates and drug resistance are discussed while emphasizing the concept of lethal mutagenesis as an alternative therapy. The development of resistance to the different classes of approved drugs and the importance of monitoring antiretroviral drug resistance are also summarized briefly. PMID:25341668

  10. Genetic variation in the CCL18-CCL3-CCL4 chemokine gene cluster influences HIV Type 1 transmission and AIDS disease progression.

    PubMed

    Modi, William S; Lautenberger, James; An, Ping; Scott, Kevin; Goedert, James J; Kirk, Gregory D; Buchbinder, Susan; Phair, John; Donfield, Sharyne; O'Brien, Stephen J; Winkler, Cheryl

    2006-07-01

    CCL3 (MIP-1 alpha), CCL4 (MIP-1 beta), and CCL18 (DC-CK1/PARC/AMAC-1) are potent chemoattractants produced by macrophages, natural killer cells, fibroblasts, mast cells, CD4(+) T cells, and CD8(+) T cells. CCL3 and CCL4 are natural ligands for the primary human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 and are also known to activate and enhance the cytotoxicity of natural killer cells. Genomic DNAs from >3,000 participants enrolled in five United States-based natural-history cohorts with acquired immunodeficiency syndrome (AIDS) were genotyped for 21 single-nucleotide polymorphisms (SNPs) in a 47-kb interval on chromosome 17q12 containing the genes CCL3, CCL4, and CCL18. All 21 SNPs were polymorphic in African Americans (AAs), whereas 7 of the 21 had minor-allele frequencies <0.01 in European Americans (EAs). Substantial linkage disequilibrium was observed in a 37-kb interval containing 17 SNPs where many pairwise D' values exceeded 0.70 in both racial groups, but particularly in EAs. Four and three haplotype blocks were observed in AAs and EAs, respectively. Blocks were strongly correlated with each other, and common haplotype diversity within blocks was limited. Two significant associations are reported that replicate an earlier study. First, among AA members of the AIDS Link to the Intravenous Experience cohort of injection drug users, frequencies of three correlated SNPs covering 2,231 bp in CCL3 were significantly elevated among highly exposed, persistently HIV-1-uninfected individuals compared with HIV-1-infected seroconvertors (P = .02-.03). Second, seven highly correlated SNPs spanning 36 kb and containing all three genes were significantly associated with more-rapid disease progression among EAs enrolled in the Multicenter AIDS Cohort Study cohort (P = .01-.02). These results reiterate the importance of chemokine gene variation in HIV-1/AIDS pathogenesis and emphasize that localized linkage disequilibrium makes the identification of causal

  11. Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity.

    PubMed Central

    Rosé, J R; Babé, L M; Craik, C S

    1995-01-01

    The human immunodeficiency virus type 1 (HIV-1) protease is the enzyme required for processing of the Gag and Gag-Pol polyproteins to yield mature, infectious virions. Although the complete absence of proteolytic activity prevents maturation, the level of activity sufficient for maturation and subsequent infectivity has not been determined. Amino acid substitutions that reduce catalytic activity without affecting substrate recognition have been engineered into the active site of the HIV-1 protease. The catalytic efficiency (kcat) of the HIV-1 protease is decreased 4-fold when threonine 26 is replaced by serine (T26S) and approximately 50-fold when alanine 28 is replaced by serine (A28S). Genes containing these mutations were cloned into a proviral vector for analysis of their effects on virion maturation and infectivity. The results show that virions containing the T26S protease variant, in which only 25% of the protease is active, are very similar to wild-type virions, although slight reductions in infectivity are observed. Virions containing the A28S protease variant are not infectious, even though a limited amount of polyprotein processing does occur. There appears to be a linear correlation between the level of protease activity and particle infectivity. Our observations suggest that a threshold of protease activity exists between a 4-fold and 50-fold reduction, below which processing is insufficient to yield infectious particles. Our data also suggest that a reduction of protease activity by 50-fold or greater is sufficient to prevent the formation of infectious particles. PMID:7535864

  12. HIV-1 Drug Resistance Mutations Among Antiretroviral-Naïve HIV-1–Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study

    PubMed Central

    Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Kantipong, Pacharee; Lee, Christopher K. C.; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G.; Phanuphak, Praphan

    2011-01-01

    (See editorial commentary by Jordan on pages 1058–1060.) Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. PMID:21460324

  13. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care. PMID:27092564

  14. HIV-1 drug discovery: targeting folded RNA structures with branched peptides.

    PubMed

    Wynn, Jessica E; Santos, Webster L

    2015-06-01

    Human immunodeficiency virus type 1 (HIV-1) is an RNA virus that is prone to high rates of mutation. While the disease is managed with current antiretroviral therapies, drugs with a new mode of action are needed. A strategy towards this goal is aimed at targeting the native three-dimensional fold of conserved RNA structures. This perspective highlights medium-sized peptides and peptidomimetics used to target two conserved RNA structures of HIV-1. In particular, branched peptides have the capacity to bind in a multivalent fashion, utilizing a large surface area to achieve the necessary affinity and selectivity toward the target RNA. PMID:25958855

  15. HIV-1 Drug Discovery: Targeting Folded RNA Structures With Branched Peptides

    PubMed Central

    Wynn, Jessica E.

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) is an RNA virus that is prone to high rates of mutation. While the disease is managed with current antiretroviral therapies, drugs with a new mode of action are needed. A strategy towards this goal is aimed at targeting the native three-dimensional fold of conserved RNA structures. This perspective highlights medium-sized peptides and peptidomimetics used to target two conserved RNA structures of HIV-1. In particular, branched peptides have the capacity to bind in a multivalent fashion, utilizing a large surface area to achieve the necessary affinity and selectivity toward the target RNA. PMID:25958855

  16. HLA Class I and KIR Genes Do Not Protect Against HIV Type 1 Infection in Highly Exposed Uninfected Individuals With Hemophilia A

    PubMed Central

    Vince, Nicolas; Bashirova, Arman A.; Lied, Alexandra; Gao, Xiaojiang; Dorrell, Lucy; McLaren, Paul J.; Fellay, Jacques; Carrington, Mary

    2014-01-01

    A recent genome-wide association study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with human immunodeficiency virus type 1 (HIV-1) did not reveal genetic variants associated with resistance to HIV-1 infection, beyond homozygosity for CCR5-Δ32. Since variation in HLA class I and KIR genes is not well interrogated by standard GWAS techniques, we tested whether these 2 loci were involved in protection from HIV-1 infection in the same hemophilia cohort, using controls from the general population. Our data indicate that HLA class I alleles, presence or absence of KIR genes, and functionally relevant combinations of the HLA/KIR genotypes are not involved in resistance to parenterally transmitted HIV-1 infection. PMID:24719475

  17. Association of cervical biopsy with HIV type 1 genital shedding among women on highly active antiretroviral therapy.

    PubMed

    Woo, Victoria G; Liegler, Teri; Cohen, Craig R; Sawaya, George F; Smith-McCune, Karen; Bukusi, Elizabeth A; Huchko, Megan J

    2013-07-01

    HIV-1 genital shedding is associated with increased HIV-1 transmission risk. Inflammation and ulceration are associated with increased shedding, while highly active antiretroviral therapy (HAART) has been shown to have a protective effect. We sought to examine the impact of cervical biopsies, a routine component of cervical cancer screening, on HIV-1 genital RNA levels in HIV-infected women on HAART. We enrolled HIV-1-infected women undergoing cervical biopsy for diagnosis of cervical intraepithelial neoplasia (CIN) 2/3 in this prospective cohort study. All were stable on HAART for at least 3 months. Clinical and demographic information as well as plasma HIV-1 viral load were collected at the baseline visit. Specimens for cervical HIV-1 RNA were collected immediately prior to biopsy, and 2 and 7 days afterward. Quantitative PCR determined HIV-1 concentration in cervical specimens at each time point to a lower limit of detection of 40 copies/specimen. Among the 30 participants, five (16.6%) women had detectable cervical HIV-1 RNA at baseline, of whom four (80%) had detectable HIV-1 RNA after cervical biopsy, with no significant increase in viral load in the follow-up specimens. Only one woman (3.3%) with undetectable baseline cervical HIV-1 RNA had detection postbiopsy. Detectable plasma HIV-1 RNA was the only factor associated with baseline cervical HIV-1 RNA. In women on HAART, an increase in cervical HIV-1 RNA detection or concentration was not associated with cervical biopsy. These findings help provide safety data regarding cervical cancer screening and diagnosis in HIV-infected women and inform postprocedure counseling. PMID:23594240

  18. Clinical Care of the HIV-Infected Drug User

    PubMed Central

    Bruce, R. Douglas; Altice, Frederick L.

    2007-01-01

    HIV/AIDS and chemical dependency, both of which are complicated by and intertwined with mental illness, are complex, overlapping spheres that adversely influence each other and the overall clinical outcomes of the affected individual [1]. Each disorder individually impacts tens of millions of people, with explosive epidemics described worldwide. Drug users have increased age matched morbidity and mortality for a number of medical and psychiatric conditions. HIV/AIDS, with its immunosuppressed states and direct virologic effects, exacerbate morbidity and mortality further among HIV-infected drug users. This article addresses the adverse consequences of HIV/AIDS, drug injection, the secondary comorbidities of both, and the impact of immunosuppression on presentation of disease as well as approaches to managing the HIV-infected drug user. PMID:17502234

  19. Drug Abuse, HIV, and HCV in Asian Countries.

    PubMed

    Hser, Yih-Ing; Liang, Di; Lan, Yu-Ching; Vicknasingam, Balasingam Kasinather; Chakrabarti, Amit

    2016-09-01

    Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections. PMID:27000123

  20. Analysis of HIV Type 1 gp41 and Enfuvirtide Susceptibility among Men in the United States Who Were HIV Infected Prior to Availability of HIV Entry Inhibitors

    PubMed Central

    Hudelson, Sarah E.; Marlowe, Natalia; Huang, Wei; Bruce, Robert; Church, Jessica D.; Husnik, Marla; Donnell, Deborah; Coates, Thomas; Jackson, J. Brooks; Chesney, Margaret; Koblin, Beryl

    2009-01-01

    Abstract We analyzed HIV gp41 from 195 men in the United States who were HIV-1 infected between 1999 and 2002, before enfuvirtide (ENF) was approved for clinical use in the United States. gp41 genotyping results were obtained for 175 samples. None of the samples had major ENF resistance mutations. Six (3.4%) samples had minor ENF resistance mutations in the HR1 region (V38G, N43K, L44M, L45M). Twenty-eight (16%) samples had the N42S polymorphism, which is associated with ENF hypersusceptibility. Accessory mutations in the HR2 region were identified in some samples (E137K, S138A). Five of the six samples with HR1 resistance mutations were analyzed with a phenotypic assay; one sample had reduced ENF susceptibility (a sample with N42S + L44M + E137K). Prior to the availability of ENF, some men in the United States were infected with HIV that contained mutations associated with ENF resistance or hypersusceptibility. However, most of the mutations were not associated with phenotypic ENF resistance. PMID:19552592

  1. International epidemiology of HIV and AIDS among injecting drug users.

    PubMed

    Des Jarlais, D C; Friedman, S R; Choopanya, K; Vanichseni, S; Ward, T P

    1992-10-01

    HIV/AIDS and iv drug use (IVDU) are of significant multinational scope and growing. Supporting increased IVDU in many countries are countries' geographical proximity to illicit drug trafficking distribution routes, law enforcement efforts which increase the demand for more efficient drug distribution and consumption, and countries' infrastructural and social modernization. Given the failures of intensified law enforcement efforts to thwart the use and proliferation of illegal drugs, countries with substantial IVDU should look away from preventing use to preventing HIV transmission within drug user populations. With HIV seroprevalence rates rapidly reaching 40-50% in some developing country IVDU groups, a variety of prevention programs is warranted. Such programs should be supported and implemented while prevention remains feasible. This paper examines the variation in HIV seroprevalence among IVD users, rapid HIV spread among users, HIV among IVDUs in Bangkok, emerging issues in HIV transmission among IVDUs, non-AIDS manifestations of HIV infection among IVDUs, prevention programs and effectiveness, and harm reduction. PMID:1466837

  2. Safety and Pharmacokinetics of Amprenavir (141W94), a Human Immunodeficiency Virus (HIV) Type 1 Protease Inhibitor, following Oral Administration of Single Doses to HIV-Infected Adults

    PubMed Central

    Sadler, Brian M.; Hanson, Cynthia D.; Chittick, Gregory E.; Symonds, William T.; Roskell, Neil S.

    1999-01-01

    We conducted a double-blind, placebo-controlled, parallel, dose-escalation trial to evaluate the pharmacokinetics and safety of single, oral doses of amprenavir (141W94; formerly VX-478), a potent inhibitor of human immunodeficiency virus (HIV) type 1 protease, administered as hard gelatin capsules in 12 HIV-infected subjects. The doses of amprenavir evaluated were 150, 300, 600, 900, and 1,200 mg. Amprenavir was rapidly absorbed, with the time to maximum concentration occurring within 1 to 2 h after dosing. On the basis of power model analysis, the increase in the maximum concentration of amprenavir in plasma (Cmax) was less than dose proportional, and the increase in the area under the concentration-time curve from time zero to infinity (AUC0–∞) was greater than dose proportional; mean slopes (with 90% confidence intervals) were 1.25 (1.16 to 1.35) and 0.78 (0.78 to 0.86) for AUC0–∞ and Cmax, respectively. Amprenavir was eliminated slowly, with a terminal-phase half-life of 8 h. A second study was conducted to determine the bioavailability of the hard gelatin capsule relative to that of a subsequently developed soft gelatin capsule. The capsules were bioequivalent in terms of AUC0–∞ but not in terms of Cmax; geometric-least-squares means ratios (with 90% confidence intervals) were 1.03 (0.92 to 1.14) and 1.25 (1.03 to 1.53) for AUC0–∞ and Cmax, respectively. Administration of soft gelatin capsules of amprenavir with a high-fat breakfast resulted in a 14% decrease in the mean AUC0–∞ (from 9.58 to 8.26 μg · h/ml), which is not likely to be clinically significant. The most common adverse events related to amprenavir were headache, nausea, and hypesthesia. Amprenavir appears to be safe and well tolerated over the dose range of 150 to 1200 mg. On the basis of the present single-dose studies, amprenavir is an HIV protease inhibitor with favorable absorption and clearance pharmacokinetics that are only minimally affected by administration with food

  3. Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A.

    PubMed Central

    Aiken, C

    1997-01-01

    Human immunodeficiency virus type 1 (HIV-1) normally enters cells by direct fusion with the plasma membrane. In this report, HIV-1 particles capable of infecting cells through an endocytic pathway are described. Chimeric viruses composed of the HIV-1 core and the envelope glycoprotein of vesicular stomatitis virus (VSV-G) were constructed and are herein termed HIV-1(VSV) pseudotypes. HIV-1(VSV) pseudotypes were 20- to 130-fold more infectious than nonpseudotyped HIV-1. Infection by HIV-1(VSV) pseudotypes was markedly diminished by ammonium chloride and concanamycin A, a selective inhibitor of vacuolar H+ ATPases, demonstrating that these viruses require endosomal acidification to achieve productive infection. HIV-1 is thus capable of performing all of the viral functions necessary for infection when entry is targeted to an endocytic route. Maximal HIV-1 infectivity requires the presence of the viral Nef protein and the cellular protein cyclophilin A (CyPA) during virus assembly. Pseudotyping by VSV-G markedly suppressed the requirement for Nef. HIV-1(VSV) particles were also resistant to inhibition by cyclosporin A; however, the deleterious effect of a gag mutation inhibiting CyPA incorporation was not relieved by VSV-G. These results suggest that Nef acts at a step of the HIV-1 life cycle that is either circumvented or facilitated by targeting virus entry to an endocytic pathway. The findings also support the hypothesis that Nef and CyPA enhance HIV-1 infectivity through independent processes and demonstrate a mechanistic difference between reduction of HIV-1 infectivity by cyclosporin A and gag mutations that decrease HIV-1 incorporation of CyPA. PMID:9223476

  4. [Experiences from two HIV prevention projects among drug abusers in Oslo. Is methadone maintenance treatment useful?].

    PubMed

    Skogstad, M

    1990-06-10

    Experience from two HIV-preventive projects among drug abusers in Oslo, Norway, shows that HIV-positive drug abusers carry on their drug abuse independent of visits to residential drug-free treatment or prison. HIV-positive former drug abusers show a tendency to relapse to drug abuse. In terms of HIV-prevention among drug abusers it is important to reduce injection of drugs among HIV-positive drug abusers. Thus, methadone maintenance programmes should be considered in HIV-prevention in Norway. PMID:2363170

  5. Toxins that are activated by HIV type-1 protease through removal of a signal for degradation by the N-end-rule pathway.

    PubMed Central

    Falnes, P O; Welker, R; Kräusslich, H G; Olsnes, S

    1999-01-01

    Diphtheria toxin enters the cytosol of mammalian cells where it inhibits cellular protein synthesis, leading to cell death. Recently we found that the addition of a signal for N-end-rule-mediated protein degradation to diphtheria toxin substantially reduced its intracellular stability and toxicity. These results prompted us to construct a toxin containing a degradation signal that is removable through the action of a viral protease. In principle, such a toxin would be preferentially stabilized, and thus activated, in cells expressing the viral protease in the cytosol, i.e. virus-infected cells, thereby providing a specific eradication of these cells. In the present work we describe the construction of toxins that contain a signal for N-end-rule-mediated degradation just upstream of a cleavage site for the protease from HIV type 1 (HIV-1 PR). We show that the toxins are cleaved by HIV-1 PR exclusively at the introduced sites, and thereby are converted from unstable to stable proteins. Furthermore, this cleavage substantially increased the ability of the toxins to inhibit cellular protein synthesis. However, the toxins were unable to selectively eradicate HIV-1-infected cells, apparently due to low cytosolic HIV-1 PR activity, since we could not detect cleavage of the toxins by HIV-1 PR in infected cells. Alternative strategies for the construction of toxins that can specifically be activated by viral proteases are discussed. PMID:10493930

  6. Human Immunodeficiency Virus Type 1 (HIV-1) Induces the Cytoplasmic Retention of Heterogeneous Nuclear Ribonucleoprotein A1 by Disrupting Nuclear Import

    PubMed Central

    Monette, Anne; Ajamian, Lara; López-Lastra, Marcelo; Mouland, Andrew J.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) co-opts host proteins and cellular machineries to its advantage at every step of the replication cycle. Here we show that HIV-1 enhances heterogeneous nuclear ribonucleoprotein (hnRNP) A1 expression and promotes the relocalization of hnRNP A1 to the cytoplasm. The latter was dependent on the nuclear export of the unspliced viral genomic RNA (vRNA) and to alterations in the abundance and localization of the FG-repeat nuclear pore glycoprotein p62. hnRNP A1 and vRNA remain colocalized in the cytoplasm supporting a post-nuclear function during the late stages of HIV-1 replication. Consistently, we show that hnRNP A1 acts as an internal ribosomal entry site trans-acting factor up-regulating internal ribosome entry site-mediated translation initiation of the HIV-1 vRNA. The up-regulation and cytoplasmic retention of hnRNP A1 by HIV-1 would ensure abundant expression of viral structural proteins in cells infected with HIV-1. PMID:19737937

  7. A novel corneal explant model system to evaluate antiviral drugs against feline herpesvirus type 1 (FHV-1).

    PubMed

    Pennington, Matthew R; Fort, Michael W; Ledbetter, Eric C; Van de Walle, Gerlinde R

    2016-06-01

    Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats. PMID:26959283

  8. Undiagnosed HIV among people who inject drugs in Manipur, India.

    PubMed

    Armstrong, Gregory; Medhi, Gajendra K; Mahanta, Jagadish; Paranjape, R S; Kermode, Michelle

    2015-01-01

    Manipur is a geographically isolated state of India characterised by a high HIV prevalence among people who inject drugs (PWID). A low-to-moderate lifetime rate of HIV testing has been documented amongst PWID in Manipur. Little is known about the extent of undiagnosed HIV in this setting and whether uptake of HIV testing (and knowledge of a positive diagnosis) leads HIV-positive PWID to change their risk behaviours. The cross-sectional data (n = 821) analysed for this paper were collected in 2009 for the Integrated Behavioural and Biological Assessment (IBBA) using interviewer-administered questionnaires and the collection of de-linked blood and urine samples. Almost one-third (30.7%) of the participants tested HIV positive. The majority knew where to obtain a confidential HIV test (80.7%), however, half of the HIV-positive participants had either never had an HIV test (37.7%), or had undertaken a test without collecting the result (12.7%). Almost one-quarter (23.4%) of the HIV-positive participants and 17.4% of the HIV-negative participants had shared a needle/syringe with at least one other injector during the preceding month. Encouragingly, HIV-positive participants were significantly more likely than HIV-negative participants to use condoms with their regular sexual partners, however, there was still a high proportion of HIV-positive participants who did not use a condom at last sex with their regular (47.2%) or casual (48.0%) partners. Having taken an HIV test and collected the result was associated with a reduction in HIV-risk behaviours among HIV-positive participants, but not among HIV-negative participants. In conclusion, we found that a substantial proportion of the HIV-positive PWID in Manipur were not aware of their positive status, and risky injecting and sexual practices were commonplace. However, HIV-positive PWID appear to reduce their high-risk behaviours when they become aware of their HIV status highlighting the importance of taking HIV testing

  9. The Roles of HIV-1 Proteins and Antiretroviral Drug Therapy in HIV-1-Associated Endothelial Dysfunction

    PubMed Central

    Kline, Erik R.; Sutliff, Roy L.

    2008-01-01

    Since the emergence of highly active antiretroviral therapy (HAART), human immunodeficiency virus-1 (HIV-1)-infected patients have demonstrated dramatic decreases in viral burden and opportunistic infections, and an overall increase in life expectancy. Despite these positive HAART-associated outcomes, it has become increasingly clear that HIV-1 patients have an enhanced risk of developing cardiovascular disease over time. Clinical studies are instrumental in our understanding of vascular dysfunction in the context of HIV-1 infection. However, most clinical studies often do not distinguish whether HIV-1 proteins, HAART, or a combination of these 2 factors cause cardiovascular complications. This review seeks to address the roles of both HIV-1 proteins and antiretroviral drugs in the development of endothelial dysfunction because endothelial dysfunction is the hallmark initial step of many cardiovascular diseases. We analyze recent in vitro and in vivo studies examining endothelial toxicity in response to HIV-1 proteins or in response to the various classes of antiretroviral drugs. Furthermore, we discuss the multiple mechanisms by which HIV-1 proteins and HAART injure the vascular endothelium in HIV-1 patients. By understanding the molecular mechanisms of HIV-1 protein- and antiretroviral-induced cardiovascular disease, we may ultimately improve the quality of life of HIV-1 patients through better drug design and the discovery of new pharmacological targets. PMID:18525451

  10. Prevention of mother-to-child transmission of HIV type 1: the role of neonatal and infant prophylaxis.

    PubMed

    Hurst, Stacey A; Appelgren, Kristie E; Kourtis, Athena P

    2015-02-01

    The prevention of mother-to-child transmission (PMTCT) of HIV is one of the great public health successes of the past 20 years. Much concerted research efforts and dedicated work have led to the achievement of very low rates of PMTCT of HIV in settings that can implement optimal prophylaxis. Though several implementation challenges remain, global elimination of pediatric HIV infection seems now more than ever to be an attainable goal. Often overlooked, the role of prophylaxis of the newborn is nevertheless a very important component of PMTCT. In this paper, we focus on the role of neonatal and infant prophylaxis, discuss mechanisms of protection, and present the clinical trial-generated evidence that led to the current recommendations for preventing infections in breastfed and non-breastfed infants. PMTCT of HIV should not end at birth; a continuum of care extending postpartum and postnatally is required to minimize the risk of new pediatric HIV infections. PMID:25578882

  11. people who inject drugs, HIV risk, and HIV testing uptake in sub-Saharan Africa.

    PubMed

    Asher, Alice K; Hahn, Judith A; Couture, Marie-Claude; Maher, Kelsey; Page, Kimberly

    2013-01-01

    Dramatic rises in injection drug use (IDU) in sub-Saharan Africa account for increasingly more infections in a region already overwhelmed by the HIV epidemic. There is no known estimate of the number of people who inject drugs (PWID) in the region, or the associated HIV prevalence in PWID. We reviewed literature with the goal of describing high-risk practices and exposures in PWID in sub-Saharan Africa, as well as current HIV prevention activities aimed at drug use. The literature search looked for articles related to HIV risk, injection drug users, stigma, and HIV testing in sub-Saharan Africa. This review found evidence demonstrating high rates of HIV in IDU populations in sub-Saharan Africa, high-risk behaviors of the populations, lack of knowledge regarding HIV, and low HIV testing uptake. There is an urgent need for action to address IDU in order to maintain recent decreases in the spread of HIV in sub-Saharan Africa. PMID:23164598

  12. Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: Direct effect of Vpr on T cell activation and immune function

    SciTech Connect

    Venkatachari, Narasimhan J.; Majumder, Biswanath; Ayyavoo, Velpandi . E-mail: velpandi@pitt.edu

    2007-02-20

    Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal host cellular immune pathways thus exploiting the cellular machinery for replication, survival and to escape host immune attack. Here we evaluated the direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr specifically downregulated the expression of CD28 and increased the expression of CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR was observed. Interferon gamma (IFN-{gamma}) production in T cells was evaluated as a measure of the downstream effector functions. Results indicate that Vpr significantly inhibited IFN-{gamma} production and this may, in part, due to Vpr's ability to inhibit the nuclear translocation of NF-{kappa}B, and its transcriptional regulation. Together these results support that HIV-1 Vpr selectively dysregulates the immune functions at multiple levels and exerts its inhibitory effects in the presence of other viral proteins.

  13. Antihuman Immunodeficiency Virus Type 1 (HIV-1) Activity of Rare Earth Metal Complexes of 4-Hydroxycoumarins in Cell Culture

    PubMed Central

    Manolov, Ilia; Raleva, Sevda; Genova, Petya; Savov, Alexey; Froloshka, Liliana; Dundarova, Daniela; Argirova, Radka

    2006-01-01

    The cerium Ce(III), lanthanum La(III), and neodymium Nd(III) complexes with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one (warfarin) (W) and 3,3′-benzylidenebis[4-hydroxycoumarin] (1) were synthesized and studied for the first time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and chronic infection. The complexes were characterized by different physicochemical methods: mass spectrometry, 1H NMR, 13C NMR, and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligands. Anti-HIV effect of the complexes/ligands was measured in MT-2 cells by microtiter infection assay. Detection of endogenous reverse transcriptase (RT) activity and RT processivity by PCR indicative for proviral DNA synthesis demonstrated that anti-HIV activity has not been linked to early stages of viral replication. No effect on late steps of viral replication has been found using cells chronically producing HIV-1LAI virus. La(W) demonstrated anti-HIV activity (IC50=21.4 μM) close to maximal nontoxic concentration. Nd(W), Ce(1), and Nd(1) demonstrated limited anti-HIV potency, so none of the complexes seems appropriate to be used in clinic. Further targeting of HIV-1 inhibition by La(W) is under progress. PMID:17497016

  14. HIV Type 1 Infection Up-Regulates TLR2 and TLR4 Expression and Function in Vivo and in Vitro

    PubMed Central

    Hernández, Juan C.; Stevenson, Mario; Latz, Eicke

    2012-01-01

    Abstract Toll-like receptors (TLRs) play a critical role in innate immunity against pathogens. Their stimulation induces the activation of NF-κB, an important inducer of HIV-1 replication. In recent years, an increasing number of studies using several cells types from HIV-infected patients indicate that TLRs play a key role in regulating the expression of proinflammatory cytokines and viral pathogenesis. In the present study, the effect of HIV-1 stimulation of monocyte-derived macrophage (MDM) and peripheral blood mononuclear cell (PBMC) subpopulations from healthy donors on the expression and functions of TLR2 and TLR4 was examined. In addition, and to complete the in vitro study, the expression pattern of TLR2 and TLR4 in 49 HIV-1-infected patients, classified according to viral load and the use of HAART, was determined and compared with 25 healthy subjects. An increase of TLR expression and production of proinflammatory cytokines were observed in MDMs and PBMCs infected with HIV-1 in vitro and in response to TLR stimulation, compared to the mock. In addition, an association between TLR expression and up-regulation of CD80 in plasmacytoid dendritic cells (pDCs) was observed. The ex vivo analysis indicated increased expression of TLR2 and TLR4 in myeloid dendritic cells (mDCs), but only of TLR2 in monocytes obtained from HIV-1-infected patients, compared to healthy subjects. Remarkably, the expression was higher in cells from patients who do not use HAART. In monocytes, there was a positive correlation between both TLRs and viral load, but not CD4+ T cell numbers. Together, our in vitro and ex vivo results suggest that TLR expression and function can be up-regulated in response to HIV-1 infection and could affect the inflammatory response. We propose that modulation of TLRs represents a mechanism to promote HIV-1 replication or AIDS progression in HIV-1-infected patients. PMID:22280204

  15. Impact of Human Immunodeficiency Virus Type 1 (HIV-1) Genetic Diversity on Performance of Four Commercial Viral Load Assays: LCx HIV RNA Quantitative, AMPLICOR HIV-1 MONITOR v1.5, VERSANT HIV-1 RNA 3.0, and NucliSens HIV-1 QT

    PubMed Central

    Swanson, Priscilla; de Mendoza, Carmen; Joshi, Yagnya; Golden, Alan; Hodinka, Richard L.; Soriano, Vincent; Devare, Sushil G.; Hackett, John

    2005-01-01

    Human immunodeficiency virus type 1 (HIV-1) evolution and changing strain distribution present a challenge to nucleic acid-based assays. Reliable patient monitoring of viral loads requires the detection and accurate quantification of genetically diverse HIV-1. A panel of 97 HIV-1-seropositive plasma samples collected from Cameroon, Brazil, and South Africa was used to compare the performance of four commercially available HIV RNA quantitative tests: Abbott LCx HIV RNA Quantitative assay (LCx), Bayer Versant HIV-1 RNA 3.0 (bDNA), Roche AMPLICOR HIV-1 MONITOR v1.5 (Monitor v1.5), and bioMérieux NucliSens HIV-1 QT (NucliSens). The panel included group M, group O, and recombinant viruses based on sequence analysis of gag p24, pol integrase, and env gp41. The LCx HIV assay quantified viral RNA in 97 (100%) of the samples. In comparison, bDNA, Monitor v1.5, and NucliSens quantified viral RNA in 96.9%, 94.8%, and 88.6% of the samples, respectively. The two group O specimens were quantified only by the LCx HIV assay. Analysis of nucleotide mismatches at the primer/probe binding sites for Monitor v1.5, NucliSens, and LCx assays revealed that performance characteristics reflected differences in the level of genetic conservation within the target regions. PMID:16081923

  16. A cell-free enzymatic activity assay for the evaluation of HIV-1 drug resistance to protease inhibitors

    PubMed Central

    Matsunaga, Satoko; Masaoka, Takashi; Sawasaki, Tatsuya; Morishita, Ryo; Iwatani, Yasumasa; Tatsumi, Masashi; Endo, Yaeta; Yamamoto, Naoki; Sugiura, Wataru; Ryo, Akihide

    2015-01-01

    Due to their high frequency of genomic mutations, human retroviruses often develop resistance to antiretroviral drugs. The emergence of drug-resistant human immunodeficiency virus type 1 (HIV-1) is a significant obstacle to the effective long-term treatment of HIV infection. The development of a rapid and versatile drug-susceptibility assay would enable acquisition of phenotypic information and facilitate determination of the appropriate choice of antiretroviral agents. In this study, we developed a novel in vitro method, termed the Cell-free drug susceptibility assay (CFDSA), for monitoring phenotypic information regarding the drug resistance of HIV-1 protease (PR). The CFDSA utilizes a wheat germ cell-free protein production system to synthesize enzymatically active HIV-1 PRs directly from PCR products amplified from HIV-1 molecular clones or clinical isolates in a rapid one-step procedure. Enzymatic activity of PRs can be readily measured by AlphaScreen (Amplified Luminescent Proximity Homogeneous Assay Screen) in the presence or absence of clinically used protease inhibitors (PIs). CFDSA measurement of drug resistance was based on the fold resistance to the half-maximal inhibitory concentration (IC50) of various PIs. The CFDSA could serve as a non-infectious, rapid, accessible, and reliable alternative to infectious cell-based phenotypic assays for evaluation of PI-resistant HIV-1. PMID:26583013

  17. Identification of Personal Lubricants That Can Cause Rectal Epithelial Cell Damage and Enhance HIV Type 1 Replication in Vitro

    PubMed Central

    Begay, Othell; Jean-Pierre, Ninochka; Abraham, Ciby J.; Chudolij, Anne; Seidor, Samantha; Rodriguez, Aixa; Ford, Brian E.; Henderson, Marcus; Katz, David; Zydowsky, Thomas; Robbiani, Melissa

    2011-01-01

    Abstract Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity and osmolality of popular lubricants. A total of 41 lubricants were examined and compared to Gynol II and Carraguard as positive and negative controls for toxicity, respectively. Cytotoxicity was assessed using the XTT assay. The MAGI assay with R5 and X4 HIV-1 laboratory strains was used to evaluate antiviral activity. The effect of the lubricants on differentiated Caco-2 cell monolayers (transepithelial electrical resistance, TEER) was also measured. None of the lubricants tested showed significant activity against HIV-1. Surprisingly, four of them, Astroglide Liquid, Astroglide Warming Liquid, Astroglide Glycerin & Paraben-Free Liquid, and Astroglide Silken Secret, significantly enhanced HIV-1 replication (p<0.0001). A common ingredient in three of these preparations is polyquaternium-15. In vitro testing of a chemically related compound (MADQUAT) confirmed that this similarly augmented HIV-1 replication. Most of the lubricants were found to be hyperosmolar and the TEER value dropped approximately 60% 2 h after exposure to all lubricants tested. Cells treated with Carraguard, saline, and cell controls maintained about 100% initial TEER value after 2–6 h. We have identified four lubricants that significantly increase HIV-1 replication in vitro. In addition, the epithelial damage caused by these and many other lubricants may have implications for enhancing HIV transmission in vivo. These data emphasize the importance of performing more rigorous safety testing on these products. PMID:21309617

  18. Identification of personal lubricants that can cause rectal epithelial cell damage and enhance HIV type 1 replication in vitro.

    PubMed

    Begay, Othell; Jean-Pierre, Ninochka; Abraham, Ciby J; Chudolij, Anne; Seidor, Samantha; Rodriguez, Aixa; Ford, Brian E; Henderson, Marcus; Katz, David; Zydowsky, Thomas; Robbiani, Melissa; Fernández-Romero, José A

    2011-09-01

    Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity and osmolality of popular lubricants. A total of 41 lubricants were examined and compared to Gynol II and Carraguard as positive and negative controls for toxicity, respectively. Cytotoxicity was assessed using the XTT assay. The MAGI assay with R5 and X4 HIV-1 laboratory strains was used to evaluate antiviral activity. The effect of the lubricants on differentiated Caco-2 cell monolayers (transepithelial electrical resistance, TEER) was also measured. None of the lubricants tested showed significant activity against HIV-1. Surprisingly, four of them, Astroglide Liquid, Astroglide Warming Liquid, Astroglide Glycerin & Paraben-Free Liquid, and Astroglide Silken Secret, significantly enhanced HIV-1 replication (p<0.0001). A common ingredient in three of these preparations is polyquaternium-15. In vitro testing of a chemically related compound (MADQUAT) confirmed that this similarly augmented HIV-1 replication. Most of the lubricants were found to be hyperosmolar and the TEER value dropped approximately 60% 2 h after exposure to all lubricants tested. Cells treated with Carraguard, saline, and cell controls maintained about 100% initial TEER value after 2-6 h. We have identified four lubricants that significantly increase HIV-1 replication in vitro. In addition, the epithelial damage caused by these and many other lubricants may have implications for enhancing HIV transmission in vivo. These data emphasize the importance of performing more rigorous safety testing on these products. PMID:21309617

  19. Evaluation of secular trends in CD4+ lymphocyte loss among human immunodeficiency virus type 1 (HIV-1)-infected men with known dates of seroconversion.

    PubMed

    O'Brien, T R; Hoover, D R; Rosenberg, P S; Chen, B; Detels, R; Kingsley, L A; Phair, J; Saah, A J

    1995-09-15

    The rate at which immunodeficiency develops in untreated human immunodeficiency virus type 1(HIV-1)-infected persons might be increasing or decreasing over time because of viral evolution or other factors. Beginning in 1984, Multicenter AIDS Cohort Study investigators recruited HIV-1-seronegative homosexual/bisexual men from four US metropolitan areas and examined them semiannually for HIV-1 seroconversion. To assess possible secular changes in the natural history of HIV-1 infection, the authors examined CD4+ lymphocyte data from 354 men who seroconverted between 1984 and 1991. To control for measurement differences among centers and over time, the authors adjusted CD4+ lymphocyte values to those of persistently seronegative participants. CD4+ lymphocyte percentage measurements at the first seropositive visit formed a U-shaped pattern, with the lowest values observed in 1988 and 1989. The authors observed no consistent secular pattern of CD4+ percentages at later visit dates, except that mean CD4+ percentages were consistently lowest in men who seroconverted in 1988. In a proportional hazards model, the time to the adjusted CD4+ lymphocyte count of < 500 cells/mm3 was not associated with the secular time of seroconversion (relative hazard = 1.05, 95% confidence interval 0.97-1.13). The authors' data do not suggest a major change in the natural history of HIV-1 infection of this population. PMID:7653474

  20. Current status of drug use and HIV/AIDS prevention in drug users in China

    PubMed Central

    Li, Jianhua; Li, Xinyue

    2014-01-01

    The objective of this paper is to review the current status of drug use and HIV/AIDS prevention for drug users in China and provide scientific evidence for HIV/AIDS prevention and control in drug users. Literature and articles related to drug abuse in China, as well as the results of prevention efforts and successful cases regarding HIV/AIDS prevention in drug users, are reviewed. Lessons learned are drawn out for the future improvement of work and the sustainable development of treatment programs. The number of drug users in China is increasing. Even though the number of opioid-type drug users is growing more slowly than in the past, the number of amphetamine-type stimulant users has increased sharply. It has been proven that methadone maintenance treatment and syringe exchange programs gradually and successfully control HIV/AIDS transmission in drug users. However, it is necessary to enhance these prevention methods and expand their coverage. In addition, the strengthening of antiretroviral therapy (ART) treatment for HIV-infected drug users is crucial for HIV/AIDS prevention and control. The rapidly growing number of amphetamine-type stimulant users, along with their high-risk behavior, poses a hidden danger of greater HIV/AIDS transmission through sexual intercourse in the near future. PMID:25284965

  1. Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection

    PubMed Central

    Hanauske-Abel, Hartmut M.; Saxena, Deepti; Palumbo, Paul E.; Hanauske, Axel-Rainer; Luchessi, Augusto D.; Cambiaghi, Tavane D.; Hoque, Mainul; Spino, Michael; Gandolfi, Darlene D'Alliessi; Heller, Debra S.; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M.; Tricta, Fernando; Connelly, John; Popowicz, Anthony M.; Cone, Richard A.; Holland, Bart; Pe’ery, Tsafi; Mathews, Michael B.

    2013-01-01

    HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal

  2. HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition.

    PubMed

    Kis, Olena; Sankaran-Walters, Sumathi; Hoque, M Tozammel; Walmsley, Sharon L; Dandekar, Satya; Bendayan, Reina

    2016-05-01

    This study investigated the effects of HIV-1 infection and antiretroviral therapy (ART) on the expression of intestinal drug efflux transporters, i.e., P-glycoprotein (Pgp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP), and metabolic enzymes, such as cytochrome P450s (CYPs), in the human upper intestinal tract. Intestinal biopsy specimens were obtained from HIV-negative healthy volunteers, ART-naive HIV-positive (HIV(+)) subjects, and HIV(+) subjects receiving ART (10 in each group). Intestinal tissue expression of drug transporters and metabolic enzymes was examined by microarray, real-time quantitative reverse transcription-PCR (qPCR), and immunohistochemistry analyses. Microarray analysis demonstrated significantly lower expression of CYP3A4 and ABCC2/MRP2 in the HIV(+) ART-naive group than in uninfected subjects. qPCR analysis confirmed significantly lower expression of ABCC2/MRP2 in ART-naive subjects than in the control group, while CYP3A4 and ABCG2/BCRP showed a trend toward decreased expression. Protein expression of MRP2 and BCRP was also significantly lower in the HIV(+) naive group than in the control group and was partially restored to baseline levels in HIV(+) subjects receiving ART. In contrast, gene and protein expression of ABCB1/Pgp was significantly increased in HIV(+) subjects on ART relative to HIV(+) ART-naive subjects. These data demonstrate that the expression of drug-metabolizing enzymes and efflux transporters is significantly altered in therapy-naive HIV(+) subjects and in those receiving ART. Since CYP3A4, Pgp, MRPs, and BCRP metabolize or transport many antiretroviral drugs, their altered expression with HIV infection may negatively impact drug pharmacokinetics in HIV(+) subjects. This has clinical implications when using data from healthy volunteers to guide ART. PMID:26902756

  3. Drug choice, spatial distribution, HIV risk, and HIV prevalence among injection drug users in St. Petersburg, Russia

    PubMed Central

    Kruse, Gina Rae; Barbour, Russell; Heimer, Robert; Shaboltas, Alla V; Toussova, Olga V; Hoffman, Irving F; Kozlov, Andrei P

    2009-01-01

    Background The HIV epidemic in Russia has been driven by the unsafe injection of drugs, predominantly heroin and the ephedrine derived psychostimulants. Understanding differences in HIV risk behaviors among injectors associated with different substances has important implications for prevention programs. Methods We examined behaviors associated with HIV risk among 900 IDUs who inject heroin, psychostimulants, or multiple substances in 2002. Study participants completed screening questionnaires that provided data on sociodemographics, drug use, place of residence and injection- and sex-related HIV risk behaviors. HIV testing was performed and prevalence was modeled using general estimating equation (GEE) analysis. Individuals were clustered by neighborhood and disaggregated into three drug use categories: Heroin Only Users, Stimulant Only Users, and Mixed Drug Users. Results Among Heroin Only Users, younger age, front/backloading of syringes, sharing cotton and cookers were all significant predictors of HIV infection. In contrast, sharing needles and rinse water were significant among the Stimulant Only Users. The Mixed Drug Use group was similar to the Heroin Only Users with age, front/back loading, and sharing cotton significantly associated with HIV infection. These differences became apparent only when neighborhood of residence was included in models run using GEE. Conclusion The type of drug injected was associated with distinct behavioral risks. Risks specific to Stimulant Only Users appeared related to direct syringe sharing. The risks specific to the other two groups are common to the process of sharing drugs in preparation to injecting. Across the board, IDUs could profit from prevention education that emphasizes both access to clean syringes and preparing and apportioning drug with these clean syringes. However, attention to neighborhood differences might improve the intervention impact for injectors who favor different drugs. PMID:19646255

  4. HIV type 1 genetic diversity in Moyale, Mandera, and Turkana based on env-C2-V3 sequences.

    PubMed

    Khamadi, Samoel A; Lihana, Raphael W; Mwaniki, D L; Kinyua, Joyceline; Lagat, Nancy; Carter, Jane Y; Ichimura, Hiroshi; Oishi, Isao; Okoth, Fredrick A; Ochieng, Washington

    2008-12-01

    The genetic diversity of HIV-1 subtypes circulating in three districts of northern Kenya, i.e., Turkana, Mandera, and Moyale, was studied. DNA sequences encoding a portion of the env-C2-V3 region of the virus were amplified by PCR and sequenced directly. One hundred and fifty-nine samples were successfully sequenced in the env-C2-V3 region and analyzed. From the analysis, 57% were subtype A1, 27% were subtype C, 9% were subtype D, and the remaining 7% were unclassified. This study showed that HIV-1 subtype A1 was the dominant subtype in circulation in this region, though there was a significant percentage of HIV-1 subtype C in circulation there. PMID:19102688

  5. Short communication: molecular epidemiology of HIV type 1 infection in Kazakhstan: CRF02_AG prevalence is increasing in the southeastern provinces.

    PubMed

    Lapovok, Ilya; Kazennova, Elena; Laga, Vita; Vasilyev, Alexander; Utegenova, Aliya; Abishev, Asylkhan; Dzissyuk, Natalya; Tukeev, Marat; Bobkova, Marina

    2014-08-01

    To analyze HIV-1 genetic variants in Kazakhstan, HIV-1 sequences were obtained from 205 antiretroviral-treated (ART) and naive patients in 2009-2013. Samples were collected in the most populous cities and provinces of Kazakhstan. On the basis of phylogenetic analyses of partial pol sequences, subtype A variant intravenous drug user (IDU)-A (which is dominant in the former Soviet Union) was found in 60.0% of the individuals, followed by CRF02_AG (34.6%); the rest of the samples were subtype B, CRF03_AB, CRF63_02A1, and CRF07_BC. The proportion of CRF02_AG has increased significantly since 2001-2003, when it was less than 5%. The majority of the CRF02_AG cases were found in Almaty, the former capital and the most populous city in Kazakhstan. The IDU-A variant dominated in the industrial regions of northern and central Kazakhstan and some other regions. Both dominant HIV-1 genetic variants were almost equally represented in the two main transmission groups: IDUs and heterosexuals. The analysis of drug-resistant mutations found a low prevalence of drug resistance in 165 therapy-naive individuals (3.0%). Thus, in the beginning of the second decade of the 2000s, the HIV epidemic in Kazakhstan is driven by two main genetic variants: IDU-A and CRF02_AG. PMID:24873898

  6. Management of the metabolic effects of HIV and HIV drugs.

    PubMed

    Brown, Todd T; Glesby, Marshall J

    2012-01-01

    Morphologic and metabolic abnormalities, including subcutaneous adipose tissue wasting, central adipose tissue accumulation, dyslipidemia and disorders of glucose metabolism are common among HIV-infected patients receiving highly active antiretroviral therapy (HAART) and contribute to the risk of cardiovascular disease in this population. The pathogenesis of these disorders is due to complicated interactions between effects of chronic HIV infection, HAART medications and patient factors, including genetic susceptibility. HAART has transformed HIV into a chronic condition for many patients and as a result the majority of HIV-infected patients in many areas of the developed world will soon be aged ≥50 years. Given that metabolic and cardiovascular diseases increase with aging, knowledge of the optimal management of these conditions is essential for practitioners caring for HIV-infected patients, including endocrine subspecialists. This Review highlights the clinical management of these disorders, focusing on the latest evidence regarding the efficacy of treatment strategies, newly available medications and potential interactions between HAART medications and medications used to treat metabolic disorders. PMID:21931374

  7. Short Communication: Current Prevalence and Risk Factors Associated with Human T Lymphotropic Virus Type 1 and Human T Lymphotropic Virus Type 2 Infections Among HIV/AIDS Patients in São Paulo, Brazil

    PubMed Central

    Sacchi, Cláudio Tavares; Gonçalves, Maria Gisele; Campos, Karoline Rodrigues; Magri, Mariana Cavalheiro; Alencar, Wong Kuen

    2015-01-01

    Abstract During the 1990s, high prevalences of HIV/human T lymphotropic virus type 1 (HTLV-1) and HIV/human T lymphotropic virus type 2 (HTLV-2) coinfections were detected in São Paulo, Brazil in association with intravenous drug use (IDU). The current prevalences and risk factors for HIV/HTLV-1/-2 were evaluated in 1,608 patients attending the AIDS/STD Reference and Training Center in São Paulo. Blood samples were analyzed for HTLV-1/2-specific antibodies using enzyme immunoassays (EIA Murex HTLV-I+II, Diasorin, and Gold ELISA HTLV-I+II, REM) and immunoblotting (HTLV Blot 2.4, MP Biomedicals and INNO-LIA HTLV-I/II, Innogenetics) and for the pol proviral DNA segments of HTLV-1 and HTLV-2 by “in-house” real-time PCR. These analyses revealed that 50 (3.11%) of the samples were HTLV positive, including 25 (1.55%) that were HTLV-1 positive, 21 (1.31%) that were HTLV-2 positive, and 4 (0.25%) that were HTLV positive (untypeable). The median age of the HIV/HTLV-coinfected individuals was 50 years versus 44 years in the overall population (p=0.000). The risk factors associated with HIV/HTLV-1/-2 coinfections were female gender (OR 3.26, 1.78–5.95), black/pardo color (OR 2.21, 1.21–4.03), infection with hepatitis B virus (HBV) (OR 4.27, 2.32–7.87) or hepatitis C virus (HCV) (OR 24.40, 12.51–48.11), and intravenous drug use (IDU) (OR 30.01, 15.21–59.29). The current low prevalence of HTLV-1/2 in HIV-infected patients in São Paulo could be explained in part by programs providing IDUs with sterile needles and syringes and changes in the drug usage patterns of individuals from injecting cocaine to smoking crack cocaine. PMID:25464979

  8. A Mathematical Model for HIV Drug-Resistance

    NASA Astrophysics Data System (ADS)

    Faedo, Ivan; Raimundo, Silvia Martorano; Venturino, Ezio

    2010-09-01

    In this paper we present a mathematical model of the transmission of HIV infection here the individuals receive antiretroviral drugs but may not respond to treatment. In such case the latter can be changed to a different therapy, and individuals may or may not respond also to this second set of drugs.

  9. Drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia.

    PubMed

    Purohit, Vishnudutt; Rapaka, Rao; Shurtleff, David

    2011-08-01

    Although the incidence of HIV-associated dementia (HAD) has declined, HIV-associated neurocognitive disorders (HAND) remain a significant health problem despite use of highly active antiretroviral therapy. In addition, the incidence and/or severity of HAND/HAD are increased with concomitant use of drugs of abuse, such as cocaine, marijuana, and methamphetamine. Furthermore, exposure to most drugs of abuse increases brain levels of dopamine, which has been implicated in the pathogenesis of HIV. This review evaluates the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. In the brain, multiplication of HIV in infected macrophages/microglia could result in the release of HIV proteins such as gp120 and Tat, which can bind to and impair dopamine transporter (DAT) functions, leading to elevated levels of dopamine in the dopaminergic synapses in the early asymptomatic stage of HIV infection. Exposure of HIV-infected patients to drugs of abuse, especially cocaine and methamphetamine, can further increase synaptic levels of dopamine via binding to and subsequently impairing the function of DAT. This accumulated synaptic dopamine can diffuse out and activate adjacent microglia through binding to dopamine receptors. The activation of microglia may result in increased HIV replication as well as increased production of inflammatory mediators such as tumor necrosis factor (TNF)-alpha and chemokines. Increased HIV replication can lead to increased brain viral load and increased shedding of HIV proteins, gp120 and Tat. These proteins, as well as TNF-alpha, can induce cell death of adjacent dopaminergic neurons via apoptosis. Autoxidation and metabolism of accumulated synaptic dopamine can lead to generation of reactive oxygen species (hydrogen peroxide), quinones, and semiquinones, which can also induce apoptosis of neurons. Increased cell death of dopaminergic neurons can eventually lead to dopamine deficit that may exacerbate the severity and

  10. [MANAGEMENT OF PSYCHOTROPIC DRUGS IN HIV-INFECTED PATIENTS].

    PubMed

    Zirulnik, Jorge L

    2015-01-01

    Here we make a revision about the rational use of psychopharmacological drugs in HIV/AIDS patients. We revised the clinical use of psychotropic drugs in this setting. In the clinical spectrum, the most frequent clinical pictures are the depression, anxiety disorders, psychosis, delirium, and the cognitive and behavioral neuropsychiatric symptoms associated with the HIV/AIDS dementia and the substance abuse-dependence. Also, we analyzed the most important pharmacological interactions between psychotropic drugs and antiretrovirals. The medical education and the interdisciplinary work are the basic topics to an adequate clinical management of this kind of patients. PMID:26650559

  11. Sequence analysis of the dimerization initiation site of concordant and discordant viral variants superinfecting HIV type 1 patients.

    PubMed

    Mayr, Luzia; Powell, Rebecca; Kinge, Thompson; Nyambi, Phillipe N

    2011-11-01

    For HIV recombination to occur, the RNAs from two infecting strains within a cell must dimerize at the dimerization initiation site (DIS). We examined the sequence identity at the DIS (697-731 bp, Hxb2 numbering engine) in patients superinfected with concordant HIV-1 strains and compared them to those with discordant strains. Viral RNA in sequential plasma from four subjects superinfected with subtype-discordant and two subjects superinfected with subtype-concordant HIV-1 strains was extracted, amplified (5' LTR-early gag: 526-1200 bp, Hxb2 numbering engine), sequenced, and analyzed to determine their compatibility for dimerization in vivo. The concordant viruses infecting the two subjects exhibited identical sequences in the 35-bp-long DIS region while sequences from the discordant viruses revealed single nucleotide changes that were located in the DIS loop (715 bp), its flanking nucleotides (710 bp and 717 bp), and the DIS stem (719 bp). Evidence from in vitro experiments demonstrates that these in vivo changes identified can abolish dimerization and reduce recombination frequency. Therefore, these results revealing differences in the DIS of discordant strains versus the similarity noted for the concordant strains may contribute to the differences in the frequency of recombination in patients superinfected with such HIV-1 variants. PMID:21453132

  12. Drugs, Alcohol and HIV/AIDS: A Consumer Guide for African Americans

    MedlinePlus

    Drugs, Alcohol and HIV/AIDS A Consumer Guide Drugs & Alcohol What do drugs and alcohol have to do with HIV? Drug and alcohol use can ... behavior that can increase your exposure to HIV/AIDS. For example, using or sharing needles or other ...

  13. HIV post-exposure therapy for drug users in treatment.

    PubMed

    O'Connor, P G

    2000-01-01

    The purpose of this study was to evaluate the attitudes of drug treatment program providers concerning human immunodeficiency virus (HIV) post-exposure therapy (PET) for drug users enrolled in drug treatment. This was a cross-sectional evaluation of drug treatment program providers in four methadone maintenance programs (MMPs) in New Haven, Connecticut. Thirty-five MMP providers including: 29 MMP treatment staff (physicians, nurses, counselors) and 6 primary care provider staff (physicians, nurse practitioners, and nurses) participated in the study. The providers were presented with four case vignettes of individuals exposed to HIV through a needle stick ("stick"): a phlebotomist with occupational exposure (Case A) and three drug users with nonoccupational exposure to HIV (Cases B, C, and D). Case B had the same estimated future risk as Case A (three sticks/4 years) and the other cases had increased risk: Case C (four to six sticks/year) and Case D (monthly "sticks"). For each vignette, providers were asked whether they would offer HIV PET ("yes" or "no"). In addition, focus groups were held within each group of providers who were asked: "What role should drug treatment programs play in the implementation of PET?" All MMP staff (29/29) and primary care providers (6/6) felt that the phlebotomist with occupational exposure should be offered PET. The percent of MMP and Primary care provider staff recommending PET for the other cases were: Case B (MMP staff: 86% [25/29], PCPs: 100% [6/6]), Case C (MMP staff: 69% [20/29], PCPs: 33% [2/6]), and Case D (MMP staff: 59% [17/29], PCPs: 17% [1/6]). The "common themes" that were identified in the focus groups included: concern that MMPs lack resources to provide PET, the ethics of withholding PET, the "limit" on the number of times PET should be offered, and the role of PET in the overall HIV prevention message. Both MMP staff and PCPs felt that MMPs should have an "indirect" role in providing HIV PET by providing education

  14. Injection drug use and HIV/AIDS transmission in China.

    PubMed

    Chu, Tian Xin; Levy, Judith A

    2005-01-01

    After nearly three decades of being virtually drug free, use of heroin and other illicit drugs has re-emerged in China as a major public health problem. One result is that drug abuse, particularly heroin injection, has come to play a predominant role in fueling China's AIDS epidemic. The first outbreak of HIV among China's IDUs was reported in the border area of Yunnan province between China and Myanmar where drug trafficking is heavy. Since then drug-related HIV has spread to all 31 provinces, autonomous regions and municipalities. This paper provides an overview to HIV/AIDS transmission through injection drug use in China. It begins with a brief history of the illicit drug trade in China, followed by a discussion of the emergence of drug related AIDS, and a profile of drug users and their sexual partners who have contracted the virus or who are vulnerable to infection. It ends by summarizing three national strategies being used by China to address both drug use and AIDS as major health threats. PMID:16354561

  15. Sparse Representation for Prediction of HIV-1 Protease Drug Resistance.

    PubMed

    Yu, Xiaxia; Weber, Irene T; Harrison, Robert W

    2013-01-01

    HIV rapidly evolves drug resistance in response to antiviral drugs used in AIDS therapy. Estimating the specific resistance of a given strain of HIV to individual drugs from sequence data has important benefits for both the therapy of individual patients and the development of novel drugs. We have developed an accurate classification method based on the sparse representation theory, and demonstrate that this method is highly effective with HIV-1 protease. The protease structure is represented using our newly proposed encoding method based on Delaunay triangulation, and combined with the mutated amino acid sequences of known drug-resistant strains to train a machine-learning algorithm both for classification and regression of drug-resistant mutations. An overall cross-validated classification accuracy of 97% is obtained when trained on a publically available data base of approximately 1.5×10(4) known sequences (Stanford HIV database http://hivdb.stanford.edu/cgi-bin/GenoPhenoDS.cgi). Resistance to four FDA approved drugs is computed and comparisons with other algorithms demonstrate that our method shows significant improvements in classification accuracy. PMID:24910813

  16. Sparse Representation for Prediction of HIV-1 Protease Drug Resistance

    PubMed Central

    Yu, Xiaxia; Weber, Irene T.; Harrison, Robert W.

    2013-01-01

    HIV rapidly evolves drug resistance in response to antiviral drugs used in AIDS therapy. Estimating the specific resistance of a given strain of HIV to individual drugs from sequence data has important benefits for both the therapy of individual patients and the development of novel drugs. We have developed an accurate classification method based on the sparse representation theory, and demonstrate that this method is highly effective with HIV-1 protease. The protease structure is represented using our newly proposed encoding method based on Delaunay triangulation, and combined with the mutated amino acid sequences of known drug-resistant strains to train a machine-learning algorithm both for classification and regression of drug-resistant mutations. An overall cross-validated classification accuracy of 97% is obtained when trained on a publically available data base of approximately 1.5×104 known sequences (Stanford HIV database http://hivdb.stanford.edu/cgi-bin/GenoPhenoDS.cgi). Resistance to four FDA approved drugs is computed and comparisons with other algorithms demonstrate that our method shows significant improvements in classification accuracy. PMID:24910813

  17. HIV Rapid Testing in Drug Treatment: Comparison Across Treatment Modalities

    PubMed Central

    Schwartz, Robert P.; Stitzer, Maxine L.; Feaster, Daniel J.; Korthuis, P. Todd; Alvanzo, Anika A. H.; Winhusen, T. M.; Donnard, Lillian; Snead, Ned; Metsch, L. R.

    2012-01-01

    Despite high rates of risky behavior among patients, many drug abuse treatment programs do not provide on-site HIV testing. This secondary analysis examined differences in outcome by program modality from a multi-site trial in which 1,281 HIV-negative patients in 3 methadone programs, 7 non-methadone outpatient programs, and 3 residential programs were randomly assigned to: (1) off-site referral for HIV risk reduction counseling and testing; or on-site rapid testing (2) with or (3) without risk reduction counseling. The parent study using generalized estimating equations with site as a cluster variable found significantly higher rates of HIV testing and feedback of results by 1 month post-enrollment for the combined on-site conditions compared to the offsite condition (RR=4.52, 97.5% CI (3.57, 5.72). Utilizing the same statistical approach, we found neither significant treatment modality nor significant treatment modality by testing condition interaction effects either for receipt of HIV test results at 1 month or for sexual or drug use HIV-risk behaviors at 6-month follow-up. On-site HIV testing is effective across treatment modalities for achieving high rates of testing and results feedback. All programs should be encouraged to adopt or expand this service. PMID:23021496

  18. Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin {alpha} interactions as a novel HIV-1 therapy

    SciTech Connect

    Suzuki, Tatsunori; Yamamoto, Norio; Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin-nosuke; Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki; Tanaka, Rie; Kato, Shingo; Aida, Yoko

    2009-03-20

    The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin {alpha}, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin {alpha} interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin {alpha} interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

  19. HIV epidemic among drug users in China: 1995 to 2011

    PubMed Central

    Wang, Lan; Guo, Wei; Li, Dongmin; Ding, Zhengwei; McGoogan, Jennifer M.; Wang, Ning; Wu, Zunyou; Wang, Lu

    2014-01-01

    Aim To describe trends in the HIV epidemic among drug users (DUs) in China from 1995 to 2011. Design, setting and participants Datasets from China's national HIV/AIDS case reporting and sentinel surveillance systems as of December 2011 were used separately for descriptive analysis. Measures Changes in the geographic distribution of the number of HIV cases and HIV prevalence among injecting drug users (IDUs) and non-IDUs were examined. We also analyzed changes in HIV prevalence among the broader DU population, and drug use-related behaviors including types of drugs used, recent injecting, and recent needle sharing in the context of the rapid scale-up of DU sentinel sites and national harm reduction programs. Findings The HIV epidemic among China's DUs is still highly concentrated in five provinces. Here, HIV prevalence peaked at 30.3% (95% CI [28.6, 32.1]) among IDUs in 1999, and then gradually decreased to 10.9% (95% CI [10.6, 11.2]) by 2011. We observed a rapid increase in the use of “nightclub drugs” among DUs from 1.3% in 2004 to 24.4% in 2011. A decline in recent needle sharing among current IDU from 19.5% (95% CI [19.4, 19.6]) in 2006 to 11.3% (95% CI [11.2, 11.4]) in 2011 was found to be correlated with the rapid scale-up of methadone maintenance treatment (MMT; r(4) = - .94, p = 0.003) harm reduction efforts. Conclusions While needle sharing among current injecting drug users in China has declined dramatically and is correlated with the scale-up of national harm reduction efforts, the recent, rapid increased use of “nightclub drugs” presents a new challenge. PMID:25533861

  20. The Challenges in Managing HIV in People Who Use Drugs

    PubMed Central

    Kamarulzaman, Adeeba; Altice, Frederick L.

    2015-01-01

    Purpose of review HIV management in PWUD is typically complex and challenging due to the presence of multiple medical and psychiatric comorbidities as well as social, physical, economic and legal factors that often disrupt the HIV continuum of care. In this review we describe the individual, health systems and societal barriers to HIV treatment access and care retention for people who use drugs. Additionally the clinical management of HIV infected PWUD is often complicated by the presence of multiple infectious and non-infectious comorbidities. Recent findings Improved ART adherence can be achieved through the provision of opiate substitution therapy (OST), directly administered antiretroviral therapy (DAART) and integration of ART with OST services. Recent advances with direct-acting antivirals (DAA) for HCV have shown superior outcomes compared to interferon based regimes in HIV-HCV co-infected patients. Newer diagnostic technologies for tuberculosis hold promise for earlier diagnosis for PWUD co-infected with TB Summary HIV-infected PWUDs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A comprehensive strategy that encompasses evidence-based prevention and treatment interventions that target the individual, family, healthcare system, legal and societal structure is required to ensure greater participation and success in HIV treatment and care. PMID:25490106

  1. Molecular epidemiology of HIV type 1 in Chile: differential geographic and transmission route distribution of B and F subtypes.

    PubMed

    Rios, M; Fernandez, J; Jaramillo, P; Paredes, V; Sanchez, J L; Laguna-Torres, V A; Carr, J K; Ramirez, E

    2005-10-01

    We examined the genetic makeup of 221 HIV-1 strains from Chilean persons living with HIV/AIDS by HMA and DNA sequencing of the env gene: 143 cases were infected by sexual contact with an already-infected partner, 76 were infected by mother-to-child transmission, and 2 were transfusion related. We found env HIV-1 subtype B in 202 cases (91.4%) and subtype F in 19 cases (8.6%). Subtype B strains were found throughout the country whereas subtype F viruses were predominantly found in cases from the metropolitan/central to the northern regions of Chile (p < 0.01). Chilean F subtypes clustered in two different groups: viruses from the central region clustered with F subtypes from Argentina, Uruguay, and Brazil, and viruses from the northern region, which independently segregated from other South American and European F strains. All of the 59 men having sex with men (MSM) were infected with B subtype strains whereas 7 (9.2%) and 12 (15.8%), respectively, of heterosexually infected females and children were infected with F subtype strains (p < 0.01). It appears that F subtype strains have been introduced into Chile by separate heterosexual transmission events from other nearby countries in the Southern Cone whereas B subtype strains have continued to persist predominantly among MSM. PMID:16225409

  2. How Can HIV-Type-1-Env Immunogenicity Be Improved to Facilitate Antibody-Based Vaccine Development?

    PubMed Central

    Sanders, Rogier W.; Cerutti, Andrea; Moore, John P.

    2012-01-01

    Abstract No vaccine candidate has induced antibodies (Abs) that efficiently neutralize multiple primary isolates of HIV-1. Preexisting high titers of neutralizing antibodies (NAbs) are essential, because the virus establishes infection before anamnestic responses could take effect. HIV-1 infection elicits Abs against Env, Gag, and other viral proteins, but of these only a subset of the anti-Env Abs can neutralize the virus. Whereas the corresponding proteins from other viruses form the basis of successful vaccines, multiple large doses of HIV-1 Env elicit low, transient titers of Abs that are not protective in humans. The inaccessibility of neutralization epitopes hinders NAb induction, but Env may also subvert the immune response by interacting with receptors on T cells, B cells, monocytes, macrophages, and dendritic cells. Here, we discuss evidence from immunizations of different species with various modified Env constructs. We also suggest how the divergent Ab responses to Gag and Env during infection may reflect differences in B cell regulation. Drawing on these analyses, we outline strategies for improving Env as a component of a vaccine aimed at inducing strong and sustained NAb responses. PMID:21495876

  3. Illicit drug use and HIV risk in the Dominican Republic: tourism areas create drug use opportunities.

    PubMed

    Guilamo-Ramos, Vincent; Lee, Jane J; Ruiz, Yumary; Hagan, Holly; Delva, Marlyn; Quiñones, Zahira; Kamler, Alexandra; Robles, Gabriel

    2015-01-01

    While the Caribbean has the second highest global human immunodeficiency virus (HIV) prevalence, insufficient attention has been paid to contributing factors of the region's elevated risk. Largely neglected is the potential role of drugs in shaping the Caribbean HIV/acquired immune deficiency syndrome epidemic. Caribbean studies have almost exclusively focused on drug transportation and seldom acknowledged local user economies and drug-related health and social welfare consequences. While tourism is consistently implicated within the Caribbean HIV epidemic, less is known about the intersection of drugs and tourism. Tourism areas represent distinct ecologies of risk often characterised by sex work, alcohol consumption and population mixing between lower and higher risk groups. Limited understanding of availability and usage of drugs in countries such as the Dominican Republic (DR), the Caribbean country with the greatest tourist rates, presents barriers to HIV prevention. This study addresses this gap by conducting in-depth interviews with 30 drug users in Sosúa, a major sex tourism destination of the DR. A two-step qualitative data analysis process was utilised and interview transcripts were systematically coded using a well-defined thematic codebook. Results suggest three themes: (1) local demand shifts drug routes to tourism areas, (2) drugs shape local economies and (3) drug use facilitates HIV risk behaviours in tourism areas. PMID:25330110

  4. T-Tropic Human Immunodeficiency Virus Type 1 (HIV-1)-Derived V3 Loop Peptides Directly Bind to CXCR-4 and Inhibit T-Tropic HIV-1 Infection

    PubMed Central

    Sakaida, Hitoshi; Hori, Toshiyuki; Yonezawa, Akihito; Sato, Akihiko; Isaka, Yoshitaka; Yoshie, Osamu; Hattori, Toshio; Uchiyama, Takashi

    1998-01-01

    Certain types of chemokine receptors have been identified as coreceptors for HIV-1 infection. The process of viral entry is initiated by the interaction between an envelope protein gp120 of HIV-1, CD4, and one of the relevant coreceptors. To understand the precise mechanism of the Env-mediated fusion and entry of HIV-1, we examined whether the V3 region of gp120 of T-cell line tropic (T-tropic) virus directly interacts with the coreceptor, CXCR-4, by using five synthetic V3 peptides: two cyclized V3 peptides (V3-BH10 and V3-ELI) which correspond to the V3 regions of the T-tropic HIV-1 IIIB and HIV-1 ELI strains, respectively, a linear V3 peptide (CTR36) corresponding to that of HIV-1 IIIB strain; and cyclized V3 peptides corresponding to that of the macrophage-tropic (M-tropic) HIV-1 ADA strain (V3-ADA) or the dualtropic HIV-1 89.6 strain (V3-89.6). FACScan analysis with a CXCR-4+ human B-cell line, JY, showed that V3-BH10, V3-ELI, and V3-89.6 but not CTR36 or V3-ADA blocked the binding of IVR7, an anti-CXCR-4 monoclonal antibody (MAb), to CXCR-4 with different magnitudes in a dose-dependent manner, while none of the V3 peptides influenced binding of an anti-CD19 MAb at all. Next, the effects of the V3 peptides on SDF-1β-induced transient increases in intracellular Ca2+ were investigated. Three V3 peptides (V3-BH10, V3-ELI, and V3-89.6) prevented Ca2+ mobilization. Furthermore, the three peptides inhibited infection by T-tropic HIV-1 in a dose-dependent manner as revealed by an MTT assay and a reverse transcriptase assay, while the other peptides had no effects. These results present direct evidence that the V3 loop of gp120 of T-tropic HIV-1 can interact with its coreceptor CXCR-4 independently of the V1/V2 regions of gp120 or cellular CD4. PMID:9811711

  5. Public health implications of antiretroviral therapy and HIV drug resistance.

    PubMed

    Wainberg, M A; Friedland, G

    1998-06-24

    Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy. PMID:9643862

  6. Female genital tract shedding of CXCR4-tropic HIV Type 1 is associated with a majority population of CXCR4-tropic HIV Type 1 in blood and declining CD4(+) cell counts.

    PubMed

    Haaland, Richard E; Sullivan, Sharon T; Evans-Strickfaden, Tammy; Lennox, Jeffrey L; Hart, Clyde E

    2012-11-01

    This study compared HIV-1 genotypes shed over time (≤3.5 years) in the vaginal secretions (VS) and blood plasma (BP) of 15 chronically infected women. Analysis of predicted coreceptor tropism (CCR5=R5, CXCR4=X4) for quasispecies shedding revealed three patterns: (1) viral quasispecies shed in both VS and BP were restricted to R5-tropism at all time points, (2) quasispecies shed in VS were restricted to R5-tropism at all time points but X4 quasispecies were identified in the BP at one or more time points, and (3) quasispecies shed in matched VS and BP both contained X4-tropic viruses. Overall, the frequency of X4 quasispecies circulation in VS was 2-fold less than in BP and detection of X4 virus in VS was more likely to occur when X4 quasispecies comprised more than 50% of BP viruses (p=0.01) and when declines in blood CD4(+) lymphocyte levels were the greatest (p=0.038). Additionally, the mean number of predicted N-glycosylation sites between matched VS and BP samples was strongly correlated (r=0.86, p<0.0001) with glycosylation densities in the following order (VS R5=BP R5 > BP X4 > VS X4). The X4 glycosylation densities may result from compartmentalization pressures in the female genital tract or the delayed appearance of these viruses in VS. Our results suggest that the presence of X4 virus in VS is associated with a threshold population of X4 quasispecies in BP, which are increasing during the HIV-induced failure of the human immune system. PMID:22369497

  7. HIV type 1 subtype C remains the predominant subtype in men having sex with men in Senegal.

    PubMed

    Ndiaye, Halimatou Diop; Tchiakpe, Edmond; Vidal, Nicole; Ndiaye, Ousseynou; Diop, Abdou Khoudia; Peeters, Martine; Mboup, Souleymane; Toure-Kane, Coumba

    2013-09-01

    HIV-1 epidemics are expanding among men who have sex with men in low- and middle-income countries. To confirm and further explore preliminary data in Senegal, we aimed to determine 3 years after a first study the HIV-1 genetic diversity in three different viral regions. From 109 samples available in 2007, 93 were sequenced in gag, 77 in env, and 60 in pol. Phylogenetic analysis showed that subtype C predominated (38-52%), followed by CRF02_AG (30-40%), subtype B (13-17%), and CRF09_cpx (2.6-5%). Subsubtype A3 and strains tightly linked to CRF43_02G were identified in env and gag, respectively, and 12% of the samples were unique recombinants. Six transmission chains involving two to seven individuals were identified. Some strains carried resistance mutations inside transmission chains. This study confirmed the existence of a dual epidemic in Senegal and emphasized the need to strengthen prevention programs to avoid strains intermixing between low-risk women and high-risk men. PMID:23742654

  8. Antiretroviral drug use and HIV drug resistance among HIV-infected Black men who have sex with men: HIV Prevention Trials Network 061

    PubMed Central

    Chen, Iris; Connor, Matthew B.; Clarke, William; Marzinke, Mark A.; Cummings, Vanessa; Breaud, Autumn; Fogel, Jessica M.; Laeyendecker, Oliver; Fields, Sheldon D.; Donnell, Deborah; Griffith, Sam; Scott, Hyman M.; Shoptaw, Steven; del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Wheeler, Darrell P.; Mayer, Kenneth H.; Koblin, Beryl A.; Eshleman, Susan H.

    2015-01-01

    BACKGROUND HPTN 061 enrolled Black men who have sex with men in the United States. Some men with low/undetectable HIV RNA had unusual patterns of antiretroviral (ARV) drug use or had drugs detected in the absence of viral suppression. This report includes a comprehensive analysis of ARV drug use and drug resistance among men in HPTN 061 who were not virally suppressed. METHODS The analysis included 169 men who had viral loads >400 copies/mL at enrollment, including three with acute infection and 13 with recent infection. By self-report, 88 were previously diagnosed, including 31 in care; 137 men reported no ARV drug use. Samples from these 169 men and 23 seroconverters were analyzed with HIV genotyping and ARV drug assays. RESULTS Forty-eight (28%) of the 169 men had ≥1 drug resistance mutation (DRM); 19 (11%) had multi-class resistance. Sixty men (36%) had ≥1 ARV drug detected, 42 (70%) of whom reported no ARV drug use. Nine (23%) of 39 newly-infected men had ≥1 DRM; 10 had ≥1 ARV drug detected. Unusual patterns of ARV drugs were detected more frequently in newly-diagnosed men than previously-diagnosed men. The rate of transmitted drug resistance (TDR) was 23% based on HIV genotyping and self-reported ARV drug use, but was 12% after adjusting for ARV drug detection. CONCLUSIONS Many men in HPTN 061 had drug-resistant HIV and many were at risk of acquiring additional DRMs. ARV drug testing revealed unusual patterns of ARV drug use and provided a more accurate estimate of TDR. PMID:25861015

  9. A Rev-independent human immunodeficiency virus type 1 (HIV-1)-based vector that exploits a codon-optimized HIV-1 gag-pol gene.

    PubMed

    Kotsopoulou, E; Kim, V N; Kingsman, A J; Kingsman, S M; Mitrophanous, K A

    2000-05-01

    The human immunodeficiency virus (HIV) genome is AU rich, and this imparts a codon bias that is quite different from the one used by human genes. The codon usage is particularly marked for the gag, pol, and env genes. Interestingly, the expression of these genes is dependent on the presence of the Rev/Rev-responsive element (RRE) regulatory system, even in contexts other than the HIV genome. The Rev dependency has been explained in part by the presence of RNA instability sequences residing in these coding regions. The requirement for Rev also places a limitation on the development of HIV-based vectors, because of the requirement to provide an accessory factor. We have now synthesized a complete codon-optimized HIV-1 gag-pol gene. We show that expression levels are high and that expression is Rev independent. This effect is due to an increase in the amount of gag-pol mRNA. Provision of the RRE in cis did not lower protein or RNA levels or stimulate a Rev response. Furthermore we have used this synthetic gag-pol gene to produce HIV vectors that now lack all of the accessory proteins. These vectors should now be safer than murine leukemia virus-based vectors. PMID:10775623

  10. A Rev-Independent Human Immunodeficiency Virus Type 1 (HIV-1)-Based Vector That Exploits a Codon-Optimized HIV-1 gag-pol Gene

    PubMed Central

    Kotsopoulou, Ekaterini; Kim, V. Narry; Kingsman, Alan J.; Kingsman, Susan M.; Mitrophanous, Kyriacos A.

    2000-01-01

    The human immunodeficiency virus (HIV) genome is AU rich, and this imparts a codon bias that is quite different from the one used by human genes. The codon usage is particularly marked for the gag, pol, and env genes. Interestingly, the expression of these genes is dependent on the presence of the Rev/Rev-responsive element (RRE) regulatory system, even in contexts other than the HIV genome. The Rev dependency has been explained in part by the presence of RNA instability sequences residing in these coding regions. The requirement for Rev also places a limitation on the development of HIV-based vectors, because of the requirement to provide an accessory factor. We have now synthesized a complete codon-optimized HIV-1 gag-pol gene. We show that expression levels are high and that expression is Rev independent. This effect is due to an increase in the amount of gag-pol mRNA. Provision of the RRE in cis did not lower protein or RNA levels or stimulate a Rev response. Furthermore we have used this synthetic gag-pol gene to produce HIV vectors that now lack all of the accessory proteins. These vectors should now be safer than murine leukemia virus-based vectors. PMID:10775623

  11. Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering.

    PubMed

    Novitsky, Vlad; Zahralban-Steele, Melissa; McLane, Mary Fran; Moyo, Sikhulile; van Widenfelt, Erik; Gaseitsiwe, Simani; Makhema, Joseph; Essex, M

    2015-08-01

    The goal of the study was to improve the methodology of HIV genotyping for analysis of HIV drug resistance and HIV clustering. Using the protocol of Gall et al. (A. Gall, B. Ferns, C. Morris, S. Watson, M. Cotten, M. Robinson, N. Berry, D. Pillay, and P. Kellam, J Clin Microbiol 50:3838-3844, 2012, doi:10.1128/JCM.01516-12), we developed a robust methodology for amplification of two large fragments of viral genome covering about 80% of the unique HIV-1 genome sequence. Importantly, this method can be applied to both viral RNA and proviral DNA amplification templates, allowing genotyping in HIV-infected subjects with suppressed viral loads (e.g., subjects on antiretroviral therapy [ART]). The two amplicons cover critical regions across the HIV-1 genome (including pol and env), allowing analysis of mutations associated with resistance to protease inhibitors, reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors [NRTIs] and nonnucleoside reverse transcriptase inhibitors [NNRTIs]), integrase strand transfer inhibitors, and virus entry inhibitors. The two amplicons generated span 7,124 bp, providing substantial sequence length and numbers of informative sites for comprehensive phylogenic analysis and greater refinement of viral linkage analyses in HIV prevention studies. The long-range HIV genotyping from proviral DNA was successful in about 90% of 212 targeted blood specimens collected in a cohort where the majority of patients had suppressed viral loads, including 65% of patients with undetectable levels of HIV-1 RNA loads. The generated amplicons could be sequenced by different methods, such as population Sanger sequencing, single-genome sequencing, or next-generation ultradeep sequencing. The developed method is cost-effective-the cost of the long-range HIV genotyping is under $140 per subject (by Sanger sequencing)-and has the potential to enable the scale up of public health HIV prevention interventions. PMID:26041893

  12. Drug–drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems

    PubMed Central

    Rao, PSS; Earla, Ravindra; Kumar, Anil

    2015-01-01

    Introduction Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. Areas covered This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. Expert opinion We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse. PMID:25539046

  13. Performance Characteristics of the QUANTIPLEX HIV-1 RNA 3.0 Assay for Detection and Quantitation of Human Immunodeficiency Virus Type 1 RNA in Plasma

    PubMed Central

    Erice, Alejo; Brambilla, Donald; Bremer, James; Jackson, J. Brooks; Kokka, Robert; Yen-Lieberman, Belinda; Coombs, Robert W.

    2000-01-01

    The QUANTIPLEX HIV-1 RNA assay, version 3.0 (a branched DNA, version 3.0, assay [bDNA 3.0 assay]), was evaluated by analyzing spiked and clinical plasma samples and was compared with the AMPLICOR HIV-1 MONITOR Ultrasensitive (ultrasensitive reverse transcription-PCR [US-RT-PCR]) method. A panel of spiked plasma samples that contained 0 to 750,000 copies of human immunodeficiency virus type 1 (HIV-1) RNA per ml was tested four times in each of four laboratories (1,344 assays). Negative results (<50 copies/ml) were obtained in 30 of 32 (94%) assays with seronegative samples, 66 of 128 (52%) assays with HIV-1 RNA at 50 copies/ml, and 5 of 128 (4%) assays with HIV-1 RNA at 100 copies/ml. The assay was linear from 100 to 500,000 copies/ml. The within-run standard deviation (SD) of the log10 estimated HIV-1 RNA concentration was 0.08 at 1,000 to 500,000 copies/ml, increased below 1,000 copies/ml, and was 0.17 at 100 copies/ml. Between-run reproducibility at 100 to 500 copies/ml was <0.10 log10 in most comparisons. Interlaboratory differences across runs were ≤0.10 log10 at all concentrations examined. A subset of the panel (25 to 500 copies/ml) was also analyzed by the US-RT-PCR assay. The within-run SD varied inversely with the log10 HIV-1 RNA concentration but was higher than the SD for the bDNA 3.0 assay at all concentrations. Log-log regression analysis indicated that the two methods produced very similar estimates at 100 to 500 copies/ml. In parallel testing of clinical specimens with low HIV-1 RNA levels, 80 plasma samples with <50 copies/ml by the US-RT-PCR assay had <50 copies/ml when they were retested by the bDNA 3.0 assay. In contrast, 11 of 78 (14%) plasma samples with <50 copies/ml by the bDNA 3.0 assay had ≥50 copies/ml when they were retested by the US-RT-PCR assay (median, 86 copies/ml; range, 50 to 217 copies/ml). Estimation of bDNA 3.0 values of <50 copies/ml by extending the standard curve of the assay showed that these samples with discrepant

  14. Two-Drug Treatment Approaches in HIV: Finally Getting Somewhere?

    PubMed

    Kelly, Sean G; Nyaku, Amesika N; Taiwo, Babafemi O

    2016-04-01

    The advent of combination antiretroviral therapy (ART) has significantly decreased AIDS-related morbidity and mortality. Nevertheless, the benefits of ART are only realized through adherence to lifelong treatment. Though contemporary antiretroviral (ARV) drugs have fewer adverse effects in comparison to older ARV drugs, many agents are associated with negative or unknown long-term effects. There is increasing evidence that two-drug (dual-therapy) regimens may be an effective alternative to the currently recommended three-drug (triple-therapy) regimens. In this review, we provide a comprehensive and critical review of recently completed and ongoing trials of dual-therapy regimens in treatment-naïve and treatment-experienced HIV-1-infected patients. We also review current HIV/AIDS society recommendations regarding dual therapy as well as future therapeutic possibilities. PMID:26886135

  15. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  16. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  17. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  18. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  19. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  20. Genetic diversity on the integrase region of the pol gene among HIV type 1-infected patients naive for integrase inhibitors in São Paulo City, Brazil.

    PubMed

    Arruda, Liã Bárbara; Fonseca, Luiz Augusto M; Duarte, Alberto J S; Casseb, Jorge

    2010-01-01

    The presence of mutations associated with integrase inhibitor (INI) resistance among INI-naive patients may play an important clinical role in the use of those drugs Samples from 76 HIV-1-infected subjects naive to INIs were submitted to direct sequencing. No differences were found between naive (25%) subjects and subjects on HAART (75%). No primary mutation associated with raltegravir or elvitegravir resistance was found. However, 78% of sequences showed at least one accessory mutation associated with resistance. The analysis of the 76 IN sequences showed a high polymorphic level on this region among Brazilian HIV-1-infected subjects, including a high prevalence of aa substitutions related to INI resistance. The impact of these findings remains unclear and further studies are necessary to address these questions. PMID:20055590

  1. New Subtypes and Genetic Recombination in HIV Type 1-Infecting Patients with Highly Active Antiretroviral Therapy in Peru (2008–2010)

    PubMed Central

    Acuña, Maribel; Gazzo, Cecilia; Salinas, Gabriela; Cárdenas, Fanny; Valverde, Ada; Romero, Soledad

    2012-01-01

    Abstract HIV-1 subtype B is the most frequent strain in Peru. However, there is no available data about the genetic diversity of HIV-infected patients receiving highly active antiretroviral therapy (HAART) here. A group of 267 patients in the Peruvian National Treatment Program with virologic failure were tested for genotypic evidence of HIV drug resistance at the Instituto Nacional de Salud (INS) of Peru between March 2008 and December 2010. Viral RNA was extracted from plasma and the segments of the protease (PR) and reverse transcriptase (RT) genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), purified, and fully sequenced. Consensus sequences were submitted to the HIVdb Genotypic Resistance Interpretation Algorithm Database from Stanford University, and then aligned using Clustal X v.2.0 to generate a phylogenetic tree using the maximum likelihood method. Intrasubtype and intersubtype recombination analyses were performed using the SCUEAL program (Subtype Classification by Evolutionary ALgo-rithms). A total of 245 samples (91%) were successfully genotyped. The analysis obtained from the HIVdb program showed 81.5% resistance cases (n=198). The phylogenetic analysis revealed that subtype B was predominant in the population (98.8%), except for new cases of A, C, and H subtypes (n=4). Of these cases, only subtype C was imported. Likewise, recombination analysis revealed nine intersubtype and 20 intrasubtype recombinant cases. This is the first report of the presence of HIV-1 subtypes C and H in Peru. The introduction of new subtypes and circulating recombinants forms can make it difficult to distinguish resistance profiles in patients and consequently affect future treatment strategies against HIV in this country. PMID:22559065

  2. High Potency of Indolyl Aryl Sulfone Nonnucleoside Inhibitors towards Drug-Resistant Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutants Is Due to Selective Targeting of Different Mechanistic Forms of the Enzyme

    PubMed Central

    Cancio, Reynel; Silvestri, Romano; Ragno, Rino; Artico, Marino; De Martino, Gabriella; La Regina, Giuseppe; Crespan, Emmanuele; Zanoli, Samantha; Hübscher, Ulrich; Spadari, Silvio; Maga, Giovanni

    2005-01-01

    Indolyl aryl sulfone (IAS) nonnucleoside inhibitors have been shown to potently inhibit the growth of wild-type and drug-resistant human immunodeficiency virus type 1 (HIV-1), but their exact mechanism of action has not been elucidated yet. Here, we describe the mechanism of inhibition of HIV-1 reverse transcriptase (RT) by selected IAS derivatives. Our results showed that, depending on the substitutions introduced in the IAS common pharmacophore, these compounds can be made selective for different enzyme-substrate complexes. Moreover, we showed that the molecular basis for this selectivity was a different association rate of the drug to a particular enzymatic form along the reaction pathway. By comparing the activities of the different compounds against wild-type RT and the nonnucleoside reverse transcriptase inhibitor-resistant mutant Lys103Asn, it was possible to hypothesize, on the basis of their mechanism of action, a rationale for the design of drugs which could overcome the steric barrier imposed by the Lys103Asn mutation. PMID:16251294

  3. Polymorphisms in HLA Class I Genes Associated with both Favorable Prognosis of Human Immunodeficiency Virus (HIV) Type 1 Infection and Positive Cytotoxic T-Lymphocyte Responses to ALVAC-HIV Recombinant Canarypox Vaccines

    PubMed Central

    Kaslow, Richard A.; Rivers, Charles; Tang, Jianming; Bender, Thomas J.; Goepfert, Paul A.; El Habib, Raphaelle; Weinhold, Kent; Mulligan, Mark J.

    2001-01-01

    Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8+ cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8+ cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B∗27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B∗57 carriers reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B∗27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4, P < 0.05) and B∗57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013) and Env (39%; OR = 9.5, P = 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines. PMID:11507213

  4. Increased density of neurons containing NADPH diaphorase and nitric oxide synthase in the cerebral cortex of patients with HIV-1 infection and drug abuse.

    PubMed

    Kuljis, Rodrigo O; Shapshak, Paul; Alcabes, Philip; Rodríguez de la Vega, Pura; Fujimura, Robert; Petito, Carol K

    2002-01-01

    To determine whether nitrogen monoxide (nitric oxide; NO) synthase (NOS) and NADPH diaphorase (NDP) co-containing cerebrocortical neurons (NOSN) neurons are affected in patients infected with human immunodeficiency virus type 1 (HIV-1) with and without associated intake of drugs of abuse, we examined the temporal neocortex of 24 individuals: 12 HIV-1 positive (including 3 drug users, 9 non-drug users) and 12 HIV-1 negative (including 6 drug users, and 6 non-drug users). Histochemical labeling for NDP-an enzymatic domain co-expressed in the NOS enzyme-was employed to visualize NOSN. Drug abuse and HIV-1 infection cause independently an increase in NOSN density, but combined they result in up to a 38-fold increase in NOSN density, suggesting that the combination of these factors induces NOS expression powerfully in neurons that normally do not synthesize NDP/NOS. This is associated with an increase in the proportion of NOSN displaying dystrophic changes, indicating that NOSN undergo massive degeneration in association with NOS synthesis induction. The increase in density of NOSN in HIV-1 infected drug abusers may be among the important sources of NO mediating cerebrocortical dysfunction, and the degeneration of NOS-containing local circuit neurons in patients with HIV-1 infection or drug abuse may underlie in part their neuropsychiatric manifestations. PMID:16873197

  5. Multiple routes of drug administration and HIV risk among injecting drug users

    PubMed Central

    Vorobjov, Sigrid; Uusküla, Anneli; Des Jarlais, Don C.; Abel-Ollo, Katri; Talu, Ave; Rüütel, Kristi

    2011-01-01

    This study assesses relationships between drug administration routes and HIV serostatus, drug-use and sexual behaviors among current injecting drug users (IDUs) in Tallinn, Estonia. We recruited 350 IDUs for a cross-sectional risk behavior survey. Adjusted odds ratios (AORs) were calculated to explore injection risk behavior, sexual behavior and HIV serostatus associated with multiple route use. Focus groups explored reasons why injectors might use non-injecting routes of administration. Those reporting multiple drug administration routes were less likely to be HIV seropositive (AOR 0.49; 95%CI 0.25-0.97), had almost twice the odds of having more than one sexual partner (AOR 1.90; 95%CI 1.01-3.60) and of reporting having sexually transmitted diseases (AOR 2.38; 95%CI 1.02-5.59). IDUs who engage in non-injecting drug use may be reducing their risk of acquiring HIV though sharing injection equipment, but if infected may be a critical group for sexual transmission of HIV to people who do not inject drugs. PMID:22116012

  6. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

    PubMed Central

    2010-01-01

    Background The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Results Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia. PMID:20932337

  7. HIV-associated risk behaviour among drug users at drug rehabilitation centres.

    PubMed

    Fauziah, M N; Anita, S; Sha'ari, B N; Rosli, B I

    2003-06-01

    A cross-sectional study to determine the prevalence of Human Immunodeficiency Virus (HIV) and HIV-associated risk behavior was conducted in February 1998 among 6,324 drug users in 26 drug rehabilitation centres in Malaysia. The majority of respondents were males (97.3%) and Malays (77.8%), administered drugs intravenously (64.6%) and of these 65.4% shared needles. About 78.1% had sexual exposure, of which 55.1% had sex with girl friends, 31.3% with prostitutes and 4.6% with male partners. The HIV prevalence rate in the group was 12.1% and significantly high among injecting drug users (IDU); those sharing needles; those who started addiction at a young age (10-15 years); those who had sexual exposures and had sex with prostitutes. PMID:14569748

  8. Drug-Eluting Fibers for HIV-1 Inhibition and Contraception

    PubMed Central

    Ball, Cameron; Krogstad, Emily; Chaowanachan, Thanyanan; Woodrow, Kim A.

    2012-01-01

    Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract. PMID:23209601

  9. Drug-eluting fibers for HIV-1 inhibition and contraception.

    PubMed

    Ball, Cameron; Krogstad, Emily; Chaowanachan, Thanyanan; Woodrow, Kim A

    2012-01-01

    Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract. PMID:23209601

  10. Effectiveness of HIV prevention social marketing with injecting drug users.

    PubMed

    Gibson, David R; Zhang, Guili; Cassady, Diana; Pappas, Les; Mitchell, Joyce; Kegeles, Susan M

    2010-10-01

    Social marketing involves applying marketing principles to promote social goods. In the context of health behavior, it has been used successfully to reduce alcohol-related car crashes, smoking among youths, and malaria transmission, among other goals. Features of social marketing, such as audience segmentation and repeated exposure to prevention messages, distinguish it from traditional health promotion programs. A recent review found 8 of 10 rigorously evaluated social marketing interventions responsible for changes in HIV-related behavior or behavioral intentions. We studied 479 injection drug users to evaluate a community-based social marketing campaign to reduce injection risk behavior among drug users in Sacramento, California. Injecting drugs is associated with HIV infection in more than 130 countries worldwide. PMID:20724686

  11. HIV Drug-Resistant Patient Information Management, Analysis, and Interpretation

    PubMed Central

    Mars, Maurice

    2012-01-01

    Introduction The science of information systems, management, and interpretation plays an important part in the continuity of care of patients. This is becoming more evident in the treatment of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), the leading cause of death in sub-Saharan Africa. The high replication rates, selective pressure, and initial infection by resistant strains of HIV infer that drug resistance will inevitably become an important health care concern. This paper describes proposed research with the aim of developing a physician-administered, artificial intelligence-based decision support system tool to facilitate the management of patients on antiretroviral therapy. Methods This tool will consist of (1) an artificial intelligence computer program that will determine HIV drug resistance information from genomic analysis; (2) a machine-learning algorithm that can predict future CD4 count information given a genomic sequence; and (3) the integration of these tools into an electronic medical record for storage and management. Conclusion The aim of the project is to create an electronic tool that assists clinicians in managing and interpreting patient information in order to determine the optimal therapy for drug-resistant HIV patients. PMID:23611761

  12. Polypharmacy, Drug-Drug Interactions, and Potentially Inappropriate Medications in Older HIV-Infected Adults

    PubMed Central

    Greene, Meredith; Steinman, Michael A.; McNicholl, Ian R.; Valcour, Victor

    2014-01-01

    Objectives To describe the frequency of medication-related problems in older HIV-infected adults Design Retrospective chart review Setting And Participants Community dwelling HIV-infected adults age 60 and older and age and sex-matched HIV-uninfected adults Measurements Total number of medications, potentially inappropriate medications as defined by the modified Beers criteria, anticholinergic drug burden as defined by the Anticholinergic Risk Scale, and drug-drug interactions using Lexi-Interact online drug interactions database. Results Of 89 HIV-infected participants, most were Caucasian (91%) and male (94%) with a median age of 64 (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and depression. Participants were taking a median of 13 medications (range 2-38), of which only a median of 4 were antiretrovirals. At least one potentially inappropriate medication was prescribed in 46 participants (52%). Sixty-two (70%) participants had at least one Category D (consider therapy modification) drug-drug interaction and 10 (11%) had a Category X (avoid combination) interaction. One-third of these interactions were between two non-antiretroviral medications. We identified 15 participants (17%) with an anticholinergic risk scale score ≥3. In contrast, HIV-uninfected participants were taking a median of 6 medications, 29% had at least one potentially inappropriate medication, and 4% had an anticholinergic risk scale score ≥ 3 (p-value <0.05 for each comparison except p=0.07 for anticholinergic burden). Conclusion HIV-infected older adults have a high frequency of medication-related problems, of which a large portion is due to medications used to treat comorbid diseases. These medication issues were substantially higher than HIV-uninfected participants. Attention to the principles of geriatric prescribing is needed as this population ages in order to minimize complications from multiple medication use. PMID:24576251

  13. Drug resistance pattern of mycobacterial isolates in HIV and non-HIV population in South India

    PubMed Central

    Shivaswamy, Umamaheshwari; Neelambike, Sumana M

    2016-01-01

    Background: Emergence of drug resistance has complicated the treatment of tuberculosis (TB). WHO reports India to be one among 27 “high burden” multidrug-resistant (MDR) TB countries. Objective: To diagnose TB and detect drug resistance of mycobacterial isolates in acid-fast bacilli (AFB) smear negative HIV reactive patients (Group A) and compare them with HIV seropositive AFB smear positive (Group B) and HIV-seronegative AFB positive cases (Group C). Materials and Methods: Clinical specimens collected in all groups were processed as per the standard protocol except blood, which was processed by lysis centrifugation technique. They were then inoculated with Lowenstein-Jensen media and the isolates obtained were subjected to drug susceptibility test (DST) by proportion method and genotype MTBDR plus assay. Results: In Group A, 162 patients were included. Of the 443 clinical samples collected, 76 mycobacterial strains were obtained from 67 (41%) patients. Of these, 50 (65.8%) were sensitive to all drugs and 26 (34.2%) resistant to one or more anti-tubercular drugs. Antibiogram of Group A when compared with Group B and C showed that the MDR rate 6.6%, 6.7% and 8% respectively) did not differ much; but resistance to at least single drug was (26 [34.2%], 3 [10%], and 8 [16%]), respectively. Conclusion: Our study suggests that HIV has no influence on the anti-tubercular resistance pattern, but increased MDR rate along with HIV in high TB burden setting stresses the need for early diagnosis and DST in providing proper regimens and improve prognosis. PMID:26933303

  14. Virtual-screening targeting Human Immunodeficiency Virus type 1 integrase-lens epithelium-derived growth factor/p75 interaction for drug development.

    PubMed

    Gu, Wan-Gang; Liu, Bai-Nan; Yuan, Jun-Fa

    2015-02-01

    Three integrase (IN) inhibitors have been approved by FDA for clinical treatment of Human Immunodeficiency Virus (HIV) infection. This stimulates more researchers to focus their studies on this target for anti-HIV drug development. Three steps regarding of IN activity have been validated for inhibitor discovery: strand transfer, 3'-terminal processing, and IN-lens epithelium-derived growth factor (LEDGF)/p75 interaction. Among them, IN-LEDGF/p75 interaction is a new target validated in recent years. Emergence of drug-resistant virus strains makes this target appealing to pharmacologists. Compared with the traditional screening methods such as AlphaScreen and cell-based screening developed for IN inhibitor discovery, virtual screening is a powerful technique in modern drug discovery. Here we summarized the recent advances of virtual-screening targeting IN-LEDFG/p75 interaction. The combined application of virtual screening and experiments in drug discovery against IN-LEDFG/p75 interaction sheds light on anti-HIV research and drug discovery. PMID:25230778

  15. Human T Cell Lymphotropic Virus Type 2a Strains Among HIV Type 1-Coinfected Patients from Brazil Have Originated Mostly from Brazilian Amerindians

    PubMed Central

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Morimoto, Helena Kaminami

    2013-01-01

    Abstract The human T cell lymphotropic virus type 2 (HTLV-2) is found mainly in Amerindians and in intravenous drug users (IDUs) from urban areas of the United States, Europe, and Latin America. Worldwide, HTLV-2a and HTLV-2b subtypes are the most prevalent. Phylogenetic analysis of HTLV-2 isolates from Brazil showed the HTLV-2a subtype, variant -2c, which spread from Indians to the general population and IDUs. The present study searched for the types of HTLV-2 that predominate among HIV-1-coinfected patients from southern and southeastern Brazil. Molecular characterization of the LTR, env, and tax regions of 38 isolates confirmed the HTLV-2c variant in 37 patients, and one HTLV-2b in a patient from Paraguay. Phylogenetic analysis of sequences showed different clades of HTLV-2 associated with risk factors and geographic region. These clades could represent different routes of virus transmission and/or little diverse evolutionary rates of virus. Taking into account the results obtained in the present study and the lack of the prototypic North American HTLV-2a strain and HTLV-2b subtypes commonly detected among HIV-coinfected individuals worldwide, we could speculate on the introduction of Brazilian HTLV-2 strains in such populations before the introduction of HIV. PMID:23484539

  16. Subtype B was the dominant strain among HIV type 1 infections except for the population of men who have sex with men in Harbin City, China.

    PubMed

    Shao, Bing; Li, Wen-Jing; Liu, Ting; Li, Qing-Hai; Li, Hang; Chang, Man-Li; Huang, Chao-Qun; Wang, Fu-Xiang; Wang, Bin-You

    2013-09-01

    We sought to identify the prevalent subtypes and study the genetic variation of HIV-1 circulating in HIV infections in Harbin City, China. Forty-seven samples from the env V3-V4 region were successfully sequenced and analyzed, which involved thirty-one men who have sex with men (MSM), eight heterosexuals, seven former plasma donors (FPD)/blood transfusion recipients (BT), and one injection drug user (IDU). In all, 46.8% of CRF01_AE, 40.4% of subtype B, and 12.8% of CRF07_BC were identified. CRF01_AE (64.5%) was the dominant strain in MSM, and subtype B (81.2%) was the chief strain in other infected subjects except for the MSM population. Among all the genotypes, the B subtype possesses greater diversity of the tetramer on the tip of V3 loop than CRF07_BC and CRF01_AE, in which the peculiar GWGR was commonly found. Because nationwide there is a trend toward the increasing presence of CRF01_AE, a consecutive surveillance campaign was necessary among all HIV vulnerable populations in this locality. PMID:23734595

  17. Comparison of HIV type 1 sequences from plasma, cell-free breast milk, and cell-associated breast milk viral populations in treated and untreated women in Mozambique.

    PubMed

    Andreotti, Mauro; Galluzzo, Clementina M; Guidotti, Giovanni; Germano, Paola; Altan, Annamaria Doro; Pirillo, Maria Franca; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Giuliano, Marina

    2009-07-01

    We analyzed the sequences of the HIV viral populations obtained from plasma, cell-free breast milk, and breast milk cells of HAART-treated (23) and untreated (30) HIV-infected women to obtain information about the origin of the breast milk virus. Sequence analyses of viruses were performed using the TruGene HIV-1 assay. Direct sequences of the reverse transcriptase (RT) and protease (PR) genes were analyzed using the Phylip 3.68 suite of sequence analysis program and pairwise evolutionary distances were calculated with the Kimura two parameter model for estimation of distances. We found that the genetic distances between the plasma and the cell-free breast milk viruses and between the cell-free and cell-associated breast milk viruses for RT were higher in HAART-receiving women than in untreated women, suggesting viral evolution under selective drug pressure in breast milk. Our data support the hypothesis of the presence of an actively replicating viral population in the breast milk compartment, distinct from that present in plasma. PMID:19552594

  18. In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV.

    PubMed

    Hazen, Richard; Harvey, Robert; Ferris, Robert; Craig, Charles; Yates, Phillip; Griffin, Philip; Miller, John; Kaldor, Istvan; Ray, John; Samano, Vincente; Furfine, Eric; Spaltenstein, Andrew; Hale, Michael; Tung, Roger; St Clair, Marty; Hanlon, Mary; Boone, Lawrence

    2007-09-01

    Brecanavir, a novel tyrosyl-based arylsulfonamide, high-affinity, human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), has been evaluated for anti-HIV activity in several in vitro assays. Preclinical assessment of brecanavir indicated that this compound potently inhibited HIV-1 in cell culture assays with 50% effective concentrations (EC(50)s) of 0.2 to 0.53 nM and was equally active against HIV strains utilizing either the CXCR4 or CCR5 coreceptor, as was found with other PIs. The presence of up to 40% human serum decreased the anti-HIV-1 activity of brecanavir by 5.2-fold, but under these conditions the compound retained single-digit nanomolar EC(50)s. When brecanavir was tested in combination with nucleoside reverse transcriptase inhibitors, the antiviral activity of brecanavir was synergistic with the effects of stavudine and additive to the effects of zidovudine, tenofovir, dideoxycytidine, didanosine, adefovir, abacavir, lamivudine, and emtricitabine. Brecanavir was synergistic with the nonnucleoside reverse transcriptase inhibitor nevirapine or delavirdine and was additive to the effects of efavirenz. In combination with other PIs, brecanavir was additive to the activities of indinavir, lopinavir, nelfinavir, ritonavir, amprenavir, saquinavir, and atazanavir. Clinical HIV isolates from PI-experienced patients were evaluated for sensitivity to brecanavir and other PIs in a recombinant virus assay. Brecanavir had a <5-fold increase in EC(50)s against 80% of patient isolates tested and had a greater mean in vitro potency than amprenavir, indinavir, lopinavir, atazanavir, tipranavir, and darunavir. Brecanavir is by a substantial margin the most potent and broadly active antiviral agent among the PIs tested in vitro. PMID:17620375

  19. HIV and drug users in Ukraine: building confidence to reduce HIV risk.

    PubMed

    Hyde, L

    1999-09-01

    This article discusses the programs of nongovernmental organizations (NGOs) towards the drug practices and sexual behaviors of HIV infected individuals and drug users in Mykolaiv, Ukraine. Blagodiynist (Charity Foundation), one of the NGOs operating in Ukraine, has been helping drug users and sex workers. This group has collaborated with other group projects to produce better and effective interventions. As such, the needle-exchange project was organized, where drug users could not only exchange needles for clean ones, but also obtain information, advice, and even condoms. Role model stories approach was also another effective method that Blagodiynist utilized to make drug users and sex workers aware not only of the risk and reality of HIV, but to encourage behavior change as well, and to generate the self-confidence needed to alter their erroneous practices. The fact that sex workers and drug users have begun to take the risks of HIV infection seriously and have taken measures to protect themselves, reflect the success of these programs. PMID:12322332

  20. Drug abuse and weight loss in HIV-infected Hispanic men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weight loss is an independent risk factor for mortality in HIV, but the role of drug use in HIV-related weight loss is not well described. We conducted this study to determine the role of drug abuse in HIV-related weight loss. Men (n=304), all of whom were Hispanic, were recruited into one of three ...

  1. Assessing dietary intake of drug abusing Hispanic adults with and without HIV infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drug abuse is an important risk factor for Human Immunodeficiency Virus (HIV) among Hispanics in the Northeastern United States and both drug abuse and HIV are associated with nutritional deficiencies. The selection of a dietary assessment method most appropriate for Hispanic adults with/without HIV...

  2. Management of HIV/AIDS in older patients–drug/drug interactions and adherence to antiretroviral therapy

    PubMed Central

    Burgess, Mary J; Zeuli, John D; Kasten, Mary J

    2015-01-01

    Patients with human immunodeficiency virus (HIV) are living longer with their disease, as HIV has become a chronic illness managed with combination antiretroviral therapy (cART). This has led to an increasing number of patients greater than 50 years old living successfully with HIV. As the number of older adults with HIV has increased, there are special considerations for the management of HIV. Older adults with HIV must be monitored for drug side effects and toxicities. Their other non-HIV comorbidities should also be considered when choosing a cART regimen. Older adults with HIV have unique issues related to medication compliance. They are more likely than the younger HIV patients to have vision loss, cognitive impairment, and polypharmacy. They may have lower expectations of their overall health status. Depression and financial concerns, especially if they are on a fixed income, may also contribute to noncompliance in the aging HIV population. PMID:26604826

  3. Agents of change: peer mentorship as HIV prevention among HIV-positive injection drug users.

    PubMed

    Mackenzie, Sonja; Pearson, Charles; Frye, Victoria; Gómez, Cynthia A; Latka, Mary H; Purcell, David W; Knowlton, Amy R; Metsch, Lisa R; Tobin, Karin E; Valverde, Eduardo E; Knight, Kelly R

    2012-04-01

    This paper presents a qualitative investigation of peer mentoring among HIV seropositive injection drug users in a randomized controlled trial, the INSPIRE study. Qualitative analyses of 68 in-depth open-ended interviews conducted in 2005 in Baltimore, New York, Miami, and San Francisco revealed that these individuals conceptualized themselves as change agents through the identity of peer mentor at the three related domains of individual, interpersonal, and community-level change. Implications for program development and future research of peer mentoring as a mechanism for HIV prevention are discussed. This study was funded by the Centers for Disease Control and Prevention and Health Resources and Services Administration (HRSA). PMID:22428820

  4. Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

    PubMed Central

    2009-01-01

    Background Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1. Methods We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively. For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry. Results We initially found that CD4+ T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4+ T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4+ T cells are more activated under HTLV-1 plus HIV co-infection. Conclusion Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4+ T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS. PMID:20028500

  5. MULTIPLE WAYS OF TARGETING APOBEC3/VIF INTERACTIONS FOR ANTI-HIV-1 DRUG DEVELOPMENT

    PubMed Central

    Smith, Jessica L.; Bu, Wei; Burdick, Ryan C.; Pathak, Vinay K.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) infections and the resulting acquired immunodeficiency syndrome (AIDS) pandemic remain a global challenge in the absence of a protective vaccine and because of rapid selection of drug-resistant viral variants in response to all currently available antiviral therapies. Development of new and highly active antiviral agents would greatly facilitate effective clinical management of HIV-1 infections and delay the onset of AIDS. Recent advances in our understanding of intracellular immunity conferred by host cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F), and the mechanism by which the virally encoded Virion Infectivity Factor (Vif) protein induces their proteasomal degradation, provide fresh opportunities for the development of novel antiviral treatments. Interestingly, the interactions between Vif-A3G and Vif-A3F that overcome this host defense mechanism are structurally distinct, and provide two potential targets for antiviral drug development. This review provides an overview of the current knowledge of APOBEC3/Vif interactions and recent efforts to target these interactions for antiviral drug development. PMID:19837465

  6. Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064.

    PubMed

    Chen, Iris; Clarke, William; Ou, San-San; Marzinke, Mark A; Breaud, Autumn; Emel, Lynda M; Wang, Jing; Hughes, James P; Richardson, Paul; Haley, Danielle F; Lucas, Jonathan; Rompalo, Anne; Justman, Jessica E; Hodder, Sally L; Eshleman, Susan H

    2015-01-01

    Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals. PMID:26445283

  7. Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064

    PubMed Central

    Chen, Iris; Clarke, William; Ou, San-San; Marzinke, Mark A.; Breaud, Autumn; Emel, Lynda M.; Wang, Jing; Hughes, James P.; Richardson, Paul; Haley, Danielle F.; Lucas, Jonathan; Rompalo, Anne; Justman, Jessica E.; Hodder, Sally L.; Eshleman, Susan H.

    2015-01-01

    Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009–2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1–4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals. PMID:26445283

  8. Unprecedented Degree of Human Immunodeficiency Virus Type 1 (HIV-1) Group M Genetic Diversity in the Democratic Republic of Congo Suggests that the HIV-1 Pandemic Originated in Central Africa

    PubMed Central

    Vidal, Nicole; Peeters, Martine; Mulanga-Kabeya, Claire; Nzilambi, Nzila; Robertson, David; Ilunga, Wantabala; Sema, Hurogo; Tshimanga, Kazadi; Bongo, Beni; Delaporte, Eric

    2000-01-01

    The purpose of this study was to document the genetic diversity of human immunodeficiency virus type 1 (HIV-1) in the Democratic Republic of Congo (DRC; formerly Zaire). A total of 247 HIV-1-positive samples, collected during an epidemiologic survey conducted in 1997 in three regions (Kinshasa [the capital], Bwamanda [in the north], and Mbuyi-Maya [in the south]), were genetically characterized in the env V3-V5 region. All known subtypes were found to cocirculate, and for 6% of the samples the subtype could not be identified. Subtype A is predominant, with prevalences decreasing from north to south (69% in the north, 53% in the capital city, and 46% in the south). Subtype C, D, G, and H prevalences range from 7 to 9%, whereas subtype F, J, K, and CRF01-AE strains represent 2 to 4% of the samples; only one subtype B strain was identified. The highest prevalence (25%) of subtype C was in the south, and CRF01-AE was seen mainly in the north. The high intersubtype variability among the V3-V5 sequences is the most probable reason for the low (45%) efficiency of subtype A-specific PCR and HMA (heteroduplex mobility assay). Eighteen (29%) of 62 samples had discordant subtype designations between env and gag. Sequence analysis of the entire envelope from 13 samples confirmed the high degree of diversity and complexity of HIV-1 strains in the DRC; 9 had a complex recombinant structure in gp160, involving fragments of known and unknown subtypes. Interestingly, the unknown fragments from the different strains did not cluster together. Overall, the high number of HIV-1 subtypes cocirculating, the high intrasubtype diversity, and the high numbers of possible recombinant viruses as well as different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV-1 group M. PMID:11044094

  9. Generic antiretroviral drugs and HIV care: An economic review.

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures. PMID:26905394

  10. Anti-HIV drug development: structural features and limitations of present day drugs and future challenges in the successful HIV/AIDS treatment.

    PubMed

    Kumari, Garima; Singh, Ramendra K

    2013-01-01

    Acquired Immune Deficiency Syndrome (AIDS), an immuno-compromized condition, a sequel to untreated human immunodeficiency virus (HIV) infection, inviting several life-threatening diseases, has become one of the most fatal disorders in the recent past because of HIV strain variance due to mutations, passive latency and reservoirs helping in replenishing and reviving the HIV-1 proviral DNA. Scientific efforts have led to the discovery of several effective drugs against HIV and lowered the morbidity and mortality all over the world. However, despite availability of a good number of anti-HIV drugs, the problem, for the foreseeable reasons, stands out as the most chronic disease due to the less tolerability and low accessibility of drugs, life-long expensive treatment, and above all, the emergence of drug resistant viral strains. This review dwells upon HIV infection and its proliferation inside the host system, drug targets, different types of drugs, their structural features and mode of interaction with viral targets and drug regimens. It further focuses on topics of latest interest regarding drug development, fixed dose combinations (FDCs), the limitations of present day drugs with their structural features along with their pharmacodynamics, pharmacokinetics and pharmacogenomics and the challenges in finding a permanent cure for HIV/AIDS. PMID:23092282

  11. [Structural changes in the brain in HIV infection complicated by drug addiction].

    PubMed

    Nasibullin, B A; Tkachev, O V; Voĭno-Iasenetskaia, O V; Pykhteev, D M

    2000-01-01

    Comparative analysis of brain alterations in drug addicts who were HIV-seropositive and died of sepsis and HIV-seronegative addicts showed similarity of these changes which manifested with ganglion cell rarefaction and losses, changed neuron content of main structural-functional types; massive satellitosis and neuronophagia, massive glycosis and leucodystrophy. These changes were diffuse in seropositive patients and rather focal in seronegative patients. The authors, on the basis of these findings, suggest a wider spread of HIV infection in drug addicts; they express doubts in the secondary nature of HIV-encephalopathy and believe that drug addiction should be considered as factor promoting HIV-infection development. PMID:11198117

  12. Differential Risk Factors for HIV Drug and Sex Risk-Taking Among Non-treatment-seeking Hospitalized Injection Drug Users

    PubMed Central

    Crooks, Denise; Tsui, Judith; Anderson, Bradley; Dossabhoy, Shernaz; Herman, Debra; Liebschutz, Jane M.; Stein, Michael D.

    2016-01-01

    Injection drug users (IDUs) are at increased risk of contracting HIV. From a clinical trial assessing an intervention to enhance the linkage of hospitalized patients to opioid treatment after discharge, we conducted multivariate analysis of baseline data from hospitalized IDUs with a history of opioid dependence (n = 104) to identify differences in factors predicting HIV drug and sex risk behaviors. Factors significantly associated with HIV drug risk were being non-Hispanic Caucasian and recent cocaine use. Being female, binge drinking, and poorer mental health were significantly associated with higher sex risk. Because factors predicting HIV sex risk behaviors differ from those predicting HIV drug risk, interventions aimed at specific HIV risks should have different behavioral and substance use targets. PMID:25063229

  13. Co-infections and transmission networks of HCV, HIV-1 and HPgV among people who inject drugs

    PubMed Central

    Tien Ng, Kim; Takebe, Yutaka; Bee Chook, Jack; Zhen Chow, Wei; Gan Chan, Kok; Abed Al-Darraji, Haider Abdulrazzaq; Kamarulzaman, Adeeba; Keng Tee, Kok

    2015-01-01

    Co-infections with human immunodeficiency virus type 1 (HIV-1) and human pegivirus (HPgV) are common in hepatitis C virus (HCV)-infected individuals. However, analysis on the evolutionary dynamics and transmission network profiles of these viruses among individuals with multiple infections remains limited. A total of 228 injecting drug users (IDUs), either HCV- and/or HIV-1-infected, were recruited in Kuala Lumpur, Malaysia. HCV, HIV-1 and HPgV genes were sequenced, with epidemic growth rates assessed by the Bayesian coalescent method. Based on the sequence data, mono-, dual- and triple-infection were detected in 38.8%, 40.6% and 20.6% of the subjects, respectively. Fifteen transmission networks involving HCV (subtype 1a, 1b, 3a and 3b), HIV-1 (CRF33_01B) and HPgV (genotype 2) were identified and characterized. Genealogical estimates indicated that the predominant HCV, HIV-1 and HPgV genotypes were introduced into the IDUs population through multiple sub-epidemics that emerged as early as 1950s (HCV), 1980s (HIV-1) and 1990s (HPgV). By determining the difference in divergence times between viral lineages (ΔtMRCA), we also showed that the frequency of viral co-transmission is low among these IDUs. Despite increased access to therapy and other harm reduction interventions, the continuous emergence and coexistence of new transmission networks suggest persistent multiple viral transmissions among IDUs. PMID:26459957

  14. Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

    PubMed Central

    Willey, Samantha J.; Reeves, Jacqueline D.; Hudson, Richard; Miyake, Koichi; Dejucq, Nathalie; Schols, Dominique; Clercq, Erik De; Bell, Jeanne; McKnight, Áine; Clapham, Paul R.

    2003-01-01

    The chemokine receptors CCR5 and CXCR4 are the major coreceptors for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). At least 12 other chemokine receptors or close relatives support infection by particular HIV and SIV strains on CD4+ transformed indicator cell lines in vitro. However, the role of these alternative coreceptors in vivo is presently thought to be insignificant. Infection of cell lines expressing high levels of recombinant CD4 and coreceptors thus does not provide a true indication of coreceptor use in vivo. We therefore tested primary untransformed cell cultures that lack CCR5 and CXCR4, including astrocytes and brain microvascular endothelial cells (BMVECs), for naturally expressed alternative coreceptors functional for HIV and SIV infection. An adenovirus vector (Ad-CD4) was used to express CD4 in CD4− astrocytes and thus confer efficient infection if a functional coreceptor is present. Using a large panel of viruses with well-defined coreceptor usage, we identified a subset of HIV and SIV strains able to infect two astrocyte cultures derived from adult brain tissue. Astrocyte infection was partially inhibited by several chemokines, indicating a role for the chemokine receptor family in the observed infection. BMVECs were weakly positive for CD4 but negative for CCR5 and CXCR4 and were susceptible to infection by the same subset of isolates that infected astrocytes. BMVEC infection was efficiently inhibited by the chemokine vMIP-I, implicating one of its receptors as an alternative coreceptor for HIV and SIV infection. Furthermore, we tested whether the HIV type 1 and type 2 strains identified were able to infect peripheral blood mononuclear cells (PBMCs) via an alternative coreceptor. Several strains replicated in Δ32/Δ32 CCR5 PBMCs with CXCR4 blocked by AMD3100. This AMD3100-resistant replication was also sensitive to vMIP-I inhibition. The nature and potential role of this alternative coreceptor(s) in HIV infection

  15. Recreational Drug Use and T Lymphocyte Subpopulations in HIV-uninfected and HIV-infected Men

    PubMed Central

    Chao, Chun; Jacobson, Lisa P; Tashkin, Donald; Martínez-Maza, Otoniel; Roth, Michael D; Margolick, Joseph B; Chmiel, Joan S; Rinaldo, Charles; Zhang, Zuo-Feng; Detels, Roger

    2009-01-01

    The effects of recreational drugs on CD4 and CD8 T cells in humans are not well understood. We conducted a longitudinal analysis of men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study to define associations between self-reported use of marijuana, cocaine, poppers and amphetamines, and CD4 and CD8 T cell parameters in both HIV-uninfected and HIV-infected MSM. For the HIV-infected MSM, we used clinical and laboratory data collected semiannually before 1996 to avoid potential effects of antiretroviral treatment. A regression model that allowed random intercepts and slopes as well as autoregressive covariance structure for within subject errors was used. Potential confounders adjusted for included length of follow-up, demographics, tobacco smoking, alcohol use, risky sexual behaviors, history of sexually transmitted infections, and antiviral therapy. We found no clinically meaningful associations between use of marijuana, cocaine, poppers, or amphetamines and CD4 and CD8 T cell counts, percentages, or rates of change in either HIV-uninfected or -infected men. The regression coefficients were of minimum magnitude despite some reaching statistical significance. No threshold effect was detected for frequent (at least weekly) or continuous substance use in the previous year. These results indicate that use of these substances does not adversely affect the numbers and percentages of circulating CD4 or CD8 T cells in either HIV-uninfected or -infected MSM. PMID:18180115

  16. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells.

    PubMed Central

    Moore, J P; Sattentau, Q J; Klasse, P J; Burkly, L C

    1992-01-01

    The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4-induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4 of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4-induced conformational changes in the envelope glycoproteins. The mechanisms of action of 5A8 and 6H10 can be further distinguished in syncytium inhibition assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks HIV-1 infection and fusion by interfering with conformational changes in gp120/gp41 and/or CD4 that are necessary for virus-cell fusion. Images PMID:1378510

  17. HIV-1 Genetic Diversity and Drug Resistance among Senegalese Patients in the Public Health System

    PubMed Central

    Thiam, Moussa; Diop-Ndiaye, Halimatou; Diouf, Aminata Diaw; Vidal, Nicole; Ndiaye, Ousseynou; Ndiaye, Ibrahima; Ngom-Gueye, Ndeye Fatou; Diallo, Sada; Diongue, Oumy Diop; Camara, Makhtar; Seck, Abdoulaye; Mboup, Souleymane

    2013-01-01

    In this study, we investigated the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations and genetic variability among Senegalese patients undergoing highly active antiretroviral therapy (ART) in the public health system. We conducted a cross-sectional study of 72 patients with suspected therapeutic failure. HIV-1 genotyping was performed with Viroseq HIV-1 Genotyping System v2.0 or the procedure developed by the ANRS AC11 resistance study group, and a phylogenetic analysis was performed. The median follow-up visit was at 40 (range, 12 to 123) months, and the median viral load was 4.67 (range, 3.13 to 6.94) log10 copies/ml. The first-line therapeutic regimen was nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) or NRTIs plus nevirapine (NVP) (54/72 patients; 75%), and the second-line therapy was NRTIs plus a protease inhibitor (PI/r) (18/72; 25%). Fifty-five patients (55/72; 76.39%) had at least one drug resistance mutation. The drug resistance rates were 72.22 and 88.89% for the first-line and second-line ARTs, respectively. In NRTI mutations, thymidine analog mutations (TAMs) were found in 50.79% and the M184V mutation was found in 34.92% of the samples. For non-NRTI resistance, we noted a predominance of the K103N mutation (46.27%). For PI/r, several cases of mutations were found with a predominance of M46I and L76V/F at 24% each. The phylogenetic analysis revealed CRF02_AG as the predominant circulating recombinant form (43/72; 59.72%). We found a high prevalence of resistance mutations and a high rate of TAMs among Senegalese patients in the public health system. These findings emphasize the need to improve virological monitoring in resource-limited settings. PMID:23241378

  18. Knowledge of AIDS and HIV transmission among drug users in Rio de Janeiro, Brazil

    PubMed Central

    2011-01-01

    Background Proper knowledge of HIV transmission is not enough for people to adopt protective behaviors, but deficits in this information may increase HIV/AIDS vulnerability. Objective To assess drug users' knowledge of HIV/AIDS and the possible association between knowledge and HIV testing. Methods A Cross-sectional study conducted in 2006/7 with a convenience sample of 295 illicit drug users in Rio de Janeiro, assessing knowledge on AIDS/HIV transmission and its relationship with HIV testing. Information from 108 randomly selected drug users who received an educational intervention using cards illustrating situations potentially associated with HIV transmission were assessed using Multidimensional Scaling (MDS). Results Almost 40% of drug users reported having never used condoms and more than 60% reported not using condoms under the influence of substances. Most drug users (80.6%) correctly answered that condoms make sex safer, but incorrect beliefs are still common (e.g. nearly 44% believed HIV can be transmitted through saliva and 55% reported that HIV infection can be transmitted by sharing toothbrushes), with significant differences between drug users who had and who had not been tested for HIV. MDS showed queries on vaginal/anal sex and sharing syringes/needles were classified in the same set as effective modes of HIV transmission. The event that was further away from this core of properly perceived risks referred to blood donation, perceived as risky. Other items were found to be dispersed, suggesting inchoate beliefs on transmission modes. Conclusions Drug users have an increased HIV infection vulnerability compared to the general population, this specific population expressed relevant doubts about HIV transmission, as well as high levels of risky behavior. Moreover, the findings suggest that possessing inaccurate HIV/AIDS knowledge may be a barrier to timely HIV testing. Interventions should be tailored to such specific characteristics. PMID:21324119

  19. Induction of a major histocompatibility complex class I-restricted cytotoxic T-lymphocyte response to a highly conserved region of human immunodeficiency virus type 1 (HIV-1) gp120 in seronegative humans immunized with a candidate HIV-1 vaccine.

    PubMed Central

    Johnson, R P; Hammond, S A; Trocha, A; Siliciano, R F; Walker, B D

    1994-01-01

    Efforts to induce broadly reactive immunity against human immunodeficiency virus type 1 (HIV-1) have been impaired by the extent of sequence variation exhibited by this lentivirus. Cytotoxic T lymphocytes (CTL) specific for other viruses such as influenza virus have been shown to mediate immunity against divergent viral strains, a property that is related to the ability of CTL to recognize processed antigen derived from conserved viral proteins. A recent candidate HIV-1 vaccine regimen has been described in which subjects receive a primary immunization with a recombinant vaccinia virus expressing gp160 and then a booster immunization with recombinant gp160. Volunteers immunized with this regimen have exhibited augmented humoral responses and have also developed CD4+ and CD8+ CTL specific for gp160. In this report, we have identified the epitopes recognized by CD4+ and CD8+ CTL obtained from two vaccines. An immunodominant CD8+ CTL response was HLA-A3.1 restricted and recognized a 10-amino-acid epitope (gp120/38-47) in a highly conserved region of gp120. CTL specific for the epitope gp120/38-47 were able to lyse targets sensitized with peptides corresponding to all known natural sequence variants in this region. In addition, other HLA class I-restricted CTL epitopes were identified in relatively conserved regions of gp120 and gp41, and CD4+ CTL were shown to recognize two different regions of gp120. Thus, in these two volunteers, immunization with a single strain of HIV-1 induced CD4+ and CD8+ CTL that are specific for multiple conserved regions of HIV-1 and would be expected to recognize a broad range of viral isolates. PMID:7908700

  20. Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals

    PubMed Central

    Winand, Raf; Theys, Kristof; Eusébio, Mónica; Aerts, Jan; Camacho, Ricardo J.; Gomes, Perpetua; Suchard, Marc A.; Vandamme, Anne-Mieke; Abecasis, Ana B.

    2015-01-01

    Objectives: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. Design: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. Methods: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. Results: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers – above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. Conclusion: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with

  1. Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages.

    PubMed Central

    Murphy, K M; Sweet, M J; Ross, I L; Hume, D A

    1993-01-01

    The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells

  2. Alcohol and HIV sexual risk behaviors among injection drug users.

    PubMed

    Arasteh, Kamyar; Des Jarlais, Don C; Perlis, Theresa E

    2008-05-01

    We analyzed data from 6341 injection drug users (IDUs) entering detoxification or methadone maintenance treatment in New York City between 1990 and 2004 to test the hypothesis that alcohol use and intoxication is associated with increased HIV sexual risk behaviors. Two types of associations were assessed: (1) a global association (i.e., the relationship between HIV sexual risk behaviors during the 6 months prior to the interview and at-risk drinking in that period, defined as more than 14 drinks per week for males or 7 drinks per week for females), and (2) an event-specific association (i.e., the relationship between HIV sexual risk behaviors during the most recent sex episode and alcohol intoxication during that episode). Sexual risk behaviors included multiple sex partners and engaging in unprotected sex. After adjusting for the effects of other variables, at-risk-drinkers were more likely to report multiple sex partners and engaging in unprotected sex with casual sex partners (both global associations). IDUs who reported both they and their casual partners were intoxicated during the most recent sex episode were more likely to engage in unprotected sex (an event-specific association). We also observed two significant interactions. Among IDUs who did not inject cocaine, moderate-drinkers were more likely to report multiple partners. Among self-reported HIV seropositive IDUs, when both primary partners were intoxicated during the most recent sex episode they were more likely to engage in unprotected sex. These observations indicate both global and event-specific associations of alcohol and HIV sexual-risk behaviors. PMID:18242009

  3. Differences between the course of the drug addict's HIV infection and that of other HIV-infected patients.

    PubMed

    Gölz, J

    1993-11-01

    Drug addicts have, in general, a less complicated course of HIV infection than homosexual HIV patients. They show fewer opportunistic infections and tumors. But this advantage is lost by unnecessary complications due to their psychic disorders. Their non-compliance and concealment of signs of disease lead to worse outcomes of infections, which could be well-treated or prevented. PMID:8300042

  4. Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

    PubMed

    de Pina-Araujo, Isabel Inês M; Guimarães, Monick L; Bello, Gonzalo; Vicente, Ana Carolina P; Morgado, Mariza G

    2014-01-01

    HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1-75) and 47 (IQR = 12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented

  5. Profile of the HIV Epidemic in Cape Verde: Molecular Epidemiology and Drug Resistance Mutations among HIV-1 and HIV-2 Infected Patients from Distinct Islands of the Archipelago

    PubMed Central

    de Pina-Araujo, Isabel Inês M.; Guimarães, Monick L.; Bello, Gonzalo; Vicente, Ana Carolina P.; Morgado, Mariza G.

    2014-01-01

    HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010–2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1–75) and 47 (IQR = 12–84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be

  6. Why Do We Need New Drug Classes for HIV Treatment and Prevention?

    PubMed

    Waheed, Abdul A; Tachedjian, Gilda

    2016-01-01

    The biomedical intervention that has had a major impact on the natural history of HIV and on the global HIV epidemic is antiretroviral therapy (ART). However, the emergence of drug-resistant HIV, an inevitable consequence of increasing use of antiretroviral drugs, poses a major threat to ART success. At the turn of this century, access to life-saving ART was accelerated in low and middle-income countries with the Millennium Development Goal of 15 million individuals receiving ART by 2015 expected to be achieved. However, ART access needs to continue to expand to help bring HIV under control by 2030. The standard of care for people living with HIV in resource- limited settings differs dramatically compared to high-income countries, and not unexpectedly, ART rollout in these settings has resulted in an increase in acquired and transmitted drug resistance. Also of concern, the same drug classes used for ART have been approved or are being progressed for HIV prevention and drug resistance could mitigate their effectiveness for treatment and prevention. In the absence of an effective HIV vaccine and cure, it is imperative that the antiretroviral drug pipeline contains new classes of HIV inhibitors that are active against circulating drug-resistant strains. Studies to advance our fundamental understanding of HIV replication needs to continue, including the interplay between virus and host cell factors, to identify and characterize new drug targets for chemotherapeutic intervention. PMID:26459806

  7. The ethics of HIV research with people who inject drugs in Africa: a desk review.

    PubMed

    Mamotte, Nicole

    2012-03-01

    Injecting drug use is a growing problem in Africa and a growing risk factor for contracting HIV in the region. It is imperative that HIV research includes injecting drug users so that they too are able to benefit from safe and effective behavioural interventions and biomedical HIV prevention and treatment products. This article relates a critical review of the findings of a desk review of previously published literature. The article examines injecting drug use in relation to HIV-related risk and research in Kenya, Mauritius, Nigeria, South Africa and Tanzania. The ethical challenges of including people who inject drugs in HIV research in Africa are also presented. The review found injecting drug use to be on the increase in all the countries reviewed. HIV-risk behaviour among people who inject drugs, such as needle-sharing and higher-risk sexual behaviour, was also found to be widespread. Furthermore, criminalisation of drug use and strict anti-drug laws are common in the countries reviewed, while harm-reduction programmes for people who inject drugs were found to be limited. The review identified a number of ethical challenges to the involvement of people who inject drugs in HIV research in Africa. This includes the illegal status and stigma surrounding injecting drug use, which may complicate participant recruitment, enrolment and retention. In addition, a lack of funding for supportive programmes to help injecting drug users may hinder the provision of appropriate standards of prevention and care and treatment for those who seroconvert. PMID:25870892

  8. HIV drug resistance interpreted by cumulative versus last genotypes in HIV-infected patients with multiple treatment failures.

    PubMed

    Punyacam, Punthiya; Iemwimangsa, Nareenart; Chantratita, Wasun; Sukasem, Chonlaphat; Sungkanuparph, Somnuek

    2012-04-01

    Genotypic resistance test has been recommended to evaluate HIV drug resistance and guide the effective regimens of antiretroviral therapy (ART) in HIV-infected patients with treatment failure. In patients with multiple treatment failures, drug resistance-associated mutations may disappear due to the loss of selective drug pressure after switching regimens. A cohort study was conducted among HIV-infected patients who had ≥2 genotypic resistance tests during 2003-2011. HIV-1 pol nucleotide sequencing of reverse transcriptase and protease region was carried out using TRUGENE HIV-1 Genotypic Assay. Sequencing data was analyzed using Stanford rule-based interpretation algorithms. Of 54 patients with mean age of 30.1 years, 46.3% were males. HIV-1 subtype A/E was observed in 88.9% of patients. At the latest failure, 55.3% were receiving protease inhibitor-based regimens. Median CD4 and HIV RNA were 167 cells/mm(3) and 22,359 copies/mL. During a median duration of ART of 38.6 months, 72.2%, 22.2%, and 5.6% had 5, 3, and 2 genotype tests, respectively. When compared between using cumulative (CG) and last genotypes (LG), CG interpreted resistance to any drug 59.3% higher than LG did. For NRTI, NNRTI, and PI drug classes, CG interpreted as resistance 42.6%, 27.8%, and 7.4% higher than LG, respectively. The most common drugs that CG interpreted resistance with the higher rate than LG were lamivudine/emtricitabine, nevirapine, efavirenz, etravirine and abacavir. In conclusion, CG interprets HIV drug resistance at a higher rate than LG and may be more accurate to use for selecting the next effective regimen of ART among HIV-infected patients with multiple treatment failures. PMID:22497699

  9. [Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

    PubMed

    Fukutake, Katsuyuki

    2015-11-01

    Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review]. PMID:26995879

  10. Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 strains at a potency similar to that for wild-type virus.

    PubMed Central

    Balzarini, J; Brouwer, W G; Dao, D C; Osika, E M; De Clercq, E

    1996-01-01

    A large variety of carboxanilide and thiocarboxanilide derivatives in which the original oxathiin or aliphatic moieties present in the prototype compounds UC84 and UC38 were replaced by an (un) substituted furanyl, thienyl, phenyl, or pyrrole entity have been evaluated for activity against wild-type human immunodeficiency virus type 1 strain IIIB [HIV-1 (IIIB)] and a series of mutant virus strains derived thereof. The mutant viruses contained either the Leu-100-->Ile, Lys-103-->Asn, Val-106-->Ala, Glu-138-->Lys, Tyr-181-->Cys, or Tyr-188-->Leu mutation in their reverse transcriptase. Several 3-(2-methylfuranyl)- and 3-(2-methylthienyl)-thiocarboxanilide ester, (thio)ether, and oxime ether derivatives showed exquisitely potent antiviral activity against wild-type HIV-1 (50% effective concentration, 0.009 to 0.021 microM). The pentenylethers of the 2-methylfuranyl and 2-methylthienyl derivatives (i.e., 313, N-[4-chloro-3-(3-methyl-2-butenyloxy)phenyl]- 2-methyl-3-furancarbothioamide or UC-781, and 314, N-[4-chloro-3-(3-methyl-2-butenyloxy)phenyl] -2-methyl-3-thiophenecarbothioamide or UC-82) proved virtually equally inhibitory for wild-type and the Ile-100, Ala-106, and Lys-138 mutant virus strains (50% effective concentration, 0.015 to 0.021 microM). Their inhibitory effect against the Asn-103 and Cys-181 reverse transcriptase mutant virus strains was decreased only four- to sevenfold compared with wildtype virus. UC-781 and UC-82 should be considered potential candidate drugs for the treatment of HIV-1-infected individuals. PMID:8726019

  11. HIV infection among persons who inject drugs: ending old epidemics and addressing new outbreaks.

    PubMed

    Des Jarlais, Don C; Kerr, Thomas; Carrieri, Patrizia; Feelemyer, Jonathan; Arasteh, Kamyar

    2016-03-27

    AIDS among persons who inject drugs, first identified in December 1981, has become a global epidemic. Injecting drug use has been reported in 148 countries and HIV infection has been seen among persons who inject drugs in 61 countries. Many locations have experienced outbreaks of HIV infection among persons who inject drugs, under specific conditions that promote very rapid spread of the virus. In response to these HIV outbreaks, specific interventions for persons who inject drugs include needle/syringe exchange programs, medicated-assisted treatment (with methadone or buprenorphine) and antiretroviral therapy. Through a 'combined prevention' approach, these interventions significantly reduced new HIV infections among persons who inject drugs in several locations including New York City, Vancouver and France. The efforts effectively ended the HIV epidemic among persons who inject drugs in those locations. This review examines possible processes through which combined prevention programs may lead to ending HIV epidemics. However, notable outbreaks of HIV among persons who inject drugs have recently occurred in several countries, including in Athens, Greece; Tel-Aviv, Israel; Dublin, Ireland; as well as in Scott County, Indiana, USA. This review also considers different factors that may have led to these outbreaks. We conclude with addressing the remaining challenges for reducing HIV infection among persons who inject drugs. PMID:26836787

  12. Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus type 1 (HIV-1): interference with early and late events in HIV-1 replication.

    PubMed

    Steinkasserer, A; Harrison, R; Billich, A; Hammerschmid, F; Werner, G; Wolff, B; Peichl, P; Palfi, G; Schnitzel, W; Mlynar, E

    1995-02-01

    SDZ NIM 811 is a cyclosporin A analog that is completely devoid of immunosuppressive capacity but exhibits potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity. The mechanism of action of SDZ NIM 811 is clearly different from those of all other anti-HIV agents described so far. In cell-free assays, it is not an inhibitor of reverse transcriptase, protease, integrase, and it does not interfere with Rev or Tat function. SDZ NIM 811 does not down-regulate CD4 or inhibit fusion between infected and uninfected, CD4-expressing cells. p24 production from chronically HIV-infected cells is not impaired either. To elucidate the mode of action of SDZ NIM 811, we performed DNA PCR analysis in HIV-1 IIIB-infected MT4 cells in one cycle of virus replication. The effects of SDZ NIM 811 on the kinetics of viral DNA synthesis, appearance of two-long terminal repeat circles (2-LTR circles), and integration of DNA were studied. SDZ NIM 811 inhibited 2-LTR circle formation in a concentration-dependent manner, which is indicative of nuclear localization of preintegration complexes. Half-maximal inhibition was achieved at 0.17 microgram/ml; this concentration is close to the 50% inhibitory concentrations (0.01 to 0.2 microgram/ml) for viral growth inhibition. As expected, integration of proviral DNA into cellular DNA was also inhibited by SDZ NIM 811. Analysis of the viral particles produced by SDZ NIM 811-treated, chronically infected cells revealed amounts of capsid proteins, reverse transcriptase activity, and viral RNA comparable to those of the untreated control. However, these particles showed a dose-dependent reduction in infectivity (50% inhibitory concentration of 0.028 microgram/ml) which indicates that the assembly process is also impaired by SDZ NIM 811. Gag proteins are postulated to play a role not only in assembly but also in early steps of viral replication, e.g., nuclear localization of the preintegration complex. Recently, it was reported that

  13. Prevention of HIV Infection among Injection Drug Users in Resource-Limited Settings

    PubMed Central

    Vlahov, David; Robertson, Angela M.; Strathdee, Steffanie A.

    2011-01-01

    Injection drug use contributes to considerable global morbidity and mortality associated with human immunodeficiency virus (HIV) infection and AIDS and other infections due to blood-borne pathogens through the direct sharing of needles, syringes, and other injection equipment. Of ~16 million injection drug users (IDUs) worldwide, an estimated 3 million are HIV infected. The prevalence of HIV infection among IDUs is high in many countries in Asia and eastern Europe and could exacerbate the HIV epidemic in sub- Saharan Africa. This review summarizes important components of a comprehensive program for prevention of HIV infection in IDUs, including unrestricted legal access to sterile syringes through needle exchange programs and enhanced pharmacy services, treatment for opioid dependence (i.e., methadone and buprenorphine treatment), behavioral interventions, and identification and treatment of noninjection drug and alcohol use, which accounts for increased sexual transmission of HIV. Evidence supports the effectiveness of harm-reduction programs over punitive drug-control policies. PMID:20397939

  14. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.

    PubMed

    De Clercq, Erik

    2009-04-01

    In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co-receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs: raltegravir). These compounds should be used in drug combination regimens to achieve the highest possible benefit, tolerability and compliance and to diminish the risk of resistance development. PMID:19108994

  15. Helping the urban poor stay with antiretroviral HIV drug therapy.

    PubMed Central

    Bamberger, J D; Unick, J; Klein, P; Fraser, M; Chesney, M; Katz, M H

    2000-01-01

    Recent studies have documented dramatic decreases in opportunistic infections, hospitalizations, and mortality among HIV-infected persons, owing primarily to the advent of highly active antiretroviral medications. Unfortunately, not all segments of the population living with HIV benefit equally from treatment. In San Francisco, only about 30% of the HIV-infected urban poor take combination highly active antiretroviral medications, as compared with 88% of HIV-infected gay men. Practitioners who care for the urban poor are reluctant to prescribe these medications, fearing inadequate or inconsistent adherence to the complicated medical regimen. Persons typically must take 2 to 15 pills at a time, 2 to 3 times a day. Some of the medications require refrigeration, which may not be available to the homeless poor. Most homeless persons do not have food available to them on a consistent schedule. Therefore, they may have difficulty adhering to instructions to take medications only on an empty stomach or with food. Lack of a safe place to store medications may be an issue for some. In addition, many urban poor live with drug, alcohol, or mental health problems, which can interfere with taking medications as prescribed. Inconsistent adherence to medication regimens has serious consequences. Patients do not benefit fully from treatments, and they will become resistant to the medications in their regimen as well as to other medications in the same classes as those in their regimen. Development of resistance has implications for the broader public health, because inadvertent transmission of multidrug-resistant strains of HIV has been demonstrated. Concern that the urban poor will not adhere to highly active antiretroviral medication regimens has led to debate on the role of clinicians and public health officials in determining who can comply with these regimens. Rather than define the characteristics that would predict adherence to these regimens, the San Francisco Department

  16. Syndemic vulnerability, sexual and injection risk behaviors, and HIV continuum of care outcomes in HIV-positive injection drug users

    PubMed Central

    Mizuno, Yuko; Purcell, David W.; Knowlton, Amy R.; Wilkinson, James D.; Gourevitch, Marc N.; Knight, Kelly R.

    2015-01-01

    Limited investigations have been conducted on syndemics and HIV continuum of care outcomes. Using baseline data from a multi-site, randomized controlled study of HIV-positive injection drug users (n=1052), we examined whether psychosocial factors co-occurred, and whether these factors were additively associated with behavioral and HIV continuum of care outcomes. Experiencing one type of psychosocial problem was significantly (p<0.05) associated with an increased odds of experiencing another type of problem. Persons with 3 or more psychosocial problems were significantly more likely to report sexual and injection risk behaviors and were less likely to be adherent to HIV medications. Persons with 4 or more problems were less likely to be virally suppressed. Reporting any problems was associated with not currently taking HIV medications. Our findings highlight the association of syndemics not only with risk behaviors, but also with outcomes related to the continuum of care for HIV-positive persons. PMID:25249392

  17. Simian-tropic HIV as a model to study drug resistance against integrase inhibitors.

    PubMed

    Wares, Melissa; Hassounah, Said; Mesplède, Thibault; Sandstrom, Paul A; Wainberg, Mark A

    2015-04-01

    Drug resistance represents a key aspect of human immunodeficiency virus (HIV) treatment failure. It is important to develop nonhuman primate models for studying issues of drug resistance and the persistence and transmission of drug-resistant viruses. However, relatively little work has been conducted using either simian immunodeficiency virus (SIV) or SIV/HIV recombinant viruses for studying resistance against integrase strand transfer inhibitors (INSTIs). Here, we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid and vif regions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1 [stHIV-1](SCA,SVIF)) to study the impact of a number of drug resistance substitutions in the integrase coding region at positions E92Q, G118R, E138K, Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral replication capacity. Our results show that each of these substitutions exerted effects that were similar to their effects in HIV-1. Substitutions associated with primary resistance against dolutegravir were more detrimental to stHIV-1(SCA,SVIF) infectiousness than were resistance substitutions associated with raltegravir and elvitegravir, consistent with data that have been reported for HIV-1. These findings support the role of stHIV-1(SCA,SVIF) as a useful model with which to evaluate the role of INSTI resistance substitutions on viral persistence, transmissibility, and pathogenesis in a nonhuman primate model. PMID:25583721

  18. HIV/AIDS, Drug Abuse Treatment, and the Correctional System.

    ERIC Educational Resources Information Center

    Lipton, Douglas S.

    1997-01-01

    Discusses in-prison prevalence and transmission of Human Immunodeficiency Virus (HIV). Focuses on epidemiology in prison settings, the role of ethnicity and gender in transmission, screening for HIV, segregating the HIV-positive inmate, condom distribution, medical treatment for HIV-positive inmates, HIV education and prevention, and tuberculosis…

  19. Sexual Risk Taking among HIV-Positive Injection Drug Users: Contexts, Characteristics, and Implications for Prevention

    ERIC Educational Resources Information Center

    Knight, Kelly R.; Purcell, David; Dawson-Rose, Carol; Halkitis, Perry N.; Gomez, Cynthia A.

    2005-01-01

    HIV-positive injection drug users (IDUs) (N = 161) were recruited to complete a qualitative interview and a quantitative survey about sexual behavior and transmission risk. We identified two contexts in which exposure encounters occurred most commonly for HIV-positive IDUs: in intimate serodiscordant relationships and in the drug/sex economy.…

  20. Insights into the mechanism of drug resistance. X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex

    SciTech Connect

    Liu, Zhigang; Yedidi, Ravikiran S.; Wang, Yong; Dewdney, Tamaria G.; Reiter, Samuel J.; Brunzelle, Joseph S.; Kovari, Iulia A.; Kovari, Ladislau C.

    2013-01-08

    Ritonavir (RTV) is a first generation HIV-1 protease inhibitor with rapidly emerging drug resistance. Mutations at residues 46, 54, 82 and 84 render the HIV-1 protease drug resistant against RTV. We report the crystal structure of multi-drug resistant (MDR) 769 HIV-1 protease (carrying resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84 and 90) complexed with RTV and the in vitro enzymatic IC50 of RTV against MDR HIV-1 protease. The structural and functional studies demonstrate significant drug resistance of MDR HIV-1 protease against RTV, arising from reduced hydrogen bonds and Van der Waals interactions between RTV and MDR HIV-1 protease.

  1. The HIV antiretroviral drug efavirenz has LSD-like properties.

    PubMed

    Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

    2013-11-01

    Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

  2. Infective endocarditis in an HIV-infected intravenous drug user.

    PubMed

    Mėlinytė, Karolina; Savickaitė, Jurgita; Rekienė, Daiva Emilija; Naudžiūnas, Albinas; Burkauskienė, Aušra; Jankauskienė, Laima

    2015-10-01

    Infective endocarditis is a common complication among injecting drug users. Disease risk among these patients is increased by the spread of HIV infection. In the following article, we discuss the exceptional clinical presentation of a 28-year-old patient who used intravenous drugs (heroin) for 10 years, had been infected with HIV for seven years and as a complication had developed Staphylococcus aureus infective endocarditis. The patient came to the hospital in serious condition, complaining of bodily pain, swelling of the legs and general weakness. During hospitalization, besides infective endocarditis, she was also diagnosed with anemia, toxic hepatitis, renal failure, ascites, sepsis, and pneumonia. A completely disrupted tricuspid valve, damaged aortic valve, and fibrosis of the mitral valve were detected. Echocardiographic and radiologic data showed that the patient's condition continued to deteriorate day by day, with significant progression of heart failure, ejection fraction decreasing from 45% to 10%, and development of myocarditis, hydrothorax and pericarditis. However, this progressive worsening of the patient's condition ceased when vancomycin was administered. To the authors' knowledge, this is the first such case described in the literature in which significant improvement was observed despite the patient's complex condition with associated complications. PMID:26417654

  3. From addiction to infection: managing drug abuse in the context of HIV/AIDS in Africa.

    PubMed

    Akindipe, Taiwo; Abiodun, Lolade; Adebajo, Sylvia; Lawal, Rahman; Rataemane, Solomon

    2014-09-01

    People who use drugs are at higher risk of HIV: directly through the sharing of injecting equipment, indirectly through associated risk behavior, and physiologically through the substances' impact on the immune system. Drug users, especially people who inject drugs (PWID) are a bridge to the general population. The treatment of drug addiction and provision of harm reduction interventions have impact on HIV transmission and incidence. Addiction treatment reduces the frequency of drug-related risky behaviors and enhances access and adherence to HIV treatment, resulting in fewer new infections. However, the drug policies of many African countries are punitive and hostile to harm reduction programs. These fuel criminalization of drug use and discrimination against the drug user thereby preventing individuals with drug addiction from accessing treatment programs. There is need to formulate policies aimed at protecting the rights of people with drug addiction and address the ethical aspects of treatment. PMID:26050376

  4. HIV Infection Among People Who Inject Drugs: The Challenge of Racial/Ethnic Disparities

    PubMed Central

    Des Jarlais, Don C.; McCarty, Dennis; Vega, William A.; Bramson, Heidi

    2013-01-01

    Racial/ethnic disparities in HIV infection, with minority groups typically having higher rates of infection, are a formidable public health challenge. In the United States, among both men and women who inject drugs, HIV infection rates are elevated among non-Hispanic Blacks and Hispanics. A meta-analysis of international research concluded that among persons who inject drugs, racial and ethnic minorities were twice as likely to acquire an HIV infection, though there was great variation across the individual studies. To examine strategies to reduce racial/ethnic disparities among persons who inject drugs, we reviewed studies on injection drug use and its role in HIV transmission. We identified four sets of evidence-based interventions that may reduce racial ethnic disparities among persons who inject drugs: HIV counseling and testing, risk reduction services, access to anti-retroviral therapy, and drug abuse treatment. Implementation of these services, however, is insufficient in many countries, including the US. Persons who inject drugs appear to be changing drug use norms and rituals to reduce risks. The challenges are to 1) develop a validated model of how racial/ethnic disparities in HIV infection arise, persist, and are reduced or eliminated over time, and 2) implement evidence-based services on a sufficient scale to eliminate HIV transmission among all persons who inject drugs. PMID:23688094

  5. Epidemic human immunodeficiency virus (HIV) infection among intravenous drug users (IVDU).

    PubMed Central

    D'Aquila, R. T.; Williams, A. B.

    1987-01-01

    Human immunodeficiency virus (HIV) infection is epidemic among intravenous drug users (IVDU), particularly in the northeastern United States. IVDU are playing a critical role in the spread of HIV by infecting their heterosexual partners and children, as well as their needle-sharing partners. The epidemiology of HIV infection among IVDU is reviewed here, including a compilation of seroprevalence data. Relevant determinants of the future spread of HIV among IVDU are discussed, including the major risk factors for HIV seropositivity, the modes of HIV transmission, and aspects of the natural history of HIV infection in IVDU. The public health policy implications of these issues include the need for education of adolescents and the general public about the risks of drug injection and heterosexual intercourse with IVDU, as well as motivation of IVDU to stop injecting, never share injection paraphernalia, or, at least, clean needles effectively. PMID:3324506

  6. HIV and Recent Illicit Drug Use Interact to Affect Verbal Memory in Women

    PubMed Central

    Meyer, Vanessa J.; Rubin, Leah H.; Martin, Eileen; Weber, Kathleen M.; Cohen, Mardge H.; Golub, Elizabeth T.; Valcour, Victor; Young, Mary A.; Crystal, Howard; Anastos, Kathryn; Aouizerat, Bradley E.; Milam, Joel; Maki, Pauline M.

    2013-01-01

    Objective HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed and executive function in the multicenter Women's Interagency HIV Study (WIHS). Methods Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age=42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test - Revised (HVLT-R) and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n=140), former users (lifetime cocaine or heroin use but not in past 6 months, n=651), and non-users (no lifetime use of cocaine or heroin, n=604). Results The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (p's<.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared to non-use) negatively impacted verbal learning and memory only in HIV-infected women (p's <0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test. Conclusion The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks. PMID:23392462

  7. In vitro model of mycobacteria and HIV-1 co-infection for drug discovery.

    PubMed

    Vijayakumar, Sudhamathi; Finney John, Sarah; Nusbaum, Rebecca J; Ferguson, Monique R; Cirillo, Jeffrey D; Olaleye, Omonike; Endsley, Janice J

    2013-12-01

    Tuberculosis (TB) has become a global health threat in the wake of the Human Immunodeficiency Virus (HIV) pandemic and is the leading cause of death in people with HIV/AIDS. Treatment of patients with Mycobacterium tuberculosis (Mtb)/HIV co-infection is complicated by drug interactions and toxicity that present huge challenges for clinical intervention. Discovery efforts to identify novel compounds with increased effectiveness and decreased drug-drug interactions against Mtb, HIV-1, or both, would be greatly aided by the use of a co-infection model for screening drug libraries. Currently, inhibitors of Mtb are screened independently in mycobacterial cell cultures or target based biochemical screens and less often in macrophages or peripheral blood leukocytes. Similarly, HIV-1 drugs are screened in vitro independently from anti-mycobacterial compounds. Here, we describe an in vitro model where primary human peripheral blood mononuclear cells or monocyte-derived macrophages are infected with Mycobacterium bovis BCG and HIV-1, and used to evaluate drug toxicity and activity in a co-infection setting. Our results with standard compounds (e.g. Azidothymidine, Rifampicin) demonstrate the utility of this in vitro model to evaluate drug effectiveness relevant to cellular toxicity, HIV-1 replication, and intracellular mycobacterial growth, through the use of ELISA, bacterial enumeration, and multi-variate flow cytometry. This model and associated assays have great value in accelerating the discovery of compounds for use in Mtb/HIV-1 co-infected patients. PMID:24388652

  8. Short Communication Phylogenetic Characterization of HIV Type 1 CRF01_AE V3 Envelope Sequences in Pregnant Women in Northern Vietnam

    PubMed Central

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca

    2012-01-01

    Abstract Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005–2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology. PMID:21936713

  9. Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors

    SciTech Connect

    Pugach, Pavel; Ketas, Thomas J.; Michael, Elizabeth; Moore, John P.

    2008-08-01

    The small molecule CCR5 inhibitors are a new class of drugs for treating infection by human immunodeficiency virus type 1 (HIV-1). They act by binding to the CCR5 co-receptor and preventing its use during HIV-1-cell fusion. Escape mutants can be raised against CCR5 inhibitors in vitro and will arise when these drugs are used clinically. Here, we have assessed the responses of CCR5 inhibitor-resistant viruses to other anti-retroviral drugs that act by different mechanisms, and their sensitivities to neutralizing antibodies (NAbs). The rationale for the latter study is that the resistance pathway for CCR5 inhibitors involves changes in the HIV-1 envelope glycoproteins (Env), which are also targets for NAbs. The escape mutants CC101.19 and D1/85.16 were selected for resistance to AD101 and vicriviroc (VVC), respectively, from the primary R5 HIV-1 isolate CC1/85. Each escape mutant was cross-resistant to other small molecule CCR5 inhibitors (aplaviroc, maraviroc, VVC, AD101 and CMPD 167), but sensitive to protein ligands of CCR5: the modified chemokine PSC-RANTES and the humanized MAb PRO-140. The resistant viruses also retained wild-type sensitivity to the nucleoside reverse transcriptase inhibitor (RTI) zidovudine, the non-nucleoside RTI nevirapine, the protease inhibitor atazanavir and other attachment and fusion inhibitors that act independently of CCR5 (BMS-806, PRO-542 and enfuvirtide). Of note is that the escape mutants were more sensitive than the parental CC1/85 isolate to a subset of neutralizing monoclonal antibodies and to some sera from HIV-1-infected people, implying that sequence changes in Env that confer resistance to CCR5 inhibitors can increase the accessibility of some NAb epitopes. The need to preserve NAb resistance may therefore be a constraint upon how escape from CCR5 inhibitors occurs in vivo.

  10. Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors.

    PubMed Central

    Balzarini, J; Karlsson, A; Vandamme, A M; Pérez-Pérez, M J; Zhang, H; Vrang, L; Oberg, B; Bäckbro, K; Unge, T; San-Félix, A

    1993-01-01

    We recently reported that a newly discovered class of nucleoside analogues--[2',5'-bis-O-(tert-butyldimethylsilyl)- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D - pentofuranosyl derivatives of pyrimidines and purines (designated TSAO)--are highly specific inhibitors of human immunodeficiency virus type 1 (HIV-1) and targeted at the nonsubstrate binding site of HIV-1 reverse transcriptase (RT). We now find that HIV-1 strains selected for resistance against three different TSAO nucleoside derivatives retain sensitivity to the other HIV-1-specific nonnucleoside derivatives (tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine, nevirapine, and pyridinone L697,661, as well as to the nucleoside analogues 3'-azido-3'-deoxythymidine, ddI, ddC, and 9-(2-phosphonylmethoxyethyl)adenine. Pol gene nucleotide sequence analysis of the TSAO-resistant and -sensitive HIV-1 strains revealed a single amino acid substitution at position 138 (Glu-->Lys) in the RT of all TSAO-resistant HIV-1 strains. HIV-1 RT in which the Glu-138-->Lys substitution was introduced by site-directed mutagenesis and expressed in Escherichia coli could not be purified because of rapid degradation. However, HIV-1 RT containing the Glu-138-->Arg substitution was stable. It lost its sensitivity to the TSAO nucleosides but not to the other HIV-1-specific RT inhibitors (i.e., TIBO and pyridinone). Our findings point to a specific interaction of the 4''-amino group on the 3'-spiro-substituted ribose moiety of the TSAO nucleosides with the carboxylic acid group of glutamic acid at position 138 of HIV-1 RT. PMID:7688467

  11. The interaction of drug use, sex work, and HIV among transgender women.

    PubMed

    Hoffman, Beth R

    2014-06-01

    Transgender women have a higher prevalence of drug use, HIV, drug use, and sex work than the general population. This article explores the interaction of these variables and discusses how sex work and drug use behaviors contribute to the high rates of HIV. A model predicting HIV rates with sex work and drug use as well as these behaviors in the transgender woman's social network is presented. Challenges to intervening with transgender women, as well as suggestions and criteria for successful interventions, are discussed. PMID:24779504

  12. Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

    PubMed

    Lee, Shinwon; Lee, Sun Hee; Mok, Jeong Ha; Lee, Su Jin; Kim, Kye Hyung; Lee, Jeong Eun; Lee, Seung Geun; Chung, Joo Seop; Kwak, Ihm Soo

    2016-11-01

    The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea. PMID:27593882

  13. Detecting primary drug-resistant mutations in Korean HIV patients using ultradeep pyrosequencing.

    PubMed

    Cho, Min-Chul; Park, Chang-Wook; Park, Borae G; Oh, Heung-Bum; Choi, Sang-Ho; Choi, Sung-Eun; Cho, Nam-Sun

    2016-08-01

    HIV primary resistance, drug resistance in treatment-naïve patients, is an emerging public health issue. The prevalence of HIV primary resistance mutations down to the level of 1% minor variants was investigated using ultradeep pyrosequencing (UDPS) in HIV-positive Korean blood donors and in treatment naïve chronic patients for the comparison. The entire pol region was sequenced from 25 HIV-positive blood donors, and 18 treatment-naïve chronic HIV patients. UDPS was successful in 19 blood donors and 18 chronic patients. In total, 1,011,338 sequence reads were aligned, and 28,093 sequence reads were aligned on average per sample. The prevalence of HIV primary resistance mutations in the HIV-positive blood donors and chronic HIV patients were 63.2% and 44.4% according to UDPS, respectively. Protease inhibitor (PI) drugs demonstrated different patterns in HIV-positive blood donors and chronic HIV patients, whereas non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and integrase inhibitor (INI) drugs showed similar patterns between the two groups. Higher level of primary resistance prevalence was observed mainly because UDPS method could detect mutations in minor variants with 1-10% frequency. The higher resistance prevalence was observed in HIV-positive blood donors than in chronic patients. Considering that treatments for HIV-infected patients were recently amended to start at an earlier stage, information about degree of drug resistance to each drug between the two groups would help to establish future policies, design additional clinical trials, assess HIV patient care in Korea. PMID:27109046

  14. Sex, drugs, and HIV: rapid assessment of HIV risk behaviors among street-based drug using sex workers in Durban, South Africa.

    PubMed

    Needle, Richard; Kroeger, Karen; Belani, Hrishikesh; Achrekar, Angeli; Parry, Charles D; Dewing, Sarah

    2008-11-01

    South Africa is experiencing significant changes in patterns of illicit drug use, including increasing injection and non-injection drug use, and the use of drugs by persons engaged in sex work, both of which could further expand the HIV/AIDS epidemic. In 2005, a rapid ethnographic assessment was conducted in Durban, South Africa, to learn more about patterns of drug use and HIV risk behaviors among drug-using, street-based sex workers. Field teams recruited 52 current injection and non-injection drug users for key informant interviews and focus groups, and they conducted mapping and observation in identified high-risk neighborhoods. Key informants were offered free, voluntary counseling and HIV rapid testing. The results of the assessment indicate that in this population, drugs play an organizing role in patterns of daily activities, with sex work closely linked to the buying, selling, and using of drugs. Participants reported using multiple drugs including crack cocaine, heroin, Ecstasy and Mandrax, and their choices were based on their expectations about the functional role and behavioral and pharmacological properties of the drugs. The organization of sex work and patterns of drug use differ by gender, with males exercising more control over daily routines and drug and sexual transactions than females. Activities of female sex workers are subject to considerable control by individual pimps, many of whom also function as landlords and drug dealers. A strong hold over the overlapping economies of drugs and sex work by a few individuals extends to control of the physical and social settings in which sex is exchanged and drugs are sold and used as well as the terms under which sex work is carried out. The potential for accelerated HIV spread is considerable given the evidence of overlapping drug-using and sexual risk behaviors and the mixing patterns across drug and sexual risk networks. PMID:18678437

  15. Activation of Latent HIV Using Drug-loaded Nanoparticles

    NASA Astrophysics Data System (ADS)

    Kovochich, Michael

    Antiretroviral therapy is currently only capable of controlling human immunodeficiency virus (HIV) replication, rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T-cells, which persists even in the presence of highly active antiretroviral therapy (HAART). It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However, no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence, novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target, activate primary human CD4+ T-cells, and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the histone deacetylase inhibitor (HDACi) sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. LNP-Bry was further tested for its in vivo biodistribution in both wild type mice (C57 black 6), as well as humanized mice (SCID-hu Thy/Liv, and bone marrow-liver-thymus [BLT]). LNP-Bry accumulated in the spleen and induced the early activation marker CD69 in wild type mice. Taken together, these data demonstrate the ability of nanotechnological approaches to

  16. Induction of human immunodeficiency virus type-1-specific immunity with a novel gene transport unit (GTU)-MultiHIV DNA vaccine.

    PubMed

    Blazevic, Vesna; Männik, Andres; Malm, Maria; Sikut, Rein; Valtavaara, Minna; Toots, Urve; Ustav, Mart; Krohn, Kai

    2006-07-01

    A multiHIV fusion gene expressing an antigenic fusion protein composed of regulatory HIV-1 proteins Rev, Nef, and Tat, as well as Gag p17/p24 and a stretch of 11 cytotoxic T lymphocyte (CTL) epitope clusters from Pol and Env, was cloned into a novel DNA vector named the Gene Transport Unit (GTU). A mouse H-2(d)-restricted HIV-1 gp120 epitope (RGPGRAFVTI) was cloned into the fusion gene as well. In addition to the HIV- 1 genes the GTU codes for a nuclear anchoring protein (bovine papilloma virus E2), ensuring the long maintenance of the vector and a high expression level of the selected immunogens. BALB/c mice were immunized with the GTU-MultiHIV DNA construct by different routes and regimens of immunization to assess the immunogenicity of the DNA vaccine in vivo. Mice developed strong CD8(+) CTL responses to HIV-1 Env and Gag measured by an ELISPOT-IFN-gamma assay and chromium release assay. In addition, T cell responses to regulatory proteins Rev, Nef, and Tat were induced. Antibody responses were detected to each of the HIV antigens encoded by the DNA construct. Minimal doses of the GTU-MultiHIV DNA delivered by gene gun were potent in inducing significant HIV-specific CTL responses. The equivalent doses of the conventional plasmid expressing MultiHIV DNA delivered by gene gun failed to do so. An ideal DNA vaccine should yield high expression of the viral antigens for a prolonged period of time, and expression of the multiple viral antigens is probably required for the induction of a broad and protective immune response. The GTU-MultiHIV DNA vaccine described is a good vaccine candidate that meets the above criteria. PMID:16831091

  17. Hepatitis C virus infection in HIV type 1-infected individuals does not accelerate a decrease in the CD4+ cell count but does increase the likelihood of AIDS-defining events.

    PubMed

    Stebbing, Justin; Waters, Laura; Mandalia, Sundhiya; Bower, Mark; Nelson, Mark; Gazzard, Brian

    2005-09-15

    Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis C, but whether hepatitis C virus (HCV) has a reciprocal effect on HIV-1 infection remains a point of controversy. In a multivariate analysis of a cohort of 5832 individuals, we found that individuals coinfected with HCV and HIV-1 (prevalence of coinfection, 5.8%) had a CD4+ cell count that decreased at a rate similar to that for individuals infected with HIV-1 alone. However, coinfection was associated with a statistically significant increased likelihood of onset of an acquired immunodeficiency syndromedefining illness or developing a CD4+ cell count of <200 cells/mm3, compared with infection with HIV-1 alone (hazard ratio, 1.52; 95% confidence interval, 1.072.17). Patients who were naive to highly active antiretroviral therapy were significantly less likely to progress to either end point, because of their higher CD4+ cell counts. In conclusion, there was an increased number of adverse events in coinfected individuals, compared with individuals infected with HIV-1 alone. PMID:16107994

  18. Risk Factors for Distress in the Adolescent Children of HIV-positive and HIV-negative Drug-Abusing Fathers

    PubMed Central

    Brook, David W.; Brook, Judith S.; Rubenstone, Elizabeth; Zhang, Chenshu; Castro, Felipe G.; Tiburcio, Nelson

    2013-01-01

    In contrast to previous research on parental drug abuse, the present study examined comorbid drug addiction and HIV infection in the father as related to his adolescent child’s psychological distress. Individual structured interviews were administered to 505 HIV-positive and HIV-negative drug-abusing fathers and one of their children, aged 12–20. Structural equation modeling tested an hypothesized model linking paternal latent variables, ecological factors, and adolescent substance use to adolescent distress. Results demonstrated a direct pathway between paternal and adolescent distress, as well as an indirect pathway; namely, paternal distress was linked with paternal teaching of coping skills to the child, which in turn was related to adolescent substance use and, ultimately, to the adolescent’s distress. There was also an association between paternal drug addiction/HIV and adolescent distress, which was mediated by both ecological factors and adolescent substance use. Findings suggest an increased risk for distress in the adolescent children of fathers with comorbid drug addiction and HIV/AIDS, which may be further complicated by paternal distress. Results suggest several opportunities for prevention and treatment programs for the children of drug-abusing fathers. PMID:18278619

  19. Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

    PubMed Central

    Shishido, Takao; Wolschendorf, Frank; Duverger, Alexandra; Wagner, Frederic; Kappes, John; Jones, Jennifer

    2012-01-01

    Reactivation of latent HIV-1 infection is considered our best therapeutic means to eliminate the latent HIV-1 reservoir. Past therapeutic attempts to systemically trigger HIV-1 reactivation using single drugs were unsuccessful. We thus sought to identify drug combinations consisting of one component that would lower the HIV-1 reactivation threshold and a synergistic activator. With aclacinomycin and dactinomycin, we initially identified two FDA-approved drugs that primed latent HIV-1 infection in T cell lines and in primary T cells for reactivation and facilitated complete reactivation at the population level. This effect was correlated not with the reported primary drug effects but with the cell-differentiating capacity of the drugs. We thus tested other cell-differentiating drugs/compounds such as cytarabine and aphidicolin and found that they also primed latent HIV-1 infection for reactivation. This finding extends the therapeutic promise of N′-N′-hexamethylene-bisacetamide (HMBA), another cell-differentiating agent that has been reported to trigger HIV-1 reactivation, into the group of FDA-approved drugs. To this end, it is also noteworthy that suberoylanilide hydroxamic acid (SAHA), a polar compound that was initially developed as a second-generation cell-differentiating agent using HMBA as a structural template and which is now marketed as the histone deacetylase (HDAC) inhibitor vorinostat, also has been reported to trigger HIV-1 reactivation. Our findings suggest that drugs with primary or secondary cell-differentiating capacity should be revisited as HIV-1-reactivating agents as some could potentially be repositioned as candidate drugs to be included in an induction therapy to trigger HIV-1 reactivation. PMID:22696646

  20. Selected drugs with reported secondary cell-differentiating capacity prime latent HIV-1 infection for reactivation.

    PubMed

    Shishido, Takao; Wolschendorf, Frank; Duverger, Alexandra; Wagner, Frederic; Kappes, John; Jones, Jennifer; Kutsch, Olaf

    2012-09-01

    Reactivation of latent HIV-1 infection is considered our best therapeutic means to eliminate the latent HIV-1 reservoir. Past therapeutic attempts to systemically trigger HIV-1 reactivation using single drugs were unsuccessful. We thus sought to identify drug combinations consisting of one component that would lower the HIV-1 reactivation threshold and a synergistic activator. With aclacinomycin and dactinomycin, we initially identified two FDA-approved drugs that primed latent HIV-1 infection in T cell lines and in primary T cells for reactivation and facilitated complete reactivation at the population level. This effect was correlated not with the reported primary drug effects but with the cell-differentiating capacity of the drugs. We thus tested other cell-differentiating drugs/compounds such as cytarabine and aphidicolin and found that they also primed latent HIV-1 infection for reactivation. This finding extends the therapeutic promise of N'-N'-hexamethylene-bisacetamide (HMBA), another cell-differentiating agent that has been reported to trigger HIV-1 reactivation, into the group of FDA-approved drugs. To this end, it is also noteworthy that suberoylanilide hydroxamic acid (SAHA), a polar compound that was initially developed as a second-generation cell-differentiating agent using HMBA as a structural template and which is now marketed as the histone deacetylase (HDAC) inhibitor vorinostat, also has been reported to trigger HIV-1 reactivation. Our findings suggest that drugs with primary or secondary cell-differentiating capacity should be revisited as HIV-1-reactivating agents as some could potentially be repositioned as candidate drugs to be included in an induction therapy to trigger HIV-1 reactivation. PMID:22696646

  1. Prevention of mother-to-child transmission of Human Immunodeficiency Virus Type 1 (HIV): the role of neonatal and infant prophylaxis

    PubMed Central

    Hurst, Stacey A.; Appelgren, Kristie E.; Kourtis, Athena P.

    2015-01-01

    Summary The prevention of mother-to-child transmission (PMTCT) of HIV is one of the great public health successes of the past 20 years. Much concerted research efforts and dedicated work have led to the achievement of very low rates of PMTCT of HIV in settings that can implement optimal prophylaxis. Though several implementation challenges remain, global elimination of pediatric HIV infection seems now more than ever to be an attainable goal. Often overlooked, the role of prophylaxis of the newborn is nevertheless a very important component of PMTCT. In this paper, we focus on the role of neonatal and infant prophylaxis, discuss mechanisms of protection, and present the clinical trial-generated evidence that led to the current recommendations for preventing infections in breastfed and nonbreastfed infants. PMTCT of HIV should not end at birth; a continuum of care extending postpartum and postnatally is required to minimize the risk of new pediatric HIV infections. PMID:25578882

  2. Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants

    PubMed Central

    Zhu, Qinchang; Yu, Zhiqiang; Kabashima, Tsutomu; Yin, Sheng; Dragusha, Shpend; El-Mahdy, Ahmed F. M.; Ejupi, Valon; Shibata, Takayuki; Kai, Masaaki

    2015-01-01

    Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR substrates. This assay protocol enables use of non-purified enzyme sources and multiple substrates for the enzymatic reaction. In this study, susceptibility of HIV mutations to drugs was evaluated by selective formation of three FL products after the enzymatic HIV-PR reaction. This proof-of-concept study indicates that the present HPLC-FL method could be an alternative to current phenotypic assays for the evaluation of HIV drug resistance. PMID:25988960

  3. Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants.

    PubMed

    Zhu, Qinchang; Yu, Zhiqiang; Kabashima, Tsutomu; Yin, Sheng; Dragusha, Shpend; El-Mahdy, Ahmed F M; Ejupi, Valon; Shibata, Takayuki; Kai, Masaaki

    2015-01-01

    Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR substrates. This assay protocol enables use of non-purified enzyme sources and multiple substrates for the enzymatic reaction. In this study, susceptibility of HIV mutations to drugs was evaluated by selective formation of three FL products after the enzymatic HIV-PR reaction. This proof-of-concept study indicates that the present HPLC-FL method could be an alternative to current phenotypic assays for the evaluation of HIV drug resistance. PMID:25988960

  4. Enhanced Secretory Leukocyte Protease Inhibitor in Human Immunodeficiency Virus Type 1-Infected Patients

    PubMed Central

    Baqui, A. A. M. A.; Meiller, Timothy F.; Falkler, William A.

    1999-01-01

    Secretory leukocyte protease inhibitor (SLPI) has been found to possess activity against the human immunodeficiency virus type 1 (HIV-1) in vitro at physiological concentrations. A study was undertaken to evaluate SLPI levels in human saliva and plasma among HIV-positive (HIV+) patients with various HIV-1 viral loads in comparison to uninfected controls. Whole blood in EDTA and unstimulated saliva samples were collected from 37 HIV+ patients, of whom 20 had a history of intravenous drug abuse (IVDA). Control samples were collected from 20 appropriate age- and sex-matched HIV-1-negative individuals. SLPI was estimated from both saliva and serum samples by an enzyme-linked immunosorbent assay. HIV viral load was determined using a quantitative reverse transcription-PCR. SLPI levels were increased 16.7% in plasma and 10.3% in saliva among HIV+ patients in comparison to uninfected controls. SLPI levels were increased 5.9% in saliva and 3.9% in plasma among HIV+ patients with a high viral load (>10,000 copies/ml) as compared to patients with a low viral load (<400 copies/ml). Only 23% of patients with a high viral load used combination therapy with protease inhibitor drugs, whereas 92.9% of HIV+ patients with a low viral load used protease inhibitors. SLPI levels did not differ significantly among the IVDA patients, patients with different viral loads, or patients using protease inhibitor drugs. There was a statistically significant increase in SLPI levels in saliva among HIV patients in comparison to non-HIV-infected controls. An increase in SLPI levels among HIV+ patients may be a natural consequence of HIV pathogenesis and an important factor in preventing oral transmission of HIV, but this increase may not be evident during plasma viremia in patients with a high viral load. PMID:10548568

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

    PubMed

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

    2016-07-01

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

  6. Tobacco Use and Nicotine Dependence among HIV-Infected and Uninfected Injection Drug Users

    PubMed Central

    Marshall, Mariah M.; Kirk, Gregory D.; Caporaso, Neil E.; McCormack, Meredith C.; Merlo, Christian A.; Hague, John C.; Mehta, Shruti H.; Engels, Eric A.

    2010-01-01

    Introduction Urban U.S. populations are burdened by intersecting epidemics of HIV-infection, injection drug use, and cigarette smoking. Given the substantial morbidity attributable to tobacco in these populations, we characterized smoking behaviors, nicotine addiction, and tobacco exposure among HIV-infected and HIV-uninfected injection drug users (IDUs) in Baltimore, Maryland. Methods Smoking behaviors among participants in the ALIVE Study were assessed using interviewer-administered questionnaires. Smoking history and nicotine dependence (Fagerstrom Index scores) were compared by HIV and drug injecting status. Serum cotinine (a nicotine metabolite) was measured for a sample of participants by enzyme immunoassay. Results Among 1,052 participants (29.7% HIV-infected, 39.8% active injectors), 85.2% were current smokers and 9.3% former smokers. Smoking prevalence, age at smoking initiation, and cumulative tobacco exposure were similar by HIV status. Median Fagerstrom scores of 4 for HIV-infected and HIV-uninfected smokers indicated moderate nicotine dependence. Daily cigarette consumption was identical by HIV status (median 10 cigarettes), although HIV-infected participants were less likely to smoke 1+ pack daily compared to HIV-uninfected participants (18.0% vs. 26.9%, p=0.001). Compared to former injectors, active injectors had higher smoking prevalence (90.5% vs. 81.7%, p=0.0001), greater daily cigarette consumption (30.7% vs. 19.6% smoked 1+ pack daily, p=0.0001), and slightly higher Fagerstrom scores (median 5 vs. 4). Cotinine levels paralleled self-reported cigarette consumption. Discussion Tobacco use is extremely common among inner city IDUs. Smoking behavior and nicotine dependence did not materially differ by HIV status but were associated with active drug injection. Cessation efforts should target the dual dependence of cigarettes and drugs experienced among this population. PMID:20875704

  7. Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi.

    PubMed

    van Oosterhout, J J; Dzinjalamala, F K; Dimba, A; Waterhouse, D; Davies, G; Zijlstra, E E; Molyneux, M E; Molyneux, E M; Ward, S

    2015-10-01

    Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/μl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 μg/ml (2.474 to 5.596 μg/ml), area under the curve from 0 to 24 h (AUC0-∞) of 21.32 μg/ml · h (13.57 to 28.60 μg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 μg/ml (2.979 to 4.544 μg/ml), AUC0-24 of 22.5 (14.75 to 34.59 μg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 μg/ml (30.00 to 41.60 μg/ml), AUC0-24 of 386.6 μg/ml · h (320.0 to 463.7 μg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 μg/ml (1.694 to 3.098 μg/ml), AUC0-24 of 20.41 μg/ml · h (16.18 to 26.27 μg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of

  8. Weight loss associated with HIV seroconversion among injection-drug users.

    PubMed

    Marmor, M; Titus, S; Harrison, C; Cord-Cruz, E A; Shore, R E; Vogler, M; Krasinski, K; Mildvan, D; Des Jarlais, D C

    1996-08-15

    To describe symptoms associated with human immunodeficiency virus (HIV) seroconversion, we studied a cohort of 366 injection-drug users (IDUs) with a study design that included recall every 3 months to collect symptom histories using a structured questionnaire. Eleven HIV seroconversions were observed in 621.5 person years at risk (PYAR), equivalent to 1.8 seroconversions/100 PYAR. Cox regression analysis showed age < or = 35 years to be a significant risk factor for HIV seroconversion after controlling for gender, race, and the frequency of drug injection. An embedded case-control analysis then compared symptom histories of HIV seroconverters with those of age-(+/- 5 years) and visit number-matched controls who remained HIV seronegative for > or = 3 months longer than the HIV-seroconverters. Multivariate case-control analysis adjusted for injection frequency yielded significant associations of HIV seroconversion with histories of weight loss > or = 4.5 kg (seven of 11 cases; odds ratio [OR] = 11.6, 95% confidence interval [CI] 3.1, 43.1) and oral ulcers (three of 11 cases; OR = 7.6, 95% CI = 1.2, 48.2) in the 3 months before the subjects' first HIV-seropositive study visit. We conclude that histories of recent symptoms reported by HIV-seroconverting IDUs differ from those reported by non-HIV-seroconverting IDUs, and weight loss may be particularly common among IDUs experiencing primary HIV infection. PMID:8757430

  9. Mapping the RNA binding sites for human immunodeficiency virus type-1 gag and NC proteins within the complete HIV-1 and -2 untranslated leader regions.

    PubMed Central

    Damgaard, C K; Dyhr-Mikkelsen, H; Kjems, J

    1998-01-01

    Encapsidation of HIV-1 genomic RNA is mediated by specific interactions between the RNA packaging signal and the Gag protein. During maturation of the virion, the Gag protein is processed into smaller fragments, including the nucleocapsid (NC) domain which remains associated with the viral genomic RNA. We have investigated the binding of glutathione- S -transferase (GST) Gag and NC fusion proteins from HIV-1, to the entire HIV-1 and -2 leader RNAencompassing the packaging signal. We have mapped the binding sites at conditions where only about two complexes are formed and find that GST-Gag and GST-NC fusion proteins bind specifically to discrete sites within the leader. Analysis of the HIV-1 leader indicated that GST-Gag strongly associates with the PSI stem-loop and to a lesser extent with regions near the primer binding site. GST-NC binds the same regions but with reversed preferences. The HIV-1 proteins also interact specifically with the 5'-leader of HIV-2 and the major site of interaction mapped to a stem-loop, with homology to the HIV-1 PSI stem-loop structure. The different specificities of Gag and NC may reflect functionally distinct roles in the viral replication, and suggest that the RNA binding specificity of NC is modulated by its structural context. PMID:9685481

  10. Drug use as a driver of HIV Risks: Re-emerging and emerging issues

    PubMed Central

    El-Bassel, Nabila; Shaw, Stacey A.; Dasgupta, Anindita; Strathdee, Steffanie A.

    2014-01-01

    Purpose of Review We reviewed papers published in 2012–2013 that focused on re-emerging and emerging injection and non-injection drug use trends driving HIV risk behaviors and transmission in some parts of the world. Recent Findings While HIV incidence has declined in many countries, HIV epidemics remain at troubling levels among key drug using populations including females who inject drugs (FWID), FWID who trade sex, sex partners of people who inject drugs (SP-PWID), young PWID, and people who use non-injection drugs in a number of low- and middle- income countries such as in Central Asia, Eastern Europe, Southeast Asia, and parts of Africa. Summary HIV epidemics occur within contexts of global economic and political forces, including poverty, human rights violations, discrimination, drug policies, trafficking, and other multi-level risk environments. Trends of injection and non-injection drug use and risk environments driving HIV epidemics in Central Asia, Eastern Europe, Southeast Asia, and parts of Africa call for political will to improve HIV and substance use service delivery, access to combination HIV prevention, and harm reduction programs. PMID:24406532

  11. Deciphering the epidemic synergy of herpes simplex virus type 2 (HSV-2) on human immunodeficiency virus type 1 (HIV-1) infection among women in sub-Saharan Africa

    PubMed Central

    2012-01-01

    Background Herpes Simplex Virus Type 2 (HSV-2) is highly prevalent in regions disproportionately affected by the human immunodeficiency virus (HIV-1) epidemic. The objective of our study was to identify the risk factors of HSV-2 and HIV-1 infections and to examine the association between the two infections. Methods The study participants were recruited through a community based cross-sectional study that was conducted from November 2002 to March 2003 in the Moshi urban district of Northern Tanzania. A two-stage sampling design was used in recruiting the study participants. Information on socio-demographics, alcohol use, sexual behaviors, and STIs symptoms were obtained. Blood and urine samples were drawn for testing of HIV-1, HSV-2 and other STIs. Results The prevalence of HSV-2 infection among all study participants was 43%. The prevalence rate of HSV-2 among the HIV-negative and HIV-positive women was 40% and 65%, respectively. We found 2.72 times odds of having HIV-1 in an HSV-2 positive woman than in an HSV-2 negative woman. Furthermore, HIV-1 and HSV-2 shared common high-risk sexual behavior factors such as early onset of sexual debut, and testing positive for other STIs. Conclusions Our findings suggest that HSV-2 may be both a biological and risk-associated cofactor for HIV-1 acquisition. In resource-limited countries, where both infections are prevalent efforts at symptomatic and diagnostic screening and treatment of HSV-2 should be part of HIV-1 prevention programs. PMID:22909236

  12. Evaluation of aldrithiol-2-inactivated preparations of HIV type 1 subtypes A, B, and D as reagents to monitor T cell responses.

    PubMed

    Rutebemberwa, A; Bess, J W; Brown, B; Arroyo, M; Eller, M; Slike, B; Polonis, V; McCutchan, F; Currier, J R; Birx, D; Robb, M; Marovich, M; Lifson, J D; Cox, J H

    2007-04-01

    The development of HIV vaccines is an urgent priority and there is need to generate reagents representing multiple subtypes that can be used to screen HIV-1-specific responses. We used Aldrithiol-2 (AT-2), a mild oxidizing reagent, to eliminate the infectivity of HIV while maintaining its structure and ability to be processed for presentation to T cells. Inactivated subtype A, B, and D viruses were evaluated for their ability to stimulate T cell responses in PBMC samples from 18 U.S. subjects infected with HIV-1 subtype B and 32 Ugandan subjects infected with subtypes A and D or recombinants AC and AD. Five HIV-1-negative samples were also analyzed. T cell responses to AT-2-inactivated viral isolates were monitored by interferon-gamma (IFN-gamma) intracellular cytokine secretion (ICS) analysis; matched microvesicle preparations served as negative controls. Among the 18 subtype B infected subjects, 39% had CD3(+) CD4 (+) IFN-gamma responses and 67% had CD3(+) CD8(+) IFN-gamma responses. Of the 32 Ugandan subjects, 34% demonstrated CD3(+) CD4(+) IFN-gamma responses and 78% demonstrated CD3(+) CD8(+) IFN-gamma responses. Both subtype-specific and cross-reactive responses were observed. Responses to the AT-2 viruses tended to be lower in magnitude than those detected by a set of overlapping gag peptides. Robust lymphoproliferative responses to AT-2 viruses were seen in a subset of subjects. In conclusion, AT-2-inactivated HIV-1 virions stimulated both CD4 and CD8 HIV-1-specific responses and may provide an additional reagent for screening HIV-1-specific responses in HIV seropositives and vaccinees. PMID:17506610

  13. Up-Regulation of TLR2 and TLR4 in Dendritic Cells in Response to HIV Type 1 and Coinfection with Opportunistic Pathogens

    PubMed Central

    Arteaga, Jose; Paul, Stéphane; Kumar, Ajit; Latz, Eicke; Urcuqui-Inchima, Silvio

    2011-01-01

    Abstract The ability to trigger an innate immune response against opportunistic pathogens associated with HIV-1 infection is an important aspect of AIDS pathogenesis. Toll-like receptors (TLRs) play a critical role in innate immunity against pathogens, but in HIV-1 patients coinfected with opportunistic infections, the regulation of TLR expression has not been studied. In this context, we have evaluated the expression of TLR2 and TLR4 in monocytes, plasmacytoid dendritic cells, and myeloid dendritic cells of HIV-1 patients with or without opportunistic infections. Forty-nine HIV-1-infected individuals were classified according to viral load, highly active antiretroviral therapy (HAART), and the presence or absence of opportunistic infections, and 21 healthy subjects served as controls. Increased expression of TLR2 and TLR4 was observed in myeloid dendritic cells of HIV-1 patients coinfected with opportunistic infections (without HAART), while TLR4 increased in plasmacytoid dendritic cells, compared to both HIV-1 without opportunistic infections and healthy subjects. Moreover, TLR2 expression was higher in patients with opportunistic infections without HAART and up-regulation of TLR expression in HIV-1 patients coinfected with opportunistic infections was more pronounced in dendritic cells derived from individuals coinfected with Mycobacterium tuberculosis. The results indicate that TLR expression in innate immune cells is up-regulated in patients with a high HIV-1 load and coinfected with opportunistic pathogens. We suggest that modulation of TLRs expression represents a mechanism that promotes HIV-1 replication and AIDS pathogenesis in patients coinfected with opportunistic pathogens. PMID:21406030

  14. Modeling HIV-1 Drug Resistance as Episodic Directional Selection

    PubMed Central

    Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L.; Scheffler, Konrad

    2012-01-01

    The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance. PMID:22589711

  15. Illicit drug use and HIV treatment outcomes in a US cohort

    PubMed Central

    Cofrancesco, Joseph; Scherzer, Rebecca; Tien, Phyllis C.; Gibert, Cynthia L.; Southwell, Heather; Sidney, Stephen; Dobs, Adrian; Grunfeld, Carl

    2011-01-01

    Objective To determine the prevalence of illicit drug use and the impact on HIV treatment. Design Multivariable regression of cross-sectional data from 1163 HIV-infected and 294 controls from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Methods An analysis of (1) prevalence of specific illicit drug use (ever, current), (2) being on HAART among those with an indication and (3) current HIV RNA and CD4 cell count among HAART users. Results Median age was 42 years, approximately 50% were non-Caucasian and 33% were women. Eighty-six percent of HIV-infected and 67% of controls reported ever using illicit drugs (P <0.0001); 28% of HIV-infected and 16% of controls reported current use (P = 0.0001). In adjusted models, current cocaine use and past heroin use were associated with not currently being on HAART. Among HAART users, those reporting past heroin use were as likely to have an undetectable HIV viral load as those who had never used heroin. Current and past cocaine use and current heroin use was associated with lower odds of undetectable HIV RNA. Past amphetamine use was associated with having an undetectable HIV. Similar results were seen for CD4 lymphocyte counts. Conclusion Illicit drug use in the US is common, although far fewer report current use than past use. Among HIV-infected patients, understanding of the type of illicit drugs used and whether drug use was in the past or ongoing is important, because of their differential effects on HIV treatment outcomes. PMID:18195562

  16. The Relationship between Housing Status and HIV Risk among Active Drug Users: A Qualitative Analysis

    PubMed Central

    Dickson-Gomez, Julia; Hilario, Helena; Convey, Mark; Corbett, A. Michelle; Weeks, Margaret; Martinez, Maria

    2009-01-01

    This paper examines the relationship between housing status and HIV risk using longitudinal, qualitative data collected in 2004-2005, from a purposeful sample of 65 active drug users in a variety of housed and homeless situations in Hartford, Connecticut. These data were supplemented with observations and in-depth interviews regarding drug use behavior collected in 2001-2005 to evaluate a peer-led HIV prevention intervention. Data reveal differences in social context within and among different housing statuses that affect HIV risky or protective behaviors including the ability to carry drug paraphernalia and HIV prevention materials, the amount of drugs in the immediate environment, access to subsidized and supportive housing, and relationships with others with whom drug users live. Policy implications of the findings, limitations to the data and future research are discussed. PMID:19142817

  17. Assessing the HIV-1 Epidemic in Brazilian Drug Users: A Molecular Epidemiology Approach

    PubMed Central

    Guimarães, Monick Lindenmeyer; Marques, Bianca Cristina Leires; Bertoni, Neilane; Teixeira, Sylvia Lopes Maia; Morgado, Mariza Gonçalves; Bastos, Francisco Inácio

    2015-01-01

    Person who inject illicit substances have an important role in HIV-1 blood and sexual transmission and together with person who uses heavy non-injecting drugs may have less than optimal adherence to anti-retroviral treatment and eventually could transmit resistant HIV variants. Unfortunately, molecular biology data on such key population remain fragmentary in most low and middle-income countries. The aim of the present study was to assess HIV infection rates, evaluate HIV-1 genetic diversity, drug resistance, and to identify HIV transmission clusters in heavy drug users (DUs). For this purpose, DUs were recruited in the context of a Respondent-Driven Sampling (RDS) study in different Brazilian cities during 2009. Overall, 2,812 individuals were tested for HIV, and 168 (6%) of them were positive, of which 19 (11.3%) were classified as recent seroconverters, corresponding to an estimated incidence rate of 1.58%/year (95% CI 0.92–2.43%). Neighbor joining phylogenetic trees from env and pol regions and bootscan analyses were employed to subtype the virus from132 HIV-1-infected individuals. HIV-1 subtype B was prevalent in most of the cities under analysis, followed by BF recombinants (9%-35%). HIV-1 subtype C was the most prevalent in Curitiba (46%) and Itajaí (86%) and was also detected in Brasília (9%) and Campo Grande (20%). Pure HIV-1F infections were detected in Rio de Janeiro (9%), Recife (6%), Salvador (6%) and Brasília (9%). Clusters of HIV transmission were assessed by Maximum likelihood analyses and were cross-compared with the RDS network structure. Drug resistance mutations were verified in 12.2% of DUs. Our findings reinforce the importance of the permanent HIV-1 surveillance in distinct Brazilian cities due to viral resistance and increasing subtype heterogeneity all over Brazil, with relevant implications in terms of treatment monitoring, prophylaxis and vaccine development. PMID:26536040

  18. Endotoxin-Mediated Downregulation of Hepatic Drug Transporters in HIV-1 Transgenic Rats.

    PubMed

    Ghoneim, Ragia H; Piquette-Miller, Micheline

    2016-05-01

    Altered expression of drug transporters and metabolic enzymes is known to occur in infection-induced inflammation. We hypothesize that in human immunodeficiency virus (HIV)-infected individuals, further alteration could occur as a result of augmented inflammation. The HIV-1 transgenic (Tg) rat is used to simulate HIV pathologies associated with the presence of HIV viral proteins. Therefore, the objective of this study was to examine the effect of endotoxin administration on the gene expression of drug transporters in the liver of HIV-Tg rats. Male and female HIV-Tg and wild-type (WT) littermates were injected with 5 mg/kg endotoxin or saline (n= 7-9/group). Eighteen hours later, rats were euthanized and tissues were collected. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure hepatic gene and protein expression, respectively, and enzyme-linked immunosorbent assay was used to measure serum cytokine levels. Although an augmented inflammatory response was seen in HIV-Tg rats, similar endotoxin- mediated downregulation of Abcb1a, Abcc2, Abcg2, Abcb11, Slco1a1, Slco1a2, Slco1b2, Slc10a1, Slc22a1, Cyp3a2, and Cyp3a9 gene expression was seen in the HIV-Tg and WT groups. A significantly greater endotoxin- mediated downregulation of Ent1/Slc29a1 was seen in female HIV-Tg rats. Basal expression of inflammatory mediators was not altered in the HIV-Tg rat; likewise, the basal expression of most transporters was not significantly different between HIV-Tg and WT rats. Our findings suggest that hepatobiliary clearances of endogenous and exogenous substrates are altered in the HIV-Tg rat after endotoxin exposure. This is of particular importance because HIV-infected individuals frequently present with bacterial or viral infections, which are a potential source for drug-disease interactions. PMID:26977098

  19. Different Patterns of Drug Use and Barriers to Continuous HIV Care Post-Incarceration

    PubMed Central

    Swan, Holly

    2015-01-01

    Individuals with a drug use history often experience drug use relapse when they are released from incarceration. This article explores the processes by which a sample of adults experienced relapse post-incarceration and consequently experienced HIV treatment interruption. Data are from in-depth interviews with 25 formerly incarcerated HIV-positive adults who have a self-reported history of drug use. Findings reveal that each participant relapsed post-incarceration. Some participants relapsed immediately after release; others remained drug free until something “triggered” a relapse. Once a participant relapsed, factors that contributed to HIV treatment interruption included re-incarceration, a lack of concern for HIV care, and the overlap of symptoms between addiction and HIV infection. The relationship between drug use and HIV treatment interruption was exacerbated when the participant reported also having a mental health disorder. Cessation of drug use facilitated HIV treatment engagement for participants. The implications of these findings for policy and practice are discussed. PMID:26028697

  20. Evolution of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy from 2000 to 2010.

    PubMed

    Colafigli, M; Torti, C; Trecarichi, E M; Albini, L; Rosi, A; Micheli, V; Manca, N; Penco, G; Bruzzone, B; Punzi, G; Corsi, P; Parruti, G; Bagnarelli, P; Monno, L; Gonnelli, A; Cauda, R; Di Giambenedetto, S

    2012-08-01

    Prevalence and predictors of transmitted drug resistance (TDR), defined as the presence of at least one WHO surveillance drug resistance mutation (SDRM), were investigated in antiretroviral-naïve HIV-1-infected patients, with a genotypic resistance test (GRT) performed ≤6 months before starting cART between 2000 and 2010. 3163 HIV-1 sequences were selected (69% subtype B). Overall, the prevalence of TDR was 12% (13.2% subtype B, 9% non-B). TDR significantly declined overall and for the single drug classes. Older age independently predicted increased odds of TDR, whereas a more recent GRT, a higher HIV-RNA and C vs. B subtype predicted lower odds of TDR. PMID:22536753

  1. Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends.

    PubMed

    Zhan, Peng; Pannecouque, Christophe; De Clercq, Erik; Liu, Xinyong

    2016-04-14

    The early effectiveness of combinatorial antiretroviral therapy (cART) in the treatment of HIV infection has been compromised to some extent by rapid development of multidrug-resistant HIV strains, poor bioavailability, and cumulative toxicities, and so there is a need for alternative strategies of antiretroviral drug discovery and additional therapeutic agents with novel action modes or targets. From this perspective, we first review current strategies of antiretroviral drug discovery and optimization, with the aid of selected examples from the recent literature. We highlight the development of phosphate ester-based prodrugs as a means to improve the aqueous solubility of HIV inhibitors, and the introduction of the substrate envelope hypothesis as a new approach for overcoming HIV drug resistance. Finally, we discuss future directions for research, including opportunities for exploitation of novel antiretroviral targets, and the strategy of activation of latent HIV reservoirs as a means to eradicate the virus. PMID:26509831

  2. Modeling the dynamic relationship between HIV and the risk of drug-resistant tuberculosis

    PubMed Central

    Sergeev, Rinat; Colijn, Caroline; Murray, Megan; Cohen, Ted

    2012-01-01

    The emergence of highly drug-resistant tuberculosis (TB) and interactions between TB and HIV epidemics pose serious challenges for TB control. Previous researchers have presented several hypotheses for why HIV-coinfected TB patients may suffer an increased risk of drug-resistant TB compared to other TB patients. Although some studies have found a positive association between an individual’s HIV status and her subsequent risk of multidrug-resistant TB (MDRTB), the observed individual-level relationship between HIV and drug-resistant TB varies substantially among settings. Here, we develop a modeling framework to explore the effect of HIV on the dynamics of drug-resistant TB. The model captures the acquisition of resistance to important classes of TB drugs, imposes fitness costs associated with resistance-conferring mutations, and allows for subsequent restoration of fitness due to compensatory mutations. Despite uncertainty in several key parameters, we demonstrate epidemic behavior that is robust over a range of assumptions. Whereas HIV facilitates the emergence of MDRTB within a community over several decades, HIV-seropositive individuals presenting with TB may, counter-intuitively, be at lower risk of drug resistant TB at early stages of the co-epidemic. This situation arises because many individuals with incident HIV infection will already harbor latent Mycobacterium Tuberculosis infection acquired at an earlier time when drug-resistance was less prevalent. We find that the rise of HIV can increase the prevalence of MDRTB within populations even as it lowers the average fitness of circulating MDRTB strains compared to similar populations unaffected by HIV. Preferential social mixing among individuals with similar HIV-status and lower average CD4 counts among HIV-seropositive individuals further increase the expected burden of MDRTB. This model suggests that the individual-level association between HIV and drug-resistant forms of TB is dynamic and therefore

  3. Prevention, control and treatment of HIV-AIDS among injecting drug use in Bandung, Indonesia.

    PubMed

    Alisjahbana, Bachti; Susanto, Herman; Roesli, Rully; Yusuf, Hadi; Hinduan, Zahrotur; Mase, Johannes C; Surahman, Eri; van der Ven, Andre

    2009-07-01

    Indonesia is facing a growing HIV-epidemic that in many areas is driven by injecting drug use (IDU). IDUs underutilize health services, partly because of legal aspects which also cause that many are held in prison, where further HIV- transmission may take place. Most HIV-infected patients present with advanced HIV-AIDS and many deaths before starting antiretroviral treatment. The growing HIV-epidemic in Indonesia has socio-economical implications for individual patients as well as for the health system and for society. IMPACT, a multidisciplinary university-based program in Bandung, West-Java, integrates HIV-prevention and treatment, combining research and implementation. Biomedical, public health and sociobehavioral expertise is used for educational programs for adolescents; scaling-up HIV-testing, harm reduction strategies and care for HIV/AIDS in hospital, community and prison; and institutional as well as individual capacity building related to IDU and HIV/AIDS. It is expected that these activities can make a significant contribution to control of HIV-AIDS in the context of injecting drug use in West-Java and Indonesia as a whole. PMID:19920301

  4. The Majority of HIV Type 1 DNA in Circulating CD4+ T Lymphocytes Is Present in Non-Gut-Homing Resting Memory CD4+ T Cells

    PubMed Central

    Xu, Yin; Bailey, Michelle; Seddiki, Nabila; Suzuki, Kazuo; Murray, John M.; Gao, Yuan; Yan, Celine; Cooper, David A.; Kelleher, Anthony D.; Koelsch, Kersten K.; Zaunders, John

    2013-01-01

    Abstract Memory CD4+ T lymphocytes in peripheral blood that express integrins α4ß7 preferentially recirculate through gut-associated lymphoid tissue (GALT), a proposed site of significant HIV-1 replication. Tregs and activated CD4+ T cells in GALT could also be particularly susceptible to infection. We therefore hypothesized that infection of these subsets of memory CD4+ T cells may contribute disproportionately to the HIV-1 reservoir. A cross-sectional study of CD4+ T cell subsets of memory CD45RO+ cells in peripheral blood mononuclear cells (PBMCs) was conducted using leukapheresis from eight subjects with untreated chronic HIV-1 infection. Real-time polymerase chain reaction (PCR) was used to quantify total and integrated HIV-1 DNA levels from memory CD4+ T cells sorted into integrin β7+ vs. β7−, CD25+CD127low Treg vs. CD127high, and activated CD38+ vs. CD38−. More than 80% of total HIV-1 DNA was found to reside in the integrin β7-negative non-gut-homing subset of CD45RO+ memory CD4+ T cells. Less than 10% was found in highly purified Tregs or CD38+ activated memory cells. Similarly, integrated HIV-1 DNA copies were found to be more abundant in resting non-gut-homing memory CD4+ T cells (76%) than in their activated counterparts (23%). Our investigations showed that the majority of both total and integrated HIV-1 DNA was found within non-gut-homing resting CD4+ T cells. PMID:23971972

  5. Evaluation of Performance Characteristics of the Aptima HIV-1 Quant Dx Assay for Detection and Quantitation of Human Immunodeficiency Virus Type 1 in Plasma and Cervicovaginal Lavage Samples.

    PubMed

    Sam, Soya S; Kurpewski, Jaclynn R; Cu-Uvin, Susan; Caliendo, Angela M

    2016-04-01

    Quantification of HIV-1 RNA has become the standard of care in the clinical management of HIV-1-infected individuals. The objective of this study was to evaluate performance characteristics and relative workflow of the Aptima HIV-1 Quant Dx assay in comparison with the Abbott RealTime HIV-1 assay using plasma and cervicovaginal lavage (CVL) specimens. Assay performance was evaluated by using an AcroMetrix HIV-1 panel, AcroMetrix positive controls, Qnostics and SeraCare HIV-1 evaluation panels, 208 clinical plasma samples, and 205 matched CVL specimens on the Panther and m2000 platforms. The Aptima assay demonstrated good linearity over the quantification range tested (2 to 5 log10copies/ml), and there was strong linear correlation between the assays (R(2)= 0.99), with a comparable coefficient of variance of <5.5%. For the plasma samples, Deming regression analyses and Bland-Altman plots showed excellent agreement between the assays, with an interassay concordance of 91.35% (kappa = 0.75; 95% confidence interval [CI], 0.65 to 0.85), and on average, the viral loads determined by the Aptima assay were 0.21 log10copies/ml higher than those determined by the RealTime assay. The assays differed in their sensitivity for quantifying HIV-1 RNA loads in CVL samples, with the Aptima and RealTime assays detecting 30% and 20%, respectively. Aptima had fewer invalid results, and on average, the viral loads in CVL samples quantified by the Aptima assay were 0.072 log10copies/ml higher than those of the RealTime assay. Our results demonstrate that the Aptima assay is sensitive and accurate in quantifying viral loads in both plasma and CVL specimens and that the fully automated Panther system has all the necessary features suitable for clinical laboratories demanding high-throughput sample processing. PMID:26842702

  6. The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120

    PubMed Central

    Billings, Erik; Rao, Mangala; Williams, Constance; Zolla-Pazner, Susan; Bailer, Robert T.; Koup, Richard A.; Madnote, Sirinan; Arworn, Duangnapa; Shen, Xiaoying; Tomaras, Georgia D.; Currier, Jeffrey R.; Jiang, Mike; Magaret, Craig; Andrews, Charla; Gottardo, Raphael; Gilbert, Peter; Cardozo, Timothy J.; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Paris, Robert; Greene, Kelli; Gao, Hongmei; Gurunathan, Sanjay; Tartaglia, Jim; Sinangil, Faruk; Korber, Bette T.; Montefiori, David C.; Mascola, John R.; Robb, Merlin L.; Haynes, Barton F.; Ngauy, Viseth; Michael, Nelson L.; Kim, Jerome H.; de Souza, Mark S.

    2012-01-01

    Abstract The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200–3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100–200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169–184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100–800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100–3200) and 3570 (range: 200–12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition. PMID:23035746

  7. Long-Term Efficacy and Safety of Atazanavir/Ritonavir Treatment in a Real-Life Cohort of Treatment-Experienced Patients with HIV Type 1 Infection

    PubMed Central

    Sönnerborg, Anders; Brockmeyer, Norbert; Thalme, Anders; Svedhem, Veronica; Dupke, Stephan; Eychenne, Jean-Luc; Nakonz, Tina; Jimenez-Exposito, Maria Jesus; Pugliese, Pascal

    2013-01-01

    Abstract Atazanavir-based regimens have established efficacy and safety in both antiretroviral (ARV)-naive and -experienced patients. However, data evaluating effectiveness beyond 2 years is sparse. Therefore, we assessed the long-term outcomes of ritonavir-boosted atazanavir (ATV/r)-containing regimens in ARV-experienced patients in a clinical setting in a noncomparative, retrospective, observational study collecting data from three European HIV databases on ARV-experienced adults with HIV-1 infection starting an ATV/r-based regimen. Data were extracted every 6 months (maximum follow-up 5 years). Primary outcome was the proportion of patients remaining on ATV/r by baseline HIV-1 RNA (<500 or ≥500 copies/ml). Secondary outcomes included time to virologic failure, reasons for discontinuation, and long-term safety profile. The duration of treatment and time to virologic failure were analyzed using the Kaplan–Meier method. Data were analyzed for 1,294 ARV-experienced patients (male 74%; mean ART exposure 5.7 years). After 3 years, 56% (95% CI: 52%, 60%) of patients with baseline HIV-1 RNA <500 copies/ml and 53% (95% CI: 49%, 58%) of those with HIV-1 RNA ≥500 copies/ml remained on ATV/r. After 3 years, 75% (95% CI: 69%, 80%) of patients with baseline HIV-1 RNA <50 copies/ml remained suppressed and 51% (95% CI: 47%, 55%) of those with baseline HIV-1 RNA ≥50 copies/ml achieved and maintained virologic suppression. Although adverse events (AEs) were the main known reason for discontinuation, no unexpected AEs were observed. In a real-life setting ATV/r-based regimens demonstrated sustained virologic suppression in ARV-experienced patients. After long-term therapy the majority of patients remained on treatment and no unexpected AEs were observed. PMID:23016535

  8. HIV and STD Knowledge, Sexual Behaviors and Drug Taking Behaviors of Adolescents in Southern Russia

    ERIC Educational Resources Information Center

    Kelley, R. Mark; Ball, Marcia; Cerullo, Jennie; Trunova, Elena

    2004-01-01

    For several years, HIV infection has increasing rapidly in Eastern Europe and Russia (UNAIDS, 2000, 2003). The purpose of the study was to investigate the HIV and STD knowledge, sexual behaviors and drug taking behaviors of adolescents in southern Russia. The instrument was compiled by the authors, professionally translated, and pilot tested. Most…

  9. HIV Infection among People Who Inject Drugs: The Challenge of Racial/Ethnic Disparities

    ERIC Educational Resources Information Center

    Des Jarlais, Don C.; McCarty, Dennis; Vega, William A.; Bramson, Heidi

    2013-01-01

    Racial/ethnic disparities in HIV infection, with minority groups typically having higher rates of infection, are a formidable public health challenge. In the United States, among both men and women who inject drugs, HIV infection rates are elevated among Hispanics and non-Hispanic Blacks. A meta-analysis of international research concluded that…

  10. Anti-HIV Drugs Decrease the Expression of Matrix Metalloproteinases in Astrocytes and Microglia

    ERIC Educational Resources Information Center

    Liuzzi, G. M.; Mastroianni, C. M.; Latronico, T.; Mengoni, F.; Fasano, A.; Lichtner, M.; Vullo, V.; Riccio, P.

    2004-01-01

    The introduction of potent antiretroviral drugs for the treatment of patients with human immunodeficiency virus (HIV) infection has dramatically reduced the prevalence of HIV-associated neurological disorders. Such diseases can be mediated by proteolytic enzymes, i.e. matrix metalloproteinases (MMPs) and, in particular gelatinases, released from…

  11. Factors Associated with Peer HIV Prevention Outreach in Drug-Using Communities

    ERIC Educational Resources Information Center

    Latkin, Carl A.; Hua, Wei; Davey, Melissa A.

    2004-01-01

    Peer education is a critical approach to HIV prevention. The current study evaluated 156 peer outreach educators 6 months after their 10-session training. Specifically, we examined factors associated with talking to network members about HIV-related topics as well as distributing risk reduction materials. Overall, current drug users were less…

  12. A Neglected Population: Drug-Using Women and Women's Methods of HIV/STI Prevention

    ERIC Educational Resources Information Center

    Gollub, Erica L.

    2008-01-01

    Women drug users are at extremely high risk of HIV and sexually transmitted infections (STIs) from sexual transmission, but remain seriously neglected in intervention research promoting women-initiated methods of HIV/STI prevention. Sparse available data indicate a high interest and enthusiasm for women-initiated methods among these women.…

  13. Rapid assessment of drug use and sexual HIV risk patterns among vulnerable drug-using populations in Cape Town, Durban and Pretoria, South Africa.

    PubMed

    Parry, Charles; Petersen, Petal; Carney, Tara; Dewing, Sarah; Needle, Richard

    2008-09-01

    This exploratory study examines the links between drug use and high-risk sexual practices and HIV in vulnerable drug-using populations in South Africa, including commercial sex workers (CSWs), men who have sex with men (MSM), injecting drug users (IDUs) and non-injecting drug users who are not CSWs or MSM (NIDUs). A rapid assessment ethnographic study was undertaken using observation, mapping, key informant interviews and focus groups in known 'hotspots' for drug use and sexual risk in Cape Town, Durban and Pretoria. Key informant (KI) and focus group interviews involved drug users and service providers. Purposeful snowball sampling and street intercepts were used to recruit drug users. Outcome measures included drug-related sexual HIV risk behaviour, and risk behaviour related to injection drug use, as well as issues related to service use. HIV testing of drug-using KIs was conducted using the SmartCheck Rapid HIV-1 Antibody Test. Non-injection drug use (mainly cannabis, methaqualone, crack cocaine and crystal methamphetamine) and injection drug use (mainly heroin) was occurring in these cities. Drug users report selling sex for money to buy drugs, and CSWs used drugs before, during and after sex. Most (70%) of the drug-using KIs offered HIV testing accepted and 28% were positive, with rates highest among CSWs and MSM. IDUs reported engaging in needle sharing and needle disposal practices that put them and others at risk for contracting HIV. There was a widespread lack of awareness about where to access HIV treatment and preventive services, and numerous barriers to accessing appropriate HIV and drug-intervention services were reported. Multiple risk behaviours of vulnerable populations and lack of access to HIV prevention services could accelerate the diffusion of HIV. Targeted interventions could play an important role in limiting the spread of HIV in and through these under-reached and vulnerable populations. PMID:18979044

  14. Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS.

    PubMed

    Shao, Jingwei; Kraft, John C; Li, Bowen; Yu, Jesse; Freeling, Jennifer; Koehn, Josefin; Ho, Rodney Jy

    2016-01-01

    Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels. A stable nanodrug combination that transports, delivers and accumulates in lymph nodes is needed to clear HIV in lymphoid tissues. This review discusses limitations of current oral combination antiretroviral therapy and advances in anti-HIV nanoformulations. A 'systems approach' has been proposed to overcome these limitations. This concept has been used to develop nanoformulations for overcoming drug insufficiency, extending cell and tissue exposure and clearing virus for treating HIV/AIDS. PMID:26892323

  15. Immunomodulatory drugs inhibit TLR4-induced type-1 interferon production independently of Cereblon via suppression of the TRIF/IRF3 pathway.

    PubMed

    Millrine, David; Miyata, Haruhiko; Tei, Mami; Dubey, Praveen; Nyati, Kishan; Nakahama, Taisuke; Gemechu, Yohannes; Ripley, Barry; Kishimoto, Tadamitsu

    2016-06-01

    Thalidomide and its derivatives, collectively referred to as immunomodulatory drugs (IMiDs), are effective inhibitors of inflammation and are known to inhibit TLR-induced TNFα production. The identification of Cereblon as the receptor for these compounds has led to a rapid advancement in our understanding of IMiD properties; however, there remain no studies addressing the role of Cereblon in mediating the suppressive effect of IMiDs on TLR responses. Here, we developed Cereblon-deficient mice using the CRISPR-Cas9 system. TLR-induced cytokine responses were unaffected by Cereblon deficiency in vivo Moreover, IMiD treatment inhibited cytokine production even in the absence of Cereblon. The IMiD-induced suppression of cytokine production therefore occurs independently of Cereblon in mice. Further investigation revealed that IMiDs are potent inhibitors of TLR-induced type-1 interferon production via suppression of the TRIF/IRF3 pathway. These data suggest that IMiDs may prove effective in the treatment of disorders characterized by the ectopic production of type-1 interferon. Significantly, these properties are mediated separately from thalidomide's teratogenic receptor, Cereblon. Thus, certain therapeutic properties of Thalidomide can be separated from its harmful side effects. PMID:26865412

  16. In Vitro Evolution of the Human Immunodeficiency Virus Type 1 Gag-Protease Region and Maintenance of Reverse Transcriptase Resistance following Prolonged Drug Exposure†

    PubMed Central

    La Seta Catamancio, Simona; De Pasquale, Maria Pia; Citterio, Paola; Kurtagic, Semir; Galli, Massimo; Rusconi, Stefano

    2001-01-01

    We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions. PMID:11230439

  17. Short communication: analysis of the integrase gene from HIV type 1-positive patients living in a rural area of West Cameroon.

    PubMed

    Turriziani, Ombretta; Montagna, Claudia; Falasca, Francesca; Bucci, Mauro; Russo, Gianluca; Lichtner, Miriam; Sobze, Martin Sanou; Vullo, Vincenzo; Pistello, Mauro; Antonelli, Guido

    2012-12-01

    Major mutations associated with HIV-I integrase inhibitors (INI) resistance are rare in INI-naive patients. However, polymorphisms at positions that may influence the genetic barrier and/or drive the selection of specific INI resistance pathways are common in HIV non-B subtypes. The aim was to evaluate the presence of natural polymorphisms and/or INI resistance mutations in HIV-1 non-B subtype samples obtained from INI-naive patients living in rural west Cameroon. Thirty-three HIV-1 non-B samples were obtained from INI-naive African women and, as controls, 15 samples of HIV-1 subtype B were obtained from antiretroviral-naive Italian patients. The integrase gene was amplified and sequenced using Trugene Core Reagents. Several amino acid positions in B and non-B subtypes were found to be polymorphic. Interestingly, two patients infected with the CRF02_AG subtype had the resistance mutations N155H and E157Q/E and 12% of African samples had an amino acid substitution at position 143. Silent mutations leading to a higher increment of genetic barriers were detected at 140 and 151 positions in non B-subtypes. Although most polymorphisms may have little effect on INI susceptibility, the IN gene variations found in the present study should be taken into consideration as they may facilitate or delay the emergence of variants fully resistant to INIs. PMID:22214532

  18. The Interactive Seminar: An Educational Approach for Voluntary HIV Testing in a Drug Dependence Treatment Unit.

    ERIC Educational Resources Information Center

    Sedhom, Laila; And Others

    1994-01-01

    A survey of 118 male patients in a drug dependence treatment unit before and after an interactive seminar with a nonjudgmental professional showed that seminar participants, especially intravenous drug users, had higher rates of voluntary HIV testing than nonparticipants. Drug users who completed detoxification and attended the seminar also had…

  19. Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.

    PubMed

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

    Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framework create some hurdles in their successful formulation development as well as in the possible drug delivery approaches. In the present article, we have discussed the general physiological aspects of the infection along with the relevance of non-polymeric nanocarriers like liposomes, solid lipid nanoparticles (SLN), ethosomes, etc. in the treatment of this disastrous disease. PMID:19913579

  20. Low Non-structured Antiretroviral Therapy Interruptions in HIV-Infected Persons Who Inject Drugs Receiving Multidisciplinary Comprehensive HIV Care at an Outpatient Drug Abuse Treatment Center.

    PubMed

    Vallecillo, Gabriel; Mojal, Sergio; Roquer, Albert; Samos, Pilar; Luque, Sonia; Martinez, Diana; Martires, Paula Karen; Torrens, Marta

    2016-05-01

    Continuous HIV treatment is necessary to ensure successful combined antiretroviral therapy (cART). The aim of this study was to evaluate the incidence of patient-initiated non-structured treatment interruptions in HIV-infected persons who inject drugs and who received a multidisciplinary comprehensive program, including medical HIV care, drug-dependence treatment and psychosocial support, at a drug outpatient addiction center. Non-structured treatment interruptions were defined as ≥30 consecutive days off cART without medical indication. During a median follow-up of 53.8 months, 37/132 (28 %) patients experienced the first non-structured treatment interruptions. The cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4-40.0). Current drug use injection ≥1/day (HR 14.77; 95 % CI 5.90-36.96) and cART naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non-structured treatment interruptions. HIV care provided at a drug addiction center is a useful strategy to sustain continuous cART, however, drug abstinence is essential for the long-term maintenance of cART. PMID:26427376

  1. Genotypic and phenotypic analysis of a novel 15-base insertion occurring between codons 69 and 70 of HIV type 1 reverse transcriptase.

    PubMed

    Lobato, Robert L; Kim, Eun-Young; Kagan, Ronald M; Merigan, Thomas C

    2002-07-01

    An HIV-1 isolate possessing a 15-base insertion between codons 69 and 70 of the reverse transcriptase (RT) gene was derived from a patient plasma sample. Investigation of the insertion sequence revealed that this mutation is an ectopic duplication of the first 15 bases of the HIV-1 envelope gene. Phenotypic analysis yielded the following increases in resistance: 371-fold to zidovudine, 84-fold to lamivudine, 32-fold to abacavir, 15-fold to stavudine, 12-fold to didanosine, and 4-fold to zalcitabine. Phenotypic studies suggested that this change does not detract from the overall fitness of the virus. Together, data from this investigation support two conclusions. First, a previously unreported mechanism exists for generating diversity in HIV-1, namely long-distance duplication of genetic material from one portion of the genome to another. Second, large insertions in this region of RT are well tolerated and can confer high levels of resistance to multiple nucleoside analogue reverse transcriptase inhibitors. PMID:12167282

  2. High HIV burden among people who inject drugs in 15 Indian cities

    PubMed Central

    Lucas, Gregory M.; Solomon, Sunil S.; Srikrishnan, Aylur K.; Agrawal, Alok; Iqbal, Syed; Laeyendecker, Oliver; McFall, Allison M.; Kumar, Muniratnam S.; Ogburn, Elizabeth; Celentano, David D.; Solomon, Suniti; Mehta, Shruti H.

    2015-01-01

    Background Injecting drug use has historically been the principal driver of the HIV epidemic in the Northeast states of India. However, recent data indicate growing numbers of people who inject drugs (PWID) in North and Central Indian cities. Methods We conducted face-to-face surveys among PWID in 7 Northeast and 8 North/Central Indian cities using respondent-driven sampling. We used a rapid HIV testing protocol to identify seropositive individuals and multi-assay algorithm to identify those with recent infection. We used multi-level regression models that incorporated sampling weights and had random intercepts for site to assess risk factors for prevalent and incident (recent) HIV infection. Results We surveyed 14,481 PWID from 15 Indian cities between January and December 2013. Participants reported high rates of needle/syringe sharing. The median (site range) estimated HIV prevalence and incidence were 18.1% (5.9, 44.9) and 2.9 per 100 person-years (0, 12.4), respectively. HIV prevalence was higher in Northeast sites while HIV incidence was higher in North/Central sites. The odds of prevalent HIV were over 3-fold higher in women than men. Other factors associated with HIV prevalence or incidence included duration since first injection, injection of pharmaceutical drugs, and needle/syringe sharing. Conclusions The burden of HIV infection is high among PWID in India, and may be increasing in cities where injecting drug use is emerging. Women who inject drugs were at substantially higher risk for HIV than men, a situation that may be mediated by dual injection-related and sexual risks. PMID:25715105

  3. Env-2dCD4 S60C complexes act as super immunogens and elicit potent, broadly neutralizing antibodies against clinically relevant human immunodeficiency virus type 1 (HIV-1).

    PubMed

    Killick, Mark A; Grant, Michelle L; Cerutti, Nichole M; Capovilla, Alexio; Papathanasopoulos, Maria A

    2015-11-17

    The ability to induce a broadly neutralizing antibody (bNAb) response following vaccination is regarded as a crucial aspect in developing an effective vaccine against human immunodeficiency virus type 1 (HIV-1). The bNAbs target the HIV-1 envelope glycoprotein (Env) which is exposed on the virus surface, thereby preventing cell entry. To date, conventional vaccine approaches such as the use of Env-based immunogens have been unsuccessful. We expressed, purified, characterized and evaluated the immunogenicity of several unique HIV-1 subtype C Env immunogens in small animals. Here we report that vaccine immunogens based on Env liganded to a two domain CD4 variant, 2dCD4(S60C) are capable of consistently eliciting potent, broadly neutralizing antibody responses in New Zealand white rabbits against a panel of clinically relevant HIV-1 pseudoviruses. This was irrespective of the Env protein subtype and context. Importantly, depletion of the anti-CD4 antibodies appeared to abrogate the neutralization activity in the rabbit sera. Taken together, this data suggests that the Env-2dCD4(S60C) complexes described here are "super" immunogens, and potentially immunofocus antibody responses to a unique epitope spanning the 2dCD4(60C). Recent data from the two available anti-CD4 monoclonal antibodies, Ibalizumab and CD4-Ig (and bispecific variants thereof) have highlighted that the use of these broad and potent entry inhibitors could circumvent the need for a conventional vaccine targeting HIV-1. Overall, the ability of the unique Env-2dCD4(S60C) complexes to elicit potent bNAb responses has not been described previously, reinforcing that further investigation for their utility in preventing and controlling HIV-1/SIV infection is warranted. PMID:26432912

  4. Treatment of medical, psychiatric, and substance-use comorbidities in people infected with HIV who use drugs

    PubMed Central

    Altice, Frederick L; Kamarulzaman, Adeeba; Soriano, Vincent V; Schechter, Mauro; Friedland, Gerald H

    2016-01-01

    HIV-infected drug users have increased age-matched morbidity and mortality compared with HIV-infected people who do not use drugs. Substance-use disorders negatively affect the health of HIV-infected drug users, who also have frequent medical and psychiatric comorbidities that complicate HIV treatment and prevention. Evidence-based treatments are available for the management of substance-use disorders, mental illness, HIV and other infectious complications such as viral hepatitis and tuberculosis, and many non-HIV-associated comorbidities. Tuberculosis co-infection in HIV-infected drug users, including disease caused by drug-resistant strains, is acquired and transmitted as a consequence of inadequate prescription of antiretroviral therapy, poor adherence, and repeated interfaces with congregate settings such as prisons. Medication-assisted therapies provide the strongest evidence for HIV treatment and prevention efforts, yet are often not available where they are needed most. Antiretroviral therapy, when prescribed and adherence is at an optimum, improves health-related outcomes for HIV infection and many of its comorbidities, including tuberculosis, viral hepatitis, and renal and cardiovascular disease. Simultaneous clinical management of multiple comorbidities in HIV-infected drug users might result in complex pharmacokinetic drug interactions that must be adequately addressed. Moreover, interventions to improve adherence to treatment, including integration of health services delivery, are needed. Multifaceted, interdisciplinary approaches are urgently needed to achieve parity in health outcomes in HIV-infected drug users. PMID:20650518

  5. Drug Network Characteristics and HIV Risk Among Injection Drug Users in Russia: The roles of Trust, Size, and Stability

    PubMed Central

    Odinokova, Veronika A.; Heimer, Robert; Grau, Lauretta E.; Lyubimova, Alexandra; Safiullina, Liliya; Levina, Olga S.; Niccolai, Linda M.

    2011-01-01

    We investigated the influence of drug network characteristics including trust, size, and stability on HIV risk behaviors and HIV testing among injection drug users (IDUs) in St. Petersburg, Russia. Overall, male and female IDUs who reported having high levels of trust in their drug networks were significantly more likely to share syringes than those with lower levels of trust (OR [95% CI]) 2.87 [1.06, 7.81] and 4.89 [1.05, 21.94], respectively). Male and female IDUs in larger drug networks were more likely to share syringes than those in smaller networks (4.21 [1.54, 11.51] and 4.80 [1.20, 19.94], respectively). Characteristics that were significantly associated with not having been HIV tested included drug network instability among men and larger network size among women. High trust, large size, and instability were positively and significantly associated with syringe sharing and not having been HIV tested. Effectiveness of interventions in Russia to reduce the risk of HIV infection may be enhanced if network characteristics are addressed. PMID:20872063

  6. Substance Abuse Treatment, HIV/AIDS, and the Continuum of Response for People Who Inject Drugs

    PubMed Central

    Kresina, Thomas F.; Lubran, Robert; Clark, H. Westley; Cheever, Laura W.

    2012-01-01

    The continuum of response (CoR) to HIV/AIDS is a framework for implementation of HIV prevention, care, and treatment programs based on a national strategic plan for HIV/AIDS services. The CoR for people who inject drugs (PWID) is an important extension of the developed CoR to HIV/AIDS. The CoR-PWID employs stakeholders who together plan, develop, pilot, and provide a full range of services that address the various prevention, care/support, and treatment needs of people, families, and communities infected or affected by HIV/AIDS and injection drug use. The CoR-PWID comprises a broad range of services that include but are not limited to the World Health Organization priority interventions for HIV/AIDS prevention, treatment, and care in the health sector and the package of essential interventions for the prevention, treatment, and care of HIV for people who inject drugs. Implementation of these well-defined, essential prevention, care/support, and treatment services, in addition to locally defined needed services, in a coordinated fashion is important to clients, their families, and communities. The CoR-PWID is, therefore, a necessary framework essential for service development for countries that address HIV/AIDS in populations of PWID. PMID:23243517

  7. Two cases of possible transmitted drug-resistant HIV: likely HIV superinfection and unmasking of pre-existing resistance

    PubMed Central

    Lee, John; Thomson, Emma; Tarrant, Nick; Hale, Antony; Lacey, Charles J

    2016-01-01

    In the UK, patients undergo HIV viral load and genotype testing before they are prescribed antiretroviral therapy. The genotype test guides clinicians in prescribing antiretroviral therapy with maximum efficacy against the patient’s specific viral strain. HIV viral load escape under antiretroviral drug therapy, to which the virus was thought to be genotypically susceptible, is commonly observed in patients with poor adherence. We observed early viral escapes in two-newly diagnosed patients, during antiretroviral treatment, with different sequences compared to their original viral resistance test and who reported excellent adherence to and tolerance of their therapy. HIV superinfection with a new viral strain was identified in a patient with multiple risk factors and co-infections with sexually transmitted infections. The second patient was a case of the emergence of primary resistant virus under drug pressure. Both suppressed their virus promptly after treatment switch. PMID:25663247

  8. Two cases of possible transmitted drug-resistant HIV: likely HIV superinfection and unmasking of pre-existing resistance.

    PubMed

    Martin, Fabiola; Lee, John; Thomson, Emma; Tarrant, Nick; Hale, Antony; Lacey, Charles J

    2016-01-01

    In the UK, patients undergo HIV viral load and genotype testing before they are prescribed antiretroviral therapy. The genotype test guides clinicians in prescribing antiretroviral therapy with maximum efficacy against the patient's specific viral strain. HIV viral load escape under antiretroviral drug therapy, to which the virus was thought to be genotypically susceptible, is commonly observed in patients with poor adherence. We observed early viral escapes in two-newly diagnosed patients, during antiretroviral treatment, with different sequences compared to their original viral resistance test and who reported excellent adherence to and tolerance of their therapy. HIV superinfection with a new viral strain was identified in a patient with multiple risk factors and co-infections with sexually transmitted infections. The second patient was a case of the emergence of primary resistant virus under drug pressure. Both suppressed their virus promptly after treatment switch. PMID:25663247

  9. Human immunodeficiency virus type 1 (HIV-1) infection among female prostitutes in Borno State of Nigeria: one year follow-up.

    PubMed

    Chikwem, J O; Mohammed, I; Ola, T

    1989-11-01

    Serological investigations on female prostitutes resident in Borno State in northeastern Nigeria have shown that the seroprevalence of HIV-1 infection has increased 9.81%--fold in one year. The highest sero-prevalence rates were found amongst prostitutes who had not benefited from previous health education campaigns. Prostitution appears to be on the increase in spite of AIDS probably because of the difficulty in finding alternative means of making a living. Attempts to halt the spread of HIV infection are hampered by the fact that most prostitutes are indifferent to the use of condoms and do not appreciate the importance of protecting themselves from the risks of HIV infection. Their frequent mobility also poses a problem as it makes it difficult for them to benefit from health education campaigns. The prevalence of HIV-1 infection among female prostitutes in Borno State (as indeed in other States in Nigeria) is likely to rise sharply in the next few years unless serious efforts are made to intensify health education campaigns targeted at the high risk groups. PMID:2606018

  10. L-chicoric acid inhibits human immunodeficiency virus type 1 integration in vivo and is a noncompetitive but reversible inhibitor of HIV-1 integrase in vitro.

    PubMed

    Reinke, Ryan A; Lee, Deborah J; McDougall, Brenda R; King, Peter J; Victoria, Joseph; Mao, Yingqun; Lei, Xiangyang; Reinecke, Manfred G; Robinson, W Edward

    2004-09-01

    The human immunodeficiency virus (HIV) integrase (IN) must covalently join the viral cDNA into a host chromosome for productive HIV infection. l-Chicoric acid (l-CA) enters cells poorly but is a potent inhibitor of IN in vitro. Using quantitative real-time polymerase chain reaction (PCR), l-CA inhibits integration at concentrations from 500 nM to 10 microM but also inhibits entry at concentrations above 1 microM. Using recombinant HIV IN, steady-state kinetic analyses with l-CA were consistent with a noncompetitive or irreversible mechanism of inhibition. IN, in the presence or absence of l-CA, was successively washed. Inhibition of IN diminished, demonstrating that l-CA was reversibly bound to the protein. These data demonstrate that l-CA is a noncompetitive but reversible inhibitor of IN in vitro and of HIV integration in vivo. Thus, l-CA likely interacts with amino acids other than those which bind substrate. PMID:15302207

  11. Design of HIV Protease Inhibitors Targeting Protein Backbone: An Effective Strategy for Combating Drug Resistance

    SciTech Connect

    Ghosh, Arun K.; Chapsal, Bruno D.; Weber, Irene T.; Mitsuya, Hiroaki

    2008-06-03

    The discovery of human immunodeficiency virus (HIV) protease inhibitors (PIs) and their utilization in highly active antiretroviral therapy (HAART) have been a major turning point in the management of HIV/acquired immune-deficiency syndrome (AIDS). However, despite the successes in disease management and the decrease of HIV/AIDS-related mortality, several drawbacks continue to hamper first-generation protease inhibitor therapies. The rapid emergence of drug resistance has become the most urgent concern because it renders current treatments ineffective and therefore compels the scientific community to continue efforts in the design of inhibitors that can efficiently combat drug resistance.

  12. Eric Freed Named Deputy Director of HIV Drug Resistance Program | Poster

    Cancer.gov

    Editor’s note: The text for this article was adapted from an e-mail announcement to the Center for Cancer Research community from Robert Wiltrout, Ph.D., on September 8, 2014. Robert Wiltrout, Ph.D., director, NCI Center for Cancer Research (CCR), recently announced the appointment of Eric Freed, Ph.D., as deputy director of the HIV Drug Resistance Program (HIV DRP). Freed will join Stephen Hughes, Ph.D., director of HIV DRP, in leading this CCR program that focuses on understanding HIV replication and pathogenesis, with the goal of developing more effective strategies for treating HIV infections, and also builds on the existing strength of HIV and retrovirus research within NCI.

  13. Perceived risk of HIV infection among deported male injection drug users in Tijuana, Mexico.

    PubMed

    Pinedo, Miguel; Burgos, José Luis; Robertson, Angela M; Vera, Alicia; Lozada, Remedios; Ojeda, Victoria D

    2014-01-01

    Deported injection drug users (IDUs) in Mexico may be vulnerable to HIV infection following expulsion from the USA. We examined factors associated with HIV risk perception among a sample of deportees in Tijuana. From January to April 2010, 313 male IDUs who reported ever being deported from the USA completed a questionnaire. Overall, 35% (N=110) of deportees perceived HIV risk. In multivariate logistic regression analyses, factors independently associated with HIV risk perception included ever having a steady female partner in Tijuana post-deportation (adjusted odds ratio [AOR]: 2.26; 95% confidence interval [CI]: 1.01-5.07) and years spent in a US prison (AOR: 1.29 per year; 95% CI: 1.13-1.48). Conversely, years of drug injection use (AOR: 0.95 per year; 95% CI: 0.91-0.99), ever witnessing family members use drugs prior to first migration trip (AOR: 0.24; 95% CI: 0.09-0.65), years of residence in the USA (AOR: 0.91 per year; 95% CI: 0.84-0.98) and being a Tijuana native (AOR: 0.40; 95% CI: 0.16-0.99) were negatively associated with HIV risk perception. US-Mexico border cities that receive deported migrants should target HIV prevention interventions to specific subgroups, including drug-using male deportees. Interventions should consider migrant's time in the USA, the role of their social networks, and reducing missed opportunities for HIV testing/education. PMID:24650124

  14. Spatial Epidemiology of HIV among Injection Drug Users in Tijuana, Mexico

    PubMed Central

    Brouwer, Kimberly C.; Rusch, Melanie L.; Weeks, John R.; Lozada, Remedios; Vera, Alicia; Magis-Rodríguez, Carlos; Strathdee, Steffanie A.

    2012-01-01

    The northwest border city of Tijuana is Mexico’s fifth largest and is experiencing burgeoning drug use and human immunodeficiency virus (HIV) epidemics. Since local geography influences disease risk, we explored the spatial distribution of HIV among injection drug users (IDUs). From 2006–2007, 1056 IDUs were recruited using respondent-driven sampling, and then followed for eighteen months. Participants underwent semi-annual surveys, mapping, and testing for HIV, tuberculosis, and syphilis. Using Average Nearest Neighbor and Getis-Ord Gi* statistics, locations where participants lived, worked, bought and injected drugs were compared with HIV status and environmental and behavioral factors. Median age was thirty-seven years; 85 percent were male. Females had higher HIV prevalence than males (10.2 percent vs. 3.4 percent; p=0.001). HIV cases at baseline (n=47) most strongly clustered by drug injection sites (Z-Score −6.173; p < 0.001), with a 16 km2 hotspot near the Mexico/U.S. border, encompassing the red-light district. Spatial correlates of HIV included syphilis infection, female gender, younger age, increased hours on the street per day, and higher number of injection partners. Almost all HIV seroconverters injected within a 2.5 block radius of each other immediately prior to seroconversion. Only history of syphilis infection and female gender were strongly associated with HIV in the area where incident cases injected. Directional trends suggested a largely static epidemic until July–December 2008, when HIV spread to the southeast, possibly related to intensified violence and policing that spiked in the latter half of 2008. While clustering allows for targeting interventions, the dynamic nature of epidemics suggests the importance of mobile treatment and harm reduction programs. PMID:23606753

  15. Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease

    PubMed Central

    Maubert, Monique E.; Pirrone, Vanessa; Rivera, Nina T.; Wigdahl, Brian; Nonnemacher, Michael R.

    2016-01-01

    In many individuals, drug abuse is intimately linked with HIV-1 infection. In addition to being associated with one-third of all HIV-1 infections in the United States, drug abuse also plays a role in disease progression and severity in HIV-1-infected patients, including adverse effects on the central nervous system (CNS). Specific systems within the brain are known to be damaged in HIV-1-infected individuals and this damage is similar to that observed in drug abuse. Even in the era of anti-retroviral therapy (ART), CNS pathogenesis occurs with HIV-1 infection, with a broad range of cognitive impairment observed, collectively referred to as HIV-1-associated neurocognitive disorders (HAND). A number of HIV-1 proteins (Tat, gp120, Nef, Vpr) have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each of the proteins in a number of tissues, including the CNS, even in ART-suppressed patients. In this review, we have made Tat the center of attention for a number of reasons. First, it has been shown to be synthesized and secreted by HIV-1-infected cells in the CNS, despite the most effective suppression therapies available to date. Second, Tat has been shown to alter the functions of several host factors, disrupting the molecular and biochemical balance of numerous pathways contributing to cellular toxicity, dysfunction, and death. In addition, the advantages and disadvantages of ART suppression with regard to controlling the genesis and progression of neurocognitive impairment are currently under debate in the field and are yet to be fully determined. In this review, we discuss the individual and concerted contributions of HIV-1 Tat, drug abuse, and ART with respect to damage in the CNS, and how these factors contribute to the development of HAND in HIV-1-infected patients. PMID:26793168

  16. Spatial Epidemiology of HIV among Injection Drug Users in Tijuana, Mexico.

    PubMed

    Brouwer, Kimberly C; Rusch, Melanie L; Weeks, John R; Lozada, Remedios; Vera, Alicia; Magis-Rodríguez, Carlos; Strathdee, Steffanie A

    2012-01-01

    The northwest border city of Tijuana is Mexico's fifth largest and is experiencing burgeoning drug use and human immunodeficiency virus (HIV) epidemics. Since local geography influences disease risk, we explored the spatial distribution of HIV among injection drug users (IDUs). From 2006-2007, 1056 IDUs were recruited using respondent-driven sampling, and then followed for eighteen months. Participants underwent semi-annual surveys, mapping, and testing for HIV, tuberculosis, and syphilis. Using Average Nearest Neighbor and Getis-Ord Gi* statistics, locations where participants lived, worked, bought and injected drugs were compared with HIV status and environmental and behavioral factors. Median age was thirty-seven years; 85 percent were male. Females had higher HIV prevalence than males (10.2 percent vs. 3.4 percent; p=0.001). HIV cases at baseline (n=47) most strongly clustered by drug injection sites (Z-Score -6.173; p < 0.001), with a 16 km(2) hotspot near the Mexico/U.S. border, encompassing the red-light district. Spatial correlates of HIV included syphilis infection, female gender, younger age, increased hours on the street per day, and higher number of injection partners. Almost all HIV seroconverters injected within a 2.5 block radius of each other immediately prior to seroconversion. Only history of syphilis infection and female gender were strongly associated with HIV in the area where incident cases injected. Directional trends suggested a largely static epidemic until July-December 2008, when HIV spread to the southeast, possibly related to intensified violence and policing that spiked in the latter half of 2008. While clustering allows for targeting interventions, the dynamic nature of epidemics suggests the importance of mobile treatment and harm reduction programs. PMID:23606753

  17. HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs.

    PubMed

    Tebit, Denis M; Patel, Hamish; Ratcliff, Annette; Alessandri, Elodie; Liu, Joseph; Carpenter, Crystal; Plantier, Jean-Christophe; Arts, Eric J

    2016-07-01

    Despite only 30,000 group O HIV-1 infections, a similar genetic diversity is observed among the O subgroups H (head) and T (tail) (previously described as subtypes A, B) as in the 9 group M subtypes (A-K). Group O isolates bearing a cysteine at reverse transcriptase (RT) position 181, predominantly the H strains are intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, their susceptibility to newer antiretroviral drugs such as etravirine, maraviroc, raltegravir (RAL), and elvitegravir (EVG) remains relatively unknown. We tested a large collection of HIV-1 group O strains for their susceptibility to four classes of antiretroviral drugs namely nucleoside RT, non-nucleoside RT, integrase, and entry inhibitors knowing in advance the intrinsic resistance to NNRTIs. Drug target regions were sequenced to determine various polymorphisms and were phylogenetically analyzed. Replication kinetics and fitness assays were performed in U87-CD4(+)CCR5 and CXCR4 cells and peripheral blood mononuclear cells. With all antiretroviral drugs, group O HIV-1 showed higher variability in IC50 values than group M HIV-1. The mean IC50 values for entry and nucleoside reverse transcriptase inhibitor (NRTI) were similar for group O and M HIV-1 isolates. Despite similar susceptibility to maraviroc, the various phenotypic algorithms failed to predict CXCR4 usage based on the V3 Env sequences of group O HIV-1 isolates. Decreased sensitivity of group O HIV-1 to integrase or NNRTIs had no relation to replicative fitness. Group O HIV-1 isolates were 10-fold less sensitive to EVG inhibition than group M HIV-1. These findings suggest that in regions where HIV-1 group O is endemic, first line treatment regimens combining two NRTIs with RAL may provide more sustained virologic responses than the standard regimens involving an NNRTI or protease inhibitors. PMID:26861573

  18. Prevalence and correlates of HIV risk behaviors among drug users in China.

    PubMed

    Yang, Xiushi; Latkin, Carl; Celentano, David; Luo, Huasong

    2006-01-01

    This study examined the prevalence and correlates of HIV risk behaviors among 1,153 current drug users in China. Chi-squared tests of differences were used to test if drug users differed from non-users; logistic regression was used to identify behavior-specific risk factors. Results indicate that 60% of drug users injected drugs and more than one third shared needles. Compared to non-users, drug users had higher rates of risky sexual behavior and HIV/STDs. Among drug users, ethnic minorities and migrants were most vulnerable to unprotected casual sex and needle sharing. Drug users who experienced social isolation were associated with lower odds of risk behaviors; those who had experiences of anti-social behaviors and commercial sex, poor HIV knowledge, and perceived greater vulnerability were more prone to unprotected casual sex and needle sharing. Additional correlates of unprotected casual sex included being single, depression, and taking drugs/alcohol during sex. Additional risk factors of needle sharing included education and initiated drug use at younger ages. It is imperative that HIV interventions in China target drug users and address behavior-specific risk factors. PMID:16323036

  19. Sex, drugs and prisons: HIV prevention strategies for over 190 000 clients in Ukraine

    PubMed Central

    Smyrnov, P.; Kumar, A. M. V.; Achanta, S.; Boyko, K.; Khogali, M.; Naik, B.; Zachariah, R.

    2014-01-01

    Setting: One hundred and forty non-governmental organisations implementing human immunodeficiency virus (HIV) prevention programmes among clients, including people who inject drugs, prisoners, female sex workers, men who have sex with men and street children in Ukraine, 2010–2011. Objective: Among enrolled clients, to assess factors associated with HIV testing, HIV retesting within a year of initial testing and HIV seroconversion. Design: Retrospective cohort study involving record reviews. Results: Of 192 487 clients, 42 109 (22%) underwent an initial HIV test (22% were positive). Among HIV-negative clients at baseline, 10 858 (27%) were retested within a year: 317 (3%) of these were HIV-positive. HIV testing and retesting rates were lower among prisoners (0.3%) and others (street children and partners of those in risk groups, 6%), and those who did not receive counselling or services such as condom and needle distribution. Individuals who were not counselled were more likely to seroconvert. Conclusions: In this large cohort of high-risk groups from Eastern Europe, HIV testing was low and HIV sero-conversion was high. This is of public health concern, bringing into question the overall quality of counselling and how well it is tailored to the specific needs of various risk groups. Qualitative studies to understand the reasons for non-testing are urgently required for designing client-specific interventions. PMID:26399206

  20. Expanding access to HIV testing and counseling and exploring vulnerabilities among spouses of HIV-positive men who inject drugs in Pakistan

    PubMed Central

    Shahid, Salman; Majeed, Mohammad Faisal; Awaan, Ahmad Bakhsh; Mirza, Humayun; Sarfraz, Nasir; Veronese, Vanessa

    2016-01-01

    Objectives To explore the utility of home and community-based HIV testing and counseling (HTC) to increase detection of undiagnosed HIV among female spouses and children of HIV-positive PWID in Punjab province, Pakistan. Design Between March 2014 and March 2015, home-based HTC was provided by a local NGO to spouses of HIV-positive PWID in Lahore, Faisalabad, and Sargodha. Convenience sampling was used to identify 2400 married, HIV-positive men who inject drugs and who were currently registered and receiving harm reduction services from the NGO ‘Roshan Rasta’ and seek consent to approach their wives. Method Trained outreach teams conducted HTC and administered a short sociodemographic and behavioral questionnaire to consenting spouses in their homes. HIV-exposed children were also tested with parental consent. Results of the 2400 married HIV positive male-injecting drug users, only 1959 spouses were approached and 1896 agreed to HTC (96.8%). HIV prevalence was 5.3% (n = 101) among spouses and they had very low level of HIV-related knowledge and protective behaviors Conclusion Home and community-based HTC was effective in identifying undiagnosed HIV among spouses of PWID, the majority of whom reported low rates of prior HIV testing and low HIV-related knowledge. Expansion of HIV prevention services and linkages to treatment and care including PMTCT are urgently needed for this group. PMID:26945140

  1. Impact of length of injecting career on HIV incidence among people who inject drugs.

    PubMed

    Montain, Jacqueline; Ti, Lianping; Hayashi, Kanna; Nguyen, Paul; Wood, Evan; Kerr, Thomas

    2016-07-01

    We examined the relationship between duration of injecting career and HIV seroconversion among people who inject drugs (PWID) in Vancouver, Canada. Data were derived from HIV-negative PWID enrolled in a prospective cohort study. We employed Kaplan-Meier methods and Cox regression to investigate the effect of length of time since injection drug use initiation on time to HIV seroconversion. In multivariable Cox analysis, duration of injecting career was negatively associated with time to HIV seroconversion (adjusted hazard ratio=0.82; 95% confidence interval [CI]: 0.69-0.97). Our findings highlight the need for interventions that target individuals who participate in high-risk drug use behaviors. PMID:26921723

  2. Network Structure and the Risk for HIV Transmission Among Rural Drug Users

    PubMed Central

    Young, A. M.; Jonas, A. B.; Mullins, U. L.; Halgin, D. S.

    2012-01-01

    Research suggests that structural properties of drug users’ social networks can have substantial effects on HIV risk. The purpose of this study was to investigate if the structural properties of Appalachian drug users’ risk networks could lend insight into the potential for HIV transmission in this population. Data from 503 drug users recruited through respondent-driven sampling were used to construct a sociometric risk network. Network ties represented relationships in which partners had engaged in unprotected sex and/or shared injection equipment. Compared to 1,000 randomly generated networks, the observed network was found to have a larger main component and exhibit more cohesiveness and centralization than would be expected at random. Thus, the risk network structure in this sample has many structural characteristics shown to be facilitative of HIV transmission. This underscores the importance of primary prevention in this population and prompts further investigation into the epidemiology of HIV in the region. PMID:23184464

  3. Predictors of HIV infection among women drug users in New York and Miami.

    PubMed

    Tortu, S; McCoy, H V; Beardsley, M; Deren, S; McCoy, C B

    1998-01-01

    In the US, the number of women diagnosed with AIDS continues to increase. In this study, women in New York City (East Harlem) and Miami, two sites with high rates of drug use and HIV infection, were first compared on sociodemographic variables and risk behaviors. Logistic regression analyses were used to identify significant, independent predictors of HIV infection in each city. In comparing women from the two cities, several differences in sociodemographic characteristics and drug use were observed. In both cities, ever exchanging sex for drugs and/or money was predictive of HIV infection; and in East Harlem only, other lifetime risk variables independently predicted HIV infection: drug injection, having a sexually transmitted disease, and not having graduated from high school. Results suggest that intervention efforts with women who exchange sex should be intensified in both cities. Also, further comparisons of women drug users in AIDS epicenter cities are necessary to provide information on similarities and differences in sociodemographic characteristics and individual risk behaviors. More research attention should be focused on examining the social context of HIV risk in order to develop innovative intervention strategies which focus on the link between contextual factors and HIV infection. PMID:9640642

  4. Correlates of lending needles/syringes among HIV-seropositive injection drug users.

    PubMed

    Metsch, Lisa R; Pereyra, Margaret; Purcell, David W; Latkin, Carl A; Malow, Robert; Gómez, Cynthia A; Latka, Mary H

    2007-11-01

    Among HIV-positive injection drug users (IDUs), we examined the correlates of lending needles/syringes with HIV-negative and unknown status injection partners. HIV-positive IDUs (N=738) from 4 cities in the United States who reported injection drug use with other IDUs in the past 3 months participated in an audio computer-assisted self-administered interview. Eighteen percent of study participants self-reported having lent their needles to HIV-negative or unknown status injection partners. Multivariate analyses showed that 6 variables were significantly associated with this high-risk injecting practice. Older IDUs, high school graduates, and those reporting more supportive peer norms for safer drug use were less likely to lend needles/syringes. Admission to a hospital for drug treatment in the past 6 months, having injected with >1 person in the past 3 months, and having more psychiatric symptoms were all associated with more risk. These findings underscore the need for a continued prevention focus on HIV-positive IDUs that recognizes the combination of drug use, mental health factors, and social factors that might affect this high-risk injecting practice, which could be associated with HIV and hepatitis C transmission. PMID:18089987

  5. Drug Users’ Willingness to Encourage Social, Sexual, and Drug Network Members to Receive an HIV Vaccine: A Social Network Analysis

    PubMed Central

    Young, A. M.; DiClemente, R. J.; Halgin, D. S.; Sterk, C. E.; Havens, J. R.

    2014-01-01

    This study examined feasibility of peer-based promotion of HIV vaccination and dyadic correlates to vaccine encouragement in risk- and non-risk networks of drug users (n = 433) in the US. Data were collected on HIV vaccine attitudes, risk compensation intentions, likelihood of encouraging vaccination, and recent (past 6 months) risk (i.e. involving sex and/or injecting drugs) and non-risk (i.e. involving co-usage of noninjected drugs and/or social support) relationships. Willingness to encourage HIV vaccination was reported in 521 and 555 risk- and non-risk relationships, respectively. However, 37 % expressed hesitancy, typically due to fear of side effects or social concerns. Encouragement was often motivated by perceived HIV risk, though 9 % were motivated by risk compensation intentions. In non-risk partnerships, encouragement was associated with drug co-usage, and in risk relationships, with perceived vaccine acceptability and encouragement by the partner. Network-based HIV vaccine promotion may be a successful strategy, but risk compensation intentions should be explored. PMID:24849621

  6. A multigene HIV type 1 subtype C modified vaccinia Ankara (MVA) vaccine efficiently boosts immune responses to a DNA vaccine in mice.

    PubMed

    Shephard, Enid; Burgers, Wendy A; Van Harmelen, Joanne H; Monroe, James E; Greenhalgh, Trish; Williamson, Carolyn; Williamson, Anna-Lise

    2008-02-01

    Heterologous prime-boost vaccine strategies have generated high frequencies of antigen-specific T cells in preclinical and clinical trials of candidate HIV vaccines. We have developed a DNA (SAAVI DNA-C) and MVA (SAAVI MVA-C) vaccine based on HIV-1 subtype C for testing in clinical trials. Both vaccines contain five subtype C genes: gag, reverse transcriptase, tat, and nef, expressed as a polyprotein, and a truncated env (gp150). The individual vaccines induced CD8(+) and CD4(+) T cells specific for the vaccine-expressed antigens in BALB/c mice. Combining the vaccines in a DNA prime and MVA boost regimen increased the cumulative peptide response compared to the DNA vaccine alone 10-fold, to over 6000 SFU/10(6) splenocytes in the IFN-gamma ELISPOT assay. Th1 cytokine IFN-gamma and TNF-alpha levels from HIV-specific CD8(+) and CD4(+) T cells increased 20- and 8-fold, respectively, with a SAAVI MVA-C boost. Effector and effector memory RT- and Env-specific memory CD8(+) T cell subsets were boosted after MVA immunization, and over time the cells returned to an intermediate memory phenotype similar to that prior to the boost. Immunization of guinea pigs with the DNA-MVA combination induced high titers of antibodies to gp120, although neutralizing activity was weak or absent. The demonstration that these vaccines induce potent cellular immune responses merits their testing in clinical trials. PMID:18240963

  7. HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK and AP-1 pathway

    PubMed Central

    Shah, Ankit; Vaidya, Naveen K.; Bhat, Hari K.; Kumar, Anil

    2016-01-01

    The ER stress-mediated apoptosis has been implicated in several neurodegenerative diseases; however, its role in HIV/neuroAIDS remains largely unexplored. The present study was undertaken to assess the involvement and detailed mechanism of IRE1α pathway in HIV-1 gp120-mediated ER stress and its possible involvement in cell death. Various signaling molecules for IRE1α pathway were assessed using SVGA cells, primary astrocytes and gp120 transgenic mice, which demonstrated gp120-mediated increase in phosphorylated JNK, XBP-1 and AP-1 leading to upregulation of CHOP. Furthermore, HIV-1 gp120-mediated activation of IRE1α also increased XBP-1 splicing. The functional consequence of gp120-mediated ER stress was determined via assessment of gp120-mediated cell death using PI staining and MTT assay. The gp120-mediated cell death also involved caspase-9/caspase-3-mediated apoptosis. These findings were confirmed with the help of specific siRNA for IRE1α, JNK, AP-1, BiP and CHOP showing significant reduction in gp120-mediated CHOP expression. Additionally, silencing all the intermediates also reduced the gp120-mediated cell death and caspase-9/caspase-3 activation at differential levels. This study provides ER-stress as a novel therapeutic target in the management of gp120-mediated cell death and possibly in the treatment of neuroAIDS. PMID:26740125

  8. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  9. Infant HIV Type 1 gp120 Vaccination Elicits Robust and Durable Anti-V1V2 Immunoglobulin G Responses and Only Rare Envelope-Specific Immunoglobulin A Responses

    PubMed Central

    Fouda, Genevieve G.; Cunningham, Coleen K.; McFarland, Elizabeth J.; Borkowsky, William; Muresan, Petronella; Pollara, Justin; Song, Lin Ye; Liebl, Brooke E.; Whitaker, Kaylan; Shen, Xiaoying; Vandergrift, Nathan A.; Overman, R. Glenn; Yates, Nicole L.; Moody, M. Anthony; Fry, Carrie; Kim, Jerome H.; Michael, Nelson L.; Robb, Merlin; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Liao, Hua-Xin; Haynes, Barton F.; Montefiori, David C.; Ferrari, Guido; Tomaras, Georgia D.; Permar, Sallie R.

    2015-01-01

    Background Infant responses to vaccines can be impeded by maternal antibodies and immune system immaturity. It is therefore unclear whether human immunodeficiency virus type 1 (HIV-1) vaccination would elicit similar responses in adults and infants. Method HIV-1 Env–specific antibody responses were evaluated in 2 completed pediatric vaccine trials. In the Pediatric AIDS Clinical Trials Group (PACTG) 230 protocol, infants were vaccinated with 4 doses of Chiron rgp120 with MF59 (n = 48), VaxGen rgp120 with aluminum hydroxide (alum; n = 49), or placebo (n = 19) between 0 and 20 weeks of age. In PACTG 326, infants received 4 doses of ALVAC-HIV-1/AIDSVAX B/B with alum (n = 9) or placebo (n = 13) between 0 and 12 weeks of age. Results By 52 weeks of age, the majority of maternally acquired antibodies had waned and vaccine Env-specific immunoglobulin G (IgG) responses in vaccinees were higher than in placebo recipients. Chiron vaccine recipients had higher and more-durable IgG responses than VaxGen vaccine recipients or ALVAC/AIDSVAX vaccinees, with vaccine-elicited IgG responses still detectable in 56% of recipients at 2 years of age. Remarkably, at peak immunogenicity, the concentration of anti-V1V2 IgG, a response associated with a reduced risk of HIV-1 acquisition in the RV144 adult vaccine trial, was 22-fold higher in Chiron vaccine recipients, compared with RV144 vaccinees. Conclusion As exemplified by the Chiron vaccine regimen, vaccination of infants against HIV-1 can induce robust, durable Env-specific IgG responses, including anti-V1V2 IgG. PMID:25170104

  10. Responsibility attribution of HIV infection and coping among injection drug users in Malaysia.

    PubMed

    Chou, Chih-Chin; Chronister, Julie; Chou, Chih-Hung; Tan, Sooyin; Macewicz, Thomas

    2013-01-01

    This study explored responsibility attribution (RA) of HIV/AIDS infection (i.e., how an individual perceives the cause of their HIV/AIDS infection) and its relationship to coping styles among injection drug users (IDUs) with HIV/AIDS. In addition, this study investigated whether self-esteem, social support, and religiosity mediate the relationship between RA and coping styles of IDUs with HIV/AIDS. Participants were 201 adult IDUs with HIV/AIDS participating in the National Drug Rehabilitation Center in Malaysia. Five measures were used to assess the above constructs. Cluster analysis, analysis of variance, and mediation analyses were conducted. Results of this study indicated that IDUs with HIV/AIDS in Malaysia can be classified into four homogenous attribution groups: external, fatalistic, internal, and indeterminate. Mediator analyses revealed that combination of self-esteem, social support, and religiosity mediate the relationship between RA and coping behaviors. Clinicians working with IDUs with HIV/AIDS need to address the role of RA, self-esteem, religiosity, and social support as these psychosocial constructs are linked to coping with HIV/AIDS. Future researchers should investigate whether enhancing self-esteem, social support, and religiosity can promote active problem-solving coping and reduce the use of avoidance coping behaviors. PMID:23713718

  11. Law Enforcement Practices Associated with HIV Infection Among Injection Drug Users in Odessa, Ukraine

    PubMed Central

    Dvoryak, Sergey; Sung-Joon, Min; Brewster, John T.; Wendt, William W.; Corsi, Karen F.; Semerik, Oleg Y.; Strathdee, Steffanie A.

    2013-01-01

    Despite HIV prevention efforts over the past 10 years in Odessa, Ukraine, HIV rates among injection drug users (IDUs) remain high. We explored whether IDUs’ experiences with the police and court system in Odessa were associated with HIV serostatus, after controlling for other factors. Qualitative methods, including semi-structured interviews with the police and members of court (N = 19), and focus groups with IDUs (N = 42), were employed to aid in developing a survey instrument for a larger quantitative phase and to assist in interpreting the findings from the quantitative phase, which included 200 participants who were interviewed and tested for HIV. Overall, 55 % tested positive for HIV. Negative experiences with the police were noted by 86 % and included having preloaded syringes taken (66 %), rushed injections due to fear of the police (57 %), police planting drugs (18 %), paying police to avoid arrest (61 %) and threatened by the police to inform on other IDUs (23 %). HIV positive participants were more likely than those who were negative to report these experiences. In a multiple logistic regression, the most significant correlate of HIV infection was rushed injections due to fear of the police. Police actions in Odessa may be contributing to the continued escalation of HIV among IDUs, underscoring the need for structural interventions. PMID:23754613

  12. Interaction of drugs of abuse and microRNA with HIV: a brief review

    PubMed Central

    Pilakka-Kanthikeel, Sudheesh; Nair, Madhavan P. N.

    2015-01-01

    MicroRNAs (miRNAs), the post-transcriptional regulators of gene expression, play key roles in modulating many cellular processes. The changes in the expression profiles of several specific miRNAs affect the interactions between miRNA and their targets in various illnesses, including addiction, HIV, cancer etc. The presence of anti-HIV-1 microRNAs (which regulate the level of infectivity of HIV-1) have been validated in the cells which are the primary targets of HIV infection. Drugs of abuse impair the intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection. Emerging evidence has implicated miRNAs are differentially expressed in response to chronic morphine treatment. Activation of mu opioid receptors (MOR) by morphine is shown to down regulate the expression of anti-HIV miRNAs. In this review, we summarize the results which demonstrate that several drugs of abuse related miRNAs have roles in the mechanisms that define addiction, and how they interact with HIV. PMID:26483757

  13. Towards a Comprehensive Approach to HIV Prevention for People who use Drugs

    PubMed Central

    Marshall, Brandon DL; Wood, Evan

    2010-01-01

    Comprehensive HIV prevention interventions are increasingly recognized as critical in the global effort to reduce HIV transmission among people who use injection drugs (IDU). Scientific evidence clearly shows that a variety of biomedical, behavioral and structural interventions can prevent and reduce IDU-driven HIV epidemics, yet social and structural barriers to their implementation remain. This review discusses the scientific evidence on the effectiveness of individual programs for reducing HIV incidence among IDU and how, by integrating individual programs as complements within a comprehensive HIV prevention approach, it is possible to achieve, and to sustain, greater results than those of individual programs alone. The paper concludes with a discussion of a critical research priority; namely, to improve the implementation of comprehensive HIV prevention interventions in settings of prevalent injection drug use, and to overcome the often complex barriers that impede them. Such an effort will require more than research alone, however. It will also require the ongoing commitment of policy makers, public health officials, and the affected communities themselves to employ comprehensive HIV treatment and prevention as the most effective strategy to reduce new HIV infections. PMID:21045595

  14. Addressing the HIV/AIDS epidemic among Puerto Rican people who inject drugs: the need for a multiregion approach.

    PubMed

    Deren, Sherry; Gelpí-Acosta, Camila; Albizu-García, Carmen E; González, Ángel; Des Jarlais, Don C; Santiago-Negrón, Salvador

    2014-11-01

    High levels of HIV risk behaviors and prevalence have been reported among Puerto Rican people who inject drugs (PRPWID) since early in the HIV epidemic. Advances in HIV prevention and treatment have reduced HIV among people who inject drugs (PWID) in the United States. We examined HIV-related data for PRPWID in Puerto Rico and the US Northeast to assess whether disparities continue. Injection drug use as a risk for HIV is still overrepresented among Puerto Ricans. Lower availability of syringe exchanges, drug abuse treatment, and antiretroviral treatment for PWID in Puerto Rico contribute to higher HIV risk and incidence. These disparities should be addressed by the development of a federally supported Northeast-Puerto Rico collaboration to facilitate and coordinate efforts throughout both regions. PMID:25211722

  15. Addressing the HIV/AIDS Epidemic Among Puerto Rican People Who Inject Drugs: The Need for a Multiregion Approach

    PubMed Central

    Deren, Sherry; Gelpí-Acosta, Camila; Albizu-García, Carmen E.; González, Ángel; Des Jarlais, Don C.; Santiago-Negrón, Salvador

    2014-01-01

    High levels of HIV risk behaviors and prevalence have been reported among Puerto Rican people who inject drugs (PRPWID) since early in the HIV epidemic. Advances in HIV prevention and treatment have reduced HIV among people who inject drugs (PWID) in the United States. We examined HIV-related data for PRPWID in Puerto Rico and the US Northeast to assess whether disparities continue. Injection drug use as a risk for HIV is still overrepresented among Puerto Ricans. Lower availability of syringe exchanges, drug abuse treatment, and antiretroviral treatment for PWID in Puerto Rico contribute to higher HIV risk and incidence. These disparities should be addressed by the development of a federally supported Northeast–Puerto Rico collaboration to facilitate and coordinate efforts throughout both regions. PMID:25211722

  16. HIV Prevalence Rates among Injection Drug Users in 96 Large US Metropolitan Areas, 1992–2002

    PubMed Central

    Lieb, Spencer; Cleland, Charles M.; Cooper, Hannah; Brady, Joanne E.; Friedman, Samuel R.

    2008-01-01

    This research presents estimates of HIV prevalence rates among injection drug users (IDUs) in large US metropolitan statistical areas (MSAs) during 1992–2002. Trend data on HIV prevalence rates in geographic areas over time are important for research on determinants of changes in HIV among IDUs. Such data also provide a foundation for the design and implementation of structural interventions for preventing the spread of HIV among IDUs. Our estimates of HIV prevalence rates among IDUs in 96 US MSAs during 1992–2002 are derived from four independent sets of data: (1) research-based HIV prevalence rate estimates; (2) Centers for Disease Control and Prevention Voluntary HIV Counseling and Testing data (CDC CTS); (3) data on the number of people living with AIDS compiled by the CDC (PLWAs); and (4) estimates of HIV prevalence in the US. From these, we calculated two independent sets of estimates: (1) calculating CTS-based Method (CBM) using regression adjustments to CDC CTS; and (2) calculating the PLWA-based Method (PBM) by taking the ratio of the number of injectors living with HIV to the numbers of injectors living in the MSA. We take the mean of CBM and PBM to calculate over all HIV prevalence rates for 1992–2002. We evaluated trends in IDU HIV prevalence rates by calculating estimated annual percentage changes (EAPCs) for each MSA. During 1992–2002, HIV prevalence rates declined in 85 (88.5%) of the 96 MSAs, with EAPCs ranging from −12.9% to −2.1% (mean EAPC = −6.5%; p < 0.01). Across the 96 MSAs, collectively, the annual mean HIV prevalence rate declined from 11.2% in 1992 to 6.2 in 2002 (EAPC, −6.4%; p < 0.01). Similarly, the median HIV prevalence rate declined from 8.1% to 4.4% (EAPC, −6.5%; p < 0.01). The maximum HIV prevalence rate across the 11 years declined from 43.5% to 22.8% (EAPC, −6.7%; p < 0.01). Declining HIV prevalence rates may reflect high continuing mortality among infected IDUs, as well as primary HIV

  17. Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure.

    PubMed

    Kyeyune, Fred; Gibson, Richard M; Nankya, Immaculate; Venner, Colin; Metha, Samar; Akao, Juliet; Ndashimye, Emmanuel; Kityo, Cissy M; Salata, Robert A; Mugyenyi, Peter; Arts, Eric J; Quiñones-Mateu, Miguel E

    2016-06-01

    Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more

  18. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

    PubMed Central

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  19. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment.

    PubMed

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A; Nekhai, Sergei; Akala, Emmanuel O

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  20. Predicting the Onset of Sexual and Drug Risk Behaviors in HIV-Negative Youths with HIV-Positive Mothers: The Role of Contextual, Self-Regulation, and Social-Interaction Factors

    ERIC Educational Resources Information Center

    Mellins, Claude A.; Dolezal, Curtis; Brackis-Cott, Elizabeth; Nicholson, Ouzama; Warne, Patricia; Meyer-Bahlburg, Heino F. L.

    2007-01-01

    HIV-negative, inner-city adolescents with HIV-infected parents are considered to be at high risk for acquiring HIV themselves. Using a modified theory of health behavior, this study examined the effects of maternal HIV infection and psychosocial variables on the onset of sexual and drug risk behavior in 144 HIV-negative adolescents with and…

  1. Expanded syringe exchange programs and reduced HIV infection among new injection drug users in Tallinn, Estonia

    PubMed Central

    2011-01-01

    Background Estonia has experienced an HIV epidemic among intravenous drug users (IDUs) with the highest per capita HIV prevalence in Eastern Europe. We assessed the effects of expanded syringe exchange programs (SEP) in the capital city, Tallinn, which has an estimated 10,000 IDUs. Methods SEP implementation was monitored with data from the Estonian National Institute for Health Development. Respondent driven sampling (RDS) interview surveys with HIV testing were conducted in Tallinn in 2005, 2007 and 2009 (involving 350, 350 and 327 IDUs respectively). HIV incidence among new injectors (those injecting for < = 3 years) was estimated by assuming (1) new injectors were HIV seronegative when they began injecting, and (2) HIV infection occurred at the midpoint between first injection and time of interview. Results SEP increased from 230,000 syringes exchanged in 2005 to 440,000 in 2007 and 770,000 in 2009. In all three surveys, IDUs were predominantly male (80%), ethnic Russians (>80%), and young adults (mean ages 24 to 27 years). The proportion of new injectors decreased significantly over the years (from 21% in 2005 to 12% in 2009, p = 0.005). HIV prevalence among all respondents stabilized at slightly over 50% (54% in 2005, 55% in 2007, 51% in 2009), and decreased among new injectors (34% in 2005, 16% in 2009, p = 0.046). Estimated HIV incidence among new injectors decreased significantly from 18/100 person-years in 2005 and 21/100 person-years in 2007 to 9/100 person-years in 2009 (p = 0.026). Conclusions In Estonia, a transitional country, a decrease in the HIV prevalence among new injectors and in the numbers of people initiating injection drug use coincided with implementation of large-scale SEPs. Further reductions in HIV transmission among IDUs are still required. Provision of 70 or more syringes per IDU per year may be needed before significant reductions in HIV incidence occur. PMID:21718469

  2. Integrating care for hepatitis C virus (HCV) and primary care for HIV for injection drug users coinfected with HIV and HCV.

    PubMed

    Kresina, Thomas F; Bruce, R Douglas; Cargill, Victoria A; Cheever, Laura W

    2005-07-01

    Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) and for at least one-third of new human immunodeficiency virus (HIV) infections. Coinfection with HCV and HIV presents complex and challenging medical conditions. Ensuring access to and maintaining care for HIV and HCV for drug users presents special challenges to the health care team that require a nonjudgmental attitude, experience, and patience. Care for HCV infection, however, can be used as an instrument to engage drug-using persons in ongoing primary care relationships. Common elements to both care for HCV infection and primary care for HIV infection are testing for and counseling about HCV and HIV, substance abuse and mental health services, social support, and subspecialty referral. These elements, in particular treatment for substance abuse, can be focal points for model care systems that provide integrative care for both HCV and HIV infections. PMID:16265621

  3. Decomposing the Energetic Impact of Drug-Resistant Mutations: The Example of HIV-1 Protease - DRV Binding

    PubMed Central

    Cai, Yufeng; Schiffer, Celia

    2016-01-01

    Summary HIV-1 protease is a major drug target for AIDS therapy. With the appearance of drug-resistant HIV-1 protease variants, understanding the mechanism of drug resistance becomes critical. Computational methods can provide more details about inhibitor-protease binding other than crystallography and isothermal titration calorimetry. Darunavir is the latest FDA approved HIV-1 protease inhibitor. In this context, the free energy component analysis is performed on the DRV binding to WT protease and ACT, a drug resistant variant, to evaluate contribution of each atoms of DRV to the binding affinity. This information can contribute to the rationale design of new HIV-1 protease inhibitors. PMID:22183557

  4. INJECTION DRUG USE AND HIV ANTIRETROVIRAL THERAPY DISCONTINUATION IN A CANADIAN SETTING

    PubMed Central

    Werb, Dan; Milloy, M-J; Kerr, Thomas; Zhang, Ruth; Montaner, Julio; Wood, Evan

    2016-01-01

    We investigated whether drug-related behaviors predicted antiretroviral therapy (ART) discontinuation among a cohort of injection drug users (IDU) in a Canadian setting. Cox regression analyses were used to investigate the impact of drug use patterns on rates of ART discontinuation among a sample of HIV-positive IDU in Vancouver, Canada between May 1996 and April 2008. In total, 408 HIV-positive IDU initiated ART during the study period, among whom 257 (63.0%) discontinued ART at least once. Rates of ART discontinuation were not significantly elevated among those who reported ongoing injection of heroin, cocaine, or other illicit drugs in comparison to those who reported not injecting drugs. However, public drug use was significantly predictive of ART discontinuation. Our findings may contribute to a reconsideration of the role of active drug use in determining retention in ART programs among IDU. PMID:22249956

  5. Most HIV type 1 non-B infections in the Spanish cohort of antiretroviral treatment-naïve HIV-infected patients (CoRIS) are due to recombinant viruses.

    PubMed

    Yebra, Gonzalo; de Mulder, Miguel; Martín, Leticia; Rodríguez, Carmen; Labarga, Pablo; Viciana, Isabel; Berenguer, Juan; Alemán, María Remedios; Pineda, Juan Antonio; García, Federico; Holguín, Africa

    2012-02-01

    HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected. PMID:22162552

  6. Most HIV Type 1 Non-B Infections in the Spanish Cohort of Antiretroviral Treatment-Naïve HIV-Infected Patients (CoRIS) Are Due to Recombinant Viruses

    PubMed Central

    Yebra, Gonzalo; de Mulder, Miguel; Martín, Leticia; Rodríguez, Carmen; Labarga, Pablo; Viciana, Isabel; Berenguer, Juan; Alemán, María Remedios; Pineda, Juan Antonio; García, Federico

    2012-01-01

    HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected. PMID:22162552

  7. Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation

    PubMed Central

    Panpradist, Nuttada; Beck, Ingrid A.; Chung, Michael H.; Kiarie, James N.; Frenkel, Lisa M.; Lutz, Barry R.

    2016-01-01

    Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories. PMID:26751207

  8. Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation.

    PubMed

    Panpradist, Nuttada; Beck, Ingrid A; Chung, Michael H; Kiarie, James N; Frenkel, Lisa M; Lutz, Barry R

    2016-01-01

    Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories. PMID:26751207

  9. Effects of Political Conflict Induced Treatment Interruptions on HIV Drug Resistance

    PubMed Central

    Mann, Marita; Lurie, Mark N.; Kimaiyo, Sylvester; Kantor, Rami

    2013-01-01

    34 million people worldwide were living with the Human Immunodeficiency Virus (HIV) by the end of 2010. Despite significant advances in antiretroviral therapy (ART), drug resistance remains a major deterrent to successful, enduring treatment. Unplanned interruptions in ART have negative effects on HIV treatment outcomes including increased morbidity and mortality, as well as development of drug resistance. Treatment interruptions due to political conflicts, not infrequent in resource-limited settings, result in disruptions in health care, infrastructure, or treatment facilities and patient displacement. Such circumstances are ideal bases for ART resistance development, however there is limited awareness of and data available on the association between political conflicts and the development of HIV drug resistance. In this review we identify and discuss this association and review how varying ART half-lives, genetic barriers, different HIV subtypes, and archived resistance can lead to lack of medication effectiveness upon post-conflict resumption of care. Optimized ART stopping strategies as well as infrastructural concerns and stable HIV treatment systems to ensure continuity of care and rapid resumption of care must be addressed in order to mitigate risks of HIV drug resistance development during and after political conflicts. Increased awareness of such associations by clinicians as well as politicians and stakeholders is essential. PMID:23449225

  10. The use of erection enhancing medication and party drugs among men living with HIV in Europe.

    PubMed

    De Ryck, Iris; Van Laeken, David; Noestlinger, Christiana; Platteau, Tom; Colebunders, Robert

    2013-08-01

    Studies have shown more erectile dysfunction (ED) in men living with HIV (MLHIV), relative to age matched HIV-negative men. Erection enhancing medication (EEM) is more frequently used by HIV-positive men than in the general male population. Increased sexually transmitted infection has been described in HIV-positive men with ED using EEM. This study investigated the use of EEM and party drugs (methyleendioxymethamfetamine (XTC), gammahydroxybutyrate (GHB) "fluid XTC" and alkyl nitrites "poppers") among MLHIV. Self-administered questionnaires were distributed consecutively to all patients attending 17 European HIV treatment centers. The sample included 1118 HIV-positive men, among whom 74.5% men having sex with men (MSM). The use of EEM was more frequent in MSM than in heterosexual men (odds ratio (OR) 3.33, p<0.001) and was associated with increased sexual risk behavior (OR 3.27, p<0.001). Nonmedically indicated use of EEM was linked to increased use of party drugs (OR 2.30, p=0.01). Physicians taking care of MLHIV need to be aware of the high prevalence of (nonmedical) use of EEM and party drugs. Medical provision of EEM should be combined with a discussion on safer sex behavior and the risk related to concomitant use of party drugs and illegal EEM. PMID:23244618

  11. Longitudinal HIV Risk Behavior among the Drug Abuse Treatment Outcome Studies (DATOS) Adult Sample

    ERIC Educational Resources Information Center

    Murphy, Debra A.; Brecht, Mary-Lynn; Herbeck, Diane; Evans, Elizabeth; Huang, David; Hser, Yih-Ing

    2008-01-01

    Longitudinal trajectories for HIV risk were examined over 5 years following treatment among 1,393 patients who participated in the nationwide Drug Abuse Treatment Outcome Studies. Both injection drug use and sexual risk behavior declined over time, with most of the decline occurring between intake and the first-year follow-up. However, results of…

  12. Effectiveness of an HIV risk reduction counseling intervention for out-of-treatment drug users.

    PubMed

    Kotranski, L; Semaan, S; Collier, K; Lauby, J; Halbert, J; Feighan, K

    1998-02-01

    This study examined and compared the effectiveness of two counseling interventions designed to reduce the HIV drug and sexual risk behaviors of 684 out-of-treatment drug users recruited from South Philadelphia, PA. All study participants received a standard intervention and one half were randomly assigned to also receive the enhanced intervention. The standard intervention provided HIV risk reduction education, HIV testing with pretest and posttest counseling, and training in condom use and needle cleaning. The enhanced intervention provided additional information on STD risk reduction. Both interventions were effective in influencing behavior change between baseline and 6-month follow-up. A higher proportion of persons reduced their drug risk behaviors compared to their sexual risk behaviors. As sexual risk behaviors are more resistant to change, there is a need for tailored interventions that target out-of-treatment drug users. PMID:9505096

  13. The Age of Initiation of Drug Use and Sexual Behavior May Influence Subsequent HIV Risk Behavior: A Systematic Review

    PubMed Central

    Potrepka, Jessica; Copenhaver, Michael

    2013-01-01

    Researchers examining injection drug users (IDUs) in drug treatment have been trying for decades to determine the optimal way to intervene to prevent the transmission and spread of human immunodeficiency virus (HIV) in this population. Although efficacious HIV risk reduction interventions are widely available, questions remain about what specific factors are most related to HIV risk behavior and defined as unprotected sexual activity and/or high risk drug use. This review involved an evaluation of the research literature in order to better understand the association between drug use and sexual behavior debut on HIV risk behavior. Findings suggest that drug use debut and sexual behavior debut may be related to subsequent HIV risk behavior. Evidence to date implies that intervening at an earlier age to assist youth to avoid or delay these high risk behaviors may be an additional means of reducing subsequent HIV risk. PMID:24381791

  14. Detection of HIV type 1 env subtypes A, B, C, and E in Asia using dried blood spots: a new surveillance tool for molecular epidemiology.

    PubMed

    Cassol, S; Weniger, B G; Babu, P G; Salminen, M O; Zheng, X; Htoon, M T; Delaney, A; O'Shaughnessy, M; Ou, C Y

    1996-10-10

    Global surveillance of HIV-1 subtypes for genetic characterization is hampered by the biohazard of processing and the difficulties of shipping whole blood or cells from many developing country regions. We developed a technique for the direct automated sequencing of viral DNA from dried blood spot (DBS) specimens collected on absorbent paper, which can be mailed unrefrigerated in sturdy paper envelopes with low biohazard risk. DBS were collected nonrandomly from HIV-1-infected, mostly asymptomatic, patients in five Asian countries in 1991, and shipped via airmail or hand carried without refrigeration to Bangkok, and then transshipped to North America for processing. After more than 2 years of storage, including 6 months at ambient temperatures, proviral DNA in the DBS was amplified by nested PCR, and a 389-nucleotide segment of the C2-V3 env gene region was sequenced, from which 287 base pairs were aligned and subtyped by phylogenetic analysis with neighbor-joining and other methods. From southern India, there were 25 infections with subtype C and 2 with subtype A. From Myanmar (Burma), we identified the first subtype E infection, as well as six subtype BB, a distinct cluster within subtype B that was first discovered in Thailand and that has now appeared in China, Malaysia, and Japan. From southwest China, one BB was identified, while a "classical" B typical of North American and European strains was found in Indonesia. From Thailand, five DBS of ambiguous serotype were identified as three B, one BB, and one E. A blinded control serotype E specimen was correctly identified, but a serotype BB control was not tested. Most HIV-1 in southern India appears to be env subtype C, with rare A, as others have reported in western and northern India. The subtypes BB and E in Myanmar, and the BB in China, suggest epidemiological linkage with these subtypes in neighboring Thailand. DBS are a practical, economical technique for conducting large-scale molecular epidemiological

  15. Patterns of HIV Prevalence and HIV Risk Behaviors among Injection Drug Users Prior to and 24 Months following Implementation of Cross-Border HIV Prevention Interventions in Northern Vietnam and Southern China

    ERIC Educational Resources Information Center

    Hammett, Theodore M.; Kling, Ryan; Johnston, Patrick; Liu, Wei; Ngu, Doan; Friedmann, Patricia; Binh, Kieu Thanh; Dong, Ha Viet; Van, Ly Kieu; Donghua, Meng; Chen, Yi; Des Jarlais, Don C.

    2006-01-01

    In 2002, we implemented a 4-year HIV prevention intervention for injection drug users (IDUs) in Lang Son Province, Vietnam, and Ning Ming County, Guangxi Province, China, a cross-border region seriously affected by inter-twined epidemics of heroin injection and HIV infection. The interventions involve peer education on HIV risk reduction and…

  16. Treat Jail Detainees' Drug Abuse to Lower HIV Transmission

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... Amphetamines Bath Salts Brain and Addiction Club Drugs Cocaine Emerging Drugs GHB Hallucinogens Heroin Illegal Drugs Inhalants ...

  17. HIV among people who use drugs: a global perspective of populations at risk.

    PubMed

    Stockman, Jamila K; Strathdee, Steffanie A

    2010-12-01

    This article examines the epidemiology of HIV among selected subgroups of drug users around the world who are "most at risk"--men who have sex with men, female sex workers, prisoners, and mobile populations. The underlying determinants of HIV infection among these populations include stigma, physical and sexual violence, mental illness, social marginalization, and economic vulnerability. HIV interventions must reach beyond specific risk groups and individuals to address the micro-level and macro-level determinants that shape their risk environments. Public health interventions that focus on the physical, social, and health policy environments that influence HIV risk-taking in various settings are significantly more likely to impact the incidence of HIV and other blood-borne and sexually transmitted infections across larger population groups. PMID:21045594

  18. Performing Drug Safety Research During Pregnancy and Lactation: Biomedical HIV Prevention Research as a Template.

    PubMed

    Beigi, Richard H; Noguchi, Lisa; Brown, Gina; Piper, Jeanna; Watts, D Heather

    2016-07-01

    Evidence-based guidance regarding use of nearly all pharmaceuticals by pregnant and lactating women is limited. Models for performing research may assist in filling these knowledge gaps. Internationally, reproductive age women are at high risk of human immunodeficiency virus (HIV) acquisition. Susceptibility to HIV infection may be increased during pregnancy, and risk of maternal-child transmission is increased with incident HIV infection during pregnancy and lactation. A multidisciplinary meeting of experts was convened at the United States National Institutes of Health to consider paradigms for drug research in pregnancy and lactation applicable to HIV prevention. This report summarizes the meeting proceedings and describes a framework for research on candidate HIV prevention agent use during pregnancy and lactation that may also have broader applications to other pharmaceutical products. PMID:23808668

  19. The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes.

    PubMed

    Xu, Weisi; Zhao, Jianxiong; Sun, Jianping; Yin, Qianqian; Wang, Yan; Jiao, Yang; Liu, Junyi; Jiang, Shibo; Shao, Yiming; Wang, Xiaowei; Ma, Liying

    2015-08-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of the highly active antiretroviral therapy (HAART) used to treat human immunodeficiency type 1 virus (HIV-1). However, because of the emergence of drug resistance and the adverse effects of current anti-HIV drugs, it is essential to develop novel NNRTIs with an excellent safety profile, improved activity against NNRTI-resistant viruses, and enhanced activity against clinical isolates of different subtypes. Here, we have identified 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dione (WPR-6), a novel NNRTI with a 50% effective concentration (EC50) of 2 to 4 nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391 with a therapeutic index of >1 × 10(4). A panel of five representative clinical virus isolates of different subtypes circulating predominantly in China was highly sensitive to WPR-6, with EC50s ranging from 1 to 6 nM. In addition, WPR-6 showed excellent antiviral potency against the most prevalent NNRTI-resistant viruses containing the K103N and Y181C mutations. To determine whether WPR-6 selects for novel resistant mutants, in vitro resistance selection was conducted with laboratory-adapted HIV-1 strain SF33 on MT-4 cells. The results demonstrated that V106I and Y188L were the two dominant NNRTI-associated resistance mutations detected in the breakthrough viruses. Taken together, these in vitro data indicate that WPR-6 has greater efficacy than the reference HEPT analogue TNK651 and the marketed drug nevirapine against HIV-1. However, to develop it as a new NNRTI, further improvement of its pharmacological properties is warranted. PMID:26055365

  20. HIV testing, care, and treatment among women who use drugs from a global perspective: progress and challenges

    PubMed Central

    Metsch, Lisa; Philbin, Morgan M.; Parish, Carrigan; Shiu, Karen; Frimpong, Jemima A.; Giang, Le Minh

    2015-01-01

    The paper reviews data on HIV testing, treatment, and care outcomes for women who use drugs in five countries across five continents. We chose countries in which the HIV epidemic has, either currently or historically, been fueled by injection and non-injection drug use, and that have considerable variation in social structural and drug policies: Argentina, Vietnam, Australia, Ukraine, and the United States. There is a dearth of available HIV care continuum outcome data (i.e., testing, linkage, retention, ART provision, viral suppression) among women drug users, particularly among non-injectors. While some progress has been made in increasing HIV testing in this population, HIV-positive women drug users in four of the five countries have not fully benefitted from ART nor are they regularly engaged in HIV care. Issues such as the criminalization of drug users, HIV-specific criminal laws, and the lack of integration between substance use treatment and HIV primary care play a major role. Strategies that effectively address the pervasive factors that prevent women drug users from engaging in HIV care and benefitting from ART and other prevention services are critical. Future success in enhancing the HIV continuum for women drug users should consider structural and contextual level barriers and promote social, economic and legal policies that overhaul the many years of discrimination and stigmatization faced by women drug users worldwide. Such efforts must emphasis the translation of policies into practice and approaches to implementation that can help HIV-infected women who use drugs engage at all points of the HIV Care Continuum. PMID:25978483

  1. HIV Testing, Care, and Treatment Among Women Who Use Drugs From a Global Perspective: Progress and Challenges.

    PubMed

    Metsch, Lisa; Philbin, Morgan M; Parish, Carrigan; Shiu, Karen; Frimpong, Jemima A; Giang, Le Minh

    2015-06-01

    The article reviews data on HIV testing, treatment, and care outcomes for women who use drugs in 5 countries across 5 continents. We chose countries in which the HIV epidemic has, either currently or historically, been fueled by injection and non-injection drug use and that have considerable variation in social structural and drug policies: Argentina, Vietnam, Australia, Ukraine, and the United States. There is a dearth of available HIV care continuum outcome data [ie, testing, linkage, retention, antiretroviral therapy (ART) provision, viral suppression] among women drug users, particularly among noninjectors. Although some progress has been made in increasing HIV testing in this population, HIV-positive women drug users in 4 of the 5 countries have not fully benefitted from ART nor are they regularly engaged in HIV care. Issues such as the criminalization of drug users, HIV-specific criminal laws, and the lack of integration between substance use treatment and HIV primary care play a major role. Strategies that effectively address the pervasive factors that prevent women drug users from engaging in HIV care and benefitting from ART and other prevention services are critical. Future success in enhancing the HIV continuum for women drug users should consider structural and contextual level barriers and promote social, economic, and legal policies that overhaul the many years of discrimination and stigmatization faced by women drug users worldwide. Such efforts must emphasis the translation of policies into practice and approaches to implementation that can help HIV-infected women who use drugs engage at all points of the HIV care continuum. PMID:25978483

  2. Concordance of HIV Type 1 Tropism Phenotype to Predictions Using Web-Based Analysis of V3 Sequences: Composite Algorithms May Be Needed to Properly Assess Viral Tropism

    PubMed Central

    Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza

    2012-01-01

    Abstract Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications. PMID:21919801

  3. Concordance of HIV type 1 tropism phenotype to predictions using web-based analysis of V3 sequences: composite algorithms may be needed to properly assess viral tropism.

    PubMed

    Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza; Brígido, Luis Fernando de Macedo

    2012-07-01

    Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications. PMID:21919801

  4. Combination Drug Products for HIV-A Word of Caution for the Transplant Clinician.

    PubMed

    Patel, S J; Kuten, S A; Musick, W L; Gaber, A O; Monsour, H P; Knight, R J

    2016-08-01

    Modern-day treatment regimens for human immunodeficiency virus (HIV) are not only highly effective, but are now more often available as convenient fixed-dose combination products. Furthermore, as medication adherence is of utmost importance in this setting, national guidelines endorse the use of such products. Transplant providers of HIV-infected patients will undoubtedly encounter these products, some of which contain medications known to drastically alter the metabolism of certain immunosuppressants. Herein, we describe an instance of drug interaction-induced calcineurin inhibitor (CNI) nephrotoxicity in a renal transplant recipient being started on a cobicistat-containing combination product for HIV. CNI toxicity, in turn, was resolved with the aid of phenytoin as an inducer of drug metabolism. This case underscores the importance of familiarity with newer combination products on the market and constant communication with HIV-positive transplant recipients and their providers. PMID:27089541

  5. Time to act: a call for comprehensive responses to HIV in people who use drugs

    PubMed Central

    Beyrer, Chris; Malinowska-Sempruch, Kasia; Kamarulzaman, Adeeba; Kazatchkine, Michel; Sidibe, Michel; Strathdee, Steffanie A

    2013-01-01

    The published work on HIV in people who use drugs shows that the global burden of HIV infection in this group can be reduced. Concerted action by governments, multilateral organisations, health systems, and individuals could lead to enormous benefits for families, communities, and societies. We review the evidence and identify synergies between biomedical science, public health, and human rights. Cost-effective interventions, including needle and syringe exchange programmes, opioid substitution therapy, and expanded access to HIV treatment and care, are supported on public health and human rights grounds; however, only around 10% of people who use drugs worldwide are being reached, and far too many are imprisoned for minor offences or detained without trial. To change this situation will take commitment, advocacy, and political courage to advance the action agenda. Failure to do so will exacerbate the spread of HIV infection, undermine treatment programmes, and continue to expand prison populations with patients in need of care. PMID:20650515

  6. [Molecular epidemiology of HIV-infection in drug addicts of Southern Ural].

    PubMed

    Kazennova, E V; Bobkova, M R; Zemerov, V B; Shantseva, N A; Fedotova, T A; Kiva, L D; Fedotova, T T; Kapizov, A S; Bagautdinov, A T; Gerasimov, V E; Seliutina, L I; Kostian, I R; Raspopin, V I; Pokrovskiĭ, V V; Bobkov, A F

    2004-01-01

    The analysis of HIV-1 variants circulating among drug addicts in 16 settlements of the Sverdlov, Chelyabinsk and Orenburg regions (72, 90 and 42 patients respectively) was carried out. As shown by the serological analysis, the spread of HIV-1 variant IDU-A among the drug addicts in this area continued in this area and could be detected in 99.5% of the samples (203 out of 204 samples). These data were confirmed by the results of the analysis of 35 samples by the Heteroduplex Mobility Assay for genes env and gag. The analysis of nucleotide sequences of gene env revealed that HIV-1 variants in the Southern Urals, where the greatest outbreak of HIV infection in Russia had been registered, were genetically related to viruses of subtype A, detected earlier in this group of risk in other regions of Russia, as well as in Ukraine, Belarus and other East European countries. PMID:15188556

  7. HIV/AIDS and Drug Use in China—Interactions, Impacts, and Issues

    PubMed Central

    Zhao, Min; Ling, Walter

    2014-01-01

    The interrelationships of HIV/AIDS and drug use and misuse result in complex problems that have been addressed by a variety of sociolegal approaches that often are in contrast to evidence-based medical practices proven effective in reducing associated harms. Like other countries struggling to reduce the incidence and consequences of addiction and HIV/AIDS, China is working to improve systems of care and to revise policies toward drug use and misuse and HIV/AIDS. Greater interaction with researchers and clinicians from around the world can foster increased awareness of effective practices and help implement effective strategies to deal with the problems of HIV/AIDS, and addiction. PMID:22676569

  8. HIV and HCV discordant injecting partners and their association to drug equipment sharing.

    PubMed

    De, Prithwish; Cox, Joseph; Boivin, Jean-Francois; Platt, Robert W; Jolly, Ann M; Alexander, Paul E

    2009-01-01

    Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concordant or discordant partners, although HIV-positive subjects did not share with HIV-negative injectors. Sharing of syringes was positively associated with discordant HIV status (OR=1.85) and negatively with discordant HCV status (OR=0.65), but both results were not statistically significant. Sharing of drug preparation equipment was positively associated with both discordant HIV (OR=1.61) and HCV (OR=1.18) status, but both results were non-significant. Factors such as large injecting networks, frequent mutual injections, younger age, and male gender were stronger predictors of equipment sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing partners based at least on their HCV infection status. The results warrant greater screening to raise awareness of infection status, post-test counselling to promote status disclosure among partners, and skill-building to avoid equipment sharing between discordant partners. PMID:19172434

  9. DNA bar coding and pyrosequencing to identify rare HIV drug resistance mutations.

    PubMed

    Hoffmann, Christian; Minkah, Nana; Leipzig, Jeremy; Wang, Gary; Arens, Max Q; Tebas, Pablo; Bushman, Frederic D

    2007-01-01

    Treatment of HIV-infected individuals with antiretroviral agents selects for drug-resistant mutants, resulting in frequent treatment failures. Although the major antiretroviral resistance mutations are routinely characterized by DNA sequencing, treatment failures are still common, probably in part because undetected rare resistance mutations facilitate viral escape. Here we combined DNA bar coding and massively parallel pyrosequencing to quantify rare drug resistance mutations. Using DNA bar coding, we were able to analyze seven viral populations in parallel, overall characterizing 118 093 sequence reads of average length 103 bp. Analysis of a control HIV mixture showed that resistance mutations present as 5% of the population could be readily detected without false positive calls. In three samples of multidrug-resistant HIV populations from patients, all the drug-resistant mutations called by conventional analysis were identified, as well as four additional low abundance drug resistance mutations, some of which would be expected to influence the response to antiretroviral therapy. Methods for sensitive characterization of HIV resistance alleles have been reported, but only the pyrosequencing method allows all the positions at risk for drug resistance mutations to be interrogated deeply for many HIV populations in a single experiment. PMID:17576693

  10. Social and structural factors associated with HIV disease progression among illicit drug users: A systematic review

    PubMed Central

    Milloy, M-J; Marshall, Brandon; Kerr, Thomas; Buxton, Jane; Rhodes, Tim; Montaner, Julio; Wood, Evan

    2014-01-01

    Objective To systematically review factors associated with HIV disease progression among illicit drug users, focusing on exposures exogenous to individuals that likely shape access and adherence to HIV treatment. Design A systematic review of peer-reviewed English-language studies among HIV-seropositive illicit drug users with at least one of these endpoint of interest: a diagnosis of AIDS; death; changes/differences in CD4 cell counts; or changes/differences in plasma HIV-1 RNA levels. Methods Articles were included if they reported factors associated with an outcome of interest among a group of illicit drug users. Studies were identified, screened and selected using systematic methods. Results Of 2,668 studies matching the search criteria, 58 (2%) met the inclusion criteria, all but one from North America or Western Europe. Overall, 41 (71%) studies contained significant individual-level clinical characteristics or behaviours (e.g., illicit drug use) associated with disease progression. Fifteen studies (26%) identified significant social, physical, economic or policy-level exposures, including incarceration, housing status or lack of legal income. Conclusion While past studies demonstrate important environmental exposures that appear to shape access to care and subsequent disease progression, the limited literature to examine these factors demonstrates the need for future research to consider risk environment characteristics and the role they may play in shaping health outcomes from HIV infection among drug users through determining access and adherence to evidence-based care. (198 words) PMID:22333747

  11. Maternal HIV and drug use: effect on health and social morbidity.

    PubMed Central

    Mok, J Y; Ross, A; Raab, G; Hamilton, B; Gilkison, S; Johnstone, F D

    1996-01-01

    A retrospective analysis of routine child health surveillance information was performed on health visitor records of 459 children, to examine the independent effects of maternal HIV infection and drug use during pregnancy on morbidity in the first 3 years of life. No significant differences were observed in the developmental progress of children born to HIV infected or drug using women when compared to community controls. The pattern of medical consultations in the first 18 months of life was significantly different, maternal drug use exerting a negative influence on outpatient visits (odds ratio 0.6, 95% confidence interval 0.4 to 1.0). At 6 weeks, the majority of children lived with their birth parent(s), and no differences were observed between the groups. By 10 months of age, only 81% of children born to HIV infected drug using women lived with their parent(s). While maternal drug use and HIV did not have adverse effects on child health and development, these findings highlight the social implications for children affected by the heterosexual spread of HIV. PMID:8787424

  12. Determinants of HIV risk among men who have homosexual sex and inject drugs.

    PubMed

    Crofts, N; Marcus, L; Meade, J; Sattler, G; Wallace, J; Sharp, R

    1995-01-01

    Men with histories of both homosexual contact and injecting drug use (IDU) are at increased risk of HIV infection over men who have only one such risk. Despite this, their special needs and circumstances have been neglected by AIDS prevention programmes. A survey of a wide spectrum of homosexual male IDUs was carried out in Melbourne and Sydney in 1993 to inform the development of specific policy and programmes for HIV prevention in these subcultures. Of 169 men, self-reported HIV prevalence was 27%. Decreasing compliance with safe sex guidelines (as measured by numbers of casual partners, participation in anal intercourse and use of condoms) was associated with HIV seropositivity, increased age, and increased participation in sex work; having a regular male partner was not protective against unsafe sexual behaviour, no matter the length of the relationship. A substantial proportion (15%) reported inconsistent condom use during anal sex with more than two partners in the preceding month: they were slightly more likely to be engaging in sex work, less 'stable' and more likely to be HIV infected. Sexual risk was not strongly associated with unsafe injecting, which was in general safe. Men who both have homosexual sex and inject drugs are groups at high risk of HIV, more from unsafe sex than from shared injecting equipment; men who believed themselves to be HIV infected were continuing to have sex in such a way that would allow transmission. These are clearly groups in need of priority targeted interventions. PMID:8652699

  13. Delay discounting is greater among drug users seropositive for hepatitis C but not HIV

    PubMed Central

    Martin, Eileen; Gonzalez, Raul; Vassileva, Jasmin; Bechara, Antoine

    2015-01-01

    Objective Substance dependent individuals (SDIs) typically overvalue immediate and undervalue (discount) delayed rewards, and level of discounting significantly predicts post-treatment relapse and other behavioral outcomes. Delay discounting has potential significance for studies of HIV prevention and adherence to antiretroviral therapy; but effects of HIV infection on delay discounting rates among SDIs are not well understood, although discounting rates are higher among individuals infected with hepatitis C virus (HCV). In this study, we investigated potential additive or interactive effects of HIV and HCV infection on delay discounting performance among a group of 239 SDIs with verified HIV and HCV serostatus. Method All participants were verified abstinent from drugs and alcohol at testing. All participants completed measures of substance abuse characteristics and comorbid disorders, and the Monetary Choice Questionnaire, a well-known measure used to derive k coefficients, which index discounting rates. Results Groups were comparable on demographic, substance use, and comorbid characteristics. Compared to uninfected controls, discounting rates were significantly higher among individuals seropositive for HCV but not HIV. Additionally, no significant group differences in discounting rates were observed among HCV+ individuals with or without coinfection with HIV. Group differences could not be attributed to aging or nonspecific effects of drug addiction. Additionally, increased discounting rates were associated with riskier injection practices. Conclusions Potential mechanisms contributing to this discrepancy in discounting rates between HIV+ and HCV+ SDIs, including decision making, are discussed and await further study. PMID:25984995

  14. The analysis of HIV/AIDS drug-resistant on networks

    NASA Astrophysics Data System (ADS)

    Liu, Maoxing

    2014-01-01

    In this paper, we present an Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) drug-resistant model using an ordinary differential equation (ODE) model on scale-free networks. We derive the threshold for the epidemic to be zero in infinite scale-free network. We also prove the stability of disease-free equilibrium (DFE) and persistence of HIV/AIDS infection. The effects of two immunization schemes, including proportional scheme and targeted vaccination, are studied and compared. We find that targeted strategy compare favorably to a proportional condom using has prominent effect to control HIV/AIDS spread on scale-free networks.

  15. Recreational drug use among individuals living with HIV in Europe: review of the prevalence, comparison with the general population and HIV guidelines recommendations

    PubMed Central

    Garin, Noe; Velasco, Cesar; De Pourcq, Jan T.; Lopez, Belen; Gutierrez, Maria del Mar; Haro, Josep M.; Feliu, Anna; Mangues, Maria A.; Trilla, Antoni

    2015-01-01

    Background: Adherence problems, interactions and higher rate of risk activities have been observed in HIV individuals using recreational drugs. Our aim was to describe recreational drug use in both HIV individuals and general population in Europe, and to assess at what extent HIV guidelines address this issue. Methods: Data on recreational drug use across Europe were obtained from the European Monitoring Centre for Drugs and Drug Addiction for the general population, and through Pubmed search. for HIV patients. We assessed the incorporation of recreational drug issues in HIV treatment guidelines for the following topics: (a) recreational drugs; (b) adherence to antiretrovirals; (c) interactions; (d) transmission risk. Guidelines included: World Health Organization; European Aids Clinical Society; U.S. Department of Health and Human Services; International Antiviral Society-USA; and seven European national guidelines. Results: 29 countries reported recreational drug use in general population. The highest prevalences were observed for Cannabis (i.e., 8–10% in Spain, France, and Czech Republic) followed by cocaine, amphetamines and ecstasy. The 13 studies selected in the systematic review showed a great variability in recreational drug use on the HIV population. Apart from classical recreational drugs, we found a relevant use of new drugs including sexual experience enhancers. Polydrug consumption was about 50% in some studies. Most guidelines included general information about recreational drugs, showing great variability on the inclusion of the evaluated topics. We found more specific, evidence-based recommendations on interactions, followed by medication adherence and transmission risk. Conclusions: Available data on the people living with HIV suggest a higher use of recreational drugs than in the general population, which is already relevant. However, recreational drug issues should be included or addressed more thoroughly in most guidelines. PMID:26236288

  16. A New Reporter Cell Line to Monitor HIV Infection and Drug Susceptibility in vitro

    NASA Astrophysics Data System (ADS)

    Gervaix, Alain; West, Daniel; Leoni, Lorenzo M.; Richman, Douglas D.; Wong-Staal, Flossie; Corbeil, Jacques

    1997-04-01

    Determination of HIV infectivity in vitro and its inhibition by antiretroviral drugs by monitoring reduction of production of p24 antigen is expensive and time consuming. Such assays also do not allow accurate quantitation of the number of infected cells over time. To develop a simple, rapid, and direct method for monitoring HIV infection, we generated a stable T-cell line (CEM) containing a plasmid encoding the green fluorescent protein (humanized S65T GFP) driven by the HIV-1 long terminal repeat. Clones were selected that displayed low constitutive background fluorescnece, but a high level of GFP expression upon infection with HIV. HIV-1 infection induced a 100- to 1,000-fold increase in relative fluorescence of cells over 2 to 4 days as monitored by fluorescence microscopy, cytofluorimetry, and flow cytometry. Addition of inhibitors of reverse transcriptase, protease, and other targets at different multiplicities of infection permitted the accurate determination of drug susceptibility. This technique also permitted quantitation of infectivity of viral preparations by assessment of number of cells infected in the first round of infection. In conclusion, the CEM-GFP reporter cell line provides a simple, rapid, and direct method for monitoring HIV infectivity titers and antiretroviral drug susceptibility of syncytium-inducing strains.

  17. Trends in HIV and hepatitis C virus infections among injecting drug users in Europe, 2005 to 2010.

    PubMed

    Wiessing, L; Likatavicius, G; Hedrich, D; Guarita, B; van de Laar, M J; Vicente, J

    2011-01-01

    Data on newly diagnosed HIV infections and HIV prevalence in 2005 to 2010 suggest falling infection rates in injecting drug users (IDUs) in the European Union (EU). However, recent increases in HIV and hepatitis C virus (HCV) infection rates in IDUs suggest increasing injecting risks in some countries. The coverage of effective prevention measures has increased, but is still low in several countries. Overall the data suggest a continued risk of new outbreaks of HIV infection among IDUs. PMID:22172300

  18. HIV behind Bars: Human Immunodeficiency Virus Cluster Analysis and Drug Resistance in a Reference Correctional Unit from Southern Brazil

    PubMed Central

    Ikeda, Maria Letícia R.; Kuhleis, Daniele; Picon, Pedro D.; Jarczewski, Carla A.; Osório, Marta R.; Sánchez, Alexandra; Seuánez, Héctor N.; Larouzé, Bernard; Soares, Marcelo A.; Soares, Esmeralda A.

    2013-01-01

    People deprived of liberty in prisons are at higher risk of infection by the human immunodeficiency virus (HIV) due to their increased exposure through intravenous drug use, unprotected sexual activity, tattooing in prison and blood exposure in fights and rebellions. Yet, the contribution of intramural HIV transmission to the epidemic is scarcely known, especially in low- and middle-income settings. In this study, we surveyed 1,667 inmates incarcerated at Presídio Central de Porto Alegre, located in southern Brazil, for HIV infection and molecular characterization. The HIV seroprevalence was 6.6% (110/1,667). Further analyses were carried out on 40 HIV-seropositive inmates to assess HIV transmission clusters and drug resistance within the facility with the use of molecular and phylogenetic techniques. The molecular epidemiology of HIV-1 subtypes observed was similar to the one reported for the general population in southern Brazil, with the predominance of HIV-1 subtypes C, B, CRF31_BC and unique BC recombinants. In particular, the high rate (24%) of URF_BC found here may reflect multiple exposures of the population investigated to HIV infection. We failed to find HIV-infected inmates sharing transmission clusters with each other. Importantly, the analysis of HIV-1 pol genomic fragments evidenced high rates of HIV primary and secondary (acquired) drug resistance and an alarming proportion of virologic failure among patients under treatment, unveiling suboptimal access to antiretroviral therapy (ARV), low ARV adherence and dissemination of drug resistant HIV strains in primary infections. Our results call for immediate actions of public authority to implement preventive measures, serological screening and, for HIV-seropositive subjects, clinical and treatment follow-up in order to control HIV infection and limit the spread of drug resistance strains in Brazilian prisons. PMID:23874857

  19. The role of harm reduction in controlling HIV among injecting drug users

    PubMed Central

    Wodak, Alex; McLeod, Leah

    2012-01-01

    Injecting drug users (IDU) now account for one in 10 new HIV infections world wide. Yet it has been known since the early 1990s that HIV among IDU can be effectively, safely and cost-effectively controlled by the early and vigorous implementation of a comprehensive package of strategies known as ’harm reduction’. This concept means that decreasing drug-related harms is accorded an even higher priority than reduction of drug consumption. Strategies required involve: explicit and peer-based education about the risk of HIV from sharing injecting equipment; needle syringe programmes; drug treatment (including especially opiate substitution treatment) and community development. Many countries experiencing or threatened by an HIV epidemic among IDU have now adopted harm reduction but often implementation has been too little and too late. Although coverage is slowly improving in many countries, HIV is still spreading faster among IDU than harm reduction programmes while coverage in correctional centres lags far behind community settings. The scientific debate about harm reduction is now over. National and international support for harm reduction is growing while almost all the major UN organizations responsible for drug policy now support harm reduction. Only a small number of countries, led by the USA, are still vehemently opposed to harm reduction. Excessive reliance on drug law enforcement remains the major barrier to increased adoption of harm reduction. Sometimes zealous drug law enforcement undermines harm reduction. A more balanced approach to drug law enforcement is required with illicit drug use recognized primarily as a health and social problem. PMID:18641473

  20. HIV prevention among injecting drug users: responses in developing and transitional countries.

    PubMed Central

    Ball, A L; Rana, S; Dehne, K L

    1998-01-01

    OBJECTIVE: Human immunodeficiency virus (HIV) infection associated with injecting drug use has been reported in at least 98 countries and territories worldwide. There is evidence that new epidemics are emerging in different regions, including Eastern Europe, Latin American, and the eastern Mediterranean. The authors provide a global overview of the situation of HIV infection associated with injecting drug use and responses that have been implemented in various developing and transitional countries. METHODS: Although there has been extensive documentation of the extent and nature of of HIV infection associated with injecting drug use in many developed countries and the various interventions implemented in those countries, there is very limited information on the situation in developing and transitional countries. This chapter brings together information from a broad range of sources, including published literature; "gray" or "fugitive" literature; data collected by the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations International Drug Control Programme (UNDCP); personal communications; and direct observation by the authors. The authors have traveled extensively to a wide range of developing and transitional countries and have accessed information not readily available to the international research community. RESULTS: A wide range of HIV prevention strategies targeting injecting drug users (IDUs) has been implemented in developing countries and countries in transition. Interventions include opioid substitution pharmacotherapy, needle syringe exchange and distribution, condom and bleach distribution, outreach to IDUs, peer education programs, and social network interventions. In some communities, completely new models of intervention and service delivery have developed in response to specific local needs and limitations. CONCLUSIONS: Although empirical data may currently be lacking to demonstrate the

  1. Global Epidemiology of HIV Among Women and Girls Who Use or Inject Drugs: Current Knowledge and Limitations of Existing Data

    PubMed Central

    Larney, Sarah; Mathers, Bradley M.; Poteat, Tonia; Kamarulzaman, Adeeba; Degenhardt, Louisa

    2016-01-01

    Background Women and girls who use and inject drugs are a critical population at risk of HIV. In this article, we review data on the epidemiology of drug use and injection among women globally and HIV prevalence among women and girls who use and inject drugs. Results Women and girls comprise one-third of people who use and inject drugs globally. There is substantial variation in HIV prevalence in this population, between and within countries. There is a pronounced lack of data examining HIV risk among particularly vulnerable subpopulations of women who use and inject drugs, including women who have sex with women, transgender women, racial and ethnic minority women, and young women. Women who use and inject drugs experience stigma and discrimination that affect access to services, and high levels of sexual risk exposures. Conclusions There are significant gaps in our understanding of the epidemiology of drug use and injecting among women and girls and HIV risk and prevalence in this population. Women are frequently underrepresented in studies of drug use and HIV risk and prevalence among people who inject drugs, limiting our understanding of possible sex differences in this population. Most research originates from developed countries and may not be generalizable to other settings. A great deal of work is needed to improve understanding of HIV among particularly vulnerable subpopulations, such as transgender women who use drugs. Better data are critical to efforts to advocate for the needs of women and girls who use and inject drugs. PMID:25978476

  2. Diabetes Type 1

    MedlinePlus

    ... blood sugar, levels are too high. With type 1 diabetes, your pancreas does not make insulin. Insulin ... eyes, kidneys, nerves, and gums and teeth. Type 1 diabetes happens most often in children and young ...

  3. Control over Drug Acquisition, Preparation, and Injection: Implications for HIV and HCV Risk among Young Female Injection Drug Users

    PubMed Central

    Wagner, Karla D.; Jackson Bloom, Jennifer; Hathazi, Susan Dodi; Sanders, Bill; Lankenau, Stephen E.

    2013-01-01

    Young female injection drug users (IDUs) are at risk for HIV/HCV, and initiating the use of a new drug may confer additional and unexpected risks. While gender differences in the social context of injection drug use have been identified, it is unknown whether those differences persist during the initiation of a new drug. This mixed-methods study examined the accounts of 30 young female IDUs in Los Angeles, CA, USA from 2004 to 2006, who described the social context of initiating injection drug use and initiating ketamine injection. The analysis aimed to understand how the social context of young women's injection events contributes to HIV/HCV risk. Women's initiation into ketamine injection occurred approximately 2 years after their first injection of any drug. Over that time, women experienced changes in some aspects of the social context of drug injection, including the size and composition of the using group. A significant proportion of women described injection events characterized by a lack of control over the acquisition, preparation, and injection of drugs, as well as reliance on friends and sexual partners. Findings suggest that lack of control over drug acquisition, preparation, and injection may elevate women's risk; these phenomena should be considered as a behavioral risk factor when designing interventions. PMID:24364027

  4. Analyzing HIV/AIDS and Alcohol and Other Drug Use as a Social Problem

    PubMed Central

    PATTERSON, DAVID A.; Wolf (Adelv unegv Waya), Silver

    2012-01-01

    Most prevention and intervention activities directed toward HIV/AIDS and alcohol and other drug use separately as well as the combining of the two (e.g., those who are both HIV/AIDS and using alcohol and other drugs) comes in the form of specific, individualized therapies without consideration of social influences that may have a greater impact on this population. Approaching this social problem from the narrowed view of individualized, mi-cro solutions disregards the larger social conditions that affect or perhaps even are at the root of the problem. This paper analyzes the social problem of HIV/AIDS and alcohol and other drug abuse using three sociological perspectives—social construction theory, ethnomethodology, and conflict theory—informing the reader of the broader influences accompanying this problem. PMID:23264724

  5. An effective HIV risk-reduction protocol for drug-using female sex workers.

    PubMed

    Surratt, Hilary L; Inciardi, James A

    2010-01-01

    Female sex workers are especially vulnerable to HIV infection, particularly those who use drugs and engage in street-based sex exchange. This study examines the risk behaviors and HIV serostatus of 806 drug-using female sex workers in Miami and assesses the relative impact of two HIV and hepatitis prevention interventions on changes in risk behavior. Drug-using sex workers were recruited using targeted sampling strategies and were randomly assigned to the NIDA Standard Intervention or an innovative Sex Worker Focused (SWF) Intervention. Outcome analyses indicate that both groups benefited from participation in the intervention trial. However, the SWF Intervention was found to be more efficacious in regard to reductions in unprotected oral sex and sexual violence. PMID:20391059

  6. HIV Infection and Geographically Bound Transmission of Drug-Resistant Tuberculosis, Argentina

    PubMed Central

    López, Beatriz; Ambroggi, Marta; Palmero, Domingo; Salvadores, Bernardo; Gravina, Elida; Mazzeo, Eduardo; Imaz, Susana; Barrera, Lucía

    2012-01-01

    During 2003–2009, the National Tuberculosis (TB) Laboratory Network in Argentina gave 830 patients a new diagnosis of multidrug-resistant (MDR) TB and 53 a diagnosis of extensively drug- resistant (XDR) TB. HIV co-infection was involved in nearly one third of these cases. Strain genotyping showed that 7 major clusters gathered 56% of patients within restricted geographic areas. The 3 largest clusters corresponded to epidemic MDR TB strains that have been undergoing transmission for >10 years. The indigenous M strain accounted for 29% and 40% of MDR and XDR TB cases, respectively. Drug-resistant TB trends in Argentina are driven by spread of a few strains in hotspots where the rate of HIV infection is high. To curb transmission, the national TB program is focusing stringent interventions in these areas by strengthening infection control in large hospitals and prisons, expediting drug resistance detection, and streamlining information-sharing systems between HIV and TB programs. PMID:23092584

  7. Towards novel therapeutics for HIV through fragment-based screening and drug design.

    PubMed

    Tiefendbrunn, Theresa; Stout, C David

    2014-01-01

    Fragment-based drug discovery has been applied with varying levels of success to a number of proteins involved in the HIV (Human Immunodeficiency Virus) life cycle. Fragment-based approaches have led to the discovery of novel binding sites within protease, reverse transcriptase, integrase, and gp41. Novel compounds that bind to known pockets within CCR5 have also been identified via fragment screening, and a fragment-based approach to target the TAR-Tat interaction was explored. In the context of HIV-1 reverse transcriptase (RT), fragment-based approaches have yielded fragment hits with mid-μM activity in an in vitro activity assay, as well as fragment hits that are active against drug-resistant variants of RT. Fragment-based drug discovery is a powerful method to elucidate novel binding sites within proteins, and the method has had significant success in the context of HIV proteins. PMID:25455312

  8. HIV risk behaviours among injecting drug users in Northeast India following scale-up of a targeted HIV prevention programme

    PubMed Central

    2011-01-01

    Background In the Northeast Indian states of Manipur and Nagaland there has been an ongoing HIV epidemic among injecting drug users (IDUs) since the mid-1990s. Project ORCHID is an Avahan-funded HIV prevention project that has been working in selected districts of Manipur and Nagaland since 2004. It supports local partner non-government organisations (NGOs) to deliver a range of harm reduction interventions, and currently reaches approximately 14,500 IDUs across the two states. To assess changes in HIV risk behaviours two Behavioural Tracking Surveys (BTS) were undertaken among IDUs in 2007 and 2009. Methods The BTS used respondent driven sampling (RDS) to recruit adult male IDUs (18 years of age and above) from Ukhrul and Chandel districts in Manipur, and Kiphire and Zunheboto districts in Nagaland. This paper reports on analysis of socio-demographics, drug use and injecting practices, sexual behaviour and condom use, knowledge of HIV, and exposure to interventions. Descriptive data were analysed using RDSAT, and odds ratios were calculated in SPSS. Results The proportion of IDUs reporting NOT sharing needles / syringes at last injection increased substantially in Ukhrul (59.6% to 91.2%) and Zunheboto (45.5% to 73.8%), remained high in Chandel (97.0% to 98.9%), and remained largely unchanged in Kiphire (63.3% to 68.8%). The use of condoms with regular partners was low in all districts at both time points. In Ukhrul, Kiphire and Zunheboto the proportion of IDUs using condoms during sexual intercourse with a casual partner increased substantially to approximately 70-85%, whilst in Chandel the increase was only marginal (57.4% to 63.6%). Exposure to NGO HIV prevention interventions was significantly associated (p<0.05) with lower odds of sharing needles during the previous month (Nagaland, OR=0.63; Manipur, OR 0.35). Conclusion Despite district-level differences, the results from this BTS study indicate that exposure to HIV prevention services, predominately

  9. Epidemiology of HIV/AIDS, hepatitis B, hepatitis C, and tuberculosis among minority injection drug users.

    PubMed Central

    Estrada, Antonio L.

    2002-01-01

    OBJECTIVE: This article reviews the literature on the impact of HIV/AIDS, hepatitis B and C viruses (HBV, HCV), and tuberculosis on minority drug injectors in the United States. OBSERVATIONS: Injection drug use is a key factor in the transmission of blood-borne pathogens, and HIV disease is exacerbated by tuberculosis infection. Minority drug injectors are disproportionately represented in the national statistics on these infections. Behavioral epidemiologic studies show that both injection-related risk factors years of injecting drugs, type of drug injected, direct and indirect sharing of injection paraphernalia) and sex-related risk factors (lack of condom use, multiple sexual partners, survival sex) are conducive to the spread of HIV, HBV, and HCV. CONCLUSIONS: Two issues must be addressed to halt the spread of HIV infection and hepatitis B and C. The capacity of syringe-exchange programs to refer participants to drug treatment programs and facilitate access to health and social services must be increased. Culturally appropriate behavioral interventions targeting risk behaviors among ethnic and racial minorities, especially women, must be developed and put in place. PMID:12435836

  10. A situational picture of HIV/AIDS and injection drug use in Vinnitsya, Ukraine

    PubMed Central

    Barcal, Katerina; Schumacher, Joseph E; Dumchev, Kostyantyn; Moroz, Larisa Vasiliyevna

    2005-01-01

    Background New and explosive HIV epidemics are being witnessed in certain countries of Eastern Europe, including Ukraine, as well as a rapid and dramatic increase in the supply, use, and negative public health consequences of illicit drugs. A majority of registered HIV cases in Ukraine occur among injection drug users (IDUs), large numbers of whom report HIV risk behaviors such as needle sharing. The purpose of this study was to apply the World Health Organization's Rapid Assessment and Response on Injection Drug Use (IDU-RAR) guide to create a situational picture in the Vinnitsya Oblast, Ukraine, a region with very scarce information about the HIV/AIDS and injection drug use (IDU) epidemics. Methods The IDU-RAR uses a combination of qualitative data collection techniques commonly employed in social science and evaluation research to quickly depict the extent and nature of the given health problem and propose locally relevant recommendations for improvement. The investigators focused their assessment on the contextual factors, drug use, and intervention and policy components of the IDU-RAR. A combination of network and block sampling techniques was used. Data collection methods included direct observation, review of existing data, structured and unstructured interviews, and focus group discussions. Key informants and locations were visited until no new information was being generated. Results The number of registered HIV cases in Vinnitsya has increased from 3 (1987–1995) to 860 (1999–10/2004), 57 of whom have already died. Ten percent of annual admissions to the area's Regional Narcological Dispensary were for opiate disorders, and the number of registered IDUs rose by 20% from 1999 to 2000. The level of HIV/AIDS awareness is generally poor among the general population but high among high-risk populations. Both HIV/AIDS and injection drug use carry a strong stigma in the community, even among medical professionals. There was very little evidence of primary HIV

  11. Predictors of Sharing Injection Equipment by HIV-Seropositive Injection Drug Users

    PubMed Central

    Latkin, Carl A.; Buchanan, Amy S.; Metsch, Lisa R.; Knight, Kelly; Latka, Mary H.; Mizuno, Yuko; Knowlton, Amy R.

    2009-01-01

    Among HIV-positive injection drug users (IDUs), we examined baseline predictors of lending needles and syringes, and sharing cookers, cotton, and rinse water in the prior 3 months at follow-up. Participants were enrolled in INSPIRE, a secondary prevention intervention for sexually active HIV-positive IDUs in four US cities during 2001–2005. The analyses involved 357 participants who reported injecting drugs in the prior six months at either the 6- or 12-months follow-up visit. About half (49%) reported at least one sharing episode. In adjusted analyses, peer norms supporting safer injection practices, and having primary HIV medical care visits in the prior 6 months were associated with reporting no sharing of injection equipment. Higher levels of psychological distress was associated with a greater likelihood of reporting drug paraphernalia sharing. These findings suggest that intervention approaches for reducing HIV-seropositive IDUs’ transmission of blood-borne infections should include peer-focused interventions to alter norms of drug paraphernalia sharing and promoting primary HIV care and mental health services. PMID:19186356

  12. Predictors of sharing injection equipment by HIV-seropositive injection drug users.

    PubMed

    Latkin, Carl A; Buchanan, Amy S; Metsch, Lisa R; Knight, Kelly; Latka, Mary H; Mizuno, Yuko; Knowlton, Amy R

    2008-12-01

    Among HIV-positive injection drug users (IDUs), we examined baseline predictors of lending needles and syringes and sharing cookers, cotton, and rinse water in the prior 3 months at follow-up. Participants were enrolled in Intervention for Seropositive Injectors-Research and Evaluation, a secondary prevention intervention for sexually active HIV-positive IDUs in 4 US cities during 2001-2005. The analyses involved 357 participants who reported injecting drugs in the prior 6 months at either the 6- or 12-month follow-up visit. About half (49%) reported at least 1 sharing episode. In adjusted analyses, peer norms supporting safer injection practices and having primary HIV medical care visits in the prior 6 months were associated with reporting no sharing of injection equipment. Higher levels of psychological distress were associated with a greater likelihood of reporting drug paraphernalia sharing. These findings suggest that intervention approaches for reducing HIV-seropositive IDUs' transmission of blood-borne infections should include peer-focused interventions to alter norms of drug paraphernalia sharing and promoting primary HIV care and mental health services. PMID:19186356

  13. Understanding the effects of different HIV transmission models in individual-based microsimulation of HIV epidemic dynamics in people who inject drugs.

    PubMed

    Monteiro, J F G; Escudero, D J; Weinreb, C; Flanigan, T; Galea, S; Friedman, S R; Marshall, B D L

    2016-06-01

    We investigated how different models of HIV transmission, and assumptions regarding the distribution of unprotected sex and syringe-sharing events ('risk acts'), affect quantitative understanding of HIV transmission process in people who inject drugs (PWID). The individual-based model simulated HIV transmission in a dynamic sexual and injecting network representing New York City. We constructed four HIV transmission models: model 1, constant probabilities; model 2, random number of sexual and parenteral acts; model 3, viral load individual assigned; and model 4, two groups of partnerships (low and high risk). Overall, models with less heterogeneity were more sensitive to changes in numbers risk acts, producing HIV incidence up to four times higher than that empirically observed. Although all models overestimated HIV incidence, micro-simulations with greater heterogeneity in the HIV transmission modelling process produced more robust results and better reproduced empirical epidemic dynamics. PMID:26753627

  14. Evaluation of novel Saquinavir analogs for resistance mutation compatibility and potential as an HIV-Protease inhibitor drug

    PubMed Central

    Jayaswal, Amit; Mishra, Ankita; Mishra, Hirdyesh; Shah, Kavita

    2014-01-01

    A fundamental issue related to therapy of HIV-1 infection is the emergence of viral mutations which severely limits the long term efficiency of the HIV-protease (HIV-PR) inhibitors. Development of new drugs is therefore continuously needed. Chemoinformatics enables to design and discover novel molecules analogous to established drugs using computational tools and databases. Saquinavir, an anti-HIV Protease drug is administered for HIV therapy. In this work chemoinformatics tools were used to design structural analogs of Saquinavir as ligand and molecular dockings at AutoDock were performed to identify potential HIV-PR inhibitors. The analogs S1 and S2 when docked with HIV-PR had binding energies of -4.08 and -3.07 kcal/mol respectively which were similar to that for Saquinavir. The molecular docking studies revealed that the changes at N2 of Saquinavir to obtain newly designed analogs S1 (having N2 benzoyl group at N1) and S2 (having 3-oxo-3phenyl propanyl group at N2) were able to dock with HIV-PR with similar affinity as that of Saquinavir. Docking studies and computationally derived pharmacodynamic and pharmacokinetic properties׳ comparisons at ACD/I-lab establish that analog S2 has more potential to evade the problem of drug resistance mutation against HIV-1 PR subtype-A. S2 can be further developed and tested clinically as a real alternative drug for HIV-1 PR across the clades in future. PMID:24966525

  15. Why the Treatment of Mental Disorders Is an Important Component of HIV Prevention among People Who Inject Drugs

    PubMed Central

    Buckingham, Elizabeth; Schrage, Ezra; Cournos, Francine

    2013-01-01

    People who inject drugs are more likely to be HIV positive and to have a mental disorder than the general population. We explore how the detection and treatment of mental illness among people who are injecting drugs are essential to primary and secondary prevention of HIV infection in this population. Aside from opioid addiction, few studies have been conducted on the links between mental disorders and injection-drug use. However, independent of the injection-drug use literature, a growing number of studies demonstrate that untreated mental illness, especially depression and alcohol/substance use disorders, is associated with HIV-related risk behaviors, acquiring HIV infection, failure to access HIV care and treatment, failure to adhere to HIV care and treatment, and increased morbidity and mortality from HIV-related diseases and comorbidities. In our review of both the published literature and gray literature we found a dearth of information on models for providing care for both opioid addiction and other mental illnesses regardless of HIV status, particularly in low- and middle-income countries. We therefore make recommendations on how to address the mental health needs of HIV-positive people who inject drugs, which include the provision of opioid substitution therapy and integrated mental health, substance abuse, and HIV services. PMID:23401785

  16. Update and Overview of Practical Epidemiologic Aspects of HIV/AIDS among Injection Drug Users in the United States

    PubMed Central

    Garfein, Richard S.; Swartzendruber, Andrea; Purcell, David W.; Paxton, Lynn A.; Greenberg, Alan E.

    2006-01-01

    In a changing public health landscape in which local, state, and federal agencies must confront threats of bioterrorism, emerging infections, and numerous chronic diseases, transmission of HIV among injection drug users (IDUs) continues to be an important public health issue and one of the driving forces behind the HIV epidemic. Using a computerized MEDLINE search of published articles from January 1981 through October 2005, we conducted a literature review of practical epidemiologic aspects of HIV/AIDS among IDUs in the United States. Although recent trends indicate a decline in the proportion of newly diagnosed HIV infections associated with injection drug use, drug-use behaviors overall still account for 32% of new HIV diagnoses. Factors in addition to syringe sharing contribute to HIV transmission among IDUs: risky sexual behaviors, sharing of drug preparation equipment and drug solutions, and contextual and social factors. Promising approaches for HIV prevention include rapid HIV testing, office-based substance abuse treatment, behavioral interventions, improved communication about syringe exchange programs, and case management. HIV among IDUs continues to be an important public health problem in the 21st century. It is imperative that public health agencies continue to monitor and combat the HIV epidemic among IDUs to ensure that hard-won gains will not be eroded. PMID:16736357

  17. Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors.

    PubMed

    Balzarini, J; De Clercq, E; Carbonez, A; Burt, V; Kleim, J P

    2000-04-10

    The novel quinoxaline GW420867X has been combined with a variety of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1(IIIB)-infected CEM cell cultures. Whereas the antiviral efficacy of combinations of GW420867X with the NRTIs lamivudine (3TC) and abacavir (ABC) proved additive when administered to HIV-1-infected cells in a short-term (4-day) infection experiment, combination of GW420867X with the NRTIs 3TC and ABC resulted in a marked delay of virus breakthrough compared with the single drugs alone in a long-term (2-month) infection experiment. Delay of virus breakthrough was less pronounced for combinations of GW420867X with the NNRTIs. Combination of GW420867X with the NRTIs and NNRTIs resulted in additive inhibitory effects on recombinant HIV-1 reverse transcriptase as evident from isobolograms. Lamivudine plus GW420867X selected for the 3TC-specific M184I mutation and a number of NNRTI-characteristic mutations (i.e., V106A, V108I, and Y188H). Abacavir plus GW420867X selected only for NNRTI-specific mutations (i.e., K101E, K103R, V106A, and Y181C), including the novel L100V mutation. Combination of GW420867X with five different NNRTIs selected solely for NNRTI-specific mutations, and also for the L100V mutation in the combined presence of efavirenz, nevirapine, or emivirine, respectively. Five single-, two double-, and two triple-mutated HIV-1 strains that emerged from this study were evaluated for their sensitivity/resistance to AZT, lamivudine, and seven different NNRTIs. In all cases, efavirenz, GW420867X, and UC-781 retained pronounced antiviral potency. Our data suggest that combinations of GW420867X with 3TC, ABC, and NNRTIs (e.g., efavirenz) would be worth pursuing as therapeutic modalities against HIV-1 infections. PMID:10777142

  18. HIV vaccine acceptability among high-risk drug users in Appalachia: a cross-sectional study

    PubMed Central

    2014-01-01

    Background A vaccine could substantially impact the HIV epidemic, but inadequate uptake is a serious concern. Unfortunately, people who use drugs, particularly those residing in rural communities, have been underrepresented in previous research on HIV vaccine acceptability. This study examined HIV vaccine acceptability among high-risk drug users in a rural community in the United States. Methods Interviewer-administered questionnaires included questions about risk behavior and attitudes toward HIV vaccination from 433 HIV-negative drug users (76% with history of injection) enrolled in a cohort study in Central Appalachia. HIV vaccine acceptability was measured on a 4-point Likert scale. Generalized linear mixed models were used to determine correlates to self-report of being “very likely” to receive a 90% effective HIV vaccine (i.e. “maximum vaccine acceptability”, or MVA). Adjusted odds ratios (AORs) and corresponding 95% confidence intervals (CIs) are reported. Results Most (91%) reported that they would accept a preventive HIV vaccine, but concerns about cost, dosing, transportation constraints, vaccine-induced seropositivity, and confidentiality were expressed. Cash incentives, oral-administration, and peer/partner encouragement were anticipated facilitators of uptake. In multivariate analysis, men were significantly less likely to report MVA (AOR: 0.33, CI: 0.21 – 0.52). MVA was more common among participants who believed that they were susceptible to HIV (AOR: 2.31, CI: 1.28 – 4.07), that an HIV vaccine would benefit them (AOR: 2.80, CI: 1.70 – 4.64), and who had positive experiential attitudes toward HIV vaccination (AOR: 1.85, CI: 1.08 – 3.17). MVA was also more common among participants who believed that others would encourage them to get vaccinated and anticipated that their behavior would be influenced by others' encouragement (AOR: 1.81, 95% 1.09 – 3.01). Conclusions To our knowledge, this study was among the first to explore and

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

    PubMed Central

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

    2016-01-01

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

  20. Unhealthy Alcohol and Illicit Drug Use are Associated with Decreased Quality of HIV Care

    PubMed Central

    Korthuis, P. Todd; Fiellin, David A.; McGinnis, Kathleen A.; Skanderson, Melissa; Justice, Amy C.; Gordon, Adam J.; Doebler, Donna Almario; Asch, Steven M.; Fiellin, Lynn E.; Bryant, Kendall; Gibert, Cynthia L.; Crystal, Stephen; Goetz, Matthew Bidwell; Rimland, David; Rodriguez-Barradas, Maria C.; Kraemer, Kevin L.

    2012-01-01

    Background HIV-infected patients with substance use experience suboptimal health outcomes, possibly to due to variations in care. Objectives To assess the association between substance use and the quality of HIV care (QOC) received. Research Design Retrospective cohort study. Subjects HIV-infected patients enrolled in the Veterans Aging Cohort Study. Measures We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score ≥4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression. Results The majority of the 3,410 patients were male (97.4%) and Black (67.0%) with a mean age of 49.1 years (SD 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD=18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use vs. not (59.3% vs. 70.0%, p<.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, p<.001). In multivariable models, unhealthy alcohol use (adjusted β −2.74; 95% CI −4.23, −1.25) and illicit drug use (adjusted β −3.51 95% CI −4.99, −2.02) remained inversely associated with the percentage of QIs received. Conclusions Though the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received. PMID:22820808

  1. Systemic barriers accessing HIV treatment among people who inject drugs in Russia: a qualitative study

    PubMed Central

    Sarang, Anya; Rhodes, Tim; Sheon, Nicolas

    2013-01-01

    Achieving ‘universal access’ to antiretroviral HIV treatment (ART) in lower income and transitional settings is a global target. Yet, access to ART is shaped by local social condition and is by no means universal. Qualitative studies are ideally suited to describing how access to ART is socially situated. We explored systemic barriers to accessing ART among people who inject drugs (PWID) in a Russian city (Ekaterinburg) with a large burden of HIV treatment demand. We undertook 42 in-depth qualitative interviews with people living with HIV with current or recent experience of injecting drug use. Accounts were analysed thematically, and supplemented here with an illustrative case study. Three core themes were identified: ‘labyrinthine bureaucracy’ governing access to ART; a ‘system Catch 22’ created by an expectation that access to ART was conditional upon treated drug use in a setting of limited drug treatment opportunity; and ‘system verticalization’, where a lack of integration across HIV, tuberculosis (TB) and drug treatment compromised access to ART. Taken together, we find that systemic factors play a key role in shaping access to ART with the potential adverse effects of reproducing treatment initiation delay and disengagement from treatment. We argue that meso-level systemic factors affecting access to ART for PWID interact with wider macro-level structural forces, including those related to drug treatment policy and the social marginalization of PWID. We note the urgent need for systemic and structural changes to improve access to ART for PWID in this setting, including to simplify bureaucratic procedures, foster integrated HIV, TB and drug treatment services, and advocate for drug treatment policy reform. PMID:23197431

  2. An international multicenter study on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing.

    PubMed

    Simen, Birgitte B; Braverman, Michael S; Abbate, Isabella; Aerssens, Jeroen; Bidet, Yannick; Bouchez, Olivier; Gabriel, Christian; Izopet, Jacques; Kessler, Harald H; Stelzl, Evelyn; Di Giallonardo, Francesca; Schlapbach, Ralph; Radonic, Aleksander; Paredes, Roger; Recordon-Pinson, Patricia; Sakwa, James; St John, Elizabeth P; Schmitz-Agheguian, Gudrun G; Metzner, Karin J; Däumer, Martin P

    2014-08-01

    The detection of mutant spectra within the viral quasispecies is critical for therapeutic management of HIV-1 infections. Routine clinical application of ultrasensitive genotyping requires reproducibility and concordance within and between laboratories. The goal of the study was to evaluate a new protocol on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing (454-UDS) in an international multicenter study. Sixteen blinded HIV-1 subtype B samples were provided for 454-UDS as both RNA and cDNA with viral titers of 88,600-573,000 HIV-1 RNA copies/ml. Eight overlapping amplicons spanning protease (PR) codons 10-99 and reverse transcriptase (RT) codons 1-251 were generated using molecular barcoded primers. 454-UDS was performed using the 454 Life Sciences/Roche GS FLX platform. PR and RT sequences were analyzed using 454 Life Sciences Amplicon Variant Analyzer (AVA) software. Quantified variation data were analyzed for intra-laboratory reproducibility and inter-laboratory concordance. Routine population sequencing was performed using the ViroSeq HIV-1 genotyping system. Eleven laboratories and the reference laboratory 454 Life Sciences sequenced the HIV-1 sample set. Data presented are derived from seven laboratories and the reference laboratory since severe study protocol execution errors occurred in four laboratories leading to exclusion. The median sequencing depth across all sites was 1364 reads per position (IQR=809-2065). 100% of the ViroSeq-reported mutations were also detected by 454-UDS. Minority HIV-1 drug resistance mutations, defined as HIV-1 drug resistance mutations identified at frequencies of 1-25%, were only detected by 454-UDS. Analysis of 10 preselected majority and minority mutations were consistently found across sites. The analysis of drug-resistance mutations detected between 1 and 10% demonstrated high intra- and inter-laboratory consistency in frequency estimates for both RNA and prepared cDNA samples, indicating robustness of the

  3. Epidemiology of Drug Use and HIV-Related Risk Behaviors among People Who Inject Drugs in Mwanza, Tanzania

    PubMed Central

    Tan, Annabel Xulin; Kapiga, Saidi; Khoshnood, Kaveh; Bruce, R. Douglas

    2015-01-01

    Heroin trafficking and consumption has increased steadily over the past decade in Tanzania, but limited information regarding HIV and drug use exists for the city of Mwanza. Our study investigates the epidemiology of drug use, and HIV risk behaviors among drug users in the northwestern city of Mwanza. Using a combination of targeted sampling and participant referral, we recruited 480 participants in Mwanza between June and August 2014. The sample was 92% male. Seventy-nine (16.4%) participants reported injecting heroin, while 434 (90.4%) reported smoking heroin. Unstable housing and cohabitation status were the only socioeconomic characteristics significantly associated with heroin injection. More than half of heroin injectors left syringes in common locations, and half reported sharing needles and syringes. Other risk behaviors such as lack of condom use during sex, and the use of illicit drugs during sex was widely reported as well. Among the study sample, there was poor awareness of health risks posed by needle/syringe sharing and drug use. Our results show that heroin use and HIV risk related behaviors are pressing problems that should not be ignored in Mwanza. Harm reduction programs are urgently needed in this population. PMID:26701616

  4. Perceived risk of HIV infection among deported male injection drug users in Tijuana, Mexico

    PubMed Central

    Pinedo, Miguel; Burgos, José Luis; Robertson, Angela M.; Vera, Alicia; Lozada, Remedios; Ojeda, Victoria D.

    2014-01-01

    Deported injection drug users (IDUs) in Mexico may be vulnerable to HIV infection following expulsion from the U.S. We examined factors associated with HIV risk perception among a sample of deportees in Tijuana. From January to April 2010, 313 male IDUs who reported ever being deported from the U.S. completed a questionnaire. Overall, 35% (N=110) of deportees perceived HIV risk. In multivariate logistic regression analyses, factors independently associated with HIV risk perception included: ever having a steady female partner in Tijuana post-deportation (Adjusted Odds Ratio (AOR): 2.26; 95% Confidence Interval (CI): 1.01-5.07) and years spent in a U.S. prison (AOR: 1.29 per year; 95% CI: 1.13-1.48). Conversely, years of drug injection use (AOR: 0.95 per year; 95% CI: 0.91-0.99), ever witnessing family members use drugs prior to first migration trip (AOR: 0.24; 95% CI: 0.09-0.65), years of residence in the United States (AOR: 0.91 per year; 95% CI: 0.84-0.98) and being a Tijuana-native (AOR: 0.40; 95% CI: 0.16-0.99) were negatively associated HIV risk perception. U.S.-Mexico border cities that receive deported migrants should target HIV prevention interventions to specific subgroups, including drug-using male deportees. Interventions should consider migrant's time in the U.S., the role of their social networks, and reducing missed opportunities for HIV testing/education. PMID:24650124

  5. Will HIV Vaccination Reshape HIV Risk Behavior Networks? A Social Network Analysis of Drug Users' Anticipated Risk Compensation

    PubMed Central

    Young, April M.; Halgin, Daniel S.; DiClemente, Ralph J.; Sterk, Claire E.; Havens, Jennifer R.

    2014-01-01

    Background An HIV vaccine could substantially impact the epidemic. However, risk compensation (RC), or post-vaccination increase in risk behavior, could present a major challenge. The methodology used in previous studies of risk compensation has been almost exclusively individual-level in focus, and has not explored how increased risk behavior could affect the connectivity of risk networks. This study examined the impact of anticipated HIV vaccine-related RC on the structure of high-risk drug users' sexual and injection risk network. Methods A sample of 433 rural drug users in the US provided data on their risk relationships (i.e., those involving recent unprotected sex and/or injection equipment sharing). Dyad-specific data were collected on likelihood of increasing/initiating risk behavior if they, their partner, or they and their partner received an HIV vaccine. Using these data and social network analysis, a "post-vaccination network" was constructed and compared to the current network on measures relevant to HIV transmission, including network size, cohesiveness (e.g., diameter, component structure, density), and centrality. Results Participants reported 488 risk relationships. Few reported an intention to decrease condom use or increase equipment sharing (4% and 1%, respectively). RC intent was reported in 30 existing risk relationships and vaccination was anticipated to elicit the formation of five new relationships. RC resulted in a 5% increase in risk network size (n = 142 to n = 149) and a significant increase in network density. The initiation of risk relationships resulted in the connection of otherwise disconnected network components, with the largest doubling in size from five to ten. Conclusions This study demonstrates a new methodological approach to studying RC and reveals that behavior change following HIV vaccination could potentially impact risk network connectivity. These data will be valuable in parameterizing future network models

  6. Dual HIV risk: receptive syringe sharing and unprotected sex among HIV-negative injection drug users in New York City.

    PubMed

    Neaigus, Alan; Reilly, Kathleen H; Jenness, Samuel M; Hagan, Holly; Wendel, Travis; Gelpi-Acosta, Camila

    2013-09-01

    HIV-negative injection drug users (IDUs) who engage in both receptive syringe sharing and unprotected sex ("dual HIV risk") are at high risk of HIV infection. In a cross-sectional study conducted in New York City in 2009, active IDUs aged ≥18 years were recruited using respondent-driven sampling, interviewed, and tested for HIV. Participants who tested HIV-negative and did not self-report as positive were analyzed (N = 439). Adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were estimated using multinomial logistic regression. The sample was: 77.7 % male; 54.4 % Hispanic, 36.9 % white, and 8.7 % African-American/black. Dual risk was engaged in by 26.2 %, receptive syringe sharing only by 3.2 %, unprotected sex only by 49.4 %, and neither by 21.2 %. Variables independently associated with engaging in dual risk versus neither included Hispanic ethnicity (vs. white) (aOR = 2.0, 95 % CI = 1.0-4.0), married or cohabiting (aOR = 6.3, 95 % CI = 2.5-15.9), homelessness (aOR = 3.4, 95 % CI = 1.6-7.1), ≥2 sex partners (aOR = 8.7, 95 % CI = 4.4-17.3), ≥2 injecting partners (aOR = 2.9, 95 % CI = 1.5-5.8), and using only sterile syringe sources (protective) (aOR = 0.5, 95 % CI = 0.2-0.9). A majority of IDUs engaged in HIV risk behaviors, and a quarter in dual risk. Interventions among IDUs should simultaneously promote the consistent use of sterile syringes and of condoms. PMID:23640654

  7. Recombination of HIV type 1C (C'/C") in Ethiopia: possible link of EthHIV-1C' to subtype C sequences from the high-prevalence epidemics in India and Southern Africa.

    PubMed

    Pollakis, Georgios; Abebe, Almaz; Kliphuis, Aletta; De Wit, Tobias F Rinke; Fisseha, Bitew; Tegbaru, Belete; Tesfaye, Girma; Negassa, Hailu; Mengistu, Yohannes; Fontanet, Arnaud L; Cornelissen, Marion; Goudsmit, Jaap

    2003-11-01

    The magnitude and complexity of the HIV-1 genetic diversity are major challenges for vaccine development. Investigation of the genotypes circulating in areas of high incidence, as well as their interactions, will be a milestone in the development of an efficacious vaccine. Because HIV-1 subtype C (HIV-1C) is responsible for most of the 36 million infections worldwide we investigated the HIV-1C strains circulating in Ethiopia in a retrospective, cross-sectional study. Serum samples from HIV-1-positive individuals were collected in seven Ethiopian cities and towns. Nucleotide sequences of the gag, pol, and env genes were analyzed. We performed phylogenetic analysis by the neighbor-joining and maximum-likelihood methods with sequences from 30 isolates, and we determined recombination by the bootscanning method as implemented in the SIMPLOT program. Sequence analyses of a 2600-nucleotide fragment (including the gag gene, the protease, and the 5' half of reverse transcriptase of the pol gene) and the corresponding V1V2/C2V3 envelope regions confirmed that two distinct HIV-1C genotypes (C' and C") are cocirculating in Ethiopia, as shown previously by the analysis of the C2V3 envelope region. We have identified intrasubtype recombination between the two HIV-1C genotypes, C' and C", with 6 of the 30 (20%) analyzed viruses being recombinants. The C' sequences were phylogenetically linked to the fast spreading viruses in India and southern Africa. Furthermore, all the recombinant viruses shared the C' V1V3 region of the envelope, suggesting that the prevalence of viruses with the C' envelope is increasing compared to the C" envelope. The possibility that viruses with a C' envelope have a biological advantage over the viruses with a C" envelope should be further investigated in biological and epidemiological studies. PMID:14678607

  8. HIV infection among injecting drug users in north-east Malaysia, 1992.

    PubMed

    Singh, S; Crofts, N

    1993-01-01

    Human immunodeficiency virus (HIV) has spread widely among injecting drug users (IDUs) in countries to the north and west of the 'Golden Triangle' region of South-East Asia; it is likely to have spread southwards to Malaysia as well. In order to assess HIV seroprevalence among IDUs in north-east Malaysia and describe risk factors for HIV infection in this population, we performed a cross-sectional seroepidemiological study among 210 IDUs recruited at the detoxification ward of the General Hospital in the capital city of the north-eastern Malaysian state, Kelantan. Subjects were sequential entrants to the detoxification ward, interviewed about HIV risk behaviour, and tested for antibody to HIV and to syphilis. Nearly a third (62/210, 30%) of these IDUs were HIV seropositive. Three-quarters (159/210) had travelled to Thailand in the preceding 5 years, of whom 32% (51/159) were HIV seropositive; this was associated with injecting in Thailand, but not with sexual contact there. Of those who had not left Malaysia in the preceding 5 years, 26% (11/43) were HIV seropositive, a rate not significantly different from those who had travelled. Travel within Malaysia was common (144/210, 69%) among IDUs interviewed, as was unsafe injecting and unsafe sexual behaviour (20% had shared injecting equipment and 21% had had unprotected intercourse) in other states. In every locale, rates of unsafe injecting behaviour were high (55% sharing in last month), even among those who knew they were HIV infected, and rates of condom usage were low (93% of 160 sexually active IDUs had never used a condom). Syphilis was not associated with HIV infection, but with contact with Thai prostitutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8218462

  9. Rapid assessment of HIV risk behavior in drug using sex workers in three cities in South Africa.

    PubMed

    Parry, Charles D H; Dewing, Sarah; Petersen, Petal; Carney, Tara; Needle, Richard; Kroeger, Karen; Treger, Latasha

    2009-10-01

    A rapid assessment was undertaken with drug using commercial sex workers (CSWs) to investigate practices putting them at risk for contracting HIV. It included key informant (KI) (N = 67) and focus group (N = 10) interviews in locations with a high prevalence of drug use in Cape Town, Durban and Pretoria, South Africa. HIV testing of KIs was conducted. Cocaine, Ecstasy, heroin and methaqualone are used by CSWs prior to, during and after sex. Drugs enhance the sexual experience and prolong sex sessions. Interviews revealed inconsistent condom use among CSWs together with other risky sexual practices such as needle sharing. Among CSWs who agreed to HIV testing, 34% tested positive. Barriers to accessing drug treatment and HIV treatment and preventive services were identified. Interventions recognizing the role of drug abuse in HIV transmission should be prioritized, and issues of access to services, stigma and power relations must be considered. PMID:18324470

  10. Bayesian analysis of complex interacting mutations in HIV drug resistance and cross-resistance.

    PubMed

    Kozyryev, Ivan; Zhang, Jing

    2015-01-01

    A successful treatment of AIDS world-wide is severely hindered by the HIV virus' drug resistance capability resulting from complicated mutation patterns of viral proteins. Such a system of mutations enables the virus to survive and reproduce despite the presence of various antiretroviral drugs by disrupting their binding capability. Although these interacting mutation patterns are extremely difficult to efficiently uncover and interpret, they contribute valuable information to personalized therapeutic regimen design. The use of Bayesian statistical modeling provides an unprecedented opportunity in the field of anti-HIV therapy to understand detailed interaction structures of drug resistant mutations. Multiple Bayesian models equipped with Markov Chain Monte Carlo (MCMC) methods have been recently proposed in this field (Zhang et al. in PNAS 107:1321, 2010 [1]; Zhang et al. in J Proteome Sci Comput Biol 1:2, 2012 [2]; Svicher et al. in Antiviral Res 93(1):86-93, 2012 [3]; Svicher et al. in Antiviral Therapy 16(7):1035-1045, 2011 [4]; Svicher et al. in Antiviral Ther 16(4):A14-A14, 2011 [5]; Svicher et al. in Antiviral Ther 16(4):A85-A85, 2011 [6]; Alteri et al. in Signature mutations in V3 and bridging sheet domain of HIV-1 gp120 HIV-1 are specifically associated with dual tropism and modulate the interaction with CCR5 N-Terminus, 2011 [7]). Probabilistically modeling mutations in the HIV-1 protease or reverse transcriptase (RT) isolated from drug-treated patients provides a powerful statistical procedure that first detects mutation combinations associated with single or multiple-drug resistance, and then infers detailed dependence structures among the interacting mutations in viral proteins (Zhang et al. in PNAS 107:1321, 2010 [1]; Zhang et al. in J Proteome Sci Comput Biol 1:2, 2012 [2]). Combined with molecular dynamics simulations and free energy calculations, Bayesian analysis predictions help to uncover genetic and structural mechanisms in the HIV treatment

  11. Two subtypes of HIV-1 among injection-drug users in southern China.

    PubMed

    Yu, X F; Chen, J; Shao, Y; Beyrer, C; Lai, S

    1998-04-25

    The rate of HIV-1 infection has increased steadily in China by about 80% annually and by the end of September 1997, 8277 HIV-1 cases had been reported, of whom more than 75% were IV drug users (IVDUs). UNAIDS, however, has estimated that up to 200,000 people could actually be infected with HIV-1 in China. Guangxi Province borders Yunnan province in the west and Vietnam to the south, and is a major transit area for heroin trafficking from the opium-growing region of Laos and Myanmar. Phylogenetic analyses of HIV-1 env sequences (C2-V3) obtained from 14 IVDUs found that 9 subjects from Pingxiang City were infected with subtype E and 5 from Baise City with subtype C. The 9 subtype E and 5 subtype C HIV-1 sequences were clustered together within each group, with significant bootstrap values of 100% and 95%, respectively. The subtype E sequences were more closely related to HIV-1 subtype E from Thailand than to those from Africa, and the subtype C sequences were clustered more closely to those from India than to those from Africa. Study results suggest 2 epidemiologically unrelated epidemics and 2 different sources; subtype C probably transmitted from Yunnan to Baise City through drug trafficking and IVDU interaction, and subtype E coming into China from Vietnam. PMID:9643749

  12. HIV-1 gp120 and Drugs of Abuse: Interactions in the Central Nervous System

    PubMed Central

    Silverstein, Peter S.; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D.P.; Kumar, Anil

    2014-01-01

    HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs. PMID:22591361

  13. HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.

    PubMed

    Silverstein, Peter S; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D P; Kumar, Anil

    2012-07-01

    HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs. PMID:22591361

  14. Structures of HIV Protease Guide Inhibitor Design to Overcome Drug Resistance

    SciTech Connect

    Weber, Irene T.; Kovalevsky, Andrey Y.; Harrison, Robert W.

    2008-06-03

    The HIV/AIDS infection continues to be a major epidemic worldwide despite the initial promise of antiviral drugs. Current therapy includes a combination of drugs that inhibit two of the virally-encoded enzymes, the reverse transcriptase and the protease. The first generation of HIV protease inhibitors that have been in clinical use for treatment of AIDS since 1995 was developed with the aid of structural analysis of protease-inhibitor complexes. These drugs were successful in improving the life span of HIV-infected people. Subsequently, the rapid emergence of drug resistance has necessitated the design of new inhibitors that target mutant proteases. This second generation of antiviral protease inhibitors has been developed with the aid of data from medicinal chemistry, kinetics, and X-ray crystallographic analysis. Traditional computational methods such as molecular mechanics and dynamics can be supplemented with intelligent data mining approaches. One approach, based on similarities to the protease interactions with substrates, is to incorporate additional interactions with main chain atoms that cannot easily be eliminated by mutations. Our structural and inhibition data for darunavir have helped to understand its antiviral activity and effectiveness on drug resistant HIV and demonstrate the success of this approach.

  15. Prediction of HIV drug resistance from genotype with encoded three-dimensional protein structure

    PubMed Central

    2014-01-01

    Background Drug resistance has become a severe challenge for treatment of HIV infections. Mutations accumulate in the HIV genome and make certain drugs ineffective. Prediction of resistance from genotype data is a valuable guide in choice of drugs for effective therapy. Results In order to improve the computational prediction of resistance from genotype data we have developed a unified encoding of the protein sequence and three-dimensional protein structure of the drug target for classification and regression analysis. The method was tested on genotype-resistance data for mutants of HIV protease and reverse transcriptase. Our graph based sequence-structure approach gives high accuracy with a new sparse dictionary classification method, as well as support vector machine and artificial neural networks classifiers. Cross-validated regression analysis with the sparse dictionary gave excellent correlation between predicted and observed resistance. Conclusion The approach of encoding the protein structure and sequence as a 210-dimensional vector, based on Delaunay triangulation, has promise as an accurate method for predicting resistance from sequence for drugs inhibiting HIV protease and reverse transcriptase. PMID:25081370

  16. Factors associated with serum retinol, x-tocopherol, carotenoids, and selenium in Hispanics with problems of HIV, chornis hepatitis, chronic hepatitis C, and drug use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C inf...

  17. Recreational drug use and related social factors among HIV-positive men in Japan.

    PubMed

    Togari, Taisuke; Inoue, Yoji; Takaku, Yosuke; Abe, Sakurako; Hosokawa, Rikuya; Itagaki, Takashi; Yoshizawa, Shigeyuki; Oki, Sachiko; Katakura, Naoko; Yamauchi, Asae; Wakabayashi, Chihiro; Yajima, Takashi

    2016-07-01

    This study aims to determine the relationship between recreational drug use in HIV-positive males in the past year and socio-economic factors and/or social support networks in Japan. A national online survey in a cross-sectional study was conducted by HIV Futures Japan project from July 2013 to February 2014. Of the 1095 HIV-positive individuals who responded, 913 responses were determined to be valid; responses from the 875 males were analysed. A total of 282 participants used addictive drugs (32.2%) in past year. New psychoactive substances were used by 121 participants (13.8%), methamphetamine or amphetamine by 47 (5.4%), air dusters/sprays/gas by 31 (3.5%), 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) by 16 (1.8%) and cannabis (1.0%) by 9. Multiple logistic regression analysis was performed with the use of alkyl nitrites, addictive drugs, air dusters and thinners, which are low illegality, as dependent variables. We found that the odds ratio (95% confidence interval) for use among participants with full-time and temp/contracted/part-time employees compared to management/administration professions were 2.59 (0.99-6.77) and 2.61 (0.91-7.51). Also, a correlation was observed between alkyl nitrites and new psychoactive substances and usage rates in people engaged in few HIV-positive networks. It is necessary to develop targeted policies for drug use prevention and user support among HIV-positive men and to support and provide care for drug users who are isolated or have a narrow HIV/AIDS support network. PMID:26887351

  18. Women who use or inject drugs: an action agenda for women-specific, multilevel and combination HIV prevention and research

    PubMed Central

    El-Bassel, Nabila; Strathdee, Steffanie A.

    2016-01-01

    Women account for more than half of all individuals living with HIV globally. Despite increasing drug and HIV epidemics among women, females who use drugs are rarely found in research, harm reduction programs, or drug and HIV treatment and care. Women who use drugs continue to face challenges that increase their vulnerability to HIV and other co-morbidities due to high rates of gender-based violence, human rights violations, incarceration, and institutional and societal stigmatization. This special issue emphasizes how the burdens of HIV, drug use and their co-occurring epidemics affect women in a global context. Papers included focus on the epidemiology of HIV, HCV and other co-morbidities; HIV treatment, prevention, and care; and policies affecting the lives of female who use drugs. This issue also highlights the state of the science of biomedical and behavioral research related to women who use drugs. The final paper highlights the major findings of papers covered and presents a call to action regarding needed research, treatment, and preventive services for women who use drugs. To address these needs, we advocate for women-specific thinking and approaches that considers the social, micro, and macro contexts of women’s lives. We present a woman-specific risk environment framework that reflects the unique lives and contexts of women who use drugs and provide a call to action for intervention, prevention, and policies. PMID:25978486

  19. Women Who Use or Inject Drugs: An Action Agenda for Women-Specific, Multilevel, and Combination HIV Prevention and Research.

    PubMed

    El-Bassel, Nabila; Strathdee, Steffanie A

    2015-06-01

    Women account for more than half of all individuals living with HIV globally. Despite increasing drug and HIV epidemics among women, women who use drugs are rarely found in research, harm reduction programs, or drug and HIV treatment and care. Women who use drugs continue to face challenges that increase their vulnerability to HIV and other comorbidities because of high rates of gender-based violence, human rights violations, incarceration, and institutional and societal stigmatization. This special issue emphasizes how the burdens of HIV, drug use, and their co-occurring epidemics affect women in a global context. Articles included focus on the epidemiologies of HIV and hepatitis C virus and other comorbidities; HIV treatment, prevention, and care; and policies affecting the lives of women who use drugs. This issue also highlights the state of the science of biomedical and behavioral research related to women who use drugs. The final article highlights the major findings of articles covered and presents a call to action regarding needed research, treatment, and preventive services for women who use drugs. To address these needs, we advocate for women-specific thinking and approaches that consider the social, micro, and macro contexts of women's lives. We present a women-specific risk environment framework that reflects the unique lives and contexts of women who use drugs and provides a call to action for intervention, prevention, and policies. PMID:25978486

  20. Unexpectedly high injection drug use, HIV and hepatitis C prevalence among female sex workers in the Republic of Mauritius.

    PubMed

    Johnston, Lisa Grazina; Corceal, Sewraz

    2013-02-01

    Female sex workers (FSW) often have a disproportionately high prevalence of HIV infection and they, along with their clients, are considered a core group contributing to the transmission of HIV in many countries. In 2010, females who reported having vaginal/anal/oral sex in the last 6 months with a male in exchange for money or gifts, aged ≥15 years, and living in Mauritius were recruited into a survey using respondent driven sampling. Consenting females (n = 299) completed a behavioral questionnaire and provided venous blood for HIV, HCV and HBV testing. HIV seroprevalence among FSW was 28.9 % and 43.8 % were infected with HCV; among HIV seropositive FSW, 88.2 % were also infected with HCV. Almost 40 % of FSW reported injecting drugs sometime in their lives and 30.5 % of all FSW reported doing so in the previous 3 months. Among those who ever injected drugs, 82.5 % did so in the past 3 months and among those 60 % reported injecting drugs at least once a day. Among FSW who ever injected drugs, 17.5 % reported sharing a needle at last injection. Regression analyses found injection drug use behaviors to be positively associated with HIV seroprevalence. These findings indicate that FSW, especially those who inject drugs, are at high risk for HIV and HCV infection and transmission and illustrates the need for gender responsive HIV and injection drug use prevention and treatment models that respond to the unique situations that affect this population. PMID:22851154

  1. Persian At-Risk Women and Barriers to Receiving HIV Services in Drug Treatment: First Report From Iran

    PubMed Central

    Samiei, Mercedeh; Moradi, Afsaneh; Noori, Roya; Aryanfard, Sepideh; Rafiey, Hassan; Naranjiha, Hooman

    2016-01-01

    Background As the most populated Persian Gulf country, in Iran, engagement with drug injection and unsafe sex are the main routes of HIV transmission among some drug-dependent women. Objectives The current study explored the barriers that a group of drug-dependent women reported in accessing and adhering to HIV services in drug use treatment. Patients and Methods Qualitative interviews were conducted with 47 Persian women at five outpatient drug treatment centers between January and December 2011. Five focus group interviews were conducted with ten key informants (KI). The interviews made use of a semi-structured interview guide, which facilitated discussion regarding the barriers. The interview transcripts were analyzed thematically using Atlas-ti software. Results The interview accounts highlighted a number of barriers, including stigmatization, a considerable lack of knowledge about free HIV centers in the community, previous traumatic events, misconceptions about the quality of HIV services, and a poor supportive referral system among drug treatment and HIV centers. Conclusions The findings highlight a need for removing stigma and providing high quality women-only HIV services. Increasing trust and knowledge of available HIV services are needed for this group of women. Increasing staff knowledge is a priority. An integrated supportive network among drug treatment and HIV centers is suggested in Iran. PMID:27622170

  2. Proliferation inhibition of astrocytes, neurons, and non-glial cells by intracellularly expressed human immunodeficiency virus type 1 (HIV-1) Tat protein.

    PubMed

    Zhou, Betty Y; He, Johnny J

    2004-04-15

    Human immunodeficiency virus type 1 Tat protein is one of the soluble neurotoxins. Most studies have to date focused on Tat as an extracellular molecule and its role in neuronal apoptosis, as recombinant Tat protein is often used in these studies. In this study, we expressed Tat protein in astrocytes and neurons, and examined its effects on these cells. We found that Tat expression resulted in growth inhibition of astrocytes, neurons, as well as non-glial cells 293T. We further showed that Tat interacted with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA. These data demonstrate that Tat inhibited cell proliferation when expressed intracellularly, and suggest that Tat interactions with multiple cell cycle regulators may account for this anti-proliferative effect. These results support the notion that Tat-induced neuropathogenesis is mediated by multiple mechanisms involving both intracellular and extracellular Tat protein. PMID:15050687

  3. IV drug users: changes in risk behaviour according to HIV status in a national survey in Spain.

    PubMed Central

    Delgado-Rodríguez, M; dé lá Fuente, L; Bravo, M J; Lardelli, P; Barrio, G

    1994-01-01

    STUDY OBJECTIVE--To determine whether HIV positive intravenous drug users (IVDUs) who were receiving outpatient treatment for opiate and cocaine abuse or dependence used practices aimed at reducing the spread of HIV. DESIGN--Cross sectional study of behaviour and HIV serostatus in IVDUs. SETTING--A nationwide sample, from 83 health centres for outpatient treatment, stratified by autonomous regions. PARTICIPANTS--Altogether 1074 IVDUs were recruited. HIV serostatus could be verified in 738 (68.7%) of these. MEASUREMENTS AND MAIN RESULTS--Crude and adjusted odds ratios and their 95% confidence intervals were estimated to assess the association between HIV serostatus and behavioural changes. In their daily interactions with other members of the same household, seropositive subjects more frequently used preventive methods aimed at avoiding transmission than seronegative patients. Treatment for abuse or dependency before the current regimen had a greater impact in HIV positive than HIV negative subjects in terms of abstaining from risk behaviours. There was a significant trend toward lower drug consumption in HIV positive subjects, and the number of seropositive and seronegative IVDUs who stopped injecting their drugs was significantly higher among the former. Seropositive subjects were also more likely to stop sharing drug injecting equipment and to change their sexual habits; they reported an increased consistent use of condoms. CONCLUSIONS--HIV positive IVDUs were more likely to change their risk behaviours than their HIV negative counterparts. PMID:7964355

  4. Adherence to HIV/AIDS antiretroviral therapy among drug users: A qualitative study in Iran

    PubMed Central

    Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood

    2016-01-01

    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

  5. New cases of HIV among people who inject drugs in Hungary: False alarm or early warning?

    PubMed

    Rácz, József; Gyarmathy, V Anna; Csák, Róbert

    2016-01-01

    Between 2009 and the first quarter of 2014, only one case of HIV (contracted outside Hungary) was detected among PWIDs in Hungary. However, more recent evidence suggests increased sharing of injecting paraphernalia among PWIDs. This is linked to the emergence of new designer drugs that require frequent injection, alongside funding cuts to the Hungarian needle exchange program (NEP) which has reduced access to sterile injecting equipment. During the past five years in Hungary, drug use has become increasingly discussed in moral as opposed to public health terms, and drug consumption has been re-criminalized. The largest NEP in Hungary was closed because of political pressure and government funding for regular HCV/HIV testing/counselling and seroprevalence studies among PWIDs has been stopped. This paper describes the detection of two new cases of HIV infection in PWIDs attending two NEPs in Budapest in May 2014. These new cases may indicate an unfolding HIV outbreak among PWIDs-similar to those reported in Greece and Romania. Yet the question remains: If no further HIV cases are detected, is this because there are no new cases or because there are no testing facilities for PWID? PMID:26251353

  6. Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations.

    PubMed

    Laird, Gregory M; Bullen, C Korin; Rosenbloom, Daniel I S; Martin, Alyssa R; Hill, Alison L; Durand, Christine M; Siliciano, Janet D; Siliciano, Robert F

    2015-05-01

    Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

  7. Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants.

    PubMed

    Noguera-Julian, M; Cozzi-Lepri, A; Di Giallonardo, F; Schuurman, R; Däumer, M; Aitken, S; Ceccherini-Silberstein, F; D'Arminio Monforte, A; Geretti, A M; Booth, C L; Kaiser, R; Michalik, C; Jansen, K; Masquelier, B; Bellecave, P; Kouyos, R D; Castro, E; Furrer, H; Schultze, A; Günthard, H F; Brun-Vezinet, F; Metzner, K J; Paredes, R

    2016-02-01

    Plasma drug-resistant minority human immunodeficiency virus type 1 variants (DRMVs) increase the risk of virological failure to first-line non-nucleoside reverse transcriptase inhibitor antiretroviral therapy (ART). The origin of DRMVs in ART-naive patients, however, remains unclear. In a large pan-European case-control study investigating the clinical relevance of pre-existing DRMVs using 454 pyrosequencing, the six most prevalent plasma DRMVs detected corresponded to G-to-A nucleotide mutations (V90I, V106I, V108I, E138K, M184I and M230I). Here, we evaluated if such DRMVs could have emerged from apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3G/F (APOBEC3G/F) activity. Out of 236 ART-naive subjects evaluated, APOBEC3G/F hypermutation signatures were detected in plasma viruses of 14 (5.9%) individuals. Samples with minority E138K, M184I, and M230I mutations, but not those with V90I, V106I or V108I, were significantly associated with APOBEC3G/F activity (Fisher's P < 0.005), defined as the presence of > 0.5% of sample sequences with an APOBEC3G/F signature. Mutations E138K, M184I and M230I co-occurred in the same sequence as APOBEC3G/F signatures in 3/9 (33%), 5/11 (45%) and 4/8 (50%) of samples, respectively; such linkage was not found for V90I, V106I or V108I. In-frame STOP codons were observed in 1.5% of all clonal sequences; 14.8% of them co-occurred with APOBEC3G/F signatures. APOBEC3G/F-associated E138K, M184I and M230I appeared within clonal sequences containing in-frame STOP codons in 2/3 (66%), 5/5 (100%) and 4/4 (100%) of the samples. In a re-analysis of the parent case control study, the presence of APOBEC3G/F signatures was not associated with virological failure. In conclusion, the contribution of APOBEC3G/F editing to the development of DRMVs is very limited and does not affect the efficacy of non-nucleoside reverse transcriptase inhibitor ART. PMID:26482266

  8. Optimizing Care for HIV-Infected People Who Use Drugs: Evidence-Based Approaches to Overcoming Healthcare Disparities

    PubMed Central

    Meyer, Jaimie P.; Althoff, Amy L.; Altice, Frederick L.

    2013-01-01

    Substance use disorders (SUDs) and human immunodeficiency virus (HIV) are pervasive epidemics that synergize, resulting in negative outcomes for HIV-infected people who use drugs (PWUDs). The expanding epidemiology of substance use demands a parallel evolution of the HIV specialist—beyond HIV to diagnosis and management of comorbid SUDs. The purpose of this paper is to describe healthcare disparities for HIV-infected PWUDs along each point of a continuum of care, and to suggest evidence-based strategies for overcoming these healthcare disparities. Despite extensive dedicated resources and availability of antiretroviral therapy (ART) in the United States, PWUDs continue to experience delayed HIV diagnosis, reduced entry into and retention in HIV care, delayed initiation of ART, and inferior HIV treatment outcomes. Overcoming these healthcare disparities requires integrated packages of clinical, pharmacological, behavioral, and social services, delivered in ways that are cost-effective and convenient and include, at a minimum, screening for and treatment of underlying SUDs. PMID:23797288

  9. Developing a Brief Scale to Measure HIV Transmission Risk Among Injecting Drug Users

    PubMed Central

    Shahesmaeili, Armita; Haghdoost, Ali Akbar; Soori, Hamid

    2015-01-01

    Background: One of the main concerns of policymakers is to measure the impact of harm reduction programs and different interventions on the risk of HIV transmission among Injecting Drug Users (IDUs). Looking simultaneously at multiple factors and conditions that affect the risk of HIV transmission may provide policymakers a better insight into the mixed nature of HIV transmission. Objectives: The present study aimed to design a simple, brief, and multi-dimensional scale for measuring HIV transmission risk among IDUs. Patients and Methods: From October 2013 to March 2014, we conducted face-to-face interviews with 147 IDUs. Eligible participants were individuals 18 years or older who had injected drugs at least once during the last year and had not participated in similar studies within the 2 months before the interview. To design a scale for measuring HIV transmission risk, we specified 11 items, which address different dimensions of HIV risk taking behaviors/situations based on experts’ opinion. We applied exploratory factor analysis (EFA) with principal component extraction to develop scales. Eigen values greater than 1 were used as a criterion for factor extraction. Results: We extracted 7 items based on first factor, which were accounted for 21% of the variations. The final scale contained 7 items: 4 items were related to injecting practice and 3 items related to sexual behaviors. The Cronbach’s α coefficient was 0.66, acceptable for such a brief scale. Conclusions: Applying a simple and brief scale that incorporates the different dimensions of HIV transmission risk may provide policymakers and harm reductionists with a better understanding of HIV transmission in this key group and may be advantageous for evaluating intervention programs. PMID:26870713

  10. Injection drug use and HIV/AIDS in China: Review of current situation, prevention and policy implications

    PubMed Central

    Qian, Han-Zhu; Schumacher, Joseph E; Chen, Huey T; Ruan, Yu-Hua

    2006-01-01

    Illicit drug abuse and HIV/AIDS have increased rapidly in the past 10 to 20 years in China. This paper reviews drug abuse in China, the HIV/AIDS epidemic and its association with injection drug use (IDU), and Chinese policies on illicit drug abuse and prevention of HIV/AIDS based on published literature and unpublished official data. As a major drug trans-shipment country with source drugs from the "Golden Triangle" and "Gold Crescent" areas in Asia, China has also become an increasingly important drug consuming market. About half of China's 1.14 million documented drug users inject, and many share needles. IDU has contributed to 42% of cumulatively reported HIV/AIDS cases thus far. Drug trafficking is illegal in China and can lead to the death penalty. The public security departments adopt "zero tolerance" approach to drug use, which conflict with harm reduction policies of the public health departments. Past experience in China suggests that cracking down on drug smuggling and prohibiting drug use alone can not prevent or solve all illicit drug related problems in the era of globalization. In recent years, the central government has outlined a series of pragmatic policies to encourage harm reduction programs; meanwhile, some local governments have not fully mobilized to deal with drug abuse and HIV/AIDS problems seriously. Strengthening government leadership at both central and local levels; scaling up methadone substitution and needle exchange programs; making HIV voluntary counseling and testing available and affordable to both urban and rural drug users; and increasing utilization of outreach and nongovernmental organizations are offered as additional strategies to help cope with China's HIV and drug abuse problem. PMID:16451717

  11. Correlations between compulsory drug abstinence treatments and HIV risk behaviors among injection drug users in a border city of South China.

    PubMed

    Chen, Huey T; Tuner, Nannette; Chen, Charlene J; Lin, Hui-yi; Liang, Shaoling; Wang, Siven

    2013-08-01

    Compulsory drug abstinence treatments (CAT) provided by the public security system have been one of the predominant methods of addressing drug abuse and HIV risks in China. This study assessed the association between CAT and HIV risk behaviors by surveying a community sample of 613 injection drug users (IDUs) at a city located in South China. The data indicated that the great majority of the participants (89.6%) had received the institutionalized treatments an average of 4.5 times. The study found that the number of compulsory drug abstinence treatments increased IDUs' HIV/AIDS knowledge. However, other HIV-related outcomes were not encouraging. The study found that the number of compulsory drug abstinence treatments was not related to an increase in condom use. Furthermore, the frequency of compulsory drug abstinence treatments was not related to needle/syringe sharing, but was positively associated with cooker/cotton/rinse water sharing and drug solution sharing. The number of compulsory drug abstinence treatments was positively associated with HIV status. In general, this study found little support that CAT has accomplished its goal in reducing HIV risks among injection drug users in the sample. Policy implications for reforming CAT are suggested. PMID:23837811

  12. Boredom, depressive symptoms, and HIV risk behaviors among urban injection drug users

    PubMed Central

    German, Danielle; Latkin, Carl A.

    2013-01-01

    Boredom is closely aligned with depression, but is understood to be conceptually distinct. Little is known about boredom among active drug users and the potential association with depression and HIV risk. Current IDUs (n=845) completed a baseline behavioral survey including socio-demographic characteristics, self-reported boredom, depressive symptoms (CESD score), and HIV risk behaviors. One-third of the sample reported high boredom in the past week. In multivariate analysis, those who reported boredom were less likely to be older, African-American, have a main partner, and to be employed at least part-time. Controlling for covariates, those with high boredom were almost five times as likely to report high depressive symptoms. Co-occurrence of boredom and depressive symptoms (28%) was strongly and independently associated with a range of injection risk behaviors and sex exchange. This study demonstrates the need for more thorough understanding of mental health and HIV risk among urban drug users. PMID:22760741

  13. Theorizing "Big Events" as a potential risk environment for drug use, drug-related harm and HIV epidemic outbreaks.

    PubMed

    Friedman, Samuel R; Rossi, Diana; Braine, Naomi

    2009-05-01

    Political-economic transitions in the Soviet Union, Indonesia, and China, but not the Philippines, were followed by HIV epidemics among drug users. Wars also may sometimes increase HIV risk. Based on similarities in some of the causal pathways through which wars and transitions can affect HIV risk, we use the term "Big Events" to include both. We first critique several prior epidemiological models of Big Events as inadequately incorporating social agency and as somewhat imprecise and over-generalizing in their sociology. We then suggest a model using the following concepts: first, event-specific HIV transmission probabilities are functions of (a) the probability that partners are infection-discordant; (b) the infection-susceptibility of the uninfected partner; (c) the infectivity of the infected--as well as (d) the behaviours engaged in. These probabilities depend on the distributions of HIV and other variables in populations. Sexual or injection events incorporate risk behaviours and are embedded in sexual and injection partnership patterns and community networks, which in turn are shaped by the content of normative regulation in communities. Wars and transitions can change socio-economic variables that can sometimes precipitate increases in the numbers of people who engage in high-risk drug and sexual networks and behaviours and in the riskiness of what they do. These variables that Big Events affect may include population displacement; economic difficulties and policies; police corruption, repressiveness, and failure to preserve order; health services; migration; social movements; gender roles; and inter-communal violence--which, in turn, affect normative regulation, youth alienation, networks and behaviours. As part of these pathways, autonomous action by neighbourhood residents, teenagers, drug users and sex workers to maintain their economic welfare, health or happiness may affect many of these variables or otherwise mediate whether HIV epidemics follow

  14. Injection drug use, unsafe medical injections, and HIV in Africa: a systematic review

    PubMed Central

    Reid, Savanna R

    2009-01-01

    The reuse of injecting equipment in clinical settings is well documented in Africa and appears to play a substantial role in generalized HIV epidemics. The U.S. and the WHO have begun to support large scale injection safety interventions, increased professional education and training programs, and the development and wider dissemination of infection control guidelines. Several African governments have also taken steps to control injecting equipment, including banning syringes that can be reused. However injection drug use (IDU), of heroin and stimulants, is a growing risk factor for acquiring HIV in the region. IDU is increasingly common among young adults in sub-Saharan Africa and is associated with high risk sex, thus linking IDU to the already well established and concentrated generalized HIV epidemics in the region. Demand reduction programs based on effective substance use education and drug treatment services are very limited, and imprisonment is more common than access to drug treatment services. Drug policies are still very punitive and there is widespread misunderstanding of and hostility to harm reduction programs e.g. needle exchange programs are almost non-existent in the region. Among injection drug users and among drug treatment patients in Africa, knowledge that needle sharing and syringe reuse transmit HIV is still very limited, in contrast with the more successfully instilled knowledge that HIV is transmitted sexually. These new injection risks will take on increased epidemiological significance over the coming decade and will require much more attention by African nations to the range of effective harm reduction tools now available in Europe, Asia, and North America. PMID:19715601

  15. The Role of Drinking Severity on Sex Risk Behavior and HIV Exposure among Illicit Drug Users

    PubMed Central

    Scherer, Michael; Trenz, Rebecca; Harrell, Paul; Mauro, Pia; Latimer, William

    2015-01-01

    Objectives The current study examined how drinking severity among injection and non-injection drug users is associated with sex risk behaviors and risk of HIV exposure. Methods The study is a secondary analysis of an investigation of risk factors among drug users in Baltimore known as the NEURO-HIV Epidemiologic Study. Participants (N = 557) completed an interview, self-reported 30-day alcohol use, lifetime injection and non-injection drug use, and provided blood samples to screen for HIV. Participants were grouped into one of three drinking severity conditions: Abstinent (no reported alcohol use in prior 30-days), Moderate Alcohol Use (≤30 drinks for females, or ≤ 60 drinks for males), or Problematic Alcohol Use (>30 drinks for females, or >60 drinks for males). Drinking severity groups were significantly different on lifetime injection drug use, heroin injection, snorting/sniffing cocaine, and smoking crack. Results Logistic regression analyses found problematic alcohol users to be more likely than alcohol abstainers to inject drugs before or during sex (AOR = 5.78; 95% CI = 2.07-16.10), and more likely than moderate alcohol users to use alcohol before/during sex (AOR = 4.96; 95% CI = 2.09-11.81), inject drugs before/during sex (AOR = 2.96; 95% CI = 1.29-6.80) and to be HIV+ among Black participants (AOR = 2.72; 95% CI = 1.14-6.49). Conclusions These results outline the necessity for research and clinical intervention among this population to reduce sex risk behaviors and potential HIV exposure, while highlighting the need to examine drinking severity as a predictor of sex risk behaviors. PMID:23617865

  16. Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS.

    PubMed

    Singh, Gurinder; Pai, Roopa S; Mustafa, Sanaul

    2015-01-01

    In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS. PMID:26559551

  17. HIV drug resistance testing by high-multiplex "wide" sequencing on the MiSeq instrument.

    PubMed

    Lapointe, H R; Dong, W; Lee, G Q; Bangsberg, D R; Martin, J N; Mocello, A R; Boum, Y; Karakas, A; Kirkby, D; Poon, A F Y; Harrigan, P R; Brumme, C J

    2015-11-01

    Limited access to HIV drug resistance testing in low- and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously. Plasma samples were collected from Canadian patients during routine drug resistance testing (n = 759) and from a Ugandan study cohort (n = 349). Amplicons spanning HIV reverse transcriptase codons 90 to 234 were sequenced with both MiSeq sequencing and conventional Sanger sequencing methods. Sequences were evaluated for nucleotide concordance between methods, using coverage and mixture parameters for quality control. Consensus sequences were also analyzed for disparities in the identification of drug resistance mutations. Sanger and MiSeq sequencing was successful for 881 samples (80%) and 892 samples (81%), respectively, with 832 samples having results from both methods. Most failures were for samples with viral loads of <3.0 log10 HIV RNA copies/ml. Overall, 99.3% nucleotide concordance between methods was observed. MiSeq sequencing achieved 97.4% sensitivity and 99.3% specificity in detecting resistance mutations identified by Sanger sequencing. Findings suggest that the Illumina MiSeq platform can yield high-quality data with a high-multiplex "wide" sequencing approach. This strategy can be used for multiple HIV subtypes, demonstrating the potential for widespread individual testing and annual population surveillance in resource-limited settings. PMID:26282425

  18. Predicting drug resistance of the HIV-1 protease using molecular interaction energy components.

    PubMed

    Hou, Tingjun; Zhang, Wei; Wang, Jian; Wang, Wei

    2009-03-01

    Drug resistance significantly impairs the efficacy of AIDS therapy. Therefore, precise prediction of resistant viral mutants is particularly useful for developing effective drugs and designing therapeutic regimen. In this study, we applied a structure-based computational approach to predict mutants of the HIV-1 protease resistant to the seven FDA approved drugs. We analyzed the energetic pattern of the protease-drug interaction by calculating the molecular interaction energy components (MIECs) between the drug and the protease residues. Support vector machines (SVMs) were trained on MIECs to classify protease mutants into resistant and nonresistant categories. The high prediction accuracies for the test sets of cross-validations suggested that the MIECs successfully characterized the interaction interface between drugs and the HIV-1 protease. We conducted a proof-of-concept study on a newly approved drug, darunavir (TMC114), on which no drug resistance data were available in the public domain. Compared with amprenavir, our analysis suggested that darunavir might be more potent to combat drug resistance. To quantitatively estimate binding affinities of drugs and study the contributions of protease residues to causing resistance, linear regression models were trained on MIECs using partial least squares (PLS). The MIEC-PLS models also achieved satisfactory prediction accuracy. Analysis of the fitting coefficients of MIECs in the regression model revealed the important resistance mutations and shed light into understanding the mechanisms of these mutations to cause resistance. Our study demonstrated the advantages of characterizing the protease-drug interaction using MIECs. We believe that MIEC-SVM and MIEC-PLS can help design new agents or combination of therapeutic regimens to counter HIV-1 protease resistant strains. PMID:18704937

  19. Multiple drug resistant mechanisms against darunavir, amprenavir, and nelfinavir of HIV-1 PR

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoqing; Dai, Qi; Xiu, Zhilong

    2013-02-01

    Acquired immune deficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV), which is infecting more humans and is expanding faster in the world. The illness interferes with the immune system, making people with AIDS much more likely to get infections, including opportunistic infections and tumors that do not affect people with working immune systems. HIV-1 PR is one of the major targets of anti-AIDS drug discovery. It is, therefore, necessary to develop some inhibitors against HIV-1 PR. In this work, we executed molecular dynamics (MDs) simulation of HIV-1 PR with drugs darunavir (DRV), amprenavir (APV), nelfinavir (NFV), and examined the resistant mechanism of L10I, G48V, I54V, and L90M mutations of this PR, aiming at designing promising drugs. The comparative analysis suggests that the existences of dodecahydroisoquinoline ring at P1' subsite, 4-aminophenylsulfonamide at P2' subsite, and bis-tetrahydrofuranylurethane at P2 subsite are helpful for maintaining the high affinity of the inhibitor for the protease and exhibiting high potency against multiple drug resistance (MDR) mutant protease.

  20. Delivering care to injection drug users coinfected with HIV and hepatitis C virus.

    PubMed

    Taylor, Lynn E

    2005-04-15

    Injection drug use has fueled the epidemic of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in the United States. Nevertheless, drug dependence is among the main reasons that coinfected persons are not being treated for HCV infection. This report describes the development and progress of an HIV clinic program (funded by the Ryan White Comprehensive AIDS Resources Emergency Act) to deliver care for HCV infection to HIV-seropositive injection drug users. To optimize safety and adherence, pegylated interferon is directly administered to patients in the context of integrated addiction, psychiatric, and HIV and HCV therapy. Ribavirin is packed weekly in pill boxes for patients to take at home. Thus far, adherence to weekly visits for treatment with interferon has been 99%. No one has had to stop treatment for HCV infection because of ongoing drug use, addiction relapse or exacerbation, or psychiatric complications. Presented here is a work in progress, rather than a finished research project or definitive model of care. PMID:15768348

  1. Sexual and Drug Use Behavior in Perinatal HIV-Infected Youth: Mental Health and Family Influences

    ERIC Educational Resources Information Center

    Mellins, Claude A.; Elkington, Katherine S.; Brackis-Cott, Elizabeth; Bauermeister, Jose A.; Dolezal, Curtis; McKay, Mary; Wiznia, Andrew; Bamji, Mahrukh; Abrams, Elaine J.

    2009-01-01

    A study found that youth and caregiver mental health problem have greater impact than key environmental factors and family functioning on sex and drug use risk behaviors in perinatally human immunodeficiency virus (HIV)-infected (PHIV+) and PHIV- youths. No differences in the rates of sexual risk behavior and substance use were observed between…

  2. HIV risk behaviors and alcohol intoxication among injection drug users in Puerto Rico.

    PubMed

    Matos, Tomás D; Robles, Rafaela R; Sahai, Hardeo; Colón, Hector M; Reyes, Juan C; Marrero, C Amalia; Calderón, José M; Shepard, Elizabeth W

    2004-12-01

    This paper reports results of an analysis of the association between alcohol intoxication and injection and sexual HIV risk behaviors among 557 Hispanic heroin and cocaine injectors, not in treatment, who were recruited in poor communities in Puerto Rico. Subjects were part of a longitudinal prevention-intervention study aimed at reducing drug use and HIV risk behaviors. Participants reported a high prevalence of co-occurring conditions, particularly symptoms of severe depression (52%) and severe anxiety (37%), measured by Beck's Depression Index and Beck's Anxiety Index, respectively. Alcohol intoxication during the last 30 days was reported by 18% of participants. Associations were found between alcohol intoxication and both injection and sexual risk behaviors. In the bivariate analysis, subjects reporting alcohol intoxication were more likely to inject three or more times per day, pool money to buy drugs, share needles, and share cotton. They were also significantly more likely to have a casual or paying sex partner and to have unprotected sex with these partners. After adjustment, sharing needles and cotton, having sex with a paying partner or casual partner, and exchanging sex for money or drugs were significantly related to alcohol intoxication. HIV prevention programs, to be effective, must address alcohol intoxication and its relation to injection and sexual risk behaviors as a central issue in HIV prevention among drug injectors. PMID:15561474

  3. Criminality among Female Drug Users Following an HIV Risk-Reduction Intervention

    ERIC Educational Resources Information Center

    Theall, Katherine P.; Elifson, Kirk W.; Sterk, Claire E.; Stewart, Eric A.

    2007-01-01

    The main objectives of this article are to determine the prevalence of criminality among a sample of female African American drug users and to examine change in criminality over time, including the correlates associated with this change. Data were collected from 336 adult women who participated in an HIV risk-reduction intervention focused on the…

  4. Transient swelling behavior and drug delivery from a dissolving film deploying anti-HIV microbicide

    NASA Astrophysics Data System (ADS)

    Tasoglu, Savas; Katz, David F.; Szeri, Andrew J.

    2010-11-01

    Despite more than two decades of HIV vaccine research, there is still no efficacious HIV vaccine. Very recently, a research group has shown that a microbicide gel formulation of antiretroviral drug Tenofovir, significantly inhibits HIV transmission to women [1]. However, there is a widespread agreement that more effective and diverse drug delivery vehicles must be developed. In this setting, there is now great interest in developing different delivery vehicles such as vaginal rings, gels, and films. Here, we develop a model for transient fluid uptake and swelling behavior, and subsequent dissolution and drug deployment from a film containing anti-HIV microbicide. In the model, the polymer structural relaxation via water uptake is assumed to follow first order kinetics. In the case of a film loaded with an osmotically active solute, the kinetic equation is modified to account for the osmotic effect. The transport rate of solvent and solute within the matrix is characterized by a diffusion equation. After the matrix is relaxed to a specified concentration of solvent, lubrication theory and convective-diffusive transport are employed for flow of the liquefied matrix and drug dispersion respectively. [1] Karim, et al., Science, 2010.

  5. Associations between availability and coverage of HIV-prevention measures and subsequent incidence of diagnosed HIV infection among injection drug users.

    PubMed

    Wiessing, Lucas; Likatavicius, Giedrius; Klempová, Danica; Hedrich, Dagmar; Nardone, Anthony; Griffiths, Paul

    2009-06-01

    HIV-prevention measures specific to injection drug users (IDUs), such as opioid substitution treatment and needle-and-syringe programs, are not provided in many countries where injection drug use is endemic. We describe the incidence of diagnosed HIV infection in IDUs and the availability and coverage of opioid substitution and needle-and-syringe programs in the European Union and 5 middle- and high-income countries. Countries with greater provision of both prevention measures in 2000 to 2004 had lower incidence of diagnosed HIV infection in 2005 and 2006. PMID:19372511

  6. Availability of HIV prevention and treatment services for people who inject drugs: findings from 21 countries

    PubMed Central

    2013-01-01

    Background About a third of the global HIV infections outside sub-Saharan Africa are related to injecting drug use (IDU), and this accounts for a growing proportion of persons living with HIV. This paper is a response to the need to monitor the state of the HIV epidemic as it relates to IDU and the availability of HIV treatment and harm reduction services in 21 high epidemic countries. Methods A data collection form was designed to cover questions on rates of IDU, prevalence and incidence of HIV and information on HIV treatment and harm reduction services available to people who inject drugs (PWID). National and regional data on HIV infection, IDU in the form of reports and journal articles were sought from key informants in conjunction with a systematic search of the literature. Results Completed data collection forms were received for 11 countries. Additional country-specific information was sourced via the literature search. The overall proportion of HIV positive PWID in the selected countries ranged from 3% in Kazakhstan to 58% in Vietnam. While IDU is relatively rare in sub-Saharan Africa, it is the main driver of HIV in Mauritius and Kenya, with roughly 47% and 36% of PWID respectively being HIV positive. All countries had antiretroviral treatment (ART) available to PWID, but data on service coverage were mainly missing. By the end of 2010, uptake of needle and syringe programmes (NSP) in Bangladesh, India and Slovakia reached the internationally recommended target of 200 syringes per person, while uptake in Kazakhstan, Vietnam and Tajikistan reached between 100-200 syringes per person. The proportion of PWID receiving opioid substitution therapy (OST) ranged from 0.1% in Kazakhstan to 32.8% in Mauritius, with coverage of less than 3% for most countries. Conclusions In order to be able to monitor the impact of HIV treatment and harm reduction services for PWID on the epidemic, epidemiological data on IDU and harm reduction service provision to PWID needs to

  7. Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse

    PubMed Central

    Kiebala, Michelle; Singh, Meera V.; Piepenbrink, Michael S.; Qiu, Xing; Kobie, James J.; Maggirwar, Sanjay B.

    2015-01-01

    Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV) infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB) inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK) activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders. PMID:26076359

  8. Diabetes Type 1

    MedlinePlus

    Diabetes means your blood glucose, or blood sugar, levels are too high. With type 1 diabetes, your pancreas does not make insulin. Insulin is ... kidneys, nerves, and gums and teeth. Type 1 diabetes happens most often in children and young adults ...

  9. HIV Drug Resistance Mutations in Proviral DNA from a Community Treatment Program

    PubMed Central

    Derache, Anne; Shin, Hyoung-Shik; Balamane, Maya; White, Elizabeth; Israelski, Dennis; Klausner, Jeffrey D.; Freeman, Alexandra H.; Katzenstein, David

    2015-01-01

    Background Drug resistance mutations archived in resting memory CD4+ cells may persist despite suppression of HIV RNA to <50 copies/ml. We sequenced pol gene from proviral DNA among viremic and suppressed patients to identify drug resistance mutations. Methods The Peninsula AIDS Research Cohort study enrolled and followed over 2 years 120 HIV infected patients from San Mateo and San Francisco Counties. HIV-1 pol genotyping by bulk sequencing was performed on 38 DNA and RNA from viremic patients and DNA only among 82 suppressed patients at baseline. Antiretroviral susceptibility was predicted by HIVDB.stanford.edu. Results Among 120 subjects, 81% were on antiretroviral therapy and had been treated for a median time of 7 years. Thirty-two viremic patients showed concordant RNA and DNA genotypes (84%); the discordant profiles were mainly observed in patients with low-level viremia. Among suppressed patients, 21 had drug resistance mutations in proviral DNA (26%) with potential resistance to one, two or three ARV classes in 16, 4 and 1 samples respectively. Conclusions The high level of genotype concordance between DNA and RNA in viremic patients suggested that DNA genotyping might be used to assess drug resistance in resource-limited settings, and further investigation of extracted DNA from dried blood spots is needed. Drug resistance mutations in proviral DNA in 26% of subjects with less than 50 copies/ml pose a risk for the transmission of drug resistant virus with virologic failure, treatment interruption or decreased adherence. PMID:25635815

  10. Genetic diversity of HIV-1 and transmitted drug resistance among newly diagnosed individuals with HIV infection in Hangzhou, China.

    PubMed

    Zhang, Jiafeng; Guo, Zhihong; Yang, Jiezhe; Pan, Xiaohong; Jiang, Jun; Ding, Xiaobei; Zhang, Wenjun; Xia, Yan; Xu, Yun; Huang, Jingjing

    2015-10-01

    HIV transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) in resource-limited countries like China where ART has been scaled up and thus leads to an important public health concern. The aim of the study was to elucidate the HIV-1 genetic characteristics and TDR in Hangzhou, China. Two-hundred eleven ART-naive, newly diagnosed individuals were enrolled during January and August 2013. Specimens were classified as recent or chronic infections using the BED capture enzyme immunoassay (BED-CEIA). The pol fragment covering the entire protease and the first 300 codons of the reverse transcriptase gene was amplified by RT-PCR and nested PCR. Genotypic drug resistance (DR) and phylogenetic analysis were performed on the 200 obtained sequences. Multiple genotypes were identified, including CRF01_AE (62.0%), CRF07_BC (31.0%), subtype B (2.0%), CRF08_BC (1.5%), CRF55_01B (1.0%), CRF18_cpx (0.5%), and unique recombinant forms (URFs, 2.0%). All the four URFs were found in men who have sex with men, consisting of a recombination of CRF01_AE with subtype B or CRF07_BC. The prevalence of primary DR in newly diagnosed individuals in Hangzhou was low (4.0%). The proportion of DR mutation to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 1.5%, 1.5%, and 1.0%, respectively. BED-CEIA revealed that 21.8% (45/211) of the specimens were associated with recent infections. The prevalence of TDR in recent infections was moderate (6.5%). High HIV diversity and relatively high prevalence of TDR in new infections has been found in Hangzhou, indicating an increasing challenge for future HIV prevention and treatment. PMID:25899877

  11. Resistant mechanism against nelfinavir of subtype C human immunodeficiency virus type 1 proteases

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoqing; Dai, Qi; Li, Lihua; Xiu, Zhilong

    2011-02-01

    Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the major targets of anti-AIDS drug discovery, and the subtype C HIV-1 is infecting more and more humans. In this work, we executed computational simulations of subtype B (labeled B(WT)) HIV-1 PR, D30N mutant B (labeled B(D30N)) HIV-1 PR, subtype C (labeled C(Ref)) HIV-1 PR, D30N mutant C (labeled C(D30N)) HIV-1 PR, and D30N/N83T mutant C (labeled C(D30N/N83T)) HIV-1 PR with drug nelfinavir (NFV), aiming at clarifying (1) the resistant mechanism against NFV due to D30N mutation in subtype C HIV-1 PR; (2) the reason that the emergence rate of N83T mutation in C(D30N) HIV-1 PR is higher than that in B(D30N) HIV-1 PR; (3) the affinity of NFV with C(D30N/N83T) HIV-1 PR is higher than B(D30N) and C(D30N) HIV-1 PRs. The results indicate: (1) D30N mutation in subtype C HIV-1 PR reduces the hydrogen bond between the 30th residue and NFV, and the binding free energy contributions of some residues decrease; (2) the hydrogen bonds between the 83th/83'th residue and the 34th/34'th residue exist in both B(D30N) and C(D30N/N83T) HIV-1 PRs, while they disappear in C(D30N) HIV-1 PR. Meanwhile, the binding free energy contribution of N30 in C(D30N) is lower than that in B(D30N) and C(D30N/N83T); (3) N83T mutation makes some residues dislocate, and the contributions of these residues to binding free energy in C(D30N/N83T) increase comparing to those in B(D30N) and C(D30N). Our findings suggest that despite the nonactive site mutations, the polymorphisms regulate the emergence rates of these drug-resistant mutants.

  12. Differences in T cell distribution and CCR5 expression in HIV-positive and HIV-exposed seronegative persons who inject drugs.

    PubMed

    Kallas, Eveli; Huik, Kristi; Türk, Silver; Pauskar, Merit; Jõgeda, Ene-Ly; Šunina, Marina; Karki, Tõnis; Des Jarlais, Don; Uusküla, Anneli; Avi, Radko; Lutsar, Irja

    2016-06-01

    Some individuals remain uninfected despite repeated exposure to HIV. This protection against HIV has been partly associated with altered T cell subset distributions and CCR5 expression levels. However, the majority of studies have been conducted in sexually exposed subjects. We aimed to assess whether HIV infection and intravenous drug use were associated with differences in CCR5 expression, immune activation on the CD4+ and CD8+ T cells and T cell distribution among Caucasian persons who inject drugs (PWIDs). Analyses of the data from 41 HIV-positive PWIDs, 47 HIV-exposed seronegative PWIDs (ESNs) and 47 age- and gender-matched HIV-negative non-drug users are presented. Of all of the study subjects, 111 (82 %) were male, and the median age was 29 years. T cell phenotyping was performed in peripheral blood mononuclear cells with multicolour flow cytometry using anti-CD3, CD4, CD8, CD45RA, CD45RO, HLA-DR and CCR5 antibodies. The ESNs exhibited greater levels of immune activation and higher percentages of CD4+ CD45RA+RO+ and CD8+ CD45RA+RO+ cells compared to the controls but not the HIV-positive people. The CCR5 expression on the CD4+ T cell subsets in the ESNs was lower than that in the controls but similar to that the HIV positives. The percentages of CCR5+ T cells were similar in all study groups and in most of the studied cell populations. Intravenous drug use was similarly associated with differences in T cell subset distributions and CCR5 expression among both the HIV-positive and HIV-negative PWIDs compared with the controls. PMID:26696529

  13. Drug use and HIV risk in Trinidad and Tobago: qualitative study.

    PubMed

    Djumalieva, D; Imamshah, W; Wagner, U; Razum, O

    2002-09-01

    Crack use is an important risk factor for HIV infection because of its association with unsafe sexual practices. We investigated factors promoting the initiation of crack cocaine use; the sexual behaviour of crack users; and their rehabilitation care seeking behaviour in Trinidad and Tobago. We conducted 40 in-depth interviews with