An analysis of respondent-driven sampling with injecting drug users in a high HIV prevalent state of India.

BACKGROUND: Personal networks are significant social spaces to spread of HIV or other blood-borne infections among hard-to-reach population, viz., injecting drug users, female sex workers, etc. Sharing of infected needles or syringes among drug users is one of the major routes of HIV transmission in Manipur, a high HIV prevalence state in India. This study was carried out to describe the network characteristics and recruitment patterns of injecting drug users and to assess the association of personal network with injecting risky behaviors in Manipur. METHODS: A total of 821 injecting drug users were recruited into the study using respondent-driven sampling (RDS) from Bishnupur and Churachandpur districts of Manipur; data on demographic characteristics, HIV risk behaviors, and network size were collected from them. Transition probability matrices and homophily indices were used to describe the network characteristics, and recruitment patterns of injecting drug users. Univariate and multivariate binary logistic regression models were performed to analyze the association between the personal networks and sharing of needles or syringes. RESULTS: The average network size was similar in both the districts. Recruitment analysis indicates injecting drug users were mostly engaged in mixed age group setting for injecting practice. Ever married and new injectors showed lack of in-group ties. Younger injecting drug users had mainly recruited older injecting drug users from their personal network. In logistic regression analysis, higher personal network was found to be significantly associated with increased likelihood of injecting risky behaviors. CONCLUSION: Because of mixed personal network of new injectors and higher network density associated with HIV exposure, older injecting drug users may act as a link for HIV transmission or other blood-borne infections to new injectors and also to their sexual partners. The information from this study may be useful to understanding the network pattern of injecting drug users for enriching the HIV prevention in this region.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions­a proxy for recent infection­yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs­K101E, K103N, Y181C, and G190A­accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Outcome of patients on second line antiretroviral therapy under programmatic condition in India.

BACKGROUND: The National AIDS Control Organization of India has been providing free second line antiretroviral therapy (ART) since 2008. This observational study reports the survival and virologic suppression of patients on second-line ART under programmatic condition and type of mutations acquired by those failing therapy. METHODS: 170 patients initiated on second-line therapy between 2008 and 2012 were followed up till 2013. Viral Load (VL) was repeated at 6 months for all patients and at 12 months for those with VL >400 copies/ml at 6 months. Adequate virological response was defined as plasma HIV-1 VL <400 copies/ml and virological failure was defined as VL >1000 copies/ml. Genotyping was done in 16 patients with virological failure. RESULTS: Out of 170 patients, 110 (64.7 %) were alive and on therapy and 35 (20.5 %) expired. In the first year the occurrence of death was 13.7 /100 person years while between 1 and 5 year it was 3.88 /100 person years. In the first year, duration of immunological failure >12 months, weight <45 kg, WHO clinical stage 3 and 4 and WHO criteria CD4 count less than pretherapy baseline [hazard ratio HR 4.2. 15.8, 11.9 & 4.1 respectively] and beyond first year poor first and second line adherence and first line CD4 count < 200/µL [HR 5.2,15.8, 3.3 respectively] had high risk of death. 119/152 (78.2 %) had adequate virological response and 27/152 (17.7 %) had virological failure. High viral load at baseline and poor second line adherence (Odds Ratio 3.4 & 2.8 respectively) had increased risk of virological failure. Among those genotyped, 50 % had major Protease Inhibitor mutation (M46I commonest) however 87.5 % were still susceptible to darunavir. CONCLUSIONS: Second line therapy has shown high early mortality but good virological suppression under programmatic conditions.

Association between alcohol use and HIV-related sexual risk behaviors among men who have sex with men (MSM): findings from a multi-site bio-behavioral survey in India.

This paper examines the association between alcohol use and HIV-related sexual risk behaviors among men who have sex with men (MSM). A cross-sectional bio-behavioral survey was conducted among 3,880 MSM, recruited using time-location cluster sampling from cruising sites in three Indian states. Nearly three-fifths of the participants reported alcohol use. Among frequent users (40 % of the sample), defined as those who consumed alcohol daily or at least once a week, 66 % were aged 25 years and above, 53 % self-identified as kothi (feminine/receptive), and 63 % consistently used condoms with male paying partners. Multivariate logistic regression demonstrated that frequent users were more likely to be aged 25 years and above, less likely to self-identify as kothi, and less likely to consistently use condoms with male paying (AOR = 0.7; 95 % CI 0.5-0.9) and male regular (AOR = 0.7; 95 % CI 0.6-0.9) partners. HIV prevention interventions for MSM need to provide tailored information on alcohol use-related sexual risk, especially for MSM in sex work and MSM with male regular partners.

Female sex worker's participation in the community mobilization process: two distinct forms of participations and associated contextual factors.

BACKGROUND: Community mobilization is a participatory intervention strategy used among Female Sex Workers (FSW's) to address HIV risks through behavior change and self empowerment. This study quantitatively measure and differentiate theoretically defined forms of FSW participation's and identify their contextual associated factors. METHOD: Data was derived from cross-sectional Integrated Bio Behavioral Assessment conducted among FSW's in Andhra Pradesh (AP) (n = 3370), Maharashtra (MH) (n = 3133) and Tamil Nadu (TN) (n = 2140) of India during 2009-2010. Information's about socio-demography, community mobilization and participation experiences were collected. Conceptual model for two contexts of mobilization entailing distinct FSW participations were defined as participation in "collective" and "public" spaces respectively. Bivariate and multiple regression analysis were used. RESULT: The level of participation in "collective" and "public" spaces was lowest in MH (43.9% & 11.7% respectively), higher in TN (82.2% & 22.5% respectively) and AP (64.7% & 33.1%). Bivariate and multivariate regression analysis highlighted the distinct nature of "participations" through their varied associations with FSW mobilization and background status.In MH, street FSWs showed significantly lower collective participation (36.5%) than brothel FSWs (46.8%) and street FSWs showed higher public participation (16.2%) than brothel FSWs (9.7%). In AP both collective and public participation were significantly high among street FSWs (62.7% and 34.7% respectively) than brothel FSW's (55.2% and 25.4% respectively).Regression analysis showed FSWs with "community identity", were more likely to participate in public spaces in TN and AP (AOR 2.4, 1.5-3.8 & AOR 4.9, CI 2.3-10.7) respectively. FSWs with "collective identity" were more likely to participate in collective spaces in TN, MH and AP (AOR 27.2 CI 13.7-53.9; AOR 7.3, CI 3.8-14.3; AOR 5.7 CI 3-10.9 respectively). FSWs exhibiting "collective agency" were more likely to participate in public spaces in TN, MH and AP (AOR 2.3 CI 1-3.4; AOR 4.5- CI 2.6-7.8; AOR 2.2 CI 1.5-3.1) respectively. CONCLUSION: Findings reveal FSWs participation as a dynamic process inherently evolving along with the community mobilization process in match with its contexts. Participation in "Collective" and Public spaces" is indicators, symbolizing FSWs passage from the disease prevention objectives towards empowerment, which would help better understand and evaluate community mobilization interventions.

Increase in condom use and decline in prevalence of sexually transmitted infections among high-risk men who have sex with men and transgender persons in Maharashtra, India: Avahan, the India AIDS Initiative.

BACKGROUND: The present study assessed coverage, changes in condom use, and prevalence of HIV and other STIs among high-risk men who have sex with men (HR-MSM; highly visible, recruited from cruising sites/sex venues) and transgender (TG; male-to-female transgender persons, also called hijras) in the Indian state of Maharashtra. METHODS: Data from Avahan's computerized management information system; two rounds of integrated behavioral and biological assessment (IBBA) surveys (Round 1 with 653 HR-MSM/TG and Round 2 with 652 HR-MSM/TG); and project-supported condom social marketing was used for the present analysis. Logistic regression models were used to assess changes in key indicators over these two rounds and to explore the association between exposure to Avahan interventions and condom use and STI prevalence in HR-MSM/TG. RESULTS: By December 2007, Avahan had reached about 90% of the estimated HR-MSM/TG population, and 83% of the estimated total population had visited STI clinics by March 2009. Free direct condom distribution by Avahan program NGOs and social marketing outlets in Maharashtra increased from about 2.7 million condoms in 2004 to 15.4 million in 2008. HR-MSM/TG were more likely to report higher consistent condom use (adjusted odds ratio [AOR]: 1.90; 95% confidence interval [CI] 1.01-3.58) with regular male partners (spouse/lover/boyfriend) in Round 2 of IBBA, compared to Round 1. HR-MSM/TG exposed to Avahan interventions were more likely to report consistent condom use with regular male partners (AOR: 2.46; CI 1.34-4.52) than those who were unexposed. Prevalence of reactive syphilis serology declined significantly from 8.8% in Round 1 to 1.1% in Round 2 (p = 0.001), while the observed change HIV prevalence (12.3% to 6.3%, p = 0.16) was insignificant. CONCLUSION: The current evaluation provides evidence for successful scale up and coverage of target population by Avahan interventions in Maharashtra. The assessment findings showed improved accessibility to condoms and reduced risk behaviours with male sexual partners. Syphilis prevalence declined; however HIV prevalence did not change and is still a major concern. Continued strengthening of core programmatic strategies are needed to effectively improve condom use with all partner types and to help bring sustained reductions in HIV risk in HR-MSM/TG and its onward transmission.

Initial virologic response and HIV drug resistance among HIV-infected individuals initiating first-line antiretroviral therapy at 2 clinics in Chennai and Mumbai, India.

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/µL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥ 70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART.

Factors associated with HIV among female sex workers in a high HIV prevalent state of India.

The study was carried out to assess the factors associated with HIV seropositivity among female sex workers (FSWs) in Dimapur, Nagaland, a high HIV prevalence state of India. A total of 426 FSWs were recruited into the study using respondent driven sampling (RDS). Data on demographic characteristics, sexual and injecting risk behaviours were collected from them and were tested for HIV, Syphilis, Neisseria gonorrhoeae and Chlamydia trachomatis. RDS-weighted univariate and multivariate logistic regression analysis was performed to assess the factors associated with HIV seropositivity. Consistent condom use with regular and occasional sexual clients was 9% and 16.4%, respectively. About 25% of the participants ever used and 5.7% ever injected illicit drugs. RDS adjusted HIV prevalence was 11.6%. In the univariate analysis, factors associated with HIV were initiating sexual intercourse before the age of 15 years, ≥2 years duration of sex work, serving clients at lodge/hotel, positive test result for one or more sexually transmitted infections (STIs), lifetime history of injecting drug use, lifetime history of consuming illicit drugs, ever having exchanged sex for drugs, having sexual partners who engaged in risky injecting practices and having been widowed or divorced. In multivariate analysis, factors found to be independently associated with HIV included lifetime injecting drug use, initiating sexual intercourse before the age of 15 years, positive test result for one or more STIs and having been widowed. Injecting drug use was found to be most potent independent risk factor for HIV (OR: 3.17, CI: 1.02-9.89). Because of lower consistent condom use among them, FSWs may act as bridge for HIV transmission to general population from injecting drug users (IDU) through their sexual clients. The informations from this study may be useful for enriching the HIV preventions effort for FSWs in this region.

Factors associated with history of drug use among female sex workers (FSW) in a high HIV prevalence state of India.

BACKGROUND: The intersection between illicit drug use and female commercial sex work has been identified as an important factor responsible for rising HIV prevalence among female sex workers (FSW) in several northeastern states of India. But, little is know about the factors associated with the use of drugs among FSWs in this region. The objective of the paper was to describe the factors associated with history of drug use among FSWs in Dimapur, an important commercial hub of Nagaland, which is a high HIV prevalence state of India. METHODS: FSWs were recruited using respondent driven sampling (RDS), and were interviewed to collect data on socio-demographic characteristics and HIV risk behaviours. Biological samples were tested for HIV, syphilis gonorrhea and Chlamydia. Logistic regression analysis was performed to identify factors associated with drug use. RESULTS: Among the 426 FSWs in the study, about 25% (n = 107) reported having ever used illicit drugs. Among 107 illicit drug users, 83 (77.6%) were non-injecting and 24 (22.4%) were injecting drug users. Drug-using FSWs were significantly more likely to test positive for one or more STIs (59% vs. 33.5%), active syphilis (27.1% vs. 11.4%) and Chlamydia infection (30% vs. 19.9%) compared to their non-drug using peers. Drug-using FSWs were also significantly more likely to be currently married, widowed or separated compared with non-drug-using FSWs. In multiple logistic regression analysis, being an alcohol user, being married, having a larger volume of clients, and having sexual partners who have ever used or shared injecting drugs were found to be independently associated with illicit drug use. CONCLUSIONS: Drug-using FSWs were more vulnerable to STIs including HIV compared to their non-drug using peers. Several important factors associated with being an FSW who uses drugs were identified in this study and this knowledge can be used to plan more effectively targeted harm reduction strategies and programs.

Establishment of reference CD4+ T cell values for adult Indian population.

BACKGROUND: CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. METHODS: A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre) healthy participants were enrolled in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS), version 15) and Prism software version 5. RESULTS: The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/µL and for female population was 447-1846 cells/µL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/µL for Indian male population and 826-2997 cells/µL for female population. CONCLUSION: The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.

Heading towards the Safer Highways: an assessment of the Avahan prevention programme among long distance truck drivers in India.

BACKGROUND: Using data from two rounds of a cross-sectional, national-level survey of long-distance truck drivers, this paper examines the extent and trend of sexual risk behavior, prevalence of STI/HIV, and the linkage between exposure to HIV prevention programs and safe sex behavior. METHODS: Following the time location cluster sampling approach, major transshipment locations covering the bulk of India's transport volume along four routes, North-East (NE), North-South (NS), North-West (NW) and South-East (SE) were surveyed. First round of the survey was conducted in 2007 (sample size 2066) whereas the second round was undertaken in 2009-2010 (sample size 2085). Long distance truck drivers were interviewed about their sexual behaviors, condom use practices, exposure to different HIV prevention interventions, and tested for HIV, reactive syphilis serology, Neiserria gonorrhoeae and Chlamydia trachomatis. The key variable of this evaluation study - exposure to HIV prevention interventions was divided into three categories - no exposure, less intensive exposure and intensive exposure. Data were analyzed using multiple logistic regression methods to understand the relationship between risk behavior and exposure to intervention and between program exposure and condom use. RESULTS: The proportion of truckers exposed to HIV prevention interventions has increased over time with much significant increase in the intensive exposure across all the four routes (NE: from 14.9% to 28%, P < 0.01; NS: from 20.9% to 38.1%; NW: 11.5% to 39.5%, P < 0.01; SE: 4.7% to 9.7%, P <0.05). Overall, the consistent condom use in sex with non-regular female partners too has increased over the time (paid female partners: from 67.1% to 73.2%, P <0.05; non-paid female partners: from 17.9% to 37.1%, P <0.05). At the aggregate level, the proportion tested HIV positive has declined from 3.2% to 2.5% in (p<0.10) and proportion tested positive for Syphilis too has reduced from 3.2% to 1.7% (p<0.05). Truckers who had sex with paid female partners (men at risk) were significantly more likely to get exposed to intensive program (aOR: 2.6, 95%CI 1.9-3.4) as compared to those who did not have sex with paid partners. Truckers who had sex with paid partners and exposed to intervention program were more likely to use condoms consistently (aOR: 2.1, 95% CI 1.2-3.7). The consistent condom use among respondents who travel through states with targeted interventions towards female sex workers was higher than those who travel through states with less intensive program among FSWs. CONCLUSIONS: These evaluation study results highlight the ability of intensive program to reach truckers who have sex outside marriage with HIV prevention interventions and promote safe sex behaviors among them. Truckers who practice safe sex behaviors with an exposure to intensive program are less likely to suffer from STIs and HIV, which has implications for HIV prevention program with truckers' population in India and elsewhere. The simultaneous targeted interventions among female sex workers appeared to have contributed to safe sexual practices among truckers.

Targeted interventions of the Avahan program and their association with intermediate outcomes among female sex workers in Maharashtra, India.

BACKGROUND: Avahan, the India AIDS Initiative has been a partner supporting targeted interventions of high risk populations under India's National AIDS Control Organisation (NACO) since 2004 in the state of Maharashtra. This paper presents an assessment of the Avahan program among female sex workers (FSWs) in Maharashtra, its coverage, outcomes achieved and their association with Avahan program. METHODS: An analytical framework based on the Avahan evaluation design was used, addressing assessment questions on program implementation, intermediate outcomes and association of outcomes with Avahan. Data from routine program monitoring, two rounds of cross-sectional Integrated Behavioural and Biological Assessments (IBBAs) conducted in 2006 (Round 1- R1) and 2009 (Round 2 - R2) and quality assessments of program clinics were used. Bi-variate and multivariate analysis were conducted using the complex samples module in SPSS 15 (IBM, Somers NY). RESULTS: The Avahan program achieved coverage of over 66% of FSWs within four years of implementation. The IBBA data showed increased contact by peers in R2 compared to R1 (AOR:2.34; p=0.001). Reported condom use with clients increased in R2 and number of FSWs reporting zero unprotected sex acts increased from 76.2% (R1) to 94.6% (R2) [AOR: 5.1, p=0.001].Significant declines were observed in prevalence of syphilis (RPR) (15.8% to 10.8%; AOR:0.54; p=0.001), chlamydia (8% to 6.2%; AOR:.0.65; p=0.010) and gonorrohoea (7.4% to 3.9; AOR:.0.60; p=0.026) between R1 and R2. HIV prevalence increased (25.8% to 27.5%; AOR:1.29; p=0.04). District-wise analysis showed decline in three districts and increase in Mumbai and Thane districts.FSWs exposed to Avahan had higher consistent condom use with occasional (94.3% vs. 90.6%; AOR: 1.55; p=0.04) and regular clients (92.5% vs. 86.0%; AOR: 1.95, p=0.001) compared to FSWs unexposed to Avahan. Decline in high titre syphilis was associated with Avahan exposure. CONCLUSION: The Avahan program was scaled up and achieved high coverage of FSWs in Maharashtra amidst multiple intervention players. Avahan coverage of FSWs was associated with improved safe sexual practices and declines in STIs. Prevalence of HIV increased requiring more detailed understanding of the data and, if confirmed, new approaches for HIV control.

The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C.

In a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not the coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but no significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a coinfection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy.

Programme coverage, condom use and STI treatment among FSWs in a large-scale HIV prevention programme: results from cross-sectional surveys in 22 districts in southern India.

OBJECTIVE: This paper evaluates Avahan programme's coverage of female sex workers (FSWs), focus on high-risk FSWs and intermediate outcomes. METHODS: First round of cross-sectional survey data, Integrated Behavioral and Biological Assessments (IBBA), conducted in 22 districts, were aggregated into district categories: Solo, where Avahan was the sole service provider covering all FSWs and Major or Minor where Avahan was not the sole provider, but intended coverage was >50% or or=15 clients in the past week had a higher chance of being exposed to core services (AOR=1.56; 95% CI 1.03 to 2.35). Exposure to the three services in Solo Avahan districts was significantly associated with correct knowledge on condom use (AOR=1.36; 95% CI 1.05 to 1.78), consistent condom use with occasional clients (AOR=3.17; 95% CI 2.17 to 4.63) and regular clients (AOR=2.47; 95% CI 1.86 to 3.28) and STI treatment-seeking behaviour (AOR=3.00; 95% CI 1.94 to 4.65). CONCLUSIONS: Higher coverage of FSWs was achieved in districts where Avahan was the only intervention compared with districts having multiple and longstanding non-Avahan programmes. Exposure in Solo districts was associated with intermediate outcomes; this need to be further evaluated in comparison with non Avahan areas and substantiated through data from next IBBA.

Risk association of BST2 gene variants with disease progression in HIV-1 infected Indian cohort.

Bone marrow stromal cell antigen 2 (BST2) is an interferon induced host restriction factor for HIV-1 that blocks the release of nascent virions from infected T cells. We aimed to characterize BST2 gene variants in HIV-1 positive individuals in Indian cohort and study the association of these variants with disease progression in long term non progressors (LTNPs) and progressors. Archived samples of 32 LTNPs, 17 progressors, and 78 controls were screened for BST2 gene polymorphisms using Sanger's sequencing method. Frequency distribution, survival analysis and bioinformatics tools were used to study the association of BST2 variants with disease progression. Eighteen variants of BST2 gene were observed in Indian cohort. Intronic SNP rs919267T/C (OR = 4.489 [0.8494-27.03], p = .04157) and exonic SNP rs13485C/G (OR = 3.887 [0.8262-25.56], p = .0488) were found to be significantly associated with disease progression. Also, rs13485C/C genotype in combination with rs919267C/T (OR = 9.406 [1.384-111], p = .0085) and rs145303329 Δ19bp (OR = 3.887 [0.826-25.5], p = .048) were found to be significantly associated with disease progression. 19 bp indel rs145303329 and its allele c.1-443_1-442insCGCCCCCAGAC[C/T]CAGGCCC from BST2 promoter also showed association with disease progression (OR = 12.97 [0.9731-850.5], p = .026). Docking of AP2 repressor with above allele showed the total binding energy of LTNPs and progressors to be -2581.42 kcal/mol and -3563.27/-3562.84 kcal/mol respectively. We have identified the novel association of three BST2 gene SNPs; rs919267, rs13485 and indel rs145303329 from Indian cohort to be associated with the risk of HIV-1 disease progression for the first time.

HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load.

HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis (Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4+ T cell responses demonstrates a marked dampening of the Mtb-specific CD4+ T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ+/interleukin-17+ (IL-17+) and significant loss of anti-inflammatory IL-10+/IL-17+ effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4+ T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4+ T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects.

Quantitation of HLA proteins incorporated by human immunodeficiency virus type 1 and assessment of neutralizing activity of anti-HLA antibodies.

Human anti-human leukocyte antigen (HLA) antibodies were assessed for neutralizing activity against human immunodeficiency virus type 1 (HIV-1) carrying HLA alleles with matching specificity. Multiparous women carrying anti-HLA antibodies were identified. Plasma samples from those women were confirmed as having antibodies that specifically bound to HLA proteins expressed on the peripheral blood mononuclear cells (PBMCs) of their husbands. A primary HIV-1 isolate was cultured in the husband's PBMCs so that the virus carried matching HLA alleles. To determine the HIV-1-neutralizing activity of anti-HLA antibodies, the infectivity of the virus for GHOST cells (which express green fluorescent protein after HIV infection) was investigated in the presence of a plasma sample positive for the respective anti-HLA antibody. A neutralization assay was also performed using purified immunoglobulin G (IgG) from two plasma samples, and two plasma samples were investigated in the presence of complement. The prerequisite for anti-HLA antibody-mediated neutralization is incorporation of HLA proteins by HIV-1. Therefore, the extent of incorporation of HLA proteins by the primary HIV-1 isolate was estimated. The ratios of HLA class I protein to HIV-1 capsid (p24) protein cultured in the PBMCs of two healthy individuals were 0.017 and 0.054. These ratios suggested that the HIV-1 strain used in the assay incorporated more HLA proteins than gp160 trimers. Anti-HLA antibody-positive plasma was found to contain antibodies that specifically reacted to HIV-1 carrying cognate HLA alleles. However, incubation of HIV-1 with anti-HLA antibody- positive plasma or purified IgG did not show a reduction in viral infectivity. HIV-1-neutralizing activity was also not detected in the presence of complement. This study shows that HIV-1 primary isolates cultured in PBMCs contain significant amounts of HLA proteins. However, the binding of antibodies to those HLA proteins does not mediate a reduction in viral infectivity.

HIV-1-Mediated Suppression of IFN-α Production Is Associated with Inhibition of IRF-7 Translocation and PI3K/akt Pathway in Plasmacytoid Dendritic Cells.

Interferon-α (IFN-α) plays a vital role in combating viral infections especially in the early control after infection. However, the HIV infection has shown substantial level of suppression of IFN-α secretion during initial phase of infection. The reasons behind this impairment are still obscure. As plasmacytoid dendritic cells (pDCs) are the major producers of this cytokine, the mechanisms of HIV-1-mediated suppression of IFN-α production by pDCs using the primary pDCs were explored. The nuclear translocation of the interferon regulatory factor (IRF)-7, a transcription factor for IFN-α genes, is essential for the initiation of IFN-α production in pDCs. The HIV-1-exposed pDCs did not show the translocation of IRF-7 into the nucleus in our experiments. Furthermore, it was also observed that HIV-1 inhibited AKT phosphorylation of PI3K/akt pathway in pDCs, an important step for IRF-7 translocation to nucleus. HIV-1-induced inhibition of AKT phosphorylation and IRF-7 translocation was evident even in the presence of Toll-like receptor-7 agonist stimulation and correlated with IFN-α suppression. The findings suggest that HIV-1 may alter AKT phosphorylation to inhibit the translocation of IRF-7 into pDC nucleus, leading to IFN-α suppression, and this may be the reason for IFN-α abrogation observed in recently infected HIV patients. Understanding of interactions between HIV-1 and signaling pathways leading to IFN-α secretion may provide targets for immune intervention.