Evaluation of key survey components of bio-behavioral surveillance among HIV high-risk subpopulation in Western India.

BACKGROUND: High-quality data are of prime importance in any health survey because survey data are considered as a gold standard for nationally representative data. The quality of data collection largely depends on the design of the questionnaire, training, and skills of the interviewer. OBJECTIVES: In the present study, we tried to evaluate three key components, such as questionnaire design, human resource and training of the field staff for Integrated Biological and Behavioural Surveillance carried out among the HIV high-risk subpopulation. METHODS: A mixed-methods approach was used. Qualitative and quantitative data collection was carried out in the year 2015 with cross-sectional survey design in western states of India. The in-depth interviews of 10 stakeholders, structured interviews of the survey respondents (n = 560), and field investigators (n = 71) were conducted. Data triangulation was used to find out the concurrence of the qualitative and quantitative data. RESULTS: Comprehensive and standardized survey questionnaire, structured training agenda, and strategic preparation for recruiting human resources were the overall strengths of the survey. However, during the implementation of the survey, there were some difficulties reported in data collection process. Overall, the respondents and investigators felt that the questionnaire was long and exhaustive. Difficulties were faced while collecting data on sexual history. The field staffs were not adequately experienced to work with sensitive population. CONCLUSIONS: In order to have accurate, reliable data, especially on sexual behavior; emphasis should be given on simple questionnaire with the use of community-friendly language, skilled and experienced interviewers for data collection, and extensive field training.

Molecular mechanisms associated with Fluconazole resistance in clinical Candida albicans isolates from India.

Resistance to azole antifungals is a significant problem in Candida albicans. An understanding of resistance at molecular level is essential for the development of strategies to tackle resistance and rationale design of newer antifungals and target-based molecular approaches. This study presents the first evaluation of molecular mechanisms associated with fluconazole resistance in clinical C.albicans isolates from India. Target site (ERG11) alterations were determined by DNA sequencing, whereas real-time PCRs were performed to quantify target and efflux pump genes (CDR1, CDR2, MDR1) in 87 [Fluconazole susceptible (n = 30), susceptible-dose dependent (n = 30) and resistant (n = 27)] C.albicans isolates. Cross-resistance to fluconazole, ketoconazole and itraconazole was observed in 74.1% isolates. Six amino acid substitutions were identified, including 4 (E116D, F145L, E226D, I437V) previously reported ones and 2 (P406L, Q474H) new ones. CDR1 over-expression was seen in 77.7% resistant isolates. CDR2 was exclusively expressed with CDR1 and their concomitant over-expression was associated with azole cross-resistance. MDR1 and ERG11 over-expression did not seem to be associated with resistance. Our results show that drug efflux mediated by Adenosine-5'-triphosphate (ATP)-binding cassette transporters, especially CDR1 is the predominant mechanism of fluconazole resistance and azole cross-resistance in C. albicans and indicate the need for research directed towards developing strategies to tackle efflux mediated resistance to salvage azoles.

The effects of antiretroviral treatment initiation on cognition in HIV-infected individuals with advanced disease in Pune, India.

There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (HAND) with advances in antiretroviral treatment (ART). But the prevalence of milder forms of HAND still remains high. Data from systematically conducted studies on the effects of ART on cognition are scanty in India, where HIV-1 clade C is prevalent. The purpose of the present study was to assess the effect of antiretroviral therapy in HIV-seropositive (HIV+) individuals (n = 92) with CD4 cell counts <200 cells/mm(3). The overall and domain-specific levels of cognitive functioning were determined using a locally recruited normative sample, and a change in neurocognitive functioning at the 1-year follow-up visit was analyzed. Results revealed cognitive impairment in 44.6 % of the HIV+ group at baseline. At the 1-year follow-up, the group showed significant improvement in the Learning domain (p < 0.05). HIV+ individuals showing improvement in the global cognitive scores had a significantly lower baseline CD4 cell count compared to others. Overall, the degree of improvement associated with the magnitude of rise in CD4 suggests the possibility that early, mild subclinical deficits may also benefit from treatment.

Differing Identities but Comparably High HIV and Bacterial Sexually Transmitted Disease Burdens Among Married and Unmarried Men Who Have Sex With Men in Mumbai, India.

BACKGROUND: Although HIV incidence has declined in India, men and transgender women who have sex with men (MSM) continue to have high rates of HIV and sexually transmitted disease (STD). Indian MSM face substantial pressures to marry and have families, but the HIV/STD burden among married Indian MSM is not well characterized. METHODS: A diverse sample of Indian MSM were recruited through respondent-driven sampling. Independent variables that produced a P value of 0.10 or less were then added to a multivariable logistic regression model. RESULTS: Most of the 307 MSM (95 married and 212 unmarried) recruited into the study were younger than 30 years, and less than one-third had more than a high school education. Almost two-thirds of the married men had children, compared with 1.4% of the unmarried men (P < 0.001). The numbers of condomless anal sex acts did not differ by marriage status. Although unmarried MSM more often identified themselves as "kothi" (receptive role), their rates of HIV or bacterial STD were similar to married MSM, with 14.3% being HIV infected. The respondent-driven sampling-adjusted prevalence of any bacterial STD was 18.3% for married MSM and 20% for unmarried MSM (not significant). Participants reported high levels of psychological distress, with 27.4% of married and 20.1% of unmarried MSM reporting depressive symptoms (not significant). CONCLUSIONS: Men who have sex with men in Mumbai had high rates of HIV, STD, and behavioral health concerns. Clinicians need to become more comfortable in eliciting sexual histories so that they can identify MSM who need HIV/STD treatment and/or prevention services.

Validation and modification of dried blood spot-based glycosylated hemoglobin assay for the longitudinal aging study in India.

OBJECTIVES: This study aims to validate a modified dried blood spot (DBS)-based glycosylated hemoglobin (HbA1c) assay protocol, after a pretest in India showed poor correlation between the original DBS-based protocol and venous results. METHODS: The original protocol was tested on different chemistry analyzers and then simplified at the University of Washington (UW). A second pretest was conducted in India to validate the modified assay protocol, using 44 quality control specimens. RESULTS: Data from UW indicated that, using the original protocol, the correlation coefficients between DBS and venous results were above 0.98 on both Bio-Rad and Olympus chemistry analyzers. The protocol worked equally well on filter paper, with or without pre-treatment, and when the recommended amount of blood spot material, or less, was used. A second pretest of the modified protocol confirmed that DBS-based levels from both Olympus and Roche chemistry analyzers were well correlated with DBS results from UW (correlation coefficients were above 0.96), as well as with venous values (correlation coefficients were above 0.94). CONCLUSIONS: The DBS-based HbA1c values are highly correlated with venous results. The pre-treatment of filter paper does not appear to be necessary. The poor results from the first pretest are probably due to factors unrelated to the protocol, such as problems with the chemistry analyzer or assay reagents.

Pseudomembranous Type of Oral Candidiasis is Associated with Decreased Salivary Flow Rate and Secretory Immunoglobulin A Levels.

Saliva plays an important role in maintaining microbial homeostasis in the oral cavity, while salivary gland hypofunction predisposes the oral mucosa to pathologic alteration and increases the risk for oral candidiasis. This study sought to determine the salivary flow rate (SFR) and secretory immunoglobulin A (SIgA) levels in HIV-positive and HIV-negative individuals and evaluate their relationship with the determinants of oral candidiasis. Sixty HIV-positive (30 with and 30 without oral candidiasis) and 30 healthy HIV-negative individuals were enrolled. Cotton pellet was weighed pre- and post-saliva collection for the assessment of SFR, while SIgA levels were estimated by commercial ELISA (Diametra, Italy) kit. The mean ± SD, SFR and SIgA levels in HIV-positive individuals with candidiasis, without candidiasis and HIV-negative controls were 0.396 ± 0.290, 0.546 ± 0.355 and 0.534 ± 0.214 ml/min and 115.891 ± 37.621, 136.024 ± 51.075 and 149.418 ± 31.765 µg/ml, respectively. A positive correlation between low CD4 counts (indicator of immunodeficiency) and SIgA was observed in HIV-positive individuals with candidiasis (r = 0.373, p = 0.045). We also report here for the first time the significant decrease in SFR and SIgA levels in individuals presenting with pseudomembranous type of oral candidiasis and Candida albicans infection.

Pneumocystis jirovecii infection and the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations in HIV-positive individuals from Pune, India.

The present study was undertaken to detect Pneumocystis jirovecii infection among HIV-positive patients presenting with symptoms of lower respiratory tract infection and analyze the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations. P. jirovecii infection was detected in 12.6% cases. We did not find DHPS gene mutations at the commonest positions of codon 55 and 57; however, mutation at codon 171 was detected in two cases. No mutations in DHFR gene were detected. The results indicate low prevalence of DHPS and DHFR mutations in Indian P. jirovecii isolates, suggesting that the selective pressure of sulfa drugs on the local strains has probably not reached the levels found in developed nations.

Clinical profile of HIV infected patients attending a HIV referral clinic in Pune, India.

BACKGROUND & OBJECTIVES: Human immunodeficiency virus (HIV) has infected several million individuals in India. Various interventions have been implemented for early detection and prevention of transmission of HIV infection. This has progressively changed the clinical profile of HIV infected individuals and this study documents the clinical presentation of individuals positive for HIV in 2010, in Pune, Maharashtra, India. METHODS: This cross-sectional study included subjects who had come to the HIV referral clinic for HIV testing from January to December 2010. Children as well as individuals with indeterminate HIV result were excluded from the study, and data for 1546 subjects were finally analysed. RESULTS: The HIV positivity rate among all referred cases for the year 2010 was 35 per cent (male 55% and females 45%). The median age (Q1, Q3) was 31 (25.75, 39) yr. The median CD4 cell count for all HIV infected individuals (whose CD4 count was available n=345) was 241 cells/µl and for asymptomatic HIV infected individuals was 319 cells/µl. There were 673 (43.5%) symptomatic and 873 (56.5%) asymptomatic participants. Fever, breathlessness, cough with expectoration, weight loss, loss of appetite, generalized weakness, pallor and lymphadenopathy (axillary and cervical) were found to be associated (P<0.001) with HIV positivity. On multivariate analysis, history of Herpes zoster [AOR 11.314 (6.111-20.949)] and TB [AOR 11.214 (6.111-20.949)] was associated with HIV positivity. INTERPRETATION & CONCLUSIONS: Signs and symptoms associated with HIV positivity observed in this study can be used by health care providers to detect HIV infection early. Moreover, similar to HIV testing in patients with tuberculosis, strategies can be developed for considering Herpes zoster as a predictor of HIV infection.

Rifapentine-proliposomes for inhalation: in vitro and in vivo toxicity.

BACKGROUND: Oral therapy for pulmonary tuberculosis (TB) treatment suffers from the limitation of hepatic metabolism leading insufficient concentration of antitubercular (anti-TB) drugs in alveolar macrophage which harbors Mycobacterium tuberculosis (MTB). Targeted aerosol delivery of antituberculous drug to lung is efficient for treating local lung TB infection. OBJECTIVE: The present study was aimed to evaluate rifapentine (RPT) loaded proliposomal dry powder for inhalation (RLDPI) for anti-TBactivity and cytotoxicity in vitro. In vivo toxicity study was also undertaken in Wistar rats to determine safe concentration of RLDPI for administration. MATERIALS AND METHODS: Anti-TB activity of developed RLDPI was assessed using drug susceptibility testing (DST) on Mycobacteria growth indicator tube (MGIT) method. In vitro cytotoxicity was performed in A549 cell lines and IC50 values were used to compare the cytotoxicity of formulation with pure RPT. In vivo repeated dose toxicity study was undertaken using Wistar rats at three different doses for 28-days by intratracheal insufflations method. RESULTS: The results of DST study revealed sensitivity of tubercle bacteria to RLDPI at concentration equivalent to 10 µg/mL of RPT. This study confirmed anti-TB potential of RPT in spray-dried RLDPI, though the spray drying method is reported to reduce activity of drugs. Cytotoxicity study in A549 cells demonstrated that RPT when encapsulated in liposomes as RLDPI was safe to cells as compared to pure RPT. In vivo toxicity study revealed that RPT in the form of RLDPI was safe at 1 and 5 mg/kg dose. However, mortality was seen at higher dose (10 mg/kg), possibly because of liver and kidney damage. CONCLUSION: Thus, these studies demonstrated safety of RLDPI for the treatment of pulmonary TB.

High rates of reinfection and incidence of bacterial sexually transmitted infections in a cohort of female sex workers from two Indian cities: need for different STI control strategies?

BACKGROUND: Female sex workers (FSWs) in India are provided a standardised package of clinical interventions for management of sexually transmitted infections (STIs). A study was conducted among FSWs at known high STI prevalence sites to determine the effectiveness of the service package. METHODS: A cohort of FSW clinic attendees in two cities, Hyderabad and Mumbai, were enrolled and followed up from October 2008 to November 2009. At each visit, behavioural and clinical data were obtained and vaginal swabs collected for laboratory testing of cervical infections (gonorrhoea and chlamydia). RESULTS: 417 participants were enrolled, of whom 360 attended at least a follow-up visit. Prevalence of cervical infections did not change between the baseline and final visits (27.7% and 21.3% respectively, p=0.08) in spite of presumptive treatment at baseline and syndromic management at all visits. The proportion of asymptomatic cervical infections increased from 36% at baseline to 77% at the final visit. Incidence rate of cervical infections was high (85.6/100 person years) and associated with a prevalent cervical infection at baseline (HR=2.7, p<0.001) and inconsistent condom use with non-commercial partners (HR=2.5, p=0.014). CONCLUSIONS: High rates of STIs persisted despite the interventions due to poor condom use, minimal partner treatment, and high prevalence and incidence of STIs with a large proportion of asymptomatic infections. High-prevalence FSW sites in India need to design more effective partner treatment strategies and consider increasing the frequency of presumptive treatment as a temporary measure for quickly reducing STI prevalence, with renewed emphasis on consistent condom use with all partners.

Use of first line antiretroviral therapy from a free ART programme clinic in Pune, India - a preliminary report.

BACKGROUND & OBJECTIVES: The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India. METHODS: Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients. results: One hundred and forty two patients with median CD4 count of 109 cells/µl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/µl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8). INTERPRETATION & CONCLUSIONS: The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.

Biofilm production in oral Candida isolates from HIV-positive individuals from Pune, India.

Biofilm formation is implicated as a potential virulence factor in Candida species and carries important clinical repercussions because of their increased resistance to antifungal treatment, ability to withstand host defences and to serve as a reservoir for continuing infections. The present study was undertaken to determine the biofilm production among oral Candida isolates from HIV-positive and HIV-negative individuals from Pune, India. Biofilm formation was determined using the spectrophotometric or microtitre plate method in 182 Candida isolates, of which 154 were from HIV-positive and 28 were from HIV-negative individuals. A total of 63.2% of the Candida isolates were biofilm producers. Significantly increased biofilm forming abilities both qualitatively as well as quantitatively were observed in Candida isolates from HIV-positive individuals (66.2%) compared to isolates from HIV-negative ones (46.4%), (P- 0.041). Eighty-one (59.6%) C. albicans isolates and 34 (73.9%) non -C. albicans Candida (NCAC) showed biofilm positivity. The NCAC showed significantly greater intensity of biofilm formation compared to the C. albicans, P- 0.032. Our results thus show the enhanced biofilm forming abilities of oral Candida isolates from HIV-infected individuals compared to HIV-uninfected ones and highlight the important role played by biofilm formation in the pathogenesis of NCAC isolates.

An exploration of elevated HIV and STI risk among male sex workers from India.

BACKGROUND: Men who have sex with men (MSM) who also report transactional sex (male sex workers or MSWs) are known to be at higher risk for HIV and sexually transmitted infections (STIs). The study aimed to profile socio-demographic characteristics and risk factors associated with high HIV prevalence among MSWs. METHODS: A cross-sectional study was conducted in 2008-9 among 483 high-risk MSM who attended STI clinics at Mumbai and Hyderabad, two large cities in India. RESULTS: About 70% of the MSM reported transactional sex. As compared to other MSM, MSWs had more male partners (8.9 versus 2.5, p < 0.001) and higher rates of receptive anal sex (96% versus 72%, p < 0.001). HIV prevalence among MSWs and other MSM was 43.6% and 18.1% respectively. HIV prevalence among MSWs was associated with the place of residence (MSWs from Hyderabad were 7.3 times more likely to be infected), positive syphilis serology (3.8 times) and duration of sex work (increased by 8% for every additional year). CONCLUSION: The study showed that MSWs are at high risk for HIV acquisition/transmission, which highlights the need for intensified interventions for personalized risk-reduction counselling and STI screening. Newer biomedical interventions such as pre-exposure prophylaxis and treatment as prevention could also be considered.

Comparison of visual inspection with acetic acid and cervical cytology to detect high-grade cervical neoplasia among HIV-infected women in India.

Human immunodeficiency virus (HIV)-infected women in India and other developing country settings are living longer on antiretroviral therapy, yet their risk for human papillomavirus (HPV)-induced cervical cancer remains unabated because of lack of cost-effective and accurate secondary prevention methods. Visual inspection after application of dilute acetic acid on the cervix (VIA) has not been adequately studied against the current standard: conventional cervical cytology (Pap smears) among HIV-infected women. We evaluated 303 nonpregnant HIV-infected women in Pune, India, by simultaneous and independent screening with VIA and cervical cytology with disease ascertainment by colposcopy and histopathology. At the cervical intraepithelial neoplasia (CIN2+) disease threshold, the sensitivity, specificity and positive and negative predictive value estimates of VIA were 80, 82.6, 47.6 and 95.4% respectively, compared to 60.5, 59.6, 22.4 and 88.7% for the atypical squamous cells of undetermined significance or severe (ASCUS+) cutoff on cytology, 60.5, 64.6, 24.8 and 89.4% for the low-grade squamous intraepithelial cells or severe (LSIL+) cutoff on cytology and 20.9, 96.0, 50.0 and 86.3% for high-grade squamous intraepithelial lesion or severe (HSIL+) cutoff on cytology. A similar pattern of results was found for women with the presence of carcinogenic HPV-positive CIN2+ disease, as well as for women with CD4+ cell counts <200 and <350 µL(-1) . Overall, VIA performed better than cytology in this study with biologically rigorous endpoints and without verification bias, suggesting that VIA is a practical and useful alternative or adjunctive screening test for HIV-infected women. Implementing VIA-based screening within HIV/acquired immunodeficiency syndrome care programs may provide an easy and practical means of complementing the highly anticipated low-cost HPV-based rapid screening tests in the near future, thereby contributing to improve program effectiveness of screening.

Antimicrobial susceptibility testing, auxotyping, and serotyping of Neisseria gonorrhoeae strains isolated in India.

Sixty-four Neisseria gonorrhoeae strains isolated from patients attending sexually transmitted disease clinics at Pune and Delhi between January 2007 and June 2008, were subjected to antimicrobial susceptibility testing, auxotyping, and serotyping. We observed 6 antibiotic resistance patterns, 6 auxotypes, 3 serogroups, and 17 serovars. The combination of auxotyping and serotyping is a potential useful method for typing N. gonorrhoeae as a result of high discriminatory index, rapidity, ease, and relatively lower cost.

Genital ulcer disease in India: etiologies and performance of current syndrome guidelines.

BACKGROUND: In India, genital ulcer disease (GUD) syndrome is clinically classified as herpetic or nonherpetic and managed accordingly; laboratory support is unavailable at most health facilities. We undertook a study to determine the etiology of GUDs in men presenting to sexually transmitted infection (STI) clinics and assess the performance of the national algorithm for syndromic management of herpetic and nonherpetic GUDs in India. METHOD: A cross-sectional study was conducted among men with complaints of genital ulcers attending 8 STI clinics in 4 states. Ulcer swabs were collected and tested by the multiplex polymerase chain reaction method to determine the etiology of GUD. RESULTS: Of the 194 men recruited, etiology was confirmed in 121 GUD cases (62%). Herpes simplex virus (48%) was the most common etiological agent identified, followed by Treponema pallidum (23%) and mixed infections (9%). One case of Haemophilus ducreyi was confirmed in this series. The overall sensitivity and specificity of the national syndromic management algorithm for GUD were 68% and 52%, respectively. Using the national algorithm, 52 (42%) cases clinically misclassified as either herpetic (18 cases) or nonherpetic (34 cases) GUD resulting in incorrect treatment. CONCLUSIONS: Our findings suggest a revision of existing national STI treatment guidelines in India to include treatment of syphilis infections of all GUD patients. Periodic studies are required to monitor changing spectrum of GUD etiologies in India.

Adherence to buccal epithelial cells, enzymatic and hemolytic activities of Candida isolates from HIV-infected individuals.

Candida spp., along with other microorganisms are usually found in the normal flora of the human oral mucosa. However in HIV-infected individuals these yeasts can become opportunistic pathogens and lead to mucosal infections. The transformation from a harmless commensal to a virulent pathogen under conditions of dysfunctional host defense system is attributable to an extensive repertoire of selectively expressed virulence determinants. The present study was undertaken to analyze the production of four important virulence factors viz. adherence to buccal epithelial cells (BEC), proteinase activity, phospholipase activity and hemolysis, and to evaluate the correlation between these virulence factors in 65 Candida isolates from HIV-infected individuals with oral candidiasis. A total of 95.3%, 67.7%, 41.5% and 100% of the Candida isolates showed adherence to BEC, and proteinase, phospholipase and hemolytic activities, respectively. Production of proteinase and phospholipase enzymes was seen in 89.7% and 59.0% of C. albicans isolates and 34.6% and 15.4% of non-Candida albicans Candida (NAC) isolates, respectively. C. albicans showed significantly greater level of virulence factor expression with regards to adherence to BEC (P < 0.001), phospholipase production (P < 0.044) and hemolysis (P = 0.037) as compared to NAC. A correlative relationship between proteinase activity and adherence to BEC, as well as phospholipase production was noted.

Mortality in HIV infected individuals in Pune, India.

BACKGROUND & OBJECTIVES: With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India. METHODS: A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death. RESULTS: Median CD4 count in study participants was 218 cells/µl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/µl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09), P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively]. Interpretation & conclusions : High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme.

Impact of targeted interventions on heterosexual transmission of HIV in India.

BACKGROUND: Targeted interventions (TIs) have been a major strategy for HIV prevention in India. We evaluated the impact of TIs on HIV prevalence in high HIV prevalence southern states (Tamil Nadu, Karnataka, Andhra Pradesh and Maharashtra). METHODS: A quasi-experimental approach was used to retrospectively compare changes in HIV prevalence according to the intensity of targeted intervention implementation. Condom gap (number of condoms required minus condoms supplied by TIs) was used as an indicator of TI intensity. Annual average number of commercial sex acts per female sex worker (FSW) reported in Behavioral Surveillance Survey was multiplied by the estimated number of FSWs in each district to calculate annual requirement of condoms in the district. Data of condoms supplied by TIs from 1995 to 2008 was obtained from program records. Districts in each state were ranked into quartiles based on the TI intensity. Primary data of HIV Sentinel Surveillance was analyzed to calculate HIV prevalence reductions in each successive year taking 2001 as reference year according to the quartiles of TI intensity districts using generalized linear model with logit link and binomial distribution after adjusting for age, education, and place of residence (urban or rural). RESULTS: In the high HIV prevalence southern states, the number of TI projects for FSWs increased from 5 to 310 between 1995 and 2008. In high TI intensity quartile districts (n = 30), 186 condoms per FSW/year were distributed through TIs as compared to 45 condoms/FSW/year in the low TI intensity districts (n = 29). Behavioral surveillance indicated significant rise in condom use from 2001 to 2009. Among FSWs consistent condom use with last paying clients increased from 58.6% to 83.7% (p < 0.001), and among men of reproductive age, the condom use during sex with non-regular partner increased from 51.7% to 68.6% (p < 0.001). A significant decline in HIV and syphilis prevalence has occurred in high prevalence southern states among FSWs and young antenatal women. Among young (15-24 years) antenatal clinic attendees significant decline was observed in HIV prevalence from 2001 to 2008 (OR = 0.42, 95% CI 0.28-0.62) in high TI intensity districts whereas in low TI intensity districts the change was not significant (OR = 1.01, 95% CI 0.67-1.5). CONCLUSION: Targeted interventions are associated with HIV prevalence decline.