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.

Rates and determinants of incidence and clearance of cervical HPV genotypes among HIV-seropositive women in Pune, India.

BACKGROUND: Several studies in recent years have documented the genotype-specific prevalence of HPV infection and wide diversity and multiplicity of HPV genotypes among HIV-seropositive women. Yet, information on changes in HPV genotype-specific incidence and clearance rates over time, and their correlation with clinical or immunologic factors among HIV-seropositive women is scarce. OBJECTIVES: We conducted a prospective study to investigate the incidence and clearance rates of cervical HPV genotypes among HIV-seropositive women in India and expand the evidence base in this area of research. STUDY DESIGN: Cervical samples were collected from n=215 HIV-seropositive women in Pune, India who underwent two screening visits separated by a median of 11-months (interquartile range: 8-18 months). HPV genotypes were determined by Roche Linear Array HPV assay. Individual genotype-specific and carcinogenicity-grouping-specific HPV incidence and clearance rates were calculated and the associations between incidence/clearance and age and HIV-related metrics were explored. RESULTS: Incidence and clearance rates for 'any HPV' and 'carcinogenic HPV' genotypes were 11.1 and 18.3, and 6.7 and 33.8, per 100 person-years, respectively. Incidence and clearance rates for HPV genotypes of alpha-9 species (HPV16, HPV31, HPV33, HPV35, HPV52 and HPV58) and alpha-7 species (HPV18, HPV39, HPV45, HPV59 and HPV68) were 5.8 and 2.04, and 32.1 and 53.5, per 100 person-years, respectively. Clearance of any HPV type was associated with increasing age of participants (odds ratio: 1.08, 95%CI: 1.004-1.17), although the association marginally lost its statistical significance when adjusted for CD4 counts and antiretroviral therapy status. CONCLUSIONS: Genotype-specific clearance rates of HPV were higher than corresponding incidence rates. The suggestion of a positive associations of increasing age with HPV clearance points to the need for etiologic studies on age-related hormonal changes on clearance of cervical HPV infection.

HIV and cancer registry linkage identifies a substantial burden of cancers in persons with HIV in India.

We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent.Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6-6.8], 17.7 [95% CI 15.8-19.8], and 11.5 [95% CI 10-12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8-17.2] and 22.6 [95% CI 14.3-33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8-30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen.Our study demonstrates the feasibility of using probabilistic record-linkage to study cancer/other comorbidities among PLHIV in India and provides preliminary population-based estimates of cancer risks in PLHIV in India. Our results, suggesting a potentially substantial burden and slightly different spectrum of cancers among PLHIV in India, support efforts to conduct multicenter linkage studies to obtain precise estimates and to monitor cancer risk in PLHIV in India.

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

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

External quality control for dried blood spot-based C-reactive protein assay: experience from the indonesia family life survey and the longitudinal aging study in India.

Measurement of C-reactive protein (CRP), a marker of inflammation, in dried blood spots has been increasingly incorporated into community-based social surveys internationally. Although the dried blood spot-based CRP assay protocol has been validated in the United States, it remains unclear whether laboratories in other less-developed countries can generate CRP results of similar quality. We therefore conducted external quality monitoring for dried blood spot-based CRP measurement for the Indonesia Family Life Survey and the Longitudinal Aging Study in India. Our results show that dried blood spot-based CRP results in these two countries have excellent and consistent correlations with serum-based values and dried blood spot-based results from the reference laboratory in the United States. Even though the results from duplicate samples may have fluctuations in absolute values over time, the relative order of C-reactive protein levels remains similar, and the estimates are reasonably precise for population-based studies that investigate the association between socioeconomic factors and health.

Evaluation of a diagnostic algorithm for sputum smear-negative pulmonary tuberculosis in HIV-infected adults.

BACKGROUND: The Revised National TB Control Program bases diagnosis of tuberculosis (TB) on sputum smear examination and response to a course of antibiotics, whereas World Health Organization recommends early chest radiography [chest x-ray (CXR)] for HIV-infected symptomatic patients. We evaluated the utility of initial CXR in the diagnostic algorithm for symptomatic HIV-infected patients with negative sputum smears. METHODS: HIV-infected ambulatory patients with cough or fever of ≥2 weeks and 3 sputum smears negative for acid-fast bacilli were enrolled in Chennai and Pune, India, between 2007 and 2009. After a CXR and 2 sputum cultures, a course of broad-spectrum antibiotics was given and patients were reviewed after 14 days. Sensitivity, specificity, positive and negative predictive values of symptoms, CXR, and various combinations for diagnosing pulmonary tuberculosis (PTB) were determined, using sputum culture as gold standard. RESULTS: Five hundred four patients (330 males; mean age: 35 years; median CD4: 175 cells per cubic millimeter) were enrolled. CXR had a sensitivity and specificity of 72% and 57%, respectively, with positive predictive value (PPV) of 21% and negative predictive value (NPV) of 93% to diagnose PTB. TB culture was positive in 49 of 235 patients (21%) with an abnormal initial CXR and 19 of 269 patients (7%) with a normal CXR (P < 0.001). Sensitivity and specificity of cough ≥2 weeks for predicting PTB was 97% and 6%, with PPV and NPV of 14% and 94%, respectively. CONCLUSIONS: Although moderately sensitive, basing a diagnosis of TB on initial CXR leads to overdiagnosis. An absence of weight loss had a high NPV, whereas none of the combinations had a good PPV. A rapid and accurate diagnostic test is required for HIV-infected chest symptomatic.

HPV genotype distribution in cervical intraepithelial neoplasia among HIV-infected women in Pune, India.

BACKGROUND: The distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer. METHODS: HIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint. RESULTS: CIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and 'carcinogenic' HPV genotypes were present in 35.3% (98/278) HIV-infected women. 'Possibly carcinogenic' and 'non/unknown carcinogenic' HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (≥ 2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple 'carcinogenic' HPV genotypes were present in just over a quarter (27.8%) of women with 'carcinogenic' HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with 'carcinogenic' HPV type detection were reporting ≥ 2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy. CONCLUSION: HPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.

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.

Prevalence and predictors of colposcopic-histopathologically confirmed cervical intraepithelial neoplasia in HIV-infected women in India.

BACKGROUND: Prevalence estimates of cervical intraepithelial neoplasia (CIN) among HIV-infected women in India have been based on cervical cytology, which may have underestimated true disease burden. We sought to better establish prevalence estimates and evaluate risk factors of CIN among HIV-infected women in Pune, India using colposcopy and histopathology as diagnostic tools. METHODOLOGY: Previously unscreened, non-pregnant HIV-infected women underwent cervical cancer screening evaluation including standardized diagnostic colposcopy by a gynecologist. Histopathologic confirmation was conducted among consenting women with clinical suspicion of CIN. The prevalence of CIN was evaluated by a composite diagnosis based on colposcopy and histopathology results. Multivariable ordinal logistic regression analysis was conducted to determine independent predictors of increasing severity of CIN. RESULTS: The median age of the n = 303 enrolled HIV-infected women was 30 years (interquartile range, 27-34). A majority of the participants were widowed or separated (187/303, 61.7%), more than one-third (114/302, 37.7%) were not educated beyond primary school, and nearly two-thirds (196/301, 64.7%) had a family per capita income of <1,000 Indian Rupees ( approximately US$22) per month. Cervical high-risk HPV-DNA was detected in 41.7% (124/297) of participants. The composite colposcopic-histopathologic diagnoses revealed no evidence of CIN in 220 out of 303 (72.6%) women, CIN1 in 33/303 (10.9%), CIN2 in 31/303 (10.2%), CIN3 in 18/303 (5.9%) and 1 (0.3%) woman was diagnosed with ICC. Thus, over a quarter of the participants [83/303: 27.7% (95% CI: 22.7-33.1)] had > or =CIN1 lesions and a sixth [50/303: 16.5% (95% CI: 12.2-21.9)] had evidence of advanced (> or =CIN2) neoplastic disease. The independent predictors of increasing severity of CIN as revealed by a proportional odds model using multivariable ordinal logistic regression included (i) currently receiving antiretroviral therapy [adjusted odds ratios (aOR): 2.24 (1.17, 4.26), p = 0.01] and (ii) presence of cervical high-risk HPV-DNA [aOR: 1.93 (1.13, 3.28), p = 0.02]. CONCLUSIONS: HIV-infected women in Pune, India have a substantial burden of cervical precancerous lesions, which may progress to invasive cervical cancer unless appropriately detected and treated. Increased attention should focus on recognizing and addressing this entirely preventable cancer among HIV-infected women, especially in the context of increasing longevity due to antiretroviral therapy.

Declining HIV incidence among patients attending sexually transmitted infection clinics in Pune, India.

OBJECTIVE: A recent report suggesting declining HIV transmission rates in southern India has been based on HIV seroprevalence data to estimate HIV incidence. We analyzed HIV incidence rates among 3 cohorts (male, female non-sex worker, female sex worker [FSW]) presenting to sexually transmitted infection (STI) clinics in Pune, India over 10 years. METHODS: Between 1993 and 2002, consenting HIV-uninfected individuals were enrolled in a prospective study of the risks for HIV seroconversion. Standardized HIV incidence estimates were calculated separately for the 3 cohorts. RESULTS: HIV acquisition risk declined by more than 70% for FSWs (P = 0.02) and men (P < 0.001) attending the STI clinics. There was no significant reduction in HIV incidence among women attending STI clinics (P = 0.74). The decline in HIVacquisition risk among male patients with STIs was associated with an increase in reported condom use with recent FSW contact and a decrease in genital ulcer disease. CONCLUSIONS: We report the first direct evidence for a decline in HIV incidence rates in FSWs and male patients with STIs over time. The lack of change in HIV infection risk among non-sex worker women highlights the need for additional targeted HIV prevention interventions.

Same-sex behavior and high rates of HIV among men attending sexually transmitted infection clinics in Pune, India (1993-2002).

OBJECTIVES: To determine HIV/sexually transmitted infection (STI) prevalence, trends, and risk behaviors of men who have sex with men (MSM) and compare these with those of non-MSM attending STI clinics in Pune, India over a 10-year period. DESIGN: Cross-sectional. METHODS: From 1993 through 2002, men attending 3 STI clinics in Pune underwent HIV/STI screening. Demographic, risk behavior, clinical, and laboratory data were collected using standardized questionnaires and laboratory procedures. RESULTS: Of 10,785 men screened, 708 (6.6%) were MSM. Among these 708 MSM, 189 (31.7%) had 10 or more lifetime partners, 253 (35.7%) were married, 163 (23.1%) had sex with a hijra (eunuch), and 87 (13.3%) had exchanged money for sex. A total of 134 (18.9%) were HIV-positive, 149 (21.5%) had genital ulcer disease (GUD), 37 (5.8%) had syphilis, and 29 (4.3%) had gonorrhea (GC). Over the decade, neither HIV nor GC prevalence changed among MSM (P = 0.7), but syphilis and GUD decreased significantly (P < 0.0001). Compared with non-MSM, MSM were more likely to initiate sexual activity at age <16 years, to have >10 lifetime partners, to have sex with a hijra, and to use condoms regularly, but they did not differ significantly in HIV prevalence and had a lower prevalence of GC, GUD, and syphilis. Independent factors associated with HIV among MSM were employment (adjusted odds ratio [AOR] = 3.08; P = 0.02), history of GUD (AOR = 1.86; P = 0.003), and syphilis (AOR = 2.09; P = 0.05). CONCLUSIONS: Same-sex and high-risk sexual behaviors are prevalent among men attending STI clinics in India. Although syphilis and GUD rates decreased, HIV prevalence remained high during the decade, highlighting the importance of additional targeted efforts to reduce HIV risk among all men, including MSM, in India.

Male circumcision and risk of HIV-1 and other sexually transmitted infections in India.

Circumcised men have a lower risk of HIV-1 infection than uncircumcised men. Laboratory findings suggest that the foreskin is enriched with HIV-1 target cells. However, some data suggest that circumcision could simply be a marker for low-risk behaviours. In a prospective study of 2298 HIV-uninfected men attending sexually transmitted infection clinics in India, we noted that circumcision was strongly protective against HIV-1 infection (adjusted relative risk 0.15; 95% CI 0.04-0.62; p=0.0089); however, we noted no protective effect against herpes simplex virus type 2, syphilis, or gonorrhoea. The specificity of this relation suggests a biological rather than behavioural explanation for the protective effect of male circumcision against HIV-1.

Recent herpes simplex virus type 2 infection and the risk of human immunodeficiency virus type 1 acquisition in India.

To estimate the impact of prevalent and incident herpes simplex virus type 2 (HSV-2) infection on the acquisition of human immunodeficiency virus type 1 (HIV-1), stored serum samples from a cohort of 2732 HIV-1-seronegative patients attending 3 sexually transmitted infection clinics and 1 reproductive tract infection clinic in Pune, India, were screened for HSV-2-specific antibodies. Incident HSV-2 infection was defined serologically as "recent" if a negative result of testing for HSV-2 could be documented within the previous 6 months or "remote" if >6 months had elapsed since the last negative test result. The prevalence of HSV-2 at enrollment was 43%. The HSV-2 incidence was 11.4 cases/100 person-years, and the HIV-1 incidence was 5.8 cases/100 person-years. The adjusted hazard ratios of HIV-1 acquisition from exposure to HSV-2 infection were 1.67 for prevalent HSV-2, 1.92 for remote incident HSV-2, and 3.81 for recent incident HSV-2. Recent incident HSV-2 infection was associated with the highest risk of HIV-1 in this study, which suggests that prevention of HSV-2 infection may reduce the risk of HIV-1 acquisition.

Incident HIV infection among men attending STD clinics in Pune, India: pathways to disparity and interventions to enhance equity.

Systematic disparities in rates of HIV incidence by socioeconomic status were assessed among men attending three sexually transmitted disease (STD) clinics in Pune, India, to identify key policy-intervention points to increase health equity. Measures of socioeconomic status included level of education, family income, and occupation. From 1993 to 2000, 2,260 HIV-uninfected men who consented to participate in the study were followed on a quarterly basis. Proportional hazards regression analysis of incident HIV infection identified a statistically significant interaction between level of education and genital ulcer disease. Compared to the lowest-risk men without genital ulcer disease who completed high school, the relative risk (RR) for acquisition of HIV was 7.02 (p < 0.001) for illiterate men with genital ulcer disease, 3.62 (p < 0.001) for men with some education and genital ulcer disease, and 3.02 (p < 0.001) for men who completed high school and had genital ulcer disease. For men with no genital ulcer disease and those with no education RR was 1.09 (p = 0.84), and for men with primary/middle school it was 1.70 (p = 0.03). The study provides evidence that by enhancing access to treatment and interventions that include counselling, education, and provision of condoms for prevention of STDs, especially genital ulcer disease, among disadvantaged men, the disparity in rates of HIV incidence could be lessened considerably. Nevertheless, given the same level of knowledge on AIDS, the same level of risk behaviour, and the same level of biological co-factors, the most disadvantaged men still have higher rates of HIV incidence.

Rapid disease progression in human immunodeficiency virus type 1-infected seroconverters in India.

To determine if the early immunological and virological events of HIV infection are unique in a setting with limited access to health care and HIV-1 subtype C infection, we undertook a prospective cohort study to characterize the early natural history of HIV viral load and CD4(+) T lymphocyte counts in individuals with recent HIV seroconversion in India. CD4(+) T lymphocyte counts were prospectively measured for up to 720 days in 46 antiviral drug-naive persons with very early HIV infection, documented by HIV antibody seroconversion. HIV viral RNA levels were measured subsequently on reposited plasma samples from these same time points. The median viral load "set point" for Indian seroconverters was 28,729 RNA copies/ml. The median CD4(+) cell count following acute primary HIV infection was 644 cells/mm(3). Over the first 2 years since primary infection, the annual rate of increase in HIV viral load was +8274 RNA copies/ml/year and the annual decline in CD4 cell count was -120 cells/year. Although the viral "set point" was similar, the median trajectory of increasing viral load in Indian seroconverters was greater than what has been reported in untreated HIV seroconverters in the United States. These data suggest that the more rapid HIV disease progression described in resource-poor settings may be due to very early virological and host events following primary HIV infection. A rapid increase in viral load within the first 2 years after primary infection may have to be considered when applying treatment guidelines for antiretroviral therapy and opportunistic infection prophylaxis.