Population and dyadic-based seroincidence of herpes simplex virus-2 and syphilis in southern India.

OBJECTIVES: Herpes simplex virus-2 (HSV-2) and syphilis are associated with increased risk of HIV, highlighting the importance of understanding their transmission dynamics. In India, most studies of HSV-2 and syphilis incidence are in high-risk populations and may not accurately reflect infectious activity. In this study, we aim to define HSV-2/syphilis incidence and risk factors in a population sample. METHODS: We conducted a longitudinal population-based survey in Andhra Pradesh, India, in two rounds: 2004-2005 and 2010-2011. Sociodemographic and behavioural data were collected, and dried blood spots tested for HSV-2 and Treponema pallidum IgG. After calculating sexually transmitted infection (STI) incidence, associated factors were assessed using modified Poisson regression and within-couple transmission rates modelled using seroconcordance/discordance data. RESULTS: 12,617 adults participated at baseline with 8494 at follow-up. Incidence of HSV-2 and syphilis per 1000 person-years was 25.6 (95% CI 24.1 to 27.2) and 3.00 (95% CI 2.52 to 3.54). Incidence of HSV-2 was higher in women vs. men (31.1 vs. 20.2) and in rural vs urban residents (31.1 vs 19.0) (p<0.05 for both). STI seroincidence increased in a step-wise fashion with age and was associated with spousal seropositivity for both sexes (incidence rate ratio (IRR) 2.59 to 6.78). Within couples the rate of transmission per 1000 couple-years from men to women vs. women to men was higher for HSV-2 (193.3 vs. 119.0) compared with syphilis (27.6 vs. 198.8), p<0.05 for both. CONCLUSIONS: HSV-2 has higher incidence among subpopulations such as women, rural residents and older-aged individuals, suggesting a need for more generalised STI prevention approaches among populations traditionally considered low risk.

HIV incidence from the first population-based cohort study in India.

BACKGROUND: Understanding about who acquires new HIV infection and the determinants of why some persons get infected and others do not is fundamental to controlling HIV in the population. We assess HIV incidence and its associations in the population of a high HIV burden district in Andhra Pradesh state in southern India by a population-based longitudinal cohort study. METHODS: We re-surveyed a population-based cohort of 12,617 adults in Guntur district of Andhra Pradesh for which we had reported a baseline HIV prevalence of 1.72% (rural 1.64%, urban 1.89%) among the 15-49 years age group in 2004-2005. We conducted interviews to assess risk behaviour and performed HIV testing again in 2010-2011. We assessed the rate of new HIV infection and its associations using multiple logistic regression. RESULTS: The participation rate in the follow-up was 74.9% and 63.9% of the baseline rural and urban samples, respectively. Over a mean follow-up of 5.63 years, the incidence of HIV was 1.26 per 1000 person-years (95% CI 0.83-1.69), after adjusting for slight compositional bias in the follow-up sample. The incidence per 1000 person-years was higher among rural men (1.68) than urban men (0.85), and among rural women (1.28) than urban women (0.54). The strongest association with incidence was a HIV positive spouse in the baseline for both men (odds ratio 266, 95% CI 62-1137) and women (odds ratio 28, 95% CI 9-88). Among men the other significant associations with HIV incidence were frequent use of condom for sex over the past 6 months, non-circumcision, more than one lifetime woman sex partner or ever visited sex worker, and transport-related occupation; for women the other significant associations were having had HIV testing other than antenatal check-up, previously married but currently not, and tobacco use. CONCLUSION: These first population-based cohort incidence data from India suggest that rural areas of high HIV burden states would need more attention to prevent new HIV infections, and that spouses of HIV positive persons and some other risk groups need to be targeted more effectively by HIV prevention programmes.

Application of Polymerase Chain Reaction to Detect HIV-1 DNA in Pools of Dried Blood Spots.

Nucleic acid tests that detect HIV infection at an early phase are available and have been applied on individual dried blood spot (DBS). The present study was undertaken with an aim to evaluate the feasibility of performing PCR for HIV-1 DNA on pools of DBS as an alternative to individual testing. Standardization of PCR by a modified Amplicor HIV-1 DNA assay version 1.5 (Roche molecular diagnostics, USA), on pooled DBS was performed using five confirmed HIV reactive samples with known low viral load of HIV-1 and HIV non-reactive samples in pools of 5, 10 and 20 DBS. After successful standardization of pooling procedure, a total of 183 pools (of 10 DBS each) were prepared from 1,823 DBS samples, collected from a population-based study that tested negative for HIV antibodies and p24 antigen. All these pools were screened for HIV-1 DNA by the Amplicor assay. Standardization of pooling procedure indicated that pooling of 10 DBS gave an optimum result. Out of 183 pools tested, one pool of 10 samples was positive and of these ten DBS that were tested individually to identify the positive DBS, one sample was detected to be positive for HIV-1 DNA. Our study demonstrates that PCR for HIV-1 DNA can be successfully performed on pools of DBS. However, this may be needed only on specialized studies of HIV and not for routine epidemiology studies as only a very small fraction of cases would be missed if only antibody/antigen testing were done.

Population-based seroprevalence of HSV-2 and syphilis in Andhra Pradesh state of India.

BACKGROUND: Understanding the prevalence and risk factors for common causes of ulcerative genital disease in the general population would inform current STI syndromic management and HIV testing strategies in high HIV prevalence regions of India. METHODS: Persons 15-49 years old from 32 rural and 34 urban clusters were sampled using a stratified random method to represent adults in the high HIV prevalence Guntur district in Andhra Pradesh state. Interviews were conducted and dry blood spots were collected on 12,617 study participants. Testing for HSV-2 and syphilis was performed. RESULTS: Adjusted HSV-2 and syphilis seroprevalence rates were 4.70% and 2.08% for men and 7.07% and 1.42% for women. For men, tattooing, >3 lifetime sex partners, tobacco use, and sex with men in the past 6 months were associated with HSV-2 or syphilis (ORs, 1.66-2.95, p < 0.05). Male circumcision was positively associated with HSV-2 infection (OR, 1.37, p = 0.028) though this could be due to residual confounding. In women, greater than one lifetime partner remained significantly associated with HSV-2 in multivariate analysis (OR, 2.61; 95% CI, 1.39-4.87). Among all behavioral risk factors and other covariates in women and men, HIV infection exhibited the strongest association with HSV-2 and syphilis (ORs, 8.2-14.2, p < 0.001). The proportion of individuals with HSV-2 who were HIV infected was less than the proportion with syphilis who were HIV infected (11.8% vs. 22.7%; p = 0.001). CONCLUSIONS: Nearly one in four persons surveyed in this population-based study that were seroprevalent for syphilis, were also HIV infected. Common population risk factors for syphilis, HSV-2 and HIV and high rates of co-seroprevalence suggest that HIV testing, STI testing and service strategies for these would benefit from direct linkage in India.

Application of human immunodeficiency virus type 1 BED enzyme immunoassay on dried blood spots in India.

Dried blood spots (DBSs) on filter paper are being used increasingly in population-based human immunodeficiency virus (HIV) studies. This study evaluated the application of a BED enzyme immunoassay (EIA) on DBSs to estimate HIV incidence in a population-based study in India. The Calypte HIV-1 BED Incidence EIA was performed on 224 HIV-1-positive DBS samples, after screening 12 617 individuals from a population-based sample in Guntur district in the southern Indian state of Andhra Pradesh. The number of recently infected HIV cases was identified using this BED assay and was used to estimate the annual HIV incidence rate based on calculations and adjustment formulae suggested by the Centers for Disease Control and Prevention (CDC). The updated BED data management software provided by the CDC was used for analyses. Of the 224 HIV-1 antibody-positive DBS samples, 29 (12.95 %) were estimated by the BED HIV-1 assay to have been infected within the past 155 days. After adjusting for age, gender and rural/urban distribution of the population, the annual incidence rate of HIV-1 infection was estimated to be 0.32 % (95 % confidence interval 0.20-0.44 %). This annual incidence was 18.6 % of the HIV prevalence of 1.72 % in this study. Thus, the BED assay revealed a higher incidence of HIV in this study than was expected from the prevalence. Correlation of the BED assay with panel testing and longitudinal incidence data in the Indian population is needed to calibrate it for use in India.

Risk factors associated with HIV in a population-based study in Andhra Pradesh state of India.

BACKGROUND: Population-based data on risk factors associated with HIV are not readily available from India. This understanding, and an estimate of the impact of addressing behavioural factors on reducing HIV, would be useful. METHODS: We interviewed a population-based sample of 12,617 persons 15-49 years old from 66 rural and urban clusters in Guntur district in the south Indian state of Andhra Pradesh and tested their dried blood spots for HIV. We used multiple logistic regression to assess the association of risk factors with HIV, and calculated population impact numbers for HIV reduction if behavioural factors were addressed. RESULTS: Among men, there was significant association between HIV and history of sex with men, blood transfusion, having ever visited sex worker or multiple lifetime women sex partners, consuming alcohol before sex, recreational drug use, male non-circumcision and tattooing (odds ratios 5.74-1.97, P < 0.03, R(2) = 0.11). Among women, the only identified behavioural factor associated with HIV was multiple lifetime men sex partners (P = 0.001, R(2) = 0.10). Taking into account the relative risk and prevalence of risk factors, the highest impact on reducing the HIV number per unit population was for male circumcision. CONCLUSIONS: Among the identified factors, male circumcision was estimated to have the highest relative impact on reducing HIV per unit population, but the feasibility of this intervention in India needs further investigation. The low explanatory power in the regression models of the usually considered risk factors for HIV suggests that better understanding of HIV dynamics at the population level in India is needed.

Causes and pattern of mortality in HIV-infected, hospitalized patients in a tertiary care hospital: a fourteen year study.

BACKGROUND: The introduction of highly active antiRetroviral therapy (HAART) in several centers in India has raised the expectation that many human immunodeficiency virus (HIV)-infected individuals will live longer. However, as most infected individuals remain undiagnosed till the late stage of infection; several continue to succumb to this infection even in the era of HAART. MATERIALS AND METHODS: A retrospective study was conducted over a 14 year period on 2,050 HIV-infected, hospitalized patients to evaluate the pattern of mortality and to determine proportion, risk factors and causes of death. RESULTS: A total of 145 deaths among HIV-infected patients were documented during hospitalization, with an overall mortality rate of 8.15%: 2.94% in the pre HAART era (1992-1996), 7.29% in the early HAART era (1997-2000) and 9.73% in the present HAART era (2001-2005). 11.7% (17/145) of deceased patients were aware of their HIV-infected status before getting admitted. Only five patients were on any antiretroviral treatment prior to admission. Ninety (62.07%) deaths were HIV-related (AIDS-defining conditions) and 55 (37.93%) were non HIV-related. DISCUSSION: Our study stresses the importance of early diagnosis of HIV infection to curb adult mortality, which will continue to rise unless effective treatment interventions are introduced.

HIV infection in women utilizing a major hospital in Andhra Pradesh, India, 1993-2004.

BACKGROUND: Despite the high prevalence rates of HIV infection in women, epidemiological studies conducted exclusively on HIV-reactive women are very sparse, particularly from the state of Andhra Pradesh, India, where the overall prevalence rate among antenatal women is 2.1%. STUDY POPULATION: Medical records of 2643 HIV-reactive women, identified during a 12-year period, were reviewed for epidemiological and clinical information about HIV in women. RESULTS: The overall prevalence of HIV-reactive women was 1.6% and trends were in parallel with those observed by the HIV sentinel surveillance study from our state. Overall 24.5% of HIV-infected cases were women, ranging from 6.3% in 1993 to 28.9% in 2004. HIV infection was increasingly found in women over 30 years of age. Heterosexual contact (87.3%) was the most common route of HIV transmission. The majority (75.2%) of the women were asymptomatic. Women, compared to men, suffered more from respiratory and bacterial infections, often pneumonia, and from gender-specific manifestations like vaginal candidal infections. Following the introduction of antiretroviral (ARV) therapy in our hospital in 1999, only 8.5% of HIV-reactive women have received ARV treatment. CONCLUSION: There is a need for gender- and age-specific HIV surveillance among women, especially from areas of high prevalence. Our study shows that there are good reasons to be concerned about the effects of HIV in women. We stress the importance of increasing the focus of attention on the impact of this pandemic on women as we enter the 25th year since its emergence.

A population-based study of human immunodeficiency virus in south India reveals major differences from sentinel surveillance-based estimates.

BACKGROUND: The human immunodeficiency virus (HIV) burden among adults in India is estimated officially by direct extrapolation of annual sentinel surveillance data from public-sector antenatal and sexually transmitted infection (STI) clinics and some high-risk groups. The validity of these extrapolations has not been systematically examined with a large sample population-based study. METHODS: We sampled 13838 people, 15-49 years old, from 66 rural and urban clusters using a stratified random method to represent adults in Guntur district in the south Indian state of Andhra Pradesh. We interviewed the sampled participants and obtained dried blood spots from them, and tested blood for HIV antibody, antigen and nucleic acid. We calculated the number of people with HIV in Guntur district based on these data, compared it with the estimate using the sentinel surveillance data and method, and analysed health services use data to understand the differences. RESULTS: In total, 12617 people (91.2% of the sampled group) gave a blood sample. Adjusted HIV prevalence was 1.72% (95% confidence interval 1.35-2.09%); men 1.74% (1.27-2.21%), women 1.70% (1.36-2.04%); rural 1.64% (1.10-2.18%), urban 1.89% (1.39-2.39%). HIV prevalence was 2.58% and 1.20% in people in the lower and upper halves of a standard of living index (SLI). Of women who had become pregnant during the past 2 years, 21.1% had used antenatal care in large public-sector hospitals participating in sentinel surveillance. There was an over-representation of the lowest SLI quartile (44.7%) in this group, and 3.61% HIV prevalence versus 1.08% in the remaining pregnant women. HIV prevalence was higher in that group even when women were matched for the same SLI half (lower half 4.39%, upper 2.63%) than in the latter (lower 1.06%, upper 1.05%), due to referral of HIV-positive/suspected women by private practitioners to public hospitals. The sentinel surveillance method (HIV prevalence: antenatal clinic 3%, STI clinic 22.8%, female sex workers 12.8%) led to an estimate of 112635 (4.38%) people with HIV, 15-49 years old, in Guntur district, which was 2.5 times the 45942 (1.79%) estimate based on our population-based study. CONCLUSION: The official method in India leads to a gross overestimation of the HIV burden in this district due to addition of substantial extra HIV estimates from STI clinics, the common practice of referral of HIV-positive/suspected people to public hospitals, and a preferential use of public hospitals by people in lower socioeconomic strata. India may be overestimating its HIV burden with the currently used official estimation method.