Abstract
People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5 – 19%). Being between the ages of 25 to 34, and 35 to 44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviors such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programs to increase early screening, vaccinations, and HBV literacy are urgently needed. Integrating HBV and HIV programs for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections.
Keywords: Hepatitis B virus, persons living with HIV, HBV-HIV co-infection, India, men who have sex with men
Introduction
Hepatitis B virus (HBV) infection is a major global health concern that can lead to chronic liver diseases and increase the risk of cirrhosis and hepatocellular carcinoma (HCC)1. While there are effective vaccines against HBV2, global HBV burden remains an estimated 296 million infections with an average 1.5 million new infections per year1. Additionally, 820,000 deaths from cirrhosis and HCC were recorded in 20191. Globally, a considerable number (> 2 million) of people living with HBV are co-infected with HIV, with higher prevalence in regions of Asia and Africa primarily due to perinatal HBV transmission1.
India is the most populous country in the world and carries the second largest burden of chronic HBV infections globally2; about 50 million people are chronically infected with HBV and the prevalence of hepatitis B surface antigen (HBsAg) is between 2 to 8% in health care settings2. HBV vaccination became part of the universal immunization program in the country in 20103 and is offered free-of-cost for all children and adolescents. Studies have demonstrated significant impact of spatial heterogeneity with low coverage of HBV vaccine clustered in the western, north-eastern regions2, leading to a significant number of unvaccinated children and adolescents. The vaccine uptake is still poor in adults, with a population-based study from India showing very low vaccination (1.9%)4, with hardly any knowing their vaccination status other than health care workers.
HBV infection is expected and common in persons living with HIV (PLWHs) due to shared routes and risk factors for transmission. Compared to HBV mono-infection, HBV-HIV co-infection is reported with a five-fold increased risk of developing chronic HBV and two-fold increase in mortality rate from end-stage liver disease5.
Moreover, there is limited data on HBV-HIV coinfections among key populations such as men who have sex with men (MSM). MSM are two to four times more likely to be infected with HBV and three to six times more likely to be infected with HIV compared to other reproductive aged adults6. In this study, we characterize prevalence and correlates of HBV among MSM living with HIV across 12 Indian cities.
Materials & Methods
Study design and population
Study participants comprised of MSM living with HIV who were already enrolled as part of the baseline assessment of a cluster-randomized trial (ClinicalTrials.gov Identifier: NCT01686750). Participants were recruited between 2012–13 using respondent driven sampling (RDS) – a chain referral strategy for recruitment of hidden populations – across 12 Indian cities: Bangalore, Belgaum, Mangalore, Bhopal, Coimbatore, Delhi, Chennai, Hyderabad, Madurai, Vijayawada, Lucknow, and Vishakapatnam. These locations were selected from six states across the country that had witnessed an HIV epidemic in MSM individuals. Brief inclusion criteria for the baseline assessment include age >18 years, self-identify as male, had anal and/or oral sex with another man in the prior 12 months, and provided informed consent to participate in the study. All participants underwent an interviewer-administered electronic survey and provided a blood sample. Detailed procedures are listed elsewhere7. HBV testing was conducted on stored specimen of all participants who tested positive for HIV, regardless of their awareness of HIV status. This study was approved by the Johns Hopkins Bloomberg School of Public Health and the YR Gaitonde Centre for AIDS Research and Education institutional review boards.
Laboratory methods
HIV testing was carried out using rapid HIV diagnostic kits as per the National AIDS Control Organization HIV testing algorithm using the following three kits (i) ‘Determine HIV-1/2, Alere Medical Co. Ltd., Chiba, Japan (Immunochromatography)’ (ii) ‘First Response HIV 1–2.0 card test (Immunochromatography), PMC, Nani Daman, India’ (iii) ‘Signal HIV, Arkray Healthcare Pvt, Ltd., (Antibody trapping by immobilization), Surat, India’ as per the manufacturer’s instructions. All HIV-1 positive specimens were subjected to ‘ARCHITECT HBsAg Next Qualitative assay, Abbott Diagnostics, Sligo Ireland’ using the ARCHITECT i1000 fully-automated platform.
Statistical methods
Descriptive statistics were used to examine RDS-weighted and unweighted proportions for HBV prevalence and demographic characteristics, including risk behavior and sexual health. Correlates of HBV prevalence were assessed using multilevel logistic regressions and included scaled RDS-II weights and a random intercept for site to account for clustering. Predictors that were significant at p<0.05 in the univariate models were retained in the final multivariate model.
Results
Among the 1125 MSM living with HIV, median age was 30 years, and 39% identified as being Kothi (prefer receptive anal intercourse). Self-reported sexual behavior was high with 34% having sex with both men and women in the past 6 months, and 83% having ever had insertive anal sex with a man or hijra (assigned male at birth, currently identifies as female or nonbinary).
The prevalence of HBsAg in this community-based sample of MSM living with HIV was 8% (Site range: 0.5% in Coimbatore – 19% in Belgaum). Age was a significant predictor of HBsAg prevalence after adjustment for other variables. Being between the ages of 25 to 34, and 35 to 44 increased the odds of having HBsAg compared to MSM ≤ 24 years [aOR: 2.7, 95% CI: 1.1, 6.7 and aOR: 2.6, 95% CI 1.1, 5.9, respectively] (Table 1). Having daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence among MSM living with HIV compared to those with monthly or weekly wages. In addition, sexual behaviors such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of testing positive for HBsAg. Ever having insertive sex with a man or hijra was negatively associated with HBV prevalence (Table 1). HbsAg seroprevalence was not associated with antiretroviral therapy (ART) use or HIV viral suppression.
Table 1.
Demographic and Risk Factors of MSM living with HIV and Univariate and Multivariate Associations with Hepatitis B Prevalence, RDS-Weighted
| Characteristics | n (%) / median (IQR) | OR† (95% CI) | Adjusted OR† (95% CI) |
|---|---|---|---|
| Prevalence of Hepatitis B | 97 (8.0) | - | - |
| Sociodemographic Characteristics | |||
| Age (in years) | |||
| ≤24 | 122 (13.3) | ref | ref |
| 25–34 | 443 (49.7) | 2.5 (1.3, 4.5)** | 2.7 (1.1, 6.7)* |
| 35–44 | 390 (26.6) | 2.5 (1.3, 4.8)** | 2.6 (1.1, 5.9)* |
| 45–54 | 134 (8.1) | 3.0 (1.1, 8.2)* | 3.1 (0.9, 11.2) |
| 55+ | 36 (2.4) | 0.01 (0.0, 0.1)** | 0.01 (0.0, 0.1)** |
| Sexual Orientation ₽ | |||
| Panthi | 186 (19.4) | ref | |
| Kothi | 516 (39.3) | 0.9 (0.4, 2.1) | |
| Double-Decker | 303 (22.0) | 1.1 (0.5, 2.2) | |
| Gay | 33 (6.8) | 0.3 (0.1, 1.0) | |
| Bisexual | 86 (12.4) | 0.7 (0.3, 1.6) | |
| Marital Status | |||
| Married | 553 (45.6) | ref | |
| Living with partner / long-term relationship | 82 (6.2) | 0.9 (0.3, 2.8) | |
| Widowed/Divorced/Separated | 71 (4.1) | 0.8 (0.3, 2.2) | |
| Never Married | 419 (44.1) | 1.3 (0.7, 2.7) | |
| Employment | |||
| Monthly/Weekly Wages | 550 (56.9) | ref | ref |
| Daily/Seasonal Wages | 511 (37.7) | 2.4 (1.8, 3.3)** | 2.1 (1.5, 3.0)** |
| Unemployed / Laid Off | 36 (2.4) | 9.7 (3.3, 28.6)** | 11.6 (3.9, 34.4)** |
| HIV and STIs | |||
| HIV Viral Suppression | 420 (30.6%) | 1.7 (0.6, 4.5) | |
| Self-Reported ART Use | |||
| Ever | 360 (68.8) | 1.0 (0.4, 2.8) | |
| Current | 345 (19.0) | 0.8 (0.6, 1.1) | |
| Ever had TB | 150 (10.0) | 1.1 (0.7, 2.0) | |
| Self-Reported Syphilis | 142 (5.1) | 0.9 (0.3, 2.5) | |
| Sexual Risk Behaviors | |||
| History of Sex Work | 78 (3.6) | 8.8 (4.6, 17.0)** | 8.6 (2.3, 32.4)** |
| Median Number of Male Partners (Lifetime) | 22 (5, 70) | 1.0 (1.0, 1.0)** | 1.0 (0.9, 1.0) |
| Median Number of Male Partners (Past 6 Months) | 2 (1, 10) | 1.00 (0.9, 1.0) | |
| Had sex with both men and women (Past 6 Months) | 414 (34.3) | 1.4 (1.0, 1.9)* | 2.1 (1.3, 3.5)** |
| Ever had insertive anal sex | 808 (82.6) | 0.5 (0.2, 0.9)* | 0.5 (0.3, 0.9)* |
| Ever had receptive anal sex | 901 (72.1) | 1.1 (0.7, 1.9) | |
| Access to Condoms | |||
| Easy or Very Easy | 920 (75.4) | ref | |
| Difficult | 99 (6.7) | 0.3 (0.1, 1.8) | |
| No Access | 84 (14.6) | 1.9 (0.5, 8.1) | |
| Don’t Know/Refused | 22 (3.3) | 1.1 (0.7, 2.0) |
OR from multilevel logistic regressions using scaled RDS-II weights and random intercepts for site to account for clustering.
p < .05.
p < .01.
Panthi (prefer penetrative anal intercourse only; Kothi (prefer receptive anal intercourse only); Double-Decker (engage in both penetrative and receptive anal intercourse)
Abbreviations: MSM, men who have sex with men; HIV, human immunodeficiency virus; RDS, respondent driven sampling; n, number; IQR, interquartile range; OR, odds ratio; STI, sexually transmitted infection; ART, antiretroviral therapy; TB, tuberculosis.
Discussion
Despite the existence of efficacious vaccines1, HBV continues to have high prevalence among PLWHs. To date, there have been no other studies from India that have focused on HBV coinfection among MSM living with HIV and limited community-based data exists from lower middle-income countries. In our sample, the overall HBV prevalence of 8% is consistent with general population seeking medical care in India2 and is the first to our knowledge examining prevalence in large community-based samples across multiple Indian cities. There was considerable site-level variability with 4 of 12 sites demonstrating HBV prevalence over 11%, emphasizing the disproportionately high burden of HBV among MSM living with HIV.
Our results also indicated that being 24 years or younger lowered the odds of HBV. This may be because younger age groups had less time to engage in risk factors associated with increased transmission of HBV or with increased uptake of HBV vaccines, though this seems unlikely as universal HBV vaccination in India was not initiated until 2010. Early screening and vaccination of MSM living with HIV could reduce the burden of HBV in older age groups. In addition to age, our findings suggest that sexual risk behaviors are strong predictors of HBV prevalence. It is possible that stigma associated with being MSM acts as a barrier for accessing prevention services, and coupled with the lack of awareness about HBV transmission could contribute to continued engagement in risky sexual behaviors and thus, increased HBV prevalence. Programs to increase HBV literacy, especially vaccine literacy, are critical.
High prevalence of HBV poses significant challenges for both HIV treatment and prevention. Despite the initiation of dual active ART, people co-infected with HIV and HBV are at a higher risk for all-cause mortality8. Further, several of the ongoing HBV cure studies only include mono-infected people – it is critical to expand these studies to include PLWHs who bear a high burden of HBV and its associated consequences. Given the high-prevalence of HBV amomg MSM living with HIV, it is critical to monitor for HBV infection among MSM on pre-expsoure prophylaxis, especially if the person is not vaccinated against HBV, as this represents a population at risk of HIV acquisition and consequently, HBV acquisition. Programs to screen and vaccinate MSM, both living with or without HIV, should be prioritized to reduce the HBV burden in this vulnerable population.
Some of the limitations of these data include the self-reported nature of the survey data and the lack of information on vaccination. Regardless, these limitations will not impact the prevalence and given the age of the participants included in the study and the timing of universal HBV vaccination, it is unlikely that the majority of participants were vaccinated. Additionally, these data were collected over 10 years ago but are still of importance as no similar data exist.
Limitations notwithstanding, these data demonstrate a high prevalence of HBV co-infection in this population-based sample of MSM living with HIV in India. Integrating HBV and HIV prevention and treatment programs could be critical in addressing this high burden and improving outcomes for both diseases.
Acknowledgements
This project was supported by the National Institutes of Health R01MH101059, and Abbott Laboratories. Dr. Syed Iqbal, Dr. Pradeep Amrose, Mr. AK Srikrishnan and Dr. Sunil Solomon serve as members of the Abbott Pandemic Defense Coalition (APDC).
Abbreviations
- ART
antiretroviral therapy
- HBV
hepatitis B virus
- HBsAg
hepatitis B surface antigen
- HCC
hepatocellular carcinoma
- MSM
men who have sex with men
- PLWHs
persons living with HIV
- RDS
respondent driven sampling
Footnotes
Conflict of Interest Statement
SSS has received grants, products and honoraria from Gilead Sciences not related to the data presented in this manuscript; SSS has received grants and products from Abbott Laboratories related to the data presented in this manuscript and honoraria not related to the present work. SHM receives materials support from Abbott Diagnostics not related to the data presented in this manuscript. MA, MR, and GC are employees and shareholders of Abbott Laboratories. Other authors report no conflict of interest.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.