Dually Active HIV/HBV Antiretrovirals as Protection Against Incident Hepatitis B Infections: Potential for Prophylaxis

Shilaih, Mohaned; Marzel, Alex; Scherrer, Alexandra U.; Braun, Dominique L; Kovari, Helen; Rougemont, Mathieu; Darling, Katharine E A; Battegay, Manuel; Hoffmann, Matthias; Bernasconi, Enos; Hirzel, Cédric; Günthard, Huldrych F.; Kouyos, Roger D.

doi:10.1093/infdis/jiw195

Cited by 39 publications

(42 citation statements)

References 27 publications

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“…Our study is unique in that it showed a protective effect of 3TC only containing regimens in a population where heterosexual HIV transmission is believed to dominate. HIV viral load suppression on ART was a strong predictor of the protective effect of ART against incident HBV in our study, consistent with earlier findings (14, 15). The mechanism of this effect could be direct suppression of HBV replication or inhibition of HIV replication altering the biology of HBV acquisition.Failure to suppress HIV could also be associated with poor adherence and higher risk behaviors that predispose to HBV infection (16).…”

Section: Discussionsupporting

confidence: 93%

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Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda

Seremba

Ssempijja

Kalibbala

et al. 2017

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Objective Antiretroviral therapy (ART) may interfere with replication of hepatitis B (HBV) raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda. Methods We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-HBc negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV. Poisson incidence methods were used to estimate incidence of HBV with 95% confidence intervals while Cox proportional regression methods were used to estimate hazard ratios. Results 39 HBV infections occurred over 3,342 person-years (p-y), incidence 1.17/100 p-y. HBV incidence was significantly lower with ART use: (0.49/100 p-y) with ART and (2.3/100 p-y) without ART [aHR=0.25 (95% CI, 0.1-0.5) p<0.001], and with lamivudine (3TC) use: (0.58/100 p-y) with 3TC and (2.25/100 p-y) without 3TC [aHR= 0.32(0.1-0.7), p=<0.007)]. No new HBV infections occurred among those on tenofovir-based ART. HBV incidence also decreased with HIV RNA suppression: (0.6/100 p-y) with ≤400 copies/mL and (4.0/100 py) with >400 copies/mL [aHR= 6.4(2.2-19.0), p<0.001] and with age: 15-29 years vs 40-50 years [aHR=3.2 (1.2-9.0)]; 30-39 years vs 40-50 years [aHR=2.1(0.9-5.3)]. Conclusion HBV continues to be acquired in adulthood among HIV-positive Ugandans and HBV incidence is dramatically reduced with HBV-active ART. In addition to widespread vaccination, initiation of ART may prevent HBV acquisition among HIV-positive adults in sub-Saharan Africa.

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Section: Discussionsupporting

confidence: 93%

“…Recent studies from the European Union and Japan also have suggested a pre-exposure protective effect of HBV active ART medications particularly TDF and 3TC (12-14). Our study is unique in that it showed a protective effect of 3TC only containing regimens in a population where heterosexual HIV transmission is believed to dominate.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda

Seremba

Ssempijja

Kalibbala

et al. 2017

Aids

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“…[15] ). We tested the association of ART (exposure) and syphilis incidence (outcome variable), where ART was coded in several hierarchical ways: ART as a binary variable; ART divided into 4 classes of nucleotide reverse transcriptase inhibitors (NRTI), non-nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and other HIV antiretroviral drug classes (integrase and fusion inhibitors, primarily Raltegravir [87%]); ART divided into NRTI, PI, other HIV antiretroviral drug classes, and the individual drugs for the NNRTI class (as drugs of this class showed a weak protective association [table S1]).…”

Section: Discussionmentioning

confidence: 99%

“…[15] In addition, ART has been shown to have a wide array of targets and functions including activity as antitumor, antibacterial, antifungal, antimalarial, anti-Severe acute respiratory syndrome and anti-influenza agent. [16] …”

Section: Introductionmentioning

confidence: 99%

Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

et al. 2017

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“…Our HIV positive population has much higher levels of vaccination than their HIV negative peers due to an active vaccination program. Furthermore lamivudine, tenofovir and emtracitabine, the most commonly used antiretroviral drugs, are known to have a powerful protective effect against HBV infection [26]. Cox regression analysis was not performed on cases of possible incident HBV infection.…”

Section: Discussionmentioning

confidence: 99%

Predictors and incidence of sexually transmitted Hepatitis C virus infection in HIV positive men who have sex with men

et al. 2017

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BackgroundSexual transmission of Hepatitis C virus (HCV) in men who have sex with men (MSM) and its interaction with HIV status, sexually transmitted infections and sexual behaviour is poorly understood. We assessed the incidence and predictors of HCV infection in HIV positive MSM.MethodsThe electronic medical record and laboratory results from HIV positive MSM in care at a large urban public specialist HIV clinic embedded in a sexual health centre in Melbourne Australia were collected. Patients with two or more HCV antibody tests between January 2008 and March 2016 and with no record of injecting drug use were included. The HCV exposure intervals were the periods between a negative HCV test and the next HCV test. We compared HCV exposure intervals temporally associated with and without newly acquired syphilis or anorectal chlamydia. HCV exposure intervals were also categorised as being before or after HIV virological suppression and by most recent and nadir CD4 cell count.ResultsThirty seven new HCV infections were diagnosed in 822 HIV positive MSM with no history of injecting drug use over 3114 person years (PY) of follow-up. Mean age was 43.1 years (±12.5) and mean CD4 cell count nadir was 362 cells/uL (±186). The incidence of HCV infection in the study population was 1.19/100PY (0.99–1.38). The incidence in exposure periods temporally close to new syphilis infection was 4.72/100PY (3.35–6.08) and to new anorectal chlamydia infection was 1.37/100PY (0.81–1.93). The incidence in men without supressed viral load was 3.19/100PY (1.89–4.49). In the multivariate Cox regression analysis only younger age (aHR 0.67 (0.48–0.92)), exposure periods temporally associated to new syphilis infection (aHR 4.96 (2.46–9.99)) and higher CD4 cell count nadir (aHR 1.26 per 100 cells/uL (1.01–1.58)) were associated with increased risk of HCV infection. During the study period the incidence of syphilis increased dramatically but the incidence of HCV infection remained the same.ConclusionsIncidence of HCV infection is associated with syphilis but not anorectal chlamydia which suggests a biological rather than behavioural risk modification. Rising syphilis incidence may offset declines in HCV transmission through HCV treatment as prevention.

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Dually Active HIV/HBV Antiretrovirals as Protection Against Incident Hepatitis B Infections: Potential for Prophylaxis

Abstract: Our study suggests that DAART, independently of CD4 cell count and risky behavior, has a potentially strong public health impact, including pre-exposure prophylaxis of HBV coinfection in the HIV infected.

Cited by 39 publications

References 27 publications

Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda

Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda

Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

Predictors and incidence of sexually transmitted Hepatitis C virus infection in HIV positive men who have sex with men

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