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Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption.

ABSTRACT: The impact of antiretroviral therapy (ART) interruption in HIV-hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study.Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV-positive) participants at baseline, and at months 1, 2, 4, 6, 8, 10, and 12.Among HBV-positive participants in the ART interruption (drug conservation) (n = 72) and ART continuation (virological suppression) (n = 62) arms, HBV DNA rebound of more than 1 log from baseline at months 1-4 was seen in 31-33% (P = 0.003) and 3-4% (P = 0.017), respectively. Thirteen HBV-positive participants had HBV DNA rebound of more than 3 log, including 12 in the drug conservation arm, of which eight were on tenofovir-containing regimens. Factors independently associated with a HBV DNA rebound were drug conservation arm (P = 0.0002), nondetectable HBV DNA at baseline (P = 0.007), and black race (P = 0.03). Time to ART reinitiation was shorter (7.5, 15.6, and 17.8 months; P < 0.0001) and proportion reinitiating greater (62.5, 46.5, and 39.7%; P = 0.0002) among HBV-positive participants as compared with hepatitis C virus-positive and non-HBV/hepatitis C virus participants in the drug conservation arm. No hepatic decompensation events occurred among HBV-positive participants in either arm.HBV DNA rebound following ART interruption is common and may be associated with accelerated immune deficiency in HIV-HBV-coinfected patients.

SUBMITTER: Dore GJ

PROVIDER: S-EPMC2881334 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption.

Dore Gregory J GJ Soriano Vicente V Rockstroh Jürgen J Kupfer Bernd B Tedaldi Ellen E Peters Lars L Neuhaus Jacqueline J Puoti Massimo M Klein Marina B MB Mocroft Amanda A Clotet Bonaventura B Lundgren Jens D JD

AIDS (London, England) 20100301 6

<h4>Background</h4>The impact of antiretroviral therapy (ART) interruption in HIV-hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study.<h4>Methods</h4>Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV-positive) participants at baseline, and at months 1, 2, 4, 6, 8, 10, and 12.<h4>Results</h4>Among HBV-positive participants in the ART interruption (drug conservation) (n = 72) and ART continuation (v ...[more]

PMID: 20216301

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Project description:Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients-between 40 and 150-will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two "Boston patients", recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual reservoir that eventually caused rebound. Together, these tools will aid HIV researchers in the evaluating new potentially-curative strategies that target the latent reservoir.

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Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption.

Publications

Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption.

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