Atazanavir and Other Determinants of Hyperbilirubinemia in a Cohort of 1150 HIV-Positive Patients: Results from 9 Years of Follow-Up.
ABSTRACT Abstract Hyperbilirubinemia is common among patients exposed to atazanavir (ATV), but its long-term significance is not well documented. The objective was to analyze hyperbilirubinemia (incidence, regression, determinants, and outcome) among 1150 HIV-positive patients followed-up in a prospective cohort between 2003 and 2012. Cumulative incidence of hyperbilirubinemia grades 3-4 and its probability of regression were estimated using Kaplan-Meier method. Cox proportional hazards model was used to study the determinants. Generalized estimating equation (GEE) regression was used to evaluate the association between hyperbilirubinemia grades 3-4 and adverse health outcome. Eight years cumulative incidence of hyperbilirubinemia was 83.6% (95% CI:79.0-87.7) and 6.6% (95% CI:4.7-9.2) among ATV users and non-users, respectively. This clinical outcome fluctuated considerably, as most patients exposed to ATV (91%) regressed, transiently, to lower grade at some point during follow-up. Determinants were atazanavir (HR=147.90, 95% CI: 33.64-604.18), ritonavir (HR=5.18, 95% CI:2.33-11.48), zidovudine (HR=2.62, 95% CI:1.07-6.46), and age (HR=1.04 95% CI:1.01-1.08). Alcohol consumption and others non-antiretroviral medications including hepatotoxic and recreational drugs were not available for analyses. Incidence of hyperbilirubinemia was very high among ATV users and, although regression to lower grade was frequent in the clinical follow-up of these patients, this was usually transient as the mean level of bilirubin stayed at a relatively high level. Importantly, long-term hyperbilirubinemia was not associated with adverse health outcome.
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ABSTRACT: Postexposure prophylaxis (PEP) with antiretroviral medication has been used as an HIV-prevention strategy for nearly 20 years. The fact that approximately 50 000 new HIV infections occur in the United States each year reflects marked underutilization of nonoccupational PEP (NPEP). There have been several advances in NPEP in the past 10 years. Clinical trials from different countries have demonstrated better tolerability, completion rates, and fewer drug-drug interactions with newer antiretroviral agents. Notably, there has been a shift from zidovudine-based to tenofovir-based regimens. Three-drug therapy is now favored for all potential HIV exposures. More recently, the US Public Health Service and the New York State Department of Health recommended tenofovir/emtricitabine and raltegravir as the first-line regimen universally for PEP. Advances in HIV testing technology may also allow shorter duration of follow-up HIV testing after a high-risk exposure. This review will discuss challenges with previously recommended regimens, newer potential candidate agents and the rationale for using them, intervals for laboratory monitoring, and cost considerations for NPEP. NPEP can be viewed as an educable moment and a potential bridge to preexposure prophylaxis, as part of a combination prevention package, for those who are likely to have recurrent higher-risk exposures. Thus, risk-reduction counseling should be an integral aspect of NPEP.AIDS (London, England) 04/2014; 28(11). DOI:10.1097/QAD.0000000000000301 · 6.56 Impact Factor