CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

708

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709 DOES THE BENEFIT OF IPT FOR PERSONS WITH HIV WHO CONSUME ALCOHOL OUTWEIGH THE RISK? J. Morgan Freiman 1 , Winnie Muyindike 2 , Karen Jacobson 3 , C. Robert Horsburgh 3 , Jerrold Ellner 1 , Judith Hahn 4 , Benjamin Linas 3

1 Boston Med Cntr, Boston, MA, USA, 2 Mbarara Univ of Sci and Tech, Mbarara, Uganda, 3 Boston Univ, Boston, MA, USA, 4 Univ of California San Francisco, San Francisco, CA, USA Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV)[1-4]. The World Health Organization recommends IPT for all PLHIV without symptoms of active TB, however, regular alcohol use is listed as a contraindication where transaminase monitoring is not routinely available[5]. This may exclude 18-35% of PLHIV in Uganda who report alcohol use despite their increased TB risk[6-9]. We postulate that the benefit of 6 months of IPT at the initiation of anti-retroviral therapy (ART) for PLHIV in Uganda who consume alcohol is greater than the risk of toxicity. Methods: We developed a Markov model to compare the risks and benefits of ART alone to ART with 6 months IPT for PLHIV in Uganda who regularly consume alcohol. IPT provided one-year without TB risk, 6 months therapy with 6 months of extended benefit. Outcomes included grade 3 or 4 non-fatal toxicity, fatal toxicity, life expectancy, cumulative TB cases and TB death. We selected base case parameters to replicate data for Uganda or sub-Saharan Africa. TB incidence varied from 6.6/100py in the first 3 months of ART to 1.2/100py after 3 years[10]. IPT toxicity was informed by the rate of grade 3 and 4 adverse events in the TEMPRANO trial[4]. For sensitivity analyses, we applied the risk ratio derived from increased toxicities reported in drinkers in Botswana[11] as well as that reported in the American Thoracic Society (ATS) guidelines[12]. Results: Life expectancy increased from 32.95 years with ART alone to 33.12 years with ART + IPT. IPT reduced the cumulative risk of TB by 16% and TB death by 1%, though toxicity developed in 15.2% and fatal toxicity in 0.8%. IPT provided longer life expectancy unless toxicity was > 23.3%. In a two-way sensitivity analysis of the probability of IPT toxicity and the incidence of TB at ART initiation, the base case favored IPT when TB incidence was >2%, whereas the ATS estimate favored IPT if incidence was > 4% (Figure 1). Conclusion: In this simulation model, the risk-benefit profile of IPT among Ugandan PLHIV who regularly consume alcohol favors IPT. IPT extends life expectancy and reduces the cumulative incidence of TB and TB death compared to ART alone. However, IPT results in a drug-related mortality of 8 deaths per 1,000 people. Better data on IPT toxicity and TB incidence among PLHIV who drink could inform strategies that withhold IPT from those at the highest risk and increase the safety profile.

Poster and Themed Discussion Abstracts

710 HEPATOTOXICITY DURING IPT AND ART IN SEVERELY IMMUNOSUPPRESSED PEOPLE McNeil Ngongondo 1 , Sachiko Miyahara 2 , Michael D. Hughes 2 , Xin Sun 2 , Amita Gupta 3 , Johnstone Kumwenda 4 , Thiago S. Torres 5 , Gregory Bisson 6 , Mina C. Hosseinipour 1 , for the Adult AIDS ClinicalTrials Group A5274 (REMEMBER) StudyTeam 1 UNC Proj-Malawi, Lilongwe, Malawi, 2 Harvard Univ, Boston, MA, USA, 3 The Johns Hopkins Univ, Baltimore, MD, USA, 4 Coll of Med-Johns Hopkins Rsr Proj, Blantyre, Malawi, 5 Inst Nacional de Infectologia (INI-Fiocruz), Rio de Janeiro, Brazil, 6 Univ of Pennsylvania, Philadelphia, PA, USA Background: Tuberculosis (TB) is a major cause of illness and death in people living with HIV (PLHIV). The World Health Organization recommends combining isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) to prevent TB. Due to potential increased hepatotoxicity in PLHIV with severe immunosuppression that are on IPT and ART, we evaluated its occurrence in this group. Methods: We conducted a secondary analysis of A5274− a randomized clinical trial that enrolled ART naïve PLHIV from 10 resource limited countries. We restricted analysis to one arm of the trial where participants started IPT for 24 weeks within 7 days of ART. Eligible participants were ≥13 years; had CD4 counts <50 cells/μL and did not have active TB. Participants with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN) were also eligible. Hepatotoxicity was defined as grade 3 (5.1–10.0 x ULN) or grade 4 (> 10.0 x ULN) AST or ALT or a diagnosis of hepatitis following initiation of IPT and ART. Raised pretreatment AST/ALT was defined as AST and/ or ALT elevations at ≥1.25x ULN and <2.5xULN at study entry. Logistic regression was used to identify baseline risk factors for hepatotoxicity. Kaplan-Meier method was used to estimate the time to hepatotoxicity. Results: Among 426 participants− 53%male, median age 35 years, median CD4 count 19 cells/µL−31 (7.3%) developed hepatotoxicity. Twenty of these participants discontinued IPT; four of these later restarted and 11 participants did not discontinue IPT. Two participants with hepatotoxicity died from TB; one died from hairy cell leukemia. In multivariate analysis conducted on 410 participants without missing data, the significant risk factors for hepatotoxicity were raised pretreatment AST (OR 3.6, 95% CI 1.7-7.7) and positive HBsAg at baseline (OR 4.7, 95% CI 1.7-12.9). Participants who had both of these conditions at baseline (N=5/11) had a higher risk (OR 19.9, 95% CI 5.3-74.3) and earlier onset of hepatotoxicity than participants who had none of these conditions (N=12/298) (Figure 1A and 1B). Conclusion: The incidence of hepatotoxicity during IPT and ART was high in this population. Severely immunosuppressed PLHIV with raised pretreatment AST/ALT or positive HBsAg at baseline should have targeted closer monitoring for hepatotoxicity. They should be considered for alternative TB preventive regimens such as use of intermittent rifapentine plus isoniazid or rifampicin plus isoniazid which are less hepatotoxic.

CROI 2017 311