CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

720 IMPACT OF INH ADHERENCE ON TB INCIDENCE AND MORTALITY BY WEEK 96 IN ACTG 5274 TRIAL Amita Gupta 1 , Xin Sun 2 , Sachiko Miyahara 2 , Mitch Matoga 3 , Deborah Langat 4 , Cynthia Riviere 5 , Gregory Bisson 6 , Johnstone Kumwenda 7 , Mina C. Hosseinipour 3 , for the ACTG A5274/ REMEMBER StudyTeam 1 Johns Hopkins Univ, Baltimore, MD, USA, 2 Harvard Univ, Boston, MA, USA, 3 Univ of North Carolina Proj–Malawi, Lilongwe, Malawi, 4 KEMRI/Walter Reed Proj, Kericho, Kenya, 5 Les Cntrs GHESKIO, Port-Au-Prince, Haiti, 6 Univ of Pennsylvania, Philadelphia, PA, USA, 7 Malawi Coll of Med–Johns Hopkins Univ Rsr Proj, Blantyre, Malawi Background: TB is a major cause of morbidity and mortality in low- and middle-income countries despite the use of antiretroviral therapy (ART). The A5274/REMEMBER trial team previously reported that a strategy of Empiric 4-drug TB therapy +ART provided no additional benefit in reducing mortality within 24 weeks after ART initiation compared to INH preventive therapy (IPT)+ART. We now present the 96 weeks results. Methods: In this multi-country randomized clinical trial, HIV-infected individuals with CD4<50 cells/mm3 were screened using a TB symptom screen, locally available diagnostics, and GeneXpert when available. Randomization was stratified by CD4 (<25 vs. ≥25 cells/mm3) and poor prognostic factors (BMI<18.5, HGB<8 g/dL, and recent hospitalization). To evaluate the effects of the intervention on longer-term outcomes, Kaplan-Meier estimates of the probabilities of death and confirmed/probable TB by week 96 were compared using a Z-test. In addition, Cox proportional hazards models were used to evaluate the association between TB medication adherence through week 24 (assessed via ACTG adherence questionnaire) and death or TB by week 96.TB adherence was defined as the number of visits with 100% adherence divided by the number of visits with available adherence assessments over all visit weeks up to week 24. Results: Of 850 enrolled, 53%were male, 90% black, median age 36 years, and median baseline CD4 18 cells/mm3. At week 96, there was no statistical difference in mortality between the Empiric and IPT arms (10.1% vs. 10.5%, respectively); absolute risk difference 0.4% (95% CI: -3.8%, 4.6%; p=0.86). At week 96, the Empiric arm had more TB compared to the IPT arm (6.1% vs. 2.7%, respectively); absolute risk difference -3.4% (95% CI:-6.2%, -0.6%; p=0.02; unchanged in competing risk analysis). The hazard of death was 23% and 20% lower per 10% increase in the proportion of 100% adherence in the Empiric and IPT arms, respectively (p<0.01). Adherence had no effect on TB in the Empiric arm (p=0.44). However, hazard of TB was 17% lower per 10% increase in the proportion of 100% IPT adherence (p=0.03). Conclusion: In this population of participants with advanced HIV, adherence to both empiric TB therapy and IPT was associated with improved survival. Adherence to IPT was associated with reduced risk of developing TB, but adherence to empiric TB therapy was not. Supporting IPT+ART initiation and adherence are critical to preventing the high TB incidence and mortality observed in those with advanced HIV. 721 WITHDRAWN 722 OUTCOMES ACROSS THE TUBERCULOSIS TREATMENT CASCADE AMONG ADOLESCENTS IN HAITI Lindsey Reif 1 , Rachel Bertrand 2 , Eric Kutscher 3 , Vanessa Rivera 3 , Pierrot Julma 2 , Serena Koenig 4 , Jean W. Pape 3 , Daniel Fitzgerald 3 , Margaret McNairy 3 1 Columbia Univ, New York, NY, USA, 2 GHESKIO, Port-au-Prince, Haiti, 3 Weill Cornell Med, New York, NY, USA, 4 Harvard Univ, Boston, MA, USA Background: Limited data are available on tuberculosis (TB) treatment outcomes among adolescents, especially among HIV co-infected adolescents. We describe the TB treatment cascade including diagnosis, treatment initiation, retention in care and treatment outcomes among adolescents with smear-positive disease, stratified by HIV status at the GHESKIO clinic in Port-au-Prince, Haiti. Methods: Adolescents and youth ages 10-24 who were diagnosed with smear-positive TB and tested for HIV at the GHESKIO TB clinic between January 2011 and October 2014 were included. Outcomes across the treatment cascade were stratified by HIV status including: 1) diagnosis of smear-positive TB, 2) treatment initiation, 3) retention at 2 months, and 4) treatment completion/cure. Cure was defined as having no positive smear at 2, 5, and 6 month tests. Treatment abandonment was defined as no clinic visit after 5 months of diagnosis, and treatment failure was defined as a smear-positive test after 5 months of treatment. Death was ascertained frommedical records. Differences were assessed by Chi-square test. Results: A total of 1,005 individuals were diagnosed with TB, of whom 41%were female, median age 20 (IQR 18-23), and 64% lived in a slum-area of Port-au-Prince. Seventy-four (7%) were HIV-positive at the time of TB diagnosis, with a median CD4 cell count of 332 cells/mL (IQR 194-558) at enrollment. Outcomes at each step in the cascade comparing HIV- positive vs. HIV-negative participants include: 73% versus 85% started treatment (p =.006), 46% versus 74%were retained at 2 months (p<.001), and 41% versus 68% completed treatment/cured (p=.002) (Figure 1). Treatment abandonment was associated with being HIV-positive (p<.001). There was no significant difference among HIV-positive and HIV-negative adolescents in treatment failure (0% versus 1%) or death (4% versus 1%). Among 846 patients who started treatment, 791 (79%) started the same day as diagnosis. Participants who started treatment the same day as diagnosis were more likely to have a treatment complete/cure outcome (p <.001). Conclusion: HIV-positive adolescents and youth are at increased risk for poor TB treatment outcomes and are in urgent need of interventions to strengthen retention and adherence. The greatest loss from the adolescent TB treatment cascade occurred between diagnosis and treatment initiation. Interventions including same-day TB treatment initiation can improve the proportion of adolescents with positive outcomes.

Poster and Themed Discussion Abstracts

CROI 2017 315