CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

viral load fromweek 0 to 4 for those who died (n=43) vs. survivors were 26 vs. 56 cells/mm 3 and -2.7 vs. -2.7 log 10 copies/mL, respectively (Table). Each 20 unit lower 4-week change in CD4 count was associated with a 25% increased risk of post week-4 mortality (adj. HR 1.25, 1.06-1.47). OIs newly detected by week 4 also increased risk of post week-4 mortality (adj. HR 2.76, 1.11-6.88). Conclusion: Sub-optimal immunologic response and newly diagnosed OIs during the first month of ART are associated with death in the first year after ART initiation. Strategies to detect OIs and improve early immune response warrant further investigation.

Poster and Themed Discussion Abstracts 718 DOES TIME TO ART INITIATION IMPACT EARLY RESPONSES TO DR-TB TREATMENT? Erika K. Mohr 1 , Johnny Daniels 1 , Odelia Muller 1 , Bongani Chabalala 1 , Jennifer Hughes 1 , Virginia de Azevedo 2 , Amir Shroufi 3 , Sarah Jane Steele 3 , Gabriella Ferlazzo 3 , Laura Trivino Duran 1 1 MSF, Khayelitsha, Cape Town, South Africa, 2 City of Cape Town Dept of Hlth, Cape Town, South Africa, 3 MSF, Cape Town, South Africa Background: Morbidity and mortality among RR-TB patients co-infected with HIV can be reduced by anti-retroviral treatment (ART). There is limited evidence on the best time to initiate ART following RR-TB treatment initiation. Methods: We conducted a retrospective analysis of pulmonary RR-TB patients, co-infected with HIV who initiated treatment in Khayelitsha, South Africa, January 2014-December 2015. Culture conversion at 6-months was stratified by time of ART initiation and chi squared tests and logistic regression analyses were conducted to ascertain statistically significant differences. Results: Of 375 patients initiated treatment for pulmonary RR-TB, 286 (76.3%) were HIV-infected; 240 were culture-positive at treatment initiation, had available laboratory information and included. Nearly half of the patients (112, 46.7%) initiated ART before RR-TB treatment; these patients were on ART for a median time of 8.4 (IQR 1.6-28.2) before RR-TB treatment. Twenty (8.3%) patients never initiated ART. Among patients who initiated ART following RR-TB treatment (108, 45.0%) median time to ART initiation was 3.9 weeks (IQR 2.4-5.2); 21 (8.8%), 70 (29.2%) and 17 (7.1%) patients initiated ART within <=2 weeks, 2-8 weeks or >8 weeks (median 14.7 weeks (IQR 12.6-24.0)), respectively. Mortality within 6-months was significantly higher among those that never initiated ART (8/20, 40.0%) compared to those that ever initiated ART (24/196, 12.2%) (OR 5.4, 95% CI 2.0-14.7, p=0.001). Among patients still alive at 6-months, there were no significant differences in the proportions of patients with culture conversion if ART was initiated after RR-TB treatment (p=0.90). Additionally, those who never initiated ART had 4.3 times the odds (95% CI 1.3-14.2, p=0.016) of being culture positive at 6-months (7/12, 58.3%) compared to those who ever initiated ART (48/196, 24.5%); overall, 26.4% (55/208) of patients remained culture positive at 6-months. Conclusion: Despite universal access to ART in South Africa, some RR-TB patients never receive ART increasing their risk of early mobility and mortality. Clinical factors impacting time to culture conversion among those who initiate ART following RR-TB treatment need to be investigated in more detail. Over ¼ of the cohort was still culture positive following 6-months of RR-TB treatment; there is an urgent need for improved RR-TB regimens, additionally ART initiation among RR-TB patients should be prioritized. 719 HIV-RELATED TB TREATMENT INTERMITTENCY IN THE CONTINUATION PHASE AND MORTALITY Brenda Crabtree-Ramírez 1 , Cathy Jenkins 2 , Bryan E. Shepherd 2 , Karu Jayathilake 2 , Valdilea Veloso 3 , Eduardo Gotuzzo 4 , Claudia P. Cortes 5 , Denis Padgett 6 , Catherine McGowan 2 , Timothy R. Sterling 2 1 Inst Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico, Mexico, 2 Vanderbilt Univ, Nashville, TN, USA, 3 Oswaldo Cruz Fndn–Fiocruz, Rio de Janeiro, Brazil, 4 Univ Peruana Cayetano Heredia, Lima, Peru, 5 Univ of Chile, Santiago, Chile, 6 Hosp Seguro Social, Tegucigalpa, Honduras Background: The 2016 ATS/CDC/IDSA tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV- infected persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across regions and countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-infected persons is unknown; we are unaware of clinical trials addressing this issue. Methods: An observational cohort study was performed of HIV-infected adults treated for TB with standard therapy (2-month initiation phase of daily isoniazid, rifampin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin, administered concomitantly with antiretroviral therapy (ART) at participating Caribbean, Central and South America network for HIV epidemiology (CCASAnet) sites (Argentina, Brazil, Chile, Honduras, Mexico, Peru) between 2000-2013. Known CD4 at TB diagnosis and timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Results: 527 TB/HIV patients met inclusion criteria: 245 (46%) received TB treatment 7 days/week, 16 (3%) 5 days/week, 84 (16%) 3 days/week, and 182 (35%) 2 days/week in the continuation phase. Intermittency varied by site: 182 / 261 (70%) of patients receiving continuation phase treatment 5-7 days/week were from Brazil, and 209 / 266 (79%) receiving treatment 2-3 days/week were from Peru. The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (P<0.001) (Figure). After adjusting for age, sex, CD4, ART use at TB diagnosis, and site of TB disease (pulmonary vs. extrapulmonary), mortality risk tended to be lower for those treated 5-7 days/week (HR 0.62, 95%CI 0.38, 1.04; P=0.07). However, after also stratifying by clinic site, there was no protective effect (HR 1.60, 95%CI 0.64-4.00; P=0.31). Conclusion: TB treatment 5-7 days/week appeared to be associated with decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase. However, although variation in TB treatment intermittency by country permitted this comparison, the results could have been driven by other differences between clinic sites. Prospective randomized trials are needed to more clearly assess optimum TB treatment frequency during the continuation phase in TB/HIV populations.

CROI 2017 314