CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

723LB WITHDRAWN 724LB EFFICACY OF BEDAQUILINE, PRETOMANID, MOXIFLOXACIN & PZA (BPAMZ) AGAINST DS- & MDR-TB Rodney Dawson 1 , Kendra Harris 2 , Almari Conradie 2 , Divan Burger 3 , Stephen Murray 4 , Carl Mendel 2 , Mel Spigelman 2 1 Univ of Cape Town, Mowbray, South Africa, 2 Global Alliance for TB Drug Development, New York, NY, USA, 3 QuintilesIMS, Bloemfontein, South Africa, 4 Mallinckrodt Pharmaceuticals, Bedminster, NJ, USA Background: New anti-tuberculosis (TB) regimens are needed to treat drug sensitive (DS) and multi-drug resistant (MDR) TB. NC-005 is an ongoing Phase 2b open-label, partly randomized trial investigating the bactericidal activity of combinations of bedaquiline (Bloading dose/tiw or B200mg), pretomanid (Pa200mg), moxifloxacin (M400mg) and pyrazinamide (Z1500mg) in the first 8 weeks of treatment of DS-TB or MDR-TB. Methods: Newly diagnosed patients with DS or MDR, smear positive pulmonary TB were enrolled. DS-TB patients were randomized to receive either B loadingdose/tiw PaZ, B 200mg PaZ or HRZE. MDR-TB patients received B 200mg PaMZ (BPaMZ). The primary outcome was bactericidal activity measured by the rate of change in time to sputum culture positivity (TTP) over 8 weeks of treatment. Upon treatment completion, all patients were referred to the local community TB clinic for treatment according to National TB Guidelines, and were scheduled to attend regular follow-up visits for 24 months. Safety was assessed by monitoring the incidence and severity of treatment emergent adverse events (TEAEs). Results: Between 23 October 2014 and 6 May 2016, 180 subjects with DS-TB and 60 subjects with MDR-TB were enrolled at ten sites in South Africa, Tanzania and Uganda. 218 subjects completed treatment and were followed through the Day 140 follow-up visit. Among all treatment arms, BPaMZ showed the highest bactericidal activity as assessed by TTP for Days 0-56 (5.302, 95% BCI [4.518-6.157]), followed by that of B 200mg PaZ (5.223, 95% BCI [4.526;5.947]), B loadingdose/t.i.w PaZ (4.906, 95% BCI [4.274; 5.585]) and HRZE (4.016, 95% BCI [3.520; 4.499]). The differences in bactericidal activity of BPaMZ, B 200mg PaZ and B loadingdose/t.i.w PaZ treatment arms versus HRZE were statistically significant. While 81.7% of patients had at least one TEAE, only 5 patients (2.1%) had a serious drug-related TEAE (2 in B loadingdose/t.i.w PaZ, 2 in BPaMZ, and 1 in HRZE). Long-term safety follow-up out to 24 months post-treatment completion is ongoing. Conclusion: The BPaMZ regimen in MDR-TB patients resulted in the highest level of bactericidal activity among all treatment arms. The BPaZ regimen was well tolerated and showed significantly higher bactericidal activity in DS-TB patients compared to HRZE. BPaZ and BPaMZ represent promising, simplified regimens to treat both DS-TB and MDR-TB. 725 Background: Partly fueled by the HIV epidemic, the prevalence and incidence of tuberculosis (TB) is higher in South Africa than any other country. It is known that the burden of TB is not evenly distributed, but the relative importance of race, socioeconomic status (SES), place of residence, and community SES in driving disparities in TB risk is not understood. Methods: We analyze data from the South Africa General Household Survey (2002–2014, n=1.2 million) to characterize the risk of TB. Respondents who indicated they had “TB or severe cough with blood” in the prior month were analyzed as prevalent cases (HIV status was not reliably reported). We use logistic regressions to predict risk of TB by household SES, race, community SES (median SES of all households in a primary sampling unit), place of residence, gender, age, and year and province fixed effects. SES is based on a household level factor analysis of floor and roof materials, toilet type, and primary cooking fuel. We included community SES given the putative importance of local environments in the transmission of TB. Results: Between 2002 and 2014, the overall prevalence of TB was 570 per 100,000 people, increasing from 590 in 2002 to 900 in 2009, before declining again through 2014. TB prevalence ranged from 770 per 100,000 in the lowest SES households to 350 in the highest. Black South Africans had the highest TB prevalence (630), followed by Coloured populations (440), and White/Asian/other (100). In the fully adjusted models, race was a consistently strong predictor of TB across SES categories. Adjusted prevalence of TB among Blacks in the highest SES households was > 4 times that of Whites/Asian/others in lowest SES households (430 and 100 per 100,000, respectively). Household SES was a bigger driver of TB prevalence than community SES or the type of place of residence – urban formal, urban informal, or rural/tribal. Specifically, the wealthiest households in the poorest communities had less than half the risk of TB than the poorest households in the wealthiest communities (predicted prevalence of 250 and 540, respectively). Conclusion: Both race and poverty predict TB risk, but Black and Coloured individuals across socioeconomic classes suffer much higher rates of TB than the even poorest whites or Asians/Indians. Household impoverishment is more closely associated with the likelihood of TB than community SES. Interventions for TB should address the striking disparities in burden of TB associated with race and poverty. TUBERCULOSIS IN SOUTH AFRICA IS MORE CONCENTRATED BY RACE THAN POVERTY Eran Bendavid , Lea Prince, Douglas K. Owens, Jeremy D. Goldhaber-Fiebert, Jason R. Andrews Stanford Univ, Stanford, CA, USA

Poster and Themed Discussion Abstracts

CROI 2017 316