CROI 2016 Abstract eBook

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Poster Abstracts

752 High TB Risk in HIV-Positive Patients on Second-Line Antiretrovirals in Pune, India Vidya Mave 1 ; Dileep Kadam 1 ; Sonali Salvi 1 ; Anita Basavaraj 1 ; Ajay Chandanwale 1 ; Samir Joshi 1 ; Nikhil Gupte 1 ; Robert Bollinger 2 ; Amita Gupta 3 1 BJ Med Coll, Pune, India; 2 Johns Hopkins Univ, Baltimore, MD, USA; 3 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA

Background: With the increasing coverage and a 2-4% rate of virologic failure on first line antiretroviral treatment (ART) regimens globally, the number of patients who will need second-line ART containing protease inhibitor (PI) based regimens is increasing. Tuberculosis (TB) continues to be the leading cause of opportunistic infection and death among HIV-infected patients. However data on the TB incidence and mortality among HIV-infected patients receiving second line ART regimens are limited. Methods: Retrospective cohort analysis of 59691 HIV-infected patients was conducted between January 2006 and June 2014 from a large public sector ART center of Byramjee- Jeejeebhoy Medical College-Sassoon General Hospitals (BJMC-SGH), Pune, India. Inclusion criteria included patients receiving PI (boosted atazanavir or lopinavir)-based second line ART regimens. TB was diagnosed either clinically or microbiologically by acid-fast bacillus smear as per the national program guidelines. Study outcomes included estimates of TB incidence and case fatality rates among patients receiving second line ART. We conducted a Poisson regression analysis to assess independent predictors of TB disease. Results: The analyses included 405 patients on second line ART regimens who were followed for a median of 3.96 person-years (interquartile range (IQR), 2.23-5.28). Median age was 35 years (IQR, 31 - 40) and 138 (34%) were females. Median CD4 count at time of initiation of second line ART was 118 (IQR, 45 – 189) cells/cumm. TB incidence was 54.5 per 1000 person-years ((PY) 95% confidence interval (CI), 43.5 – 67.4). The median time to TB incidence was 1.92 (IQR, 1.04-2.93) PY. The risk factors for TB included male gender (adjusted incidence rate ratio (AIRR), 3.45, 1.33 – 9.09, p=0.01), and unit decrease in hemoglobin (AIRR, 1.17; 95% CI, 1.04 – 1.32, p = 0.009). All-cause case-fatality was 26.7 (95% CI, 8.7 – 62.3) /1000 PY among TB co-infected patients receiving 2 nd line ART. Conclusions: Our study documents a high TB incidence and mortality among patients receiving second line PI-based ART. Since the high TB incidence on second line ART pose treatment challenges due to drug interactions between rifampin and PIs, long recommended World Health Organization’s TB prevention strategies such as isoniazid prophylaxis need to be prioritized among all HIV-infected patients in India and other high TB burden countries. 753 TB Outcomes With ATV/r and Two Rifamycin-Containing TB Regimens in HIV/TB in India Jeffrey D. Jenks 1 ; Constance A. Benson 1 ; Nagalingeswaran Kumarasamy 2 ; Ezhilarasi Chandrasekaran 2 ; Pradeep Ambrose 2 ;TokughaYepthomi 2 ; Chitra Devaraj 2 ; Poongulali Selvamuthu 2 1 Univ of California San Diego, San Diego, CA, USA; 2 YRG Cntr for AIDS Rsr and Educ, Chennai, India Background: Tuberculosis (TB) is the leading cause of death globally in HIV-infected individuals, and drug interactions can complicate treatment in this population. For those requiring antiretroviral therapy (ART) that includes a boosted protease inhibitor (PI), rifabutin is the recommended rifamycin, although the optimal dose is still in question. Our hypothesis was that HIV/TB co-infected patients treated with a second-line boosted ATV/r ART regimen coupled with a thrice weekly rifabutin-containing TB treatment would have less favorable TB outcomes than those receiving first-line NNRTIs coupled with daily rifampicin-containing TB treatment. Methods: We retrospectively evaluated TB treatment outcomes for two cohorts of HIV/TB co-infected individuals seen at YRG Care Medical Center in Chennai, India, comparing those treated with an atazanavir/ritonavir (ATV/r) ART regimen plus a 150 mg daily or thrice weekly rifabutin-containing TB regimen with those treated with an NNRTI-based ART regimen in conjunction with a daily rifampicin-containing TB regimen. Results: Between 1996 and 2014, 4032 HIV/TB co-infected individuals were treated at YRG CARE, of which 3740 (92.8%) were treated with an NNRTI-based ART regimen and a rifampicin TB regimen (Rifampicin + ) and 292 (7.2%) an ATV/r-based ART regimen with a rifabutin TB regimen (Rifabutin + ). Those in the Rifabutin + group were less likely to develop relapsed/recurrent TB (relative risk 0.32, 95% CI 0.20-0.49) and had lower all-cause mortality (relative risk 0.45, 95% CI 0.22-0.96) compared to those in the Rifampicin + group. In addition, those in the Rifabutin + group that received intermittent rifabutin had lower clinical cure rates compared to those who received daily rifabutin (relative risk 0.60, 95% CI 0.48-0.75), although there was no statistically significant difference in rate of relapse/recurrent TB and all-cause mortality between these two subgroups. Conclusions: This large, retrospective study observed that ATT with rifabutin overall was effective, and daily rifabutin dosing may be more effective than intermittently-dosed rifabutin for the treatment of uncomplicated TB in HIV/TB co-infected individuals on a boosted PI-based ART regimen. This study expands our current knowledge about optimal rifabutin dosing with PI-based ART. 754 Incorporation of Bedaquiline in the South African National TB Programme Norbert Ndjeka ; for the Bedaquiline Implementers of the South African NationalTB Programme Natl Dept of Hlth, Pretoria, South Africa Background: In 2014, 844 extensively drug-resistant (XDR TB) cases were diagnosed in South Africa. Following a successful clinical access programme (December 2012 to February 2015) and drug registration with the national regulatory authority in October 2014, a national framework was compiled to support the introduction of bedaquiline into the South African National TB Programme (SA NTP). Methods: SA NTP guideline indications for bedaquiline (updated June 2015) include at least rifampicin-resistant TB patients with resistance to a fluoroquinolone or/and a second-line injectable drug (pre/XDR TB), both inhA/katG mutations for isoniazid resistance, intolerance or toxicity to standardized second-line regimen (e.g. ototoxicity, renal dysfunction, or psychosis), or surgical intervention. In patients with pre/XDR TB, linezolid is started in combination with bedaquiline. Patients with HIV infection, including those on antiretroviral therapy (ART), are eligible. Guidelines advise ART initiation for all TB patients with HIV infection. Inpatient admission is recommended for first two weeks or until culture conversion if XDR TB. Surveillance for BDQ resistance is done on baseline, 8-week, and 24-week sputum specimens using minimum inhibitory concentration testing by the national TB reference laboratory. Standardized forms for all patients are completed with proposed background second-line regimen, submitted centrally to the NTP, and reviewed by provincial or national clinical committee. Results: FromMarch to end September 2015, 598 patients have been initiated on bedaquiline in 7 of 9 provinces. As of end July 2015, most bedaquiline patients had either preXDR (40%) or XDR TB (39%); 65%were HIV-infected. The most common reason for cases being declined for bedaquiline initiation was patients with insufficient potentially effective drugs in the proposed background regimen. Provinces that were able to scale-up quickly were those that had access to stock of linezolid, genotypic second-line drug resistance results, and capacity to detect high-frequency hearing loss. Conclusions: Political commitment, national and provincial leadership, facilitation, and monitoring enabled rapid incorporation of clinical trial findings for rifampicin-resistant TB into the SA NTP. Increased access to capacitated inpatient and outpatient patient management, ECG monitoring, and enhanced pharmacovigilance are needed to continue this rapid expansion. 755 Treatment Outcomes for HIV/MDR-TB Coinfection in the Era of Antiretroviral Therapy Sanghyuk S. Shin 1 ; Chawangwa Modongo 2 ; Nicola Zetola 3 1 Univ of California Los Angeles Sch of PH, Los Angeles, CA, USA; 2 Botswana Univ of Pennsylvania Partnership, Gaborone, Botswana; 3 Univ of Pennsylvania, Philadelphia, PA, USA Background: The convergence of HIV and multidrug-resistant tuberculosis (MDR-TB) epidemics is a major global health threat. HIV co-infection has been shown to increase the risk of poor treatment outcomes among MDR-TB patients, but few studies have examined whether concomitant administration of antiretroviral therapy (ART) at a programmatic- level could achieve high rates of treatment success among HIV-infected MDR-TB patients. Here, we describe treatment outcomes among MDR-TB patients in Botswana during the period of ART expansion. Methods: We analyzed data from 5 clinics in Botswana’s decentralized MDR-TB treatment program. We included all patients with confirmed MDR-TB who started therapy during 2006-2013. Treatment success was defined as microbiological evidence of cure or completion of the full treatment course. Separate multivariable logistic regression models were

Poster Abstracts

314

CROI 2016