CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

482 HIV PRETREATMENT DRUG RESISTANCE IN CAMEROON: FIRST NATIONWIDE STUDY Gaëlle F. Tchouwa 1 , Jenny Domyeum 1 , Sabrina Eymard-Duvernay 2 , Amandine Cournil 2 , Eric Delaporte 2 , Martine Peeters 2 , Elliot Raizes 3 , Eitel Mpoudi-Ngole 1 , Avelin F. Aghokeng 4 1 CREMER, Yaoundé, Cameroon, 2 Univ de Montpellier, Montpellier, France, Montpellier, France, 3 CDC, Atlanta, GA, USA, 4 IRD, Yaoundé, Cameroon Background: The ongoing scale-up of antiretroviral treatment (ART) in sub-Saharan Africa has nowmoved to a new era with the recent WHO recommendations to test and immediately treat HIV-positive individuals. Pre-treatment drug resistance (PDR) may significantly compromise ART efficacy if high PDR frequency is found for common first-line antiretrovirals (ARVs). We present here the first nationally-representative PDR study conducted in Cameroon, West Africa. Methods: We adapted the recently published WHO PDR protocol to the situation of Cameroon. HIV-infected individuals eligible for first-line ART initiation as per national recommendations were recruited from 24 clinics that were randomly selected in urban and rural regions. Recruitments were conducted during a period of six months, from February to July 2015, and the dried blood spot specimens (DBS) collected were centralized in a WHO-accredited laboratory in Yaoundé, Cameroon, for genotyping and sequencing. HIV drug resistance (HIVDR) mutations were identified using the Stanford algorithm. Results: Overall, 379 participants were recruited and 335 pol sequences were successfully obtained. Two hundred and eighteen sequences were from patients attending urban ART sites and 117 from patients seen at rural facilities. Ten percent (32/335) were from participants with reported previous exposure to ARVs, through PMTCT intervention or ART. PDR frequency among all initiators was 9.7% (95% CI: 6.6-14.2%) overall, 13.3% (8.3-20.4%) in urban regions and 4.1% (1.7-9.5%) in rural regions. Among participants with no prior exposure to ARVs, PDR frequency was 9.8% (6.2-15.1%) overall, and 12.9% (7.5-21.2%) and 5.1% (2.1-11.7%) in urban and rural regions, respectively. Ninety-three percent of major PDR mutations were NNRTI mutations, essentially K103N and Y181C, and only a few (<3%) major NRTI and PI mutations were found. Conclusion: Our study is the first nationwide evaluation of PDR in Cameroon and indicates that 10% of patients initiating the first-line ART carry a mutated virus and may be at risk of premature treatment failure. Before implementing the test and treat strategy in Cameroon as recommended by WHO, interventions to prevent HIVDR must be urgently implemented, especially in urban regions where higher levels of PDR prevalence were observed. 483 LOW PREVALENCE OF HIV DRUG RESISTANCE WITH MODERN AGENTS Thibaut Davy , Laurence Brunet, Sonia Napravnik, Oksana Zakharova, Ann M. Dennis, Joseph J. Eron Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Resistance to antiretrovirals limits the impact of potent combination therapy. The resistance profile of patients has evolved with the introduction of new drugs. In this study, we estimated the annual prevalence of cumulative HIV drug resistance between 2000 and 2015 by drug class and year of ART initiation. Methods: We included ART-experienced patients in the UNC CFAR HIV Clinical Cohort (UCHCC) with at least 1 HIV RNA viral load between 2000 and 2015. For each year, we calculated the prevalence of total drug resistance burden by class. We examined mutations associated with reduced susceptibility based on the 2015 IAS-USA guidelines. Resistance profile was imputed for years when genotype testing had not been performed. Patients with viral load ≤ 1000 and no prior resistance detected were assumed to have no resistance, while the resistance profile of those with a viral load > 1000 after 90 days of ART was multiply imputed using age, sex, race, HIV risk factor, CD4 cell count, HIV RNA and initial ART regimen. Prevalence time trends were tested using linear regression with year as the predictor. The prevalence of resistance burden was also estimated in a subgroup analysis of patients initiating ART in 2007 or later. Results: The study population comprised 3,681 patients who were 71%male, 60% African-American, 41%men who have sex with men, and 13% injection drug users. Of all participants, 2,234 (61%) had at least 1 viral load > 1000 after 90 days of ART, and 2,301 (63%) had at least 1 genotype test performed. The prevalence of resistance to NRTIs, NNRTIs, any drug class, and 2 or more classes increased between 2000 and 2005 and subsequently decreased until the end of the study period (Figure, all p<0.05). The prevalence of resistance to PIs and to 3 or more classes remained stable between 2000 and 2005 (p=0.34 and 0.13, respectively) but decreased in the following years (both p<0.01). The prevalence of INSTI resistance increased slightly between 2009 and 2015 but remained low (p<0.01). Among 685 patients initiating ART in 2007 or later, the 2015 resistance prevalence was 21% for any class (95% CI 17%, 24%), 17% for NNRTIs (14%, 20%), 6% for NRTIs (4%, 8%), 2% for PIs (1%, 4%), 1% for INSTIs (0%, 2%), 5% for 2 or more classes (3%, 7%), and 1% for 3 or more classes (0%, 2%). Conclusion: The prevalence of drug resistance has declined in the last decade and is very low for patients who initiated antiretroviral therapy in the modern treatment era. Little resistance to INSTI agents has emerged.

Poster and Themed Discussion Abstracts

CROI 2017 202