CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

484 LOW PREVALENCE OF NRTI, NNRTI, AND PI DRUG RESISTANCE MUTATIONS IN BOTSWANA Sikhulile Moyo 1 , Simani Gaseitsiwe 1 , Melissa Zahralban-Steele 2 , Dorcas Maruapula 1 , Phillimon P. Sebogodi 1 , Madisa Mine 3 , Elliot Raizes 4 , Shahin Lockman 2 , Max Essex 2 , Vlad Novitsky 2 1 Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana, 2 Harvard Univ, Boston, MA, 3 Natl Hlth Lab, Gaborone, Botswana, 4 CDC, Atlanta, GA, USA Background: Monitoring of HIV-1 drug resistance is essential in the era of expanded access to antiretroviral treatment. This study aimed to survey the population prevalence of HIV-1 mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) in a cohort of HIV-1 clade C-infected patients in Botswana. Methods: Blood samples were collected from HIV-positive participants in the Botswana Combination Prevention Project (BCPP) who reside in 15 communities, predominantly in the southern region of Botswana. A long-range HIV genotyping protocol was applied. Both viral RNA and proviral DNA templates were used for amplification, as the majority of participants were receiving ART. NRTI, NNRTI and PI resistance mutations were analyzed according to the WHO 2009 and IAS-USA 2015 lists. All viral sequences were screened for G-to-A hypermutations (HM). Mutations in sequences with adjusted HM rate above the 3rd quartile of the subset of viral sequences without mutations were considered to be generated by HM, and were not counted toward drug-resistant mutations. Viral suppression was considered at HIV-1 RNA 400 copies/mL. Results: The majority of genotyped individuals, 413 of 665 (62.1%; 95% CI 58.3–65.8%), were receiving ART and 405 (60.9%; 95% CI 57.1–64.6%) had undetectable HIV-1 RNA 400 copies/mL. Among individuals on ART who were virologically suppressed (n=391), NRTI-, NNRTI- and PI-associated mutation were found in 2.8%, 4.1% and 1.3%, respectively. Among individuals on ART who were not suppressed (n=20), NRTI-, NNRTI- and PI-associated mutation were found in 25%, 25% and 0%, respectively. Among HIV-infected individuals not on ART (n=221), NRTI-, NNRTI- and PI-associated mutation were found in 1.8%, 3,2% and 0%, respectively. The overall distribution of specific mutations to 3 classes of drugs are presented in the Table. Conclusion: This is the first large surveillance for the prevalence of NRTI, NNRTI and PI resistance mutations on a population level in Botswana. The low prevalence of primary and secondary resistance mutations supports the rationale for a treat-all strategy as the national policy in Botswana. HM analysis and proviral DNA amplification is critical for surveillance in the era of highly suppressive ART scale-up.

Poster and Themed Discussion Abstracts

485 ARV RESISTANCE MUTATIONS IN PATIENTS RECEIVING A WHO TDF-CONTAINING 1ST-LINE REGIMEN Soo-Yon Rhee 1 , John Gregson 2 , Ravindra K. Gupta 3 , Robert Shafer 1 , for theTenoRes Study Group 1 Stanford Univ, Stanford, CA, USA, 2 London Sch of Hygiene and Trop Med, London, UK, 3 Univ Coll London, London, UK Background: TDF has replaced thymidine analogs (TAs) as the preferred NRTI for the initial treatment of HIV in LMICs. However, few data are available on the NRTI drug resistance mutations (DRMs) associated with virological failure (VF) in pts receiving TDF-containing 1st-line regimens in such settings. Methods: We assembled sequences from 2,233 pts with VF on a 1st-line regimen of TDF + 3TC/FTC + NVP/EFV that included 1,573 sequences from the TenoRes collaboration and 660 sequences from recently published studies. 61% of pts were from a LMIC; 39% from an UIC. Virus load (VL) was available at VF in 61% of pts. 247 sequences with >=1 canonical TA mutation (TAM) were excluded. We compared the proportions of mutations in TDF pts with those in 50,801 ARV-naïve pts to identify significant TDF regimen-associated mutations (TRAMs) following adjustment for multiple comparisons and subtype composition. We then compared the proportion of each TRAM in TDF pts with its proportion in 7,283 pts receiving a TA-containing 1st-line regimen and assessed the association of TRAMs with VL at time of VF. Results: We identified 78 TRAMs including 31 NRTI-TRAMs, 39 NNRTI-TRAMs, and 8 novel mutations. The 31 NRTI-TRAMs included 16 established NRTI DRMs (62V, 65RN, 69del, 70EQTN, 74VI, 75MIL, 115F, 184VI), 10 mutations at 5 positions previously associated with NRTI therapy (68GDN, 69I, 88SC, 165LV, 228RQ), and 5 non-canonical TAMs (67G, 203K, 218E, 219NR). Ten NRTI-TRAMs (62V, 65RN, 68GN, 70EQN, 74I, 115F, 184I) and 2 NNRTI-TRAMs (100I, 190E) were more common in the TDF compared to the TA pts. The most strongly correlated TRAM pairs were 65R-62V, 65R-68GN, 65R-184V, and 70E-228R. 65R was positively correlated with 70T but negatively correlated with 70QE. In a univariate analysis,

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