CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: The patient was treated with TDF/FTC plus DTG as initial therapy (HIV RNA 1,970,000 copies/ml and CD4 78 cells/mm 3 ) Population sequencing showed no clinically significant resistance mutations in reverse transcriptase (RT) or protease (PR). Baseline IN genotype was not performed. HIV RNA initially decreased to 2,770 copies/ml after two weeks, but then increased to 15,700 copies/ml and plasma samples were collected serially over an eight day period. Deep sequencing of these samples generated a mean of 2,483,155 reads covering the region IN amino acids 142-165. The initial time point showed no significant IN mutations, however the next two time points showed rapid evolution of mutations as shown in Figure, notably the emergence of Q148K. Population sequencing corresponding to the middle time point showed RT mutations M184V and V118I and confirmed IN mutation G163E. Conclusion: Rapid emergence of known integrase inhibitor resistance mutations during failure of virologic suppression suggest that INI resistance may have contributed to failure on the initial regimen in this case. To our knowledge, this is the first description of potential DTG-resistance in a treatment naive individual.

Poster and Themed Discussion Abstracts

501 CROSS-RESISTANCE PROFILES OF THE NNRTIS IN DEVELOPMENT TO PREVENT HIV-1 INFECTION Nicholas S. Giacobbi , Nicolas Sluis-Cremer Univ of Pittsburgh, Pittsburgh, PA, USA

Background: The NNRTIs dapivirine (DAP), rilpivirine (RPV) and the phenylethylthiazolylthiourea analog MIV-150 are in development as pre-exposure prophylaxis (PrEP) modalities to prevent the acquisition of HIV-1 infection. Currently, there is a paucity of information in regard to the resistance and cross-resistance profiles of DAP and MIV-150, which we addressed in this study. Methods: Twenty-eight subtype B HIV-1LAI infectious viruses containing single NNRTI resistance mutations spanning 17 different codons (V90I; L100I/V; K101E/P; K103N/S; V106I; V108I; E138A/K; V179D/F, G190A/S; I181C/I/V; Y188C/H/L; H221Y; P225H; F227C/L; M230L; P236L; N348I) were constructed by site-directed mutagenesis. Drug susceptibility in a single cycle assay using TZM-bl cells was determined for RPV, DAP and MIV-150. Low-, intermediate- and high-level resistance was defined as 2-8, 8-20, and >20-fold changes in drug susceptibility compared to the wild type virus. Results: Of the 3 NNRTIs studied, RPV exhibited the best antiviral activity across the panel of HIV-1 variants tested. RPV was found to be active against 19 of 28 variants, with low-level resistance conferred by the E138A/K, F227C, K101E, Y188L and M230L mutant viruses, and high-level resistance conferred by Y181I/V and K101P. DAP was active against only 15 of the 28 viruses. The K101E, E138K, K103N/S, F227C, Y181C and L100V viruses conferred low resistance to RPV; whereas the L100I and M230L and Y188L, K101P and Y181I/V viruses were found to confer intermediate and high-level resistance, respectively. MIV-150 was also active against only 15 of the HIV-1 variants tested: K101E and L100I/V; F227C and Y181C; and M230L, K103N/S, Y181I/V, Y188L and K101P mutations conferred low-, intermediate and high-level resistance, respectively. Conclusion: DAP and MIV-150 activity is compromised by many HIV-1 variants containing a single NNRTI resistance mutation. Both NNRTIs exhibit decreased susceptibility toward the K101E, K103N and Y181C mutations which are major NNRTI transmitted drug resistance mutations in all geographic regions and HIV-1 subtypes. 502 DRUG RESISTANCE AFTER CESSATION OF EFAVIRENZ-BASED ANTIRETROVIRAL TREATMENT Gbolahan Ajibola 1 , Christopher Rowley 2 , Kathleen M. Powis 3 , Sikhulile Moyo 1 , Jean Leidner 4 , Kara Bennett 5 , Florence Chilisa 1 , Joseph Makhema 1 , Roger L. Shapiro 2 , Shahin Lockman 2 1 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana, 2 Harvard Univ, Boston, MA, USA, 3 Massachusetts General Hosp, Boston, MA, USA, 4 Goodtables Consulting, Oklahoma, OK, USA, 5 Bennett Statistical Consulting Inc, New York, NY, USA Background: Little is known about the risk of antiretroviral resistance following cessation of efavirenz (EFV)-based antiretroviral treatment (ART), particularly when an NRTI “tail” is administered. Until 2015, Botswana’s Option “B” program for preventing mother-to-child transmission (PMTCT) recommended discontinuation of efavirenz (EFV)/ emtricitabine (FTC)/tenofovir (TDF) after delivery (with an FTC/TDF tail) for women with higher CD4, allowing a unique opportunity to study resistance patterns following discontinuation of this regimen. Methods: Resistance testing was performed on specimens obtained from a subset of HIV-infected women participating in the Botswana Mpepu study. Women with CD4>350 cells/mm3 initiated EFV/FTC/TDF in pregnancy for PMTCT, and discontinued at 6 weeks postpartum if formula-feeding or 6 weeks after last breastfeeding. A 7-day tail of FTC/TDF was recommended after stopping EFV. ART provision and management decisions occurred at government clinics. HIV-1 RNA and partial pol sequencing were performed on samples obtained 4-6 weeks after stopping EFV/FTC/TDF (regardless of whether an ARV tail was received). Stanford HIV Drug Resistance Database was used to identify major mutations.

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