CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Background: We assessed drug resistance in a sample of patients at GHESKIO in Port-au-Prince, Haiti (largest provider of HIV care in the Caribbean), to inform treatment guidelines. Methods: From September 2018 to July 2019, we conducted HIV genotypes for patients who were ART-naïve or with virologic failure on first-line ART; tenofovir (TDF)/lamivudine (3TC)/dolutegravir (DTG) (TLD) replaced efavirenz (EFV)/ TDF/3TC as first-line ART in November 2018. Resistance was defined by the Stanford HIV Drug Resistance Database score: ³15 at least low-level resistance; ³30 at least intermediate resistance. Results: HIV genotypes were conducted for 266 patients who were ART-naïve and 91 on NNRTI-based first-line ART. Of those, 56.7%were female and median age was 35 (IQR: 26, 44). Among ART-naïve patients, 24.8% had intermediate or higher resistance to EFV, with score >30 (27.5% among females). NRTI resistance (score >30) was detected in 8.6%, including 3.4% for both TDF and 3TC; M184V/I was detected in 7.5%, K65R/N in 2.3%, and both mutations in 1.9%. Among patients failing a first-line NNRTI-based regimen, 91.2% had EFV resistance score >30. NRTI resistance (score >30) was detected in 63.7%, including 35.2% for both TDF and 3TC. M184V/I was detected in 46.2%, K65R/N in 28.6%, and both mutations in 15.4%. Rates of PI resistance were low. Less than 1% of patients had intermediate or high-level resistance to any PI. Conclusion: There are high levels of NNRTI and NRTI resistance among ART- naïve and ART-experienced adults and children in Haiti. The use of EFV-based ART regimens for pregnant women as an alternative first line is of concern, as ART resistance testing is not conducted. DTG and PI based regimens should be prioritized. The high rate of abacavir resistance in children, and TDF cross- resistance, limits future treatment options in that age group. High levels of TDF and 3TC resistance in adults warrant caution in the implementation of new guidelines and roll out of TLD in patients failing NNRTI-based therapy 518 PRETREATMENT HIV DRUG RESISTANCE AND 48-WEEK VIROLOGIC OUTCOMES IN THE ADVANCE TRIAL Mark J. Siedner 1 , Michelle A. Moorhouse 2 , Andrew Hill 3 , Tulio de Oliveira 4 , Richard Lessells 4 , Bryony Simmons 5 , Godspower Akpomiemie 2 , Celicia M. Serenata 2 , Willem D. Venter 2 , Ravindra K. Gupta 6 1 Massachusetts General Hospital, Boston, MA, USA, 2 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 3 University of Liverpool, Liverpool, UK, 4 KwaZulu-Natal Research Institute for TB and HIV, Durban, South Africa, 5 Imperial College London, London, UK, 6 Cambridge University, Cambridge, UK Background: Increasing prevalence of pretreatment HIV drug resistance (PDR) has motivated guideline changes to avoid non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy (ART) regimens. Empiric data on the performance of ART regimens in the face of PDR are lacking in sub-Saharan Africa. Methods: The ADVANCE study is a randomized controlled trial in South Africa that compares efavirenz (EFV) with dolutegravir (DTG), both with two NNRTIs, as first-line ART. We performed pre-treatment genotypic drug resistance testing in 197 randomly selected participants with next generation sequencing using the Illumina platform at KRISP and set detection thresholds for resistant variants at >20%, 5-20%, 2-5%. For our primary outcome, we compared the proportion of individuals who achieved virologic suppression (<40 copies/mL) at 48-weeks with EFV versus DTG-based ART, by presence or absence of PDR at 20% threshold, defined with the WHO drug resistance mutation (DRM) list. In secondary analyses, we assessed the effect of resistance at 2 and 5% thresholds on outcomes and the effect of PDR on treatment failure, redefined as virologic failure, death or loss from observation. Results: We successfully sequenced pre-treatment HIV RNA from 165 individuals, of whom 48 (29%) received EFV and 117 (71%) received DTG. Twenty of 165 (12%) had ≥1 DRMs, with no difference in PDR by study arm, sex (56% female), age (median 32 years) or pre-treatment CD4 count (median 284). The most common mutation was K103N (9%); K65R and M184V were both found in only 2 (1%) of individuals. The proportion achieving our primary outcome was

similar in the EFV (36/40, 90%) and DTG groups (93/101, 91%), P=0.69. However, rates of confirmed virologic suppression among those with and without PDR was 25% (1/4) and 97% (35/36) in the EFV-arm, and 89% (8/9) and 92% (85/93) in the DTG arms, respectively (P<0.001 for interaction between PDR and treatment arm). These trends were similar when redefining PDR thresholds at 2-5% and 5-20%, and when redefining failure to include death and loss from observation. Conclusion: PDR, primarily to NNRTIs, was associated with significantly diminished efficacy of EFV-based, but not DTG-based three drug ART in South Africa. These data support the use of integrase inhibitors as initial therapy in individuals with known drug resistance or in populations with a very high prevalence of circulating NNRTI PDR.

Poster Abstracts

519 IMPACT OF PREEXISTING DRUG RESISTANCE ON RISK OF VIROLOGIC FAILURE IN SOUTH AFRICA Jonathan Z. Li 1 , Natalia Stella-Ascariz 1 , Manish Choudhary 1 , Aneela Javed 1 , Katherine Rodriguez 2 , Heather Ribaudo 2 , Mahomed-Yunus Moosa 3 , Jaysingh Brijkumar 3 , Pillay Selvan 3 , Henry Sunpath 3 , Marc Noguera-Julian 4 , Brent Johnson 5 , Alex Edwards 6 , Vincent C. Marconi 6 , Daniel R. Kuritzkes 1 1 Brigham and Women's Hospital, Boston, MA, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 University of KwaZulu-Natal, Durban, South Africa, 4 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 5 University of Rochester, Rochester, NY, USA, 6 Emory University, Atlanta, GA, USA Background: There is conflicting evidence on the impact of pre-existing HIV drug resistance mutations (DRM) in patients infected with non-B subtype virus initiating first-line antiretroviral therapy (ART). Using next-generation sequencing, we assessed the impact of HIV DRMs on the risk of virologic failure (VF) in South African patients initiating an NNRTI-based ART regimen. Methods: We performed a case-cohort substudy of the HIV Drug Resistance Surveillance Study (DRSS), which enrolled 1,000 peri-urban and rural patients initiating first-line efavirenz/tenofovir/emtricitabine in KwaZulu-Natal. Pre-ART DRMs were detected by multiplexed Illumina sequencing of HIV pol and sequence analysis performed using PASeq software. Individual genotypic susceptibility scores at varying minority variant (MV) thresholds (0.5-20%) were calculated using the Stanford HIV database. DRMs present at ≥20% of the viral population were labeled as “majority” variants likely detectable by Sanger sequencing. Weighted Cox proportional hazards models estimated the association between pre-ART DRMs and risk of VF, defined as confirmed HIV-1 RNA ≥1,000 copies/mL after ≥5 months of ART. Results: The evaluable case-cohort sample included 178 participants from the randomly selected subcohort (16 with VF, 162 without VF) and 83 additional participants with VF. In the random subcohort, 16% of participants harbored at least one majority DRM that conferred intermediate or greater ART resistance (Stanford score ≥30). The presence of any significant majority DRM was associated with a 3-fold risk of VF (p=0.002). In those with <2 active drugs due to majority DRMs, the risk of VF increased to 9.2-fold (p<0.001) compared to those with 3 active drugs. Thirteen percent of participants in the random subcohort harbored any MV DRMs in the absence of majority DRMs. The most commonly detected high-level majority DRMs (K103N, V106M, M184V) were rarely detected as MVs. Presence of MVs alone had no significant impact on the risk of VF. Inclusion of pre-ART MVs with majority DRMs improved the sensitivity, but reduced the specificity of predicting VF of first-line ART.

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