1)

1).7,8 HIV integrase genotyping was performed for 141 (41%) of the 348 men who were HIV infected at enrollment and 23 (82%) of the 28 seroconverters; the remaining men either experienced viral loads 400 copies/ml or no sample Rabbit Polyclonal to CSFR available for additional screening. or polymorphic INSTI-associated mutations. The most frequently detected mutation was E157Q. These findings are encouraging because INSTI-based regimens are now recommended for first-line antiretroviral treatment and because long-acting cabotegravir is being evaluated for pre-exposure prophylaxis. strong class=”kwd-title” Keywords:?: HIV integrase, integrase inhibitor, drug resistance, men who have sex with men Regimens that include integrase strand transfer inhibitors (INSTIs) have excellent efficacy, security, and tolerability profiles in both antiretroviral (ARV) treatment (ART)-naive and ART-experienced patients.1 The first INSTI approved by the United States Food and Drug Administration (FDA) was raltegravir in 2007, followed by dolutegravir in 2013, and elvitegravir in 2014.2 INSTI-based regimens have been recommended for first-line ART since 2009. New INSTIs are currently under development, and a long-acting injectable form of the INSTI, cabotegravir, is being evaluated for pre-exposure prophylaxis (PrEP).3,4 The emergence of drug-resistant HIV has important implications, both for HIV-infected persons receiving ART and for at-risk uninfected individuals who could benefit from ARV-based prevention strategies. The U.S. Department of Health and Human Services recommends HIV drug resistance screening for all those HIV-infected individuals entering care.5 Standard HIV drug resistance testing assesses resistance to sAJM589 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs); screening for INSTI resistance is only recommended when clinically suspected by a supplier.5 The overall prevalence of INSTI resistance in the United States, particularly among men who have sex with men (MSM), is not well characterized. One U.S. study sAJM589 found that 16% of individuals who received clinically indicated screening for INSTI resistance had mutations associated with resistance to raltegravir or elvitegravir.6 The HIV prevention trials network (HPTN) 061 study (“type”:”clinical-trial”,”attrs”:”text”:”NCT 00951249″,”term_id”:”NCT00951249″NCT 00951249) is the largest longitudinal U.S. cohort of black MSM to date.7,8 The HPTN 061 study was designed to assess the feasibility and acceptability of a multicomponent intervention to reduce HIV incidence in black MSM in the United States. HIV-uninfected black MSM at sAJM589 a high risk of HIV acquisition and men already living with HIV were enrolled between 2009 and 2010, after raltegravir was approved by the U.S. FDA but before the first reported cases of transmitted INSTI resistance.9,10 Men were enrolled in six U.S. cities (Atlanta, Boston, Los Angeles, New York sAJM589 City, San Francisco, and Washington, D.C.) and followed for 1 year.7,8 HIV drug resistance to NRTIs, NNRTIs, and PIs was frequently detected in the HPTN 061 cohort,11 as described previously: 28% of the HIV-infected men had drug-resistant HIV at enrollment and 22% of the HIV seroconverters had drug-resistant HIV at the first HIV-positive study visit.11 In this statement, we analyzed INSTI resistance in the HPTN 061 cohort and in HIV seroconverters in a follow-up study, HPTN 073 (“type”:”clinical-trial”,”attrs”:”text”:”NCT 01808352″,”term_id”:”NCT01808352″NCT 01808352; 2013C2015), that evaluated PrEP uptake and adherence among black MSM in three U.S. cities (Raleigh/Durham, Los Angeles, and Washington, D.C.).12 HIV RNA was prepared using the ViroSeq HIV-1 Genotyping System (Abbott Molecular, Des Plaines, IL).11 INSTI resistance screening was performed using the ViroSeq HIV-1 Integrase Genotyping Kit (research use only; Abbott Molecular); samples were analyzed from men who experienced viral loads 400 copies/ml. In brief, a 1.1?kb amplicon of the HIV-1 integrase gene was amplified from HIV RNA using a one-step, reverse transcription polymerase chain reaction. Samples were sequenced using two forward and two reverse primers, amplifying the entire HIV integrase gene (864 base pairs). An Applied BioSystems 3130xl Genetic Analyzer was utilized for sequence analysis (Thermo Fisher Scientific, Waltham, MA). INSTI resistance was predicted using the ViroSeq Algorithm Advisor included in the software package. In HPTN 061, 348 men were HIV infected at enrollment and 28 men seroconverted during study follow-up (Fig. 1).7,8 HIV integrase genotyping was performed for 141 (41%) of the 348 men who were HIV infected at enrollment and 23 (82%) of the 28 seroconverters; the remaining men either experienced viral loads 400 copies/ml or no sample available for additional screening. HIV integrase genotyping was successful for 134 (95%) of the 141 enrollment samples and all 23 seroconverter samples. In HPTN 073, eight men seroconverted during study follow-up; HIV integrase genotyping was successful for all those eight seroconverter samples. All men included in this analysis were infected with HIV-1 subtype B. Open in a separate windows FIG. 1. HIV integrase genotyping among HIV-infected black MSM enrolled in HPTN 061. HIV integrase genotyping was performed for 141 (41%) of the 348 men who were HIV infected at enrollment and 23 (82%) of the 28 seroconverters in.