HIV Drug Resistance in a Cohort of HIV-Infected MSM in the United States

Jessica M. Fogel; Mariya V. Sivay; Vanessa Cummings; Ethan A. Wilson; Stephen Hart; Theresa Gamble; Oliver Laeyendecker; Reinaldo E. Fernandez; Carlos Del Rio; D. Scott Batey; Kenneth H. Mayer; Jason E. Farley; Laura McKinstry; James P. Hughes; Robert H. Remien; Chris Beyrer; Susan H. Eshleman

Disclosures

AIDS. 2020;34(1):91-101. 

In This Article

Abstract and Introduction

Abstract

Objective: To analyze HIV drug resistance among MSM recruited for participation in the HPTN 078 study, which evaluated methods for achieving and maintaining viral suppression in HIV-infected MSM.

Methods: Individuals were recruited at four study sites in the United States (Atlanta, Georgia; Baltimore, Maryland; Birmingham, Alabama; and Boston, Massachusetts; 2016–2017). HIV genotyping was performed using samples collected at study screening or enrollment. HIV drug resistance was evaluated using the Stanford v8.7 algorithm. A multiassay algorithm was used to identify individuals with recent HIV infection. Clustering of HIV sequences was evaluated using phylogenetic methods.

Results: High-level HIV drug resistance was detected in 44 (31%) of 142 individuals (Atlanta: 21%, Baltimore: 29%, Birmingham: 53%, Boston: 26%); 12% had multiclass resistance, 16% had resistance to tenofovir or emtricitabine, and 8% had resistance to integrase strand transfer inhibitors (INSTIs); 3% had intermediate-level resistance to second-generation INSTIs. In a multivariate model, self-report of ever having been on antiretroviral therapy (ART) was associated with resistance (P = 0.005). One of six recently infected individuals had drug resistance. Phylogenetic analysis identified five clusters of study sequences; two clusters had shared resistance mutations.

Conclusion: High prevalence of drug resistance was observed among MSM. Some had multiclass resistance, resistance to drugs used for preexposure prophylaxis (PrEP), and INSTI resistance. These findings highlight the need for improved HIV care in this high-risk population, identification of alternative regimens for PrEP, and inclusion of integrase resistance testing when selecting ART regimens for MSM in the United States.

Introduction

In the United States, the current administration's plan, 'Ending the HIV Epidemic: A Plan for America', includes interventions such as early antiretroviral therapy (ART) to achieve viral suppression and preexposure prophylaxis (PrEP).[1] Goals of this program and other programs for HIV treatment and prevention may be compromised by HIV drug resistance.[2,3] Acquired drug resistance can emerge in HIV-infected individuals with sub-optimal adherence to ART, in individuals who become HIV-infected while taking PrEP,[4,5] and in those taking antiretroviral (ARV) drugs for other reasons. Individuals can also be infected with drug-resistant HIV [transmitted drug resistance (TDR)]. Some studies have reported decreases in acquired drug resistance in high-income countries,[6,7] which may reflect increased use of drugs with high genetic barriers for resistance and increased use of HIV genotyping and viral load monitoring to guide treatment. However, the frequency of acquired drug resistance remains high in many settings, and TDR has also increased in some settings.[8–10]

Approximately two-thirds of new HIV infections in the United States occur in MSM.[11] In 2015, only 62% of MSM diagnosed with HIV were receiving care, and only 52% were virally suppressed.[12] Surveillance data have shown that most HIV infections among MSM in the United States are linked to infections in other MSM,[13] and phylogenetic studies have found that active transmission clusters are more concentrated among MSM than other risk groups.[14] Data on drug resistance among MSM in the United States are limited. In a study of Black MSM in six cities in the United States [HIV Prevention Trials Network (HPTN) 061; enrollment 2009–2010], 28% of 169 HIV-infected study participants had drug resistance; 36% of those with resistance had ARV drugs detected, including many who did not report being in care.[15] Resistance to integrase strand transfer inhibitors (INSTIs) was not observed in that cohort.[16] Some studies have also reported higher rates of TDR among MSM compared with other risk groups.[8,17,18]

HPTN 078 evaluated an HIV prevention strategy focused on achieving and maintaining viral suppression in HIV-infected MSM in the United States (screening/enrollment: 2016–2017). The study enrolled HIV-infected individuals who were not virally suppressed at study sites in four US cities, including two study sites that participated in HPTN 061. Many individuals were recruited using respondent-driven sampling (RDS), which has been shown to help identify most-at-risk populations, including Black and Hispanic MSM and MSM with lower socioeconomic status.[19–21] In this study, we analyzed HIV drug resistance and the phylogenetic relationships of HIV among individuals recruited for participation in HPTN 078.

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