Pretreatment and Acquired Antiretroviral Drug Resistance Among Persons Living With HIV in Four African Countries.

BACKGROUND: Emerging HIV drug resistance (HIVDR) could jeopardize the success of standardized HIV management protocols in resource-limited settings. We characterized HIVDR among antiretroviral therapy (ART)-naive and experienced participants in the African Cohort Study (AFRICOS). METHODS: From January 2013 to April 2019, adults with HIV-1 RNA >1000 copies/mL underwent ART history review and HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. We calculated resistance scores for specific drugs and tallied major mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naive participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted. RESULTS: HIVDR testing was performed on 972 participants with median age 35.7 (interquartile range [IQR] 29.7-42.7) years and median CD4 295 (IQR 148-478) cells/mm3. Among 801 ART-naive participants, the prevalence of SDRMs was 11.0%, NNRTI mutations 8.2%, NRTI mutations 4.7%, and PI mutations 0.4%. Among 171 viremic ART-experienced participants, NNRTI mutation prevalence was 83.6%, NRTI 67.8%, and PI 1.8%. There were 90 ART-experienced participants with resistance to both efavirenz and lamivudine, 33 (36.7%) of whom were still prescribed these drugs. There were 10 with resistance to both tenofovir and lamivudine, 8 (80.0%) of whom were prescribed these drugs. CONCLUSIONS: Participants on failing ART regimens had a high burden of HIVDR that potentially limited the efficacy of standardized first- and second-line regimens. Management strategies that emphasize adherence counseling while delaying ART switch may promote drug resistance and should be reconsidered.

Impact of Early Antiretroviral Therapy on Detection of Cell-Associated HIV-1 Nucleic Acid in Blood by the Roche Cobas TaqMan Test.

The Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test, v2.0 (the CAP/CTM assay), was used to quantify cell-associated HIV-1 (CAH) nucleic acid in peripheral blood mononuclear cells (PBMC) from well-characterized clinical specimens from HIV-1-infected individuals on antiretroviral therapy (ART). Chronically infected individuals on ART with no detectable plasma HIV-1 RNA demonstrated average CAH burdens of 3.2 HIV-1 log10 copies/million cells. Assay sensitivity and specificity were 98.9% and 100%, respectively, with the positive and negative predictive values being 100% and 98.6%, respectively. The CAH burden was also measured at weeks 0, 1, 2, 8, and 60 in 37 participants (RV254/SEARCH010, Bangkok, Thailand) stratified by Fiebig stage (Fiebig stage I [FI] to FVI) at ART initiation. Prior to ART initiation, the average CAH burden was 1.4, 4.1, and 3.6 log10 copies/million PBMCs for individuals who initiated ART at FI, FII, and FIII to FVI, respectively. Initiation of ART resulted in a rapid decline of CAH in all individuals, with the greatest decrease being observed in individuals who initiated ART at FI to FIII. By week 60, 100% (FI), 71.8% (FII/FIII), and 20.5% (FIV to FVI) of samples from individuals initiating treatment were at or near the limit of quantitation. Residual CAH was detectable at 60 weeks in most individuals who initiated ART at later stages (FIV to FVI) and averaged 1.9 ± 0.7 log10 copies/million PBMCs. The modified Roche CAP/CTM assay provides a convenient, standardized approach to measure residual HIV in blood and may be useful for monitoring patients under therapy or those participating in HIV remission studies.

Serological and RT-PCR Surveillance for COVID-19 in an Asymptomatic US Army Trainee Population.

BACKGROUND: Significant variability exists in the application of infection control policy throughout the US Army initial entry training environment. To generate actionable information for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) transmission among new recruits, active enhanced surveillance was conducted for evidence of and exposure to SARS-CoV-2/COVID-19. METHODS: We serially tested recruits with a reverse transcriptase polymerase chain reaction (RT-PCR) COVID-19 and/or total antibody to SARS-CoV-2 tests at days 0, 14, and week 10 upon arrival for basic combat training at a location in the Southern United States. RESULTS: Among 1403 recruits who were enrolled over a 6-week period from August 25 through October 11, 2020, 84 recruits tested positive by RT-PCR, with more than half (55%, 46/84) testing positive at arrival and almost two-thirds (63%, 53/84) also testing seropositive at arrival. Similarly, among an overall 146 recruits who tested seropositive for SARS-CoV-2 during the period of observation, a majority (86%) tested seropositive at arrival; no hospitalizations were observed among seropositive recruits, and antibody response increased at week 10. CONCLUSIONS: These findings that suggest serological testing may complement current test-based measures and provide another tool to incorporate in COVID-19 mitigation measures among trainees in the US Army.