AIDS research and human retroviruses
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AIDS Res. Hum. Retroviruses · Jan 2020
Randomized Controlled Trial Multicenter StudyWeek 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points. ⋯ D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response.
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AIDS Res. Hum. Retroviruses · Jan 2019
Multicenter Study Observational StudyImmunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV.
To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIV-infected persons, we investigated whether associations of CD4 count and HIV viral load (VL) with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol [HDL-C] differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ≥21 years with ≥1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. ⋯ Although no age differences were detected for HDL-C, VL ≥200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/μL [β = -7.0 mg/dL (95% CI: -9.7 to -4.3)] versus 200-500 cells/μL [β = -4.2 (95% CI: -5.9 to -2.6)] or >500 cells/μL [β = -2.2 (95% CI: -3.7 to -0.8)] (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.
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AIDS Res. Hum. Retroviruses · Nov 2018
Broad-Spectrum and Personalized Guide RNAs for CRISPR/Cas9 HIV-1 Therapeutics.
The clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 system has been used to excise the HIV-1 proviral genome from latently infected cells, potentially offering a cure for HIV-infected patients. Recent studies have shown that most published HIV-1 guide RNAs (gRNAs) do not account for the diverse viral quasispecies within or among patients, which continue to diversify with time even in long-term antiretroviral therapy (ART)-suppressed patients. Given this observation, proviral genomes were deep sequenced from 23 HIV-1-infected patients in the Drexel Medicine CNS AIDS Research and Eradication Study cohort at two different visits. ⋯ Using a mixed design with the top three BS gRNAs plus one personalized gRNA (BS3 + PS1) resulted in predicted excision of provirus from 45 of 48 patient samples with 90% efficiency. In summary, these studies used an algorithmic design strategy to identify potential BS gRNAs to target a spectrum of HIV-1 long teriminal repeat (LTR) quasispecies for use with a small HIV-1-infected population. This approach should advance CRISPR/Cas9 excision technology taking into account the extensive molecular heterogeneity of HIV-1 that persists in situ after prolonged ART.
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AIDS Res. Hum. Retroviruses · Oct 2018
Short Communication: Assessing Estimates of HIV Incidence with a Recent Infection Testing Algorithm That Includes Viral Load Testing and Exposure to Antiretroviral Therapy.
A recent infection testing algorithm (RITA) that includes a test for recent HIV infection and a viral load (VL) test is the recommended strategy to estimate national HIV incidence, reducing false-recent misclassification to <1%. The inclusion of information on exposure to antiretroviral therapy (ART), as a supplement to VL testing, could improve RITA performance by further lowering false-recent misclassification of true long-term infection. In 2012, Kenya and South Africa conducted national population-based surveys that collected information on HIV recency (i.e., HIV antibody seroconversion, on average, in the past 130 days) using the Limiting Antigen avidity (LAg-Avidity) enzyme immunoassay, HIV RNA levels, and ART exposure among HIV-infected respondents aged 15-49 years. ⋯ In South Africa, RITA-derived incidence was 2.2% on RITA #1 and 1.7% on RITA #2. Among specimens testing recent with unsuppressed VL in Kenya and South Africa, 16.0% and 19.7% had evidence of ART exposure, respectively. Although the performance of a VL- and ART-based RITA was encouraging, additional research is needed across HIV-1 subtypes and subpopulations to calibrate and validate this algorithm.
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AIDS Res. Hum. Retroviruses · Apr 2018
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialSuperior Efficacy and Improved Renal and Bone Safety After Switching from a Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through 96 Weeks of Treatment.
We previously demonstrated superior efficacy and safety advantages in HIV-infected, virologically suppressed adults switched to a regimen containing tenofovir alafenamide (TAF) as compared with those remaining on a tenofovir disoproxil fumarate (TDF) regimen through week 48. We now report long-term data through week 96. In this randomized, active-controlled, multicenter, open-label, noninferiority trial (ClinicalTrials.gov No. ⋯ Significant improvements in urine protein or albumin to creatinine ratios were also seen among those in the TAF group versus TDF through week 96 (p < .001). There were no cases of investigator-reported proximal renal tubulopathy in the TAF group as compared with one case in the TDF group. Switching to EVG/COBI/FTC/TAF (E/C/F/TAF) was associated with statistically significant efficacy and safety advantages over remaining on a standard-of-care TDF-based regimen.