HIV‐DNA decrease during treatment in primary HIV‐1 infection with three different drug regimens: Italian Network of Acute HIV Infection (INACTION) clinical trial

• Published in: Journal of medical virology 2023-09, Vol.95 (9), p.e29114-e29114
• Main Authors: Bruzzesi, Elena, Gabrieli, Arianna, Bernasconi, Davide, Marchetti, Giulia, Calcagno, Andrea, Ripamonti, Diego, Antinori, Andrea, Squillace, Nicola, Cingolani, Antonella, Muscatello, Antonio, Bandera, Alessandra, Gori, Andrea, Rusconi, Stefano, Nozza, Silvia
• Format: Article
• Language: English
• Subjects: Antiretroviral agents; Antiretroviral therapy; CD4 antigen; CD8 antigen; COVID-19; Deoxyribonucleic acid; DNA; Emtricitabine; HIV; Human immunodeficiency virus; Infections; Leukocytes (mononuclear); Pandemics; Peripheral blood mononuclear cells; Ribonucleic acid; RNA; Tenofovir; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.29114

As the introduction of antiretroviral therapy (ART) during primary HIV‐1 infection (PHI) could restrict the establishment of HIV reservoirs, we aimed to assess the effect of three different ART regimens on HIV‐DNA load in people living with HIV (PLWH), who started ART in PHI. Randomized, open‐label, multicentric study, including subjects in PHI (defined as an incomplete HIV‐1 Western blot and detectable plasma HIV‐RNA) in the Italian Network of Acute HIV Infection cohort. Participants were randomly assigned (10:10:8) to a fixed‐dose combination of tenofovir alafenamide fumarate (TAF) 10 mg plus emtricitabine (FTC) 200 mg, darunavir 800 mg, and cobicistat 150 mg once daily (group A), or TAF 25 mg plus FTC 200 mg, dolutegravir 50 mg once daily (group B), or an intensified four‐drug regimen (TAF 10 mg plus FTC 200 mg, dolutegravir 50 mg, darunavir 800 mg, and cobicistat 150 mg once daily) (group C). The primary endpoint was the decrease of HIV‐DNA copies/10 6 peripheral blood mononuclear cells (PBMCs) at weeks (W) 12 and 48. Secondary endpoints were increased in CD4+ cells and in CD4+/CD8+ ratio and percentage of PLWH reaching undetectable HIV‐RNA. HIV‐DNA was quantified by Droplet Digital PCR (Biorad QX100) and normalized to RPP30 reference gene. This study was registered in ClinicalTrials.gov (number NCT04225325). Among 78 participants enrolled, 30 were randomized to group 1, 28 to group 2, and 20 to group 3. At baseline, median CD4+ count was 658/µL (476–790), HIV‐RNA 5.37 (4.38, 6.12) log 10  copies/mL, without statistical difference in their change among groups at weeks 12 and 48 ( p  = 0.432 and 0.234, respectively). The trial was prematurely discontinued for slow accrual and for COVID‐19 pandemic‐associated restrictions. In the per‐protocol analysis, PLWH ( n  = 72) with undetectable viral load was 54.3% at W12 and 86.4% at W48. Interestingly, the CD4/CD8 ratio progressively increased over time, up to normalization in almost half of the cohort by week 48, despite a deflection in group 3; no difference was observed by the Fiebig stage (I–III vs. IV–VI). HIV‐DNA decreased from 4.46 (4.08, 4.81) log 10  copies/10 6 PBMCs to 4.22 (3.79, 4.49) at week 12, and 3.87 (3.46, 4.34) at week 48, without difference among groups. At multivariable analysis, HIV‐DNA delta at W48 was associated only with the increase of CD4+ count by 100 cells/mm 3 but not with the Fiebig stage, the CD4+/CD8+ ratio, and treatment arm, despite a higher decrease in group 3. Six adverse e