Four-Drug Antiretroviral Regimens Well Tolerated in Patients With HIV-1

Computer artwork of HIV in the bloodstream.
Cancer, particularly non-Hodgkin lymphoma, remains a leading cause of death in patients with HIV who are being treated with antiretroviral therapy.
Researchers sought to evaluate the tolerability of 4-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study.

Antiretroviral treatment (ART) regimens for primary HIV-1 infection consisting of 4 drugs were found to be well tolerated with good adherence, according to study results published in HIV Medicine.

In this study, 54 men diagnosed with primary HIV-1 infection who were treatment naive or newly commencing ART were either started on or intensified to a 4-drug regimen within 4 weeks of being diagnosed. In total 20 (37%) started the 4-drug regimen and 34 (63%) had their treatment intensified. The median age of participants was 32 years, and 42.6% had a viral load of ≥100,000 HIV-1 RNA copies/mL.

Viral loads of <50 copies/mL were observed in 37%, 69%, and 94% of participants at weeks 4, 12, and 24 following enrollment, respectively. At weeks 4, 12, 22, and 24, the percentages of participants reporting 100% adherence were 88.9%, 87.0%, 82.4%, and 94.1%.

Before week 24, a total of 3 patients withdrew from the study or were lost to follow-up. Overall, 5 patients changed to a 3-drug regimen at week 7, 24, 26, or 40, and another 3 patients changed components but maintained the 4-drug regimen. Two patients changed their 4-drug regimen following randomization at week 24, one due to renal function decline and the other due to nausea and vomiting.

The patient population in this study consisted of a small number of participants who were all men and highly motivated; these factors limit the generalizability of the results to other cohorts. However, the researchers did conclude that their “data demonstrate that four-drug regimens are feasible in the PHI setting, including for rapid ART initiation.”

According to the investigators, 4-drug regimens offer flexibility among treatment options for people newly diagnosed with HIV wishing to promptly start treatment. They added, “In these scenarios, clinical teams may also be reassured that a robust regimen is being utilized pending initial investigations; the regimen can then easily be rationalized when results are available or when viral suppression has been achieved.”


Burns JE, Stöhr W, Kinloch-De Loes S, et al. Tolerability of four-drug antiretroviral combination therapy in primary HIV-1 infection. HIV Med. Published online May 8, 2021. doi:10.1111/hiv.13118