The Effect of Protease Inhibitor-Based Dual Antiretroviral Regimens on CD4/CD8 Ratio During the First Year of Therapy in ART-Naïve Patients With HIV-Infection

MI Figueroa; A Camiro-Zuñiga; PF Belaunzaran-Zamudio; J Sierra Madero; J Andrade Villanueva; JR Arribas; JR Lama; DM Cecchini; G Lopardo; B Crabtree-Ramírez; A Gun; P Patterson; VI Fink; OG Sued; P Cahn


HIV Medicine. 2021;22(4):254-261. 

In This Article

Abstract and Introduction


Objectives: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials.

Methods: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann–Whitney U-test and the χ 2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/μL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy.

Results: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences.

Conclusion: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.


The requirement for lifelong antiretroviral therapy (ART) to maintain viral suppression in people living with HIV (PLWH) has increased the interest in developing effective dual therapy (DT) regimens to reduce cumulative drug exposure and cost, and to simplify regimens.[1,2] Several studies have demonstrated that when compared with triple therapy (TT), DT has non-inferior virological responses and CD4 cell recoveries when used as a switch strategy in virologically suppressed, ART-experienced patients.[3–5] Randomized clinical trials have demonstrated similar results in ART-naïve patients starting treatment, when comparing DT regimens based on boosted protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) with similar TT regimens.[6–8] The available evidence regarding non-inferiority of DT has been enough to warrant the inclusion of dolutegravir/lamivudine (DTG/3TC) as a regimen recommended for most people with HIV in the latest updates of the Department of Health and Human Services (DHHS) and European AIDS Clinical Society (EACS) guidelines, being approved for patients without hepatitis B virus co-infection, with viral loads < 500 000 HIV RNA copies/mL and with CD4 count > 200 cells/μL.[9,10]

A recent retrospective cohort study from the ICONA foundation study group aiming to explore the effect of DT as a switch strategy over CD4/CD8 ratio suggests that when compared with TT, DT regimens might decrease the CD4/CD8 ratio, due to a higher increase in CD8 cell counts at 12 and 24 months after switching to DT regimens.[11] These results raised concerns about the possibility of a poorer immune response in DT regimes and its long-term clinical implications, considering that higher CD4/CD8 ratios are associated with reduced systemic inflammation in chronic HIV infection and reduced HIV viral reservoir. More importantly, a low CD4/CD8 ratio has been associated with an increased risk of morbidity and mortality due to serious non-AIDS events[12,13] independently of CD4 count.[14–17]

Observational retrospective cohort studies are subject to different types of bias and observed or unobserved confounding factors that limit the validity of its conclusions. Thus, to address this subject we analysed the data collected in two different randomized clinical trials that compared the efficacy of boosted PIs plus 3TC-based DT and TT as first-line ART regimens to evaluate the impact of DT in the CD4/CD8 ratio during the first year of ART.