Comparative Immuno-Virological and Clinical Responses to Antiretroviral Therapy between HIV-1 Group O- and HIV-1 Group M-Infected Patients (ANRS 12168 DynaMO Study)

Backgroud: HIV-1/O presents a high level of genetic divergence relative to HIV-1/M which impacts viral load monitoring and drug susceptibility; however, its impact on therapeutic outcomes is still poorly known. The aim of this study was to determine if responses to standardised cART based on 2NRTIs 1IP/r were similar between group O and M infections despite strain divergence. Methods: We performed an open non-randomised study comparing the immunological, virological and clinical responses to cART, in naive and paired HIV-1/O- versus HIV-1/M-infected patients. Each HIV-1/O patient was matched to two HIV-1/M patients on sex, age, CD4 cell count, haemoglobin level, and HBsAg status. The primary endpoint was the proportion of patients with an undetectable plasma viral load (pVL<60cp/mL) at W48. Secondary endpoints were: the proportion of patients with an undetectable pVL at W24 and W96, and the proportion of patients with a CD4 cell count gain of more than 50% maintained at W96. Findings: 47 HIV-1/O patients and 94 HIV-1/M patients were included, whose mean pVL at baseline was significantly lower for HIV-1/O (4·2 log cp/mL) compared to HIV-1/M (5·2 log cp/mL; p<0.001). At W48, no significant difference was observed in the ITT population with 80·9 % of HIV-1/O patients having undetectable pVL compared to 75·5 % of HIV-1/M patients. Differences at W24 and W96 were not significant either. Regarding the immunological response, a difference in the gain of more than 50% of CD4 cells at W96 was observed in favour of HIV-1/M. Interpretation: Our data demonstrate the non-inferiority of 2NRTIs 1IP/r for treating HIV-1/O infections. This result should now lead to consideration of such combinations as a solid alternative in a context of natural resistance of O strains to NNRTI class. This study also shows significant differences in baseline replication and CD4 recovery, suggesting a specific pathophysiology which now needs to be explored. Clinical Trial Number: This study is registered with ClinicalTrial.gov with the number NCT00658346. Funding Statement: This work was supported by the Agence Nationale de Recherche sur le SIDA – Inserm ANRS – (grant number 12168). Declaration of Interests: The authors declared no conflict of interest. Ethics Approval Statement: The research protocol was approved by the Cameroon National Ethics Committee, the Cameroon Health Ministry, the French Ethics Committee of Saint Germain en Laye (France), the CCTIRS (Comite Consultatif sur le Traitement de l’Information en matiere de Recherche dans le domaine de la Sante) and the CNIL (Commission Nationale de l’Information et des Libertes).