Starting antiretroviral therapy on integrase inhibitor (INSTI)-based regimens, relative to starting on non-INSTI regimens, increases the likelihood of CD4/CD8 count normalization and optimal immunological recovery—but coinfection with cytomegalovirus (CMV) reduces that likelihood, an Italian study published in Journal of Acquired Immune Deficiency Syndromes showed.
Current U.S. HIV treatment guidelines preferentially recommend INSTIs as first-line treatment due to their efficacy and tolerability. This study confirms that choice, adding immunology as a further factor in favor of INSTI use.
The 1,428 treatment-naive participants in the retrospective multicenter study were not randomized: 22% started on INSTI-based regimens, 45% on PI-based regimens, and 34% on NNRTI-based regimens. The study assessed markers—CD4/CD8 ratio and an index called OIR, which is composed of CD4 count, CD4 percentage, and CD4/CD8 ratio—that can indicate unbalanced immune function despite virological control and CD4 count increase.
After a median 13 months of follow-up, the overall CD4/CD8 count had normalized in 39% of participants, and OIR was normalized in 33%. The probability of both markers normalizing was higher for those on INSTI-based treatment, with the exception of one key subset of participants: the 55% of participants who had positive CMV antibodies at baseline.
Better tolerability for INSTIs may have increased adherence, the study authors theorized; conversely, they suggested, CMV’s association with socioeconomic disparities may have resulted in lower adherence among that group, thus suppressing lab normalization. (Neither socioeconomic factors nor adherence were recorded in the study.)
The study authors called for CMV testing to identify those at risk of immunological failure, along with further clinical trials to learn whether the treatment of asymptomatic CMV might improve immune recovery.