Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction

Background. Persistent human immunodeficiency virus (HIV) within the CD4+ T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication. Methods. A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4+ T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection. Results. Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was−1.03 log DNA copies/106 CD4+ T cells versus−.84 log in the standard and intensive groups, respectively (P =.056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4+ T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent. Conclusions. Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compare