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

摘要

>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 compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.