Background: According to studies in animal models, Postexposure Prophylaxis (PEP) has to be maintained 4 weeks to be effective. However, with the diversity of the actual regimens, the consequences of those temporary window treatments at immunological level are not well characterized.
The objective of this pilot study was to assess the immunological effects of antiretroviral therapy during 28 days of PEP comparing the standard of care Lopinavir/r (LPV/r) vs Maraviroc (MVC) or vs Raltegravir (RAL), all of them with Tenofovir/Emtricitabine (TVD).
Methods: Peripheral blood mononuclear cells (PBMCs) and mononuclear cells (MNC) from rectal biopsy specimens were collected from 30 men who have sex with men (MSM) with a potential sexual exposure. All of them were selected from two different PEP randomized clinical trials. Three arms (TVD plus LPV/r (n=9) or plus MVC (n=11) or plus RAL (n=10)) and four follow-up visits were scheduled (day 1, 7, 28 and basal). Flow cytometry was used to measure immune activation (CD38 and HLA-DR), senescence (CD57 and CD28) and CCR5 expression in CD4 and CD8 T cells. Additionally levels of naïve, effector and memory T cells (CCR7 and CD45RA) were also evaluated.
Results: In PBMCs senescence and activation of CD4 T cells improved significantly in RAL arm between basal and day 28 (CD28: 93.5% vs 97.5%, p= 0.02; CD57: 4.8% vs 1.5%, p=0.03; CD38+DR+: 5.8% vs 2.6%, p=0.05, respectively) whereas no changes were observed in the other two regimens. At the same time points MVC arm, increased significantly the expression of CCR5 in both lineages CD4 (4.7% vs 15%, p=0.002) and CD8 (6.3% vs 16.1%, p=0.004) T cells, probably as a consequence of blockade of its internalization. No differences were detected at basal time among arms and only at day 28 was observed that RAL arm reduced significantly the mentioned percentage of CD4+CD38+DR+ in comparison with MVC arm (7.4% vs 2.6%, p=0.02, respectively). Regarding rectal biopsies not significant differences were detected among arms except for a marked increase in the proportion of CD4 naïve T cells in MVC arm (RA+CCR7+:35.8% vs 46%, p=0.03).
Conclusions: The rates of activation and senescence of the immune system were significantly lower in CD4 T cells from individuals on PEP with TVD plus RAL as compared with those with the other two regimens. Although these data should be confirmed due the low number of patients, our findings in combination with the results of better adherence and tolerance strongly support RAL regimens for PEP.