Effects on immune system and viral reservoir of a short-cycle antiretroviral therapy in virologically suppressed HIV-positive patients.

BACKGROUND: Atripla dose reduction decreases subclinical toxicity and maintains viral suppression in HIV+ individuals but the virological efficacy and immunological safety of this strategy needs to be further confirmed. METHODS: Virologically suppressed HIV-infected adults on Atripla once-daily were randomized 1 : 1 to reduce therapy to 3 days a week (3W, n = 30) or to maintain it unchanged (once-daily, n = 31). HIV-1 reservoir (total and integrated HIV-1 DNA in CD4 cells) and immunological cell activation (CD38 and HLA-DR), senescence (CD57 and CD28), apoptosis (annexinV) as well as T-naive, effector memory (TEM) (CCR7, CD45RA) and stem cell memory (TSCM) (CD954 and CD27) populations were measured at baseline, 24 and 48 weeks. RESULTS: No differences on activation, senescence or apoptosis of both CD4 and CD8 T cells were observed on follow-up. Nave CD4 T-cell proportion showed a significant decrease in the 3W group (mean ±â€ŠSD): 24.6 ±â€Š13.7 vs. 20.5 ±â€Š12.9 (P = 0.002). No differences in both plasma viral load and HIV reservoir were detected on follow-up. CD4 TSCM levels at 48 weeks correlated with basal integrated HIV-1 DNA in the 3W group but not in the once-daily group. A post hoc analysis of data prior to the study entry revealed a higher viral load zenith and a trend to lower CD4 nadir in 3W vs. once-daily group. CONCLUSION: No significant immunological or viral changes were induced in the 3W group confirming the virological efficacy and immunogical safety of this strategy. In-depth virological and immunological analyses are useful in providing additional information in antiretroviral switching studies (Clinical Trials.gov: NCT01778413).

Differential microRNA expression profile between stimulated PBMCs from HIV-1 infected elite controllers and viremic progressors.

BACKGROUND: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. RESULTS: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200 cp/ml) and 5 uninfected individuals (HIV-) through TaqMan Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs became significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. CONCLUSIONS: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.