Protease inhibitor monotherapy is effective in controlling human immunodeficiency virus 1 shedding in the male genital tract.

Cross-sectional study comparing seminal human immunodeficiency virus type 1 (HIV-1) shedding in patients receiving boosted protease inhibitor monotherapy (mtPI/rtv) (n = 66) versus triple therapy (TT) (n = 61). Seminal HIV-1 shedding rates in patients with undetectable plasma HIV-RNA were 16.0% on mtPI/rtv compared with 28.6% on TT (p 0.173). Aviraemic status and time on viral suppression were independently associated with lack of seminal HIV-1 shedding. During TT, non PI/rtv-based regimens were associated with a better control of HIV infection in semen despite similar time on viral suppression. The use of mtPI/rtv in well-controlled patients is not associated with increased seminal HIV excretion compared with TT.

Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.

Low concordance and resistance mutation emergence in the HIV protease gene among circulating and cell-associated viruses at viral replication episodes during darunavir/ritonavir monotherapy.

OBJECTIVE: To assess the changes on the HIV protease gene in plasma and peripheral blood mononuclear cell (PBMC) compartments during viral replication episodes in patients on boosted-darunavir monotherapy (mtDRV/rtv). METHODS: A prospective study was carried out in which adult HIV-1-infected patients who started mtDRV/rtv after viral suppression for ≥ 6 months with no major darunavir-related resistance mutations were enrolled. Patients with two consecutive plasma HIV RNA measurements >200 HIV-1 RNA copies/mL were considered as having virological failure (VF), while patients with two consecutive plasma HIV RNA measurements >50 copies/mL without meeting the VF criteria were considered to have virological rebound (VR). HIV protease genotypic profiles from plasma and PBMCs were performed at baseline and at VF and VR episodes. RESULTS: One hundred and fifty patients were included in the study, with overall VF and VR rates of 14% (n=21) and 14.7% (n=22), respectively. No major darunavir resistance mutations were observed in the plasma or PBMC samples. Circulating and cell-associated viruses showed a wild-type protease gene sequence in 54% and 23% of patients, respectively while the remainder patients only harboured minor protease inhibitor-associated mutations. Full concordance between plasma RNA and PBMC DNA protease genotypes was found in 23% of the sequences. CONCLUSIONS: No darunavir-related mutations were found in patients with VF or VR, either in plasma or in PBMCs; thus, simplification to mtDRV/rtv does not comprise future antiretroviral treatment options.

Impact of the peginterferon-α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV-co-infected patients with the unfavourable non-CC IL28B genotypes.

Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and 4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 µg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.

Immune activation throughout a boosted darunavir monotherapy simplification strategy.

Our aim was to assess the evolution and the impact that blips, intermittent low-level viraemia and virological failure (VF) episodes have on patients' immune activation (IA) profiles during ritonavir-boosted darunavir monotherapy (mtDRV/rtv). A prospective cohort of human immunodeficiency virus-1-infected patients who switched to mtDRV/rtv was followed for 2 years. Cellular IA was assessed according to HLA-DR and CD38 expression in CD4(+) and CD8(+) T-cells and their naïve, effector memory and central memory subpopulations, and systemic IA was evaluated according to sCD14 and D-dimer levels. Seventy-five patients from the MonDAR cohort were selected for this substudy, and classified according to viral outcome as having continuous undetectable viraemia (n = 19), blips (n = 19), intermittent viraemia (n = 21), and VF (n = 16). The IA profile was closely linked to viral behaviour. Patients on viral suppression for 24 months showed a significant decrease in CD4(+) and CD8(+) T-cell activation and sCD14 and D-dimer levels. Patients with transient low-level viraemia episodes (blips and intermittent viraemia) showed cellular and systemic IA similar to baseline values. In contrast, significant increases in T-cell activation and sCD14 and D-dimer levels were observed in patients with VF. Baseline levels of HLA-DR(+)CD38(+)CD8(+) T-cells of >6.4% were independently associated with the emergence of VF. Therefore, mtDRV/rtv might be considered as a safe simplification strategy, on the basis of the IA results, whenever viral replication is under medium-term and long-term control. Transient low-level viraemia episodes do not affect patients' IA status. Moreover, HLA-DR(+)CD38(+)CD8(+) T-cell baseline levels should be considered when patients are switched to mtDRV/rtv.