Associations of statins and antiretroviral drugs with the onset of type 2 diabetes among HIV-1-infected patients.

BACKGROUND: Statin use is associated with a modest increase in the incidence of type 2 diabetes mellitus (DM) among the general population. However, HIV-infected patients have a higher risk of developing DM, and it is unclear whether statins have a diabetogenic effect in these patients. Therefore, we investigated the associations of statin use and exposure to antiretroviral drugs with type 2 DM onset in a cohort of HIV-infected patients. METHODS: This retrospective, controlled, cohort study identified HIV-1-infected patients who did not have DM and were not receiving statins at their antiretroviral treatment (ART) initiation. Follow-up was accrued from ART initiation to the earliest instance of a DM diagnosis, loss to follow-up, death, or last available visit. The incidence of DM was estimated according to statin use, which was adjusted for periods without statin treatment. The Fine-Gray competing risk model was used in the multivariate analysis to identify risk factors for developing DM. RESULTS: The analyses evaluated 6,195 patients followed for 9.8 years (interquartile range: 4.3-16.3 years). During 64,149 person-years of follow-up (PYFU), 235 patients developed DM (crude incidence: 3.66 [95%CI: 3.20-4.13] per 1,000 PYFU), and 917 (14%) patients used statins. After adjusting for potential confounders, statin use was associated with a non-significant increase in the risk of DM (AHR: 1.21, 95% CI: 0.71-2.07; P = 0.47). DM was more likely among patients who were ever treated with stavudine, and less likely among those ever treated using emtricitabine, tenofovir, abacavir, efavirenz, nevirapine, atazanavir or darunavir. CONCLUSIONS: A higher risk of diabetes mellitus was not associated with statin treatment but with traditional risk factors and stavudine use while a reduced risk of DM was associated with the use of emtricitabine, tenofovir, abacavir, efavirenz, nevirapine, atazanavir or darunavir.

Immune recovery and T cell subset analysis during effective treatment with maraviroc.

OBJECTIVES: Patients treated with maraviroc frequently show high CD4+ T cell increases. The aim of this study was to detail the characteristics of maraviroc-induced immune recovery. PATIENTS AND METHODS: We studied T cell subsets from frozen peripheral blood mononuclear cells of patients treated with raltegravir, etravirine and either maraviroc (REM, n = 24) or darunavir/ritonavir (RED, n = 17). RESULTS: The two groups showed a similar decrease in activated CD4+ and CD8+ T cells. A greater loss of naive CD4+ T cells and a reduction in cells expressing CXCR4 were observed in REM patients, while RED patients showed a greater loss of cells expressing CCR5. CONCLUSIONS: Our findings do not support a role for reduction in activated T cell subsets to explain the greater maraviroc-induced immune recovery. Reduction in CXCR4+CD4+ and higher expression of CCR5+CD4+ T cells might represent a potential protection from non-R5 tropic viral strain overgrowth.

Residual viremia in HIV-infected patients who continue a two-drug or switch to a three-drug integrase strand transfer inhibitor based regimen.

In this randomized, single-centre, open-label, 96-week, superiority, controlled trial of 50 HIV-infected patients with HIV-RNA less than 50 copies/ml on a two-drug regimen based on dolutegravir as well as one reverse transcriptase inhibitor (RTI), switching to a single-tablet regimen of cobicistat, elvitregravir, emtricitabine along with tenofovir alafenamide did not appear to mitigate the burden of residual viremia, both at week 48 and at week 96. The immunological changes observed during follow-up and the safety of the two regimens were similar.

Optimal dietary calcium intake in HIV treated patients: no femoral osteoporosis but higher cardiovascular risk.

BACKGROUND & AIMS: We performed a cross-sectional study on adult HIV-infected patients, on HAART, without calcium or vitamin D supplementation to evaluate if the cardiovascular risk or the presence of osteoporosis may be predictive factors of an optimal daily calcium intake (DCI>1000 mg/day). METHODS: Patients underwent a dual-energy X-ray absorptiometry, measured biochemical parameters and compiled a validated questionnaire for the assessment of DCI. Osteoporosis (OP) was defined according to the WHO classification at either the vertebral spine or femoral neck. Cardiovascular risk was assessed by the 10-year Framingham cardiovascular risk score. RESULTS: 200 HIV-infected patients evaluated: 171 (86%) males with a median age of 48.1 (42.3-53.8) years and 10.6 (4.3-13.6) years of HAART exposure. DCI was 889 (589-1308) mg/day and 79 (40%) patients had an optimal DCI. Framingham risk>20% was found in 13 (6.7%) patients and femoral OP was diagnosed in 12 (6%) pts. By multivariate analysis, optimal DCI was more likely in patients with a Framingham risk>20% [OR = 5.547, 95% CI:1.337, p = 0.025] and less likely in patients with femoral osteoporosis [OR = 0.159, 95% CI: 0.018-0.790, p = 0.047]. CONCLUSIONS: We found that an optimal dietary calcium intake was more likely in patients with high cardiovascular risk and no femoral osteoporosis.

Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression: 48-week efficacy and safety results.

OBJECTIVES: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml. METHODS: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100 mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification. RESULTS: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with two NRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with two NRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification = failure), treatment success was 73% in ATV/r arm and 85% in ATV/r along with two NRTIs [difference -12.1%, 95% confidence interval (95% CI) -27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92% in ATV/r arm and 85% in the ATV/r along with two NRTIs arm (difference 7.5%, 95% CI -4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P = 0.003) and grade 3-4 drug-related (P = 0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)-cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs. CONCLUSION: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.

Long-term glucose tolerance in highly experienced HIV-infected patients receiving nucleoside analogue-sparing regimens.

Thirty-nine HIV-1-infected patients treated for 156 weeks with a new nucleoside analogue-sparing regimen [raltegravir, etravirine and maraviroc (REM) or raltegravir, etravirine and darunavir/ritonavir (RED)] showed a uniform increase in fasting glucose levels and a uniform decrease in insulin secretory capacity. Diabetes mellitus occurred in one RED-treated and four REM-treated patients. A worsening glucose tolerance was observed in highly treatment-experienced HIV-infected patients receiving effective antiretroviral therapy after virological failure.