Impact of randomized antiretroviral therapy initiation on glucose metabolism: AIDS clinical trials group study A5224s.
Prior studies have found that early HIV protease inhibitors contribute to glucose dysregulation. Few randomized trials have evaluated glucose indices in antiretroviral-naive individuals on newer antiretroviral therapy (ART).
A5224s was a substudy of A5202, a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). Analyses used two-sample t-tests, Spearman correlation coefficients and linear regression.
A5224s included 269 nondiabetic individuals: 85% men, 47% white non-Hispanic, baseline median age 38 years, HIV-1 RNA 4.6 log10 copies/ml and CD4 cell count 233 cells/μl. Overall, significant 96-week increases occurred in fasting glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), P ≤ 0.004. Assignment to EFV (versus ATV/r) resulted in significantly greater glucose increase [mean difference 4.4; 95% confidence interval (CI) 1.3, 7.5 mg/dl; P = 0.006] but not insulin or HOMA-IR (P ≥ 0.72). Glucose indices were not significantly different between ABC/3TC and TDF/FTC arms, P ≥ 0.18. Significant correlations were detected between changes in glucose indices and changes in BMI; all r ≥ 0.23, P ≤ 0.001. In multivariable analyses, in addition to the EFV effect, higher baseline HIV-1 RNA and greater BMI change were significant independent factors associated with greater glucose increase.
Changes in glucose metabolism were not significantly different between TDF/FTC and ABC/3TC-based regimens. A small but significantly greater increase in glucose was observed in those assigned to EFV. As glucose dysregulation may increase with time on ART, longer term studies will be needed to further clarify the clinical significance of these findings.
Available from: Stefano Rusconi
[Show abstract] [Hide abstract]
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.
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.
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.
ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.
[Show abstract] [Hide abstract]
ABSTRACT: Diabetes mellitus (DM) is a common condition with significant associated morbidity and mortality. DM diagnosis and management
among human immunodeficiency virus (HIV)-infected patients is a particularly relevant topic as the HIV-infected population
ages and more HIV-infected individuals live with chronic medical comorbidities. Although there is mixed evidence regarding
HIV as an independent risk factor for DM, multiple factors related to HIV and its treatment are associated with DM. This review
covers the epidemiology of DM in HIV-infected patients, and diagnosis, management, and treatment goals for DM in HIV-infected
patients. We highlight the most recent DM treatment guidelines from the American Diabetes Association and the European Association
for the Study of Diabetes, emphasizing individualization of DM medication therapy and treatment goals. Finally, we review
a comprehensive approach to cardiovascular disease risk reduction in HIV-infected patients with DM and measures to prevent
other complications of DM.
[Show abstract] [Hide abstract]
ABSTRACT: Among patients with HIV infection, changes in the kidney filtration marker cystatin C after initiation of antiretroviral therapy (ART) may be related to changes in body composition or biomarkers of inflammation.
ACTG A5224s was a substudy of A5202, which randomly assigned ART-naive HIV-infected subjects to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or ritonavir-boosted atazanavir. This analysis explored changes in cystatin C from 0 to 96 weeks.
Of the 269 subjects, 85% were male and 66% white non-Hispanics; baseline mean CD4 count was 236 cells per cubic millimeter and cystatin C was 0.89 mg/L. Cystatin C decreased significantly within each arm; however, ritonavir-boosted atazanavir attenuated the beneficial effects of ART on cystatin C compared to EFV. Compared to ABC/3TC, TDF/FTC led to a marginally significant attenuation for percent change analyses only. Higher baseline body mass index and HIV RNA were associated with larger reductions in cystatin C in multivariable models. At baseline, cystatin C was positively correlated with high-sensitivity C-reactive protein (Spearman r = 0.25), interleukin 6 (r = 0.34), soluble intercellular adhesion molecule (r = 0.36), soluble vascular cell adhesion molecule (r = 0.54), tumor necrosis factor α (r = 0.57), and soluble TNF-α receptor I (r = 0.70, all P < 0.001). Reductions in cystatin C from 0 to 96 weeks correlated with reductions in all inflammatory biomarkers (r = 0.39-0.58, P < 0.001) except for high-sensitivity C-reactive protein (r = 0.01, P = 0.89) and IL-6 (r = 0.08, P = 0.24).
The beneficial effect of ART on cystatin C concentrations is attenuated by boosted ATV when compared to EFV. Reductions in cystatin C after ART are associated with reductions in systemic inflammation.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.