Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis.

OBJECTIVES: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL). METHODS: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m2 . RESULTS: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. CONCLUSIONS: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection.

OBJECTIVES: Monocyte activation, endothelial dysfunction and platelet activation all potentially contribute to the increased risk of cardiovascular disease (CVD) reported in those with HIV-1 infection. To date, no study has examined how initiation of antiretroviral therapy (ART) affects markers of all three processes. We aimed to compare markers of monocyte, endothelial and platelet function between untreated HIV-positive subjects and HIV-negative controls and to examine the early effects of ART initiation on these markers. METHODS: We measured monocyte [soluble CD14 (sCD14) and sCD163], endothelial [von Willebrand factor (vWF), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1)] and platelet [soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L) and soluble glycoprotein VI (sGPVI)] biomarkers before and at weeks 4 and 12 post ART initiation in HIV-positive and well-matched HIV-negative controls. RESULTS: We examined 40 subjects, 25 HIV-positive subjects and 15 controls, with a median age of 34 years [interquartile range (IQR) 31, 40 years], of whom 60% were male and 47.5% Caucasian. Pre-ART, all biomarkers (monocyte, endothelial and platelet) were significantly higher in HIV-positive patients versus controls (all P < 0.05) and decreased with ART initiation, except for sCD14, which remained unchanged [median 1680 (IQR 1489, 1946) ng/mL at week 12 versus 1570 (IQR 1287, 2102) ng/mL at week 0; P = 0.7]. Although platelet activation markers reduced to levels comparable to those in controls, endothelial dysfunction markers remained elevated, as did sCD163 [at week 12, median 1005 (IQR 791, 1577) ng/mL in HIV-positive patients versus 621 (IQR 406, 700) ng/mL in controls; P < 0.0001]. CONCLUSIONS: ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.

Insulin resistance in treated HIV infection.

Insulin resistance (IR) was one of the first metabolic complications reported with highly active antiretroviral therapy for HIV infection. It continues to be of concern despite the introduction of newer antiretrovirals with safer metabolic profiles and is associated with inflammation and the development of diabetes mellitus. As the HIV-infected population ages, the prevalence of IR is likely to rise. Specific antiretrovirals can increase insulin resistance through two principal mechanisms, either directly by interfering with insulin signalling at the cellular level or indirectly as a consequence of defects in lipid metabolism (lipotoxocity) arising from antiretroviral toxicities such as the IR observed in those with HIV-associated lipodystrophy. There is considerable overlap between different antiretrovirals in their propensity to cause IR making it more difficult to attribute development of IR to a particular antiretroviral medication. In addition, in the setting of a generalised epidemic of obesity that exists in many populations worldwide, HIV-infected patients may be more prone to the consequences of antiretroviral-induced insulin resistance and diabetes mellitus. Optimal screening and treatment strategies for IR in treated HIV infection have not been established. In this article we review current opinion on insulin resistance in HIV and identify potential areas for future research.

Hyperlactataemia in HIV-infected subjects initiating antiretroviral therapy in a large randomized study (a substudy of the INITIO trial).

OBJECTIVE: The aim of the study was to evaluate the predictive value of clinical and molecular risk factors, including peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), for the development of lactic acidosis (LA) and symptomatic hyperlactataemia (SHL). METHODS: In a substudy of a large multicentre, randomized trial of three antiretroviral regimens, all containing didanosine (ddI) and stavudine (d4T), in antiretroviralnaïve, HIV-1-infected patients, patients with LA/SHL ('cases') were compared with those without LA/SHL in a univariate analysis, with significant parameters analysed in a multivariate model. In a molecular substudy, PBMC mtDNA and mtRNA from cases and matched controls at baseline and time of event were examined. RESULTS: In 911 subjects followed for a median of 192 weeks, 24 cases were identified (14 SHL and 10 LA). In univariate analysis, cases were more likely to be female (P=0.05) and to have a high body mass index (BMI) (P=0.02). In multivariate analyses, only BMI remained an independent predictor of the development of LA/SHL (P=0.03). Between cases and controls there was no significant difference in mtDNA copy number at baseline (389 vs. 411 copies/cell, respectively; P=0.60) or at time of event (329 vs. 474 copies/cell, respectively; P=0.21), in the change in mtDNA copy number from baseline to event (-65 vs. +113 copies/cell, respectively; P=0.12), in mtRNA expression at baseline or time of event, or in the change in mtRNA expression from baseline to event. CONCLUSION: The development of LA/SHL was associated with increased BMI, but PBMC mtDNA and mtRNA did not predict LA/SHL. This demonstrates the ineffectiveness of routine measurement of PBMC mtDNA in patients on ddI and d4T as a means of predicting development of LA/SHL.