To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. Prospective study of 1046 patients at 47 French clinical sites. Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.

Early in the HIV epidemic, lipodystrophy, characterized by subcutaneous fat loss (lipoatrophy), with or without central fat accumulation (lipohypertrophy), was recognized as a frequent condition among people living with HIV (PLWH) receiving combination antiretroviral therapy. The subsequent identification of thymidine analogue nucleoside reverse transcriptase inhibitors as the cause of lipoatrophy led to the development of newer antiretroviral agents; however, studies have demonstrated continued abnormalities in fat and/or lipid storage in PLWH treated with newer drugs (including integrase inhibitor-based regimens), with fat gain due to restoration to health in antiretroviral therapy-naive PLWH, which is compounded by the rising rates of obesity. The mechanisms of fat alterations in PLWH are complex, multifactorial and not fully understood, although they are known to result in part from the direct effects of HIV proteins and antiretroviral agents on adipocyte health, genetic factors, increased microbial translocation, changes in the adaptive immune milieu after infection, increased tissue inflammation and accelerated fibrosis. Management includes classical lifestyle alterations with a role for pharmacological therapies and surgery in some patients. Continued fat alterations in PLWH will have an important effect on lifespan, healthspan and quality of life as patients age worldwide, highlighting the need to investigate the critical uncertainties regarding pathophysiology, risk factors and management.

Background: Antiretroviral therapy (ART)-controlled HIV-infected patients have elevated levels of systemic inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6, which correlate with increased cardiovascular risk and/or mortality. Persistent low-level viral replication could be involved in this inflammatory state. We evaluated whether residual viral load (VL) correlated with the level of systemic inflammatory/immune markers in ART-controlled HIV-infected patients. Methods: We evaluated 122 antiretroviral-controlled patients with VL 1–500 copies/ml for circulating levels of high-sensitivity (hs)CRP, hsIL-6, IL-8, soluble (s)CD14 and soluble tumour necrosis factor (TNF) receptors, sTNFR1 and sTNFR2. Results: The patients were 80.3% men, the median age was 47 years, the median CD4 ⁺ T-cell count was 519 cells/ mm ³ , the median nadir CD4 ⁺ T-cell count was 180 cells/ mm ³ , the median VL was 28 copies/ml and the median body mass index was 23.3 kg/m ² . The median (range) values for IL-6, CRP, IL-8, sCD14, sTNFR1 and sTNFR2 were 0.685 pg/ml (0.15–5.46), 1.8 mg/l (0.2–9.7), 10.0 pg/ml (1.6–71.1), 1,174 ng/ml (214–3,145), 1,112 pg/ml (583–5,834) and 2,412 pg/ml (1,142–7,688), respectively. IL-6 values correlated positively with HIV VL (rho=0.217, P=0.017). The VL threshold value for significantly increased IL-6 was 31 copies/ml ( P=0.023). IL-6 values correlated with markers of immune dysfunction: the CD4/CD8 ratio (rho=- 0.248, P=0.011), CD4 nadir level (rho=-0.186, P=0.04) and nadir CD4/CD8 ratio (rho=-0.257, P=0.008). They negatively correlated with markers of immune activation sCD14 (rho=-0.236, P=0.011) and IL-8 (rho=-0.290, P=0.002). We found no correlation between VL and CRP or other markers of inflammation/immune dysfunction including sTNFR1, sTNFR2, sCD14 and IL-8. Conclusions: We report here that low-range IL-6 levels correlated with low-range VL and inversely with sCD14 and IL-8. Our findings suggest that maintaining VL<30 copies/ ml in HIV-infected patients might therefore reduce IL-6.

Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2(AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARΓ. Importantly, lamin A/Cmutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their etiology is generally unknown, they could be associated with signs of autoimmunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardiovascular and hepatic complications.