Epidemiology, assessment, and management of excess abdominal fat in persons with HIV infection.
; Moutschen, Michel ; et al
in AIDS Reviews (2010), 12(1), 3-14
Metabolic and morphologic abnormalities in persons with HIV remain common contributors to stigma and morbidity. Increased abdominal circumference and visceral adiposity were first recognized in the late ... [more ▼]
Metabolic and morphologic abnormalities in persons with HIV remain common contributors to stigma and morbidity. Increased abdominal circumference and visceral adiposity were first recognized in the late 1990s, soon after the advent of effective combination antiretroviral therapy. Visceral adiposity is commonly associated with metabolic abnormalities including low HDL-cholesterol, raised triglycerides, insulin resistance, and hypertension, a constellation of risk factors for cardiovascular disease and diabetes mellitus known as "the metabolic syndrome". Medline and conference abstracts were searched to identify clinical research on factors associated with visceral adiposity and randomized studies of management approaches. Data were critically reviewed by physicians familiar with the field. A range of host and lifestyle factors as well as antiretroviral drug choice were associated with increased visceral adiposity. Management approaches included treatment switching and metformin, both of which have shown benefit for insulin-resistant individuals with isolated fat accumulation. Testosterone supplements may also have benefits in a subset of individuals. Supra-physiological doses of recombinant human growth hormone and the growth hormone releasing hormone analog tesamorelin both significantly and selectively reduce visceral fat over 12-24 weeks; however, the benefits are only maintained if doping is continued. In summary, the prevention and management of visceral adiposity remains a substantial challenge in clinical practice. [less ▲]Detailed reference viewed: 21 (1 ULg)
Apoptosis characterizes immunological failure of HIV infected patients
; ; Fonteneau, Raphaël et al
in Control Engineering Practice (2009), 17(7), 798-804
This paper studies the influence of apoptosis in the dynamics of the HIV infection. A new modeling of the healthy CD4+ T-cells activation-induced apoptosis is used. The parameters of this model are ... [more ▼]
This paper studies the influence of apoptosis in the dynamics of the HIV infection. A new modeling of the healthy CD4+ T-cells activation-induced apoptosis is used. The parameters of this model are identified by using clinical data generated by monitoring patients starting Highly Active Anti-Retroviral Therapy (HAART). The sampling of blood tests is performed to satisfy the constraints of dynamical system parameter identification. The apoptosis parameter, which is inferred from clinical data, is then shown to play a key role in the early diagnosis of immunological failure. [less ▲]Detailed reference viewed: 67 (17 ULg)
Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection.
; ; et al
in New England Journal of Medicine [=NEJM] (2008), 359(14), 1442-55
BACKGROUND: We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to ... [more ▼]
BACKGROUND: We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients. METHODS: We analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed. RESULTS: A treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline. CONCLUSIONS: Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.) [less ▲]Detailed reference viewed: 47 (1 ULg)