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Abstract: Objective: The aim of the study was to identify the most useful clinical criteria to measure effectiveness and adherence to antiretroviral treatment in a rural area of Cameroon. Patients and method: All patients under antiretroviral therapy followed for at least 3 months at the Tokombéré UPEC hospital were eligible. Therapeutic failure was defined according to clinical criteria including weight, Karnofsky''s index, or occurrence of WHO stage IV conditions. The criteria for drug adherence were based on patient statement (drugs taken over the last 4 days) and pharmacy-controlled drug delivery. Patient sociodemographic characteristics were collected via a questionnaire. Results: Fifty-six patients were included, most of whom were at AIDS stage on treatment initiation. The mean duration of antiretroviral therapy was 1year. 21, 10, and 19% of patients were in therapeutic failure according to “weight”, “Karnofsky''s index”, and “WHO stage IV”, respectively. Non-adherence was reported in 5% of patients according to the declarative method and 20% according to pharmacy controlled drug delivery. Weight modification during treatment was significantly correlated with the evolution of Karnofsky''s index (p =0.03). A significant correlation between therapeutic failure and non-observance was only found when using the weight criterion and the declarative method (p =0.004). Conclusion: The effectiveness and adherence to antiretroviral therapy can be evaluated by simple clinical criteria. Using these criteria can be recommended in rural areas until access to biological follow-up becomes available in developing countries. [Copyright &y& Elsevier]

Background The world-wide AIDS epidemic is reflected in Western Europe in an increasing number of HIV-infected persons who originate from Africa. We describe the characteristics and response to antiretroviral therapy (ART) of HIV-infected patients born in Africa and living in France. Methods Analysis of data from the (Anti PROtéase COhorte APROCO) cohort study of HIV-infected patients initiating ART was carried out. Included in the study were 90 patients born in sub-Saharan Africa, 53 in North Africa and 771 in metropolitan France. Results At baseline, there was a higher proportion of women and of the heterosexual transmission route of infection among patients born in sub-Saharan Africa, a higher proportion of injecting drug users among patients born in North Africa and a higher frequency of unemployment and of unstable housing conditions among patients born in both sub-Saharan and North Africa as compared with patients born in France. The median CD4 cell count was lower in patients born in both sub-Saharan and North Africa (sub-Saharan Africa: 197 cells/μL; North Africa: 222 cells/μL) than in patients born in France (307 cells/μL). Median HIV-1 viral loads were similar. After a median follow-up time of 36 months (2506 patient-years), the Kaplan–Meier estimations of probability of survival without new AIDS-defining events were not different. After 36 months of ART, in multivariate analysis, median CD4 cell count, CD4/CD8 ratio and viral load were not statistically different according to birthplace, but the median CD4 percentage was lower in patients born in both sub-Saharan and North Africa. The adherence profiles were similar. Conclusions Although clinical response and adherence to ART did not appear to differ in patients according to their birthplace, the reasons for the more advanced HIV infection observed at ART initiation among patients born in Africa should be further investigated. [ABSTRACT FROM AUTHOR]

Background Inhibition of DNA polymerase γ by nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial dysfunction and cellular toxicity. Hyperlactataemia, which is a consequence of a shift in the metabolism of pyruvate, is an indicator of nucleoside-related mitochondrial toxicity. Methods We evaluated exercise and oxidative capacities as well as circulatory and ventilatory responses to exercise in 24 HIV-infected patients on NRTIs presenting hyperlactataemia [mean (±standard deviation) fasted lactate=3.5±1.1 mmol/L]; 27 NRTI-treated patients with normal baseline lactate concentrations were used as controls (mean fasted lactate=1.6±0.3 mmol/L). Results In the patients with hyperlactataemia, the average peak work capacity (1.7±0.6 W/kg) and peak oxygen consumption (VO2) (21±4 mL/kg/min) were significantly lower ( P<0.01) than in control subjects (work, 2.1±0.4 W/kg; VO2, 25±4 mL/kg/min). The capacity to increase oxygen extraction during exercise was significantly diminished in the hyperlactataemia group, as shown by a low peak systemic arteriovenous oxygen difference (a-vO2) difference compared with controls (11±3 vs 14±3 mL/dL; P=0.008), and as indicated by a linear correlation between VO2 and systemic a-vO2 difference ( r2=0.76). During exercise, the increases in cardiac output relative to VO2 (mean Δ cardiac output (Q)/ΔVO2=8±3.6) and ventilation (mean Δ ventilation (VE)/ΔVO2=48.6±13.2) were significantly higher in hyperlactataemia patients compared with controls (mean cardiac output Δ(Q)/ΔVO2=6±2; mean ΔVE/ΔVO2=42±12.7; P=0.03). Conclusions The degree of exercise limitation in patients with nucleoside-related mitochondrial toxicity correlates directly with the severity of impaired muscle oxidative phosphorylation, as indicated by the capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation. [ABSTRACT FROM AUTHOR]

There is a growing concern about an increased risk for cardiovascular disease in HIV infected patients receiving antiretroviral therapy (ART). This risk could be related to metabolic abnormalities associated with long-term use of antiretroviral drugs. In fact, well recognized cardiovascular risk factors such as hypertension, dyslipidaemia, diabetes mellitus and central fat deposition are increasingly seen in HIV patients on ART. These factors can also be associated with non reversible risk factors, such as male sex, age greater than 40 years and family history of premature coronary artery disease. In addition, cigarette smoking and sedentary lifestyle may predispose these patients to significant cardiovascular disease. A direct atherogenic effect of HIV infection itself or antiretroviral drugs is unlikely. Epidemiological studies have suggested an increased risk for coronary artery disease in HIV infected persons; nevertheless, only long term follow-up could confirm this statement. Despite these uncertainties, it seems reasonable to identify and manage cardiovascular risk factors in HIV infected patients. [Copyright &y& Elsevier]

Background Abnormalities in lipid levels and lipodystrophy (LD) have been commonly reported after commencement of highly active antiretroviral therapy (HAART). A major mechanism by which plasma low-density lipoprotein (LDL) cholesterol levels may be influenced is via the regulation of hepatic LDL receptor expression. The activity of LDL receptors is under hormonal control. Moreover, HIV infection and HAART are associated with important modifications of hormonal status. As the cause of these adverse reactions is unknown, the effects of HAART and lipodystrophy on LDL receptors were evaluated. Materials and methods Thirty-nine HIV treated patients (21 with a protease inhibitor (PI) containing regimen, 18 without PI use) and 22 control subjects were tested for insulin resistance (HOMA model assessment), lipid profile, serum concentration of dehydroepiandrosterone (DHEA) and LDL-R expression. LDL-R on mononuclear cells were quantified by flow cytrometry. Results Among the 39 HIV infected patients, 14 patients had a lipodystrophy (LD). Patients with LD had significantly higher levels of triglyceride (TG) and insulin resistance compared to patients without LD. There was no significant difference in LDL-R count between patients with or without PI use. In contrast, LDL-R count was significantly lower in patients with LD compared with those without (8504 ± 3901 vs. 13 200 ± 4532, P= 0.001). There was no difference in LDL-R count between patients without LD and control subjects. Patients with LD had lower levels of DHEA compared to patients without LD. In HIV-infected patients, we found a significant correlation between LDL-R expression and TG (r = -0·32; P= 0·04) and LDL cholesterol (r=-0·33; P= 0·04). In contrast, we did not observe a correlation between DHEA level and LDL-R count or LDL cholesterol level. Conclusions HIV-lipodystrophy is associated with a lower expression of LDL-R. This decreased expression of LDL-R seems... [ABSTRACT FROM AUTHOR]

The prevalence of silent myocardial ischemia (SMI) and the factors associated with SMI were evaluated in patients infected with human immunodeficiency virus (HIV) who had been receiving highly active antiretroviral therapy (HAART) for ≥ 12 months and did not have known coronary artery disease or cardiac symptoms. Patients prospectively underwent exercise stress testing. The prevalence of SMI was 11% (11 of 99 patients). Patients who had SMI were significantly older than were patients who did not ( mean ± SD, 51 ± 8 years vs. 42 ± 9 years; P=0.001) and were more likely to have trunk obesity (54% of patients vs. 17%; ). A significant correlation was found between a positive exercise test result and obesity (correlation, .006), waist-to- hip ratio (.007), and glucose and cholesterol levels (.04; p=.03 ). In multivariate analysis, age, central fat accumulation, and cholesterol level were independent variables associated with the detection of SMI. Exer-cise testing might be recommended for patients with HIV who have central fat accumulation and hyper-cholesterolemia. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Disseminated non-tuberculosis mycobacterial infections are associated with a defect of the cellular immune response. They have been mainly reported in AIDS patients. Cases related to the presence of anti-interferon-γ autoantibodies are rare. Case report: We report a non HIV-infected 45-year-old Thai woman, with a past medical history of Graves’ disease. She presented with recurrent disseminated and severe non-tuberculous mycobacterial infections that were related to the production of anti-interferon-γ autoantibody. The diagnosis was suspected in the presence of a negative interferon-γ release assay (IGRA) including with the positive control, and evidenced by the identification of specific antibodies. Conclusion: Anti-interferon-γ autoantibody production is a rare cause of non tuberculous mycobacterial infection. Such a mechanism should be suspected in non HIV-infected patients and especially in those having an Asiatic ethnicity or an associated immune disorder. A negative IGRA (including with the positive control) is a reliable diagnostic tool and should be completed with the identification of specific autoantibodies. [Copyright &y& Elsevier]

Presents a study that determined the frequency of incomplete genotypic resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI) among HIV-infected persons treated with nevirapine. Definition of incomplete genotypic resistance; Determination of full susceptibility and partial susceptibility of patients to NNRTI; Recommendations.