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Objective: To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. Methods: This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998–2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011–2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014–2015. Four periods were defined according to ART eligibility expansions and Senegal’s HIV care history: 1998–2003 (P 1), 2004–2010 (P 2), 2011–2013 (P3), and 2014–2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). Results: A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32–48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014–2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3–11) in P1 to 0.8 months (IQR: 0–2) in P4. Eligible patients with more advanced disease (CD4<200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be ART initiated than those with CD4≥200 cells/mm3 and/or clinical stage 1 or 2 at each stage of ART eligibility expansion. Conclusion: ART eligibility expansions were marked by a sharp increase in the proportion of eligible patients initiating treatment. These results show that in terms of management, the target of "Test and Treat" can be easily reached but that HIV testing will remain a key element to improve treatment success, as illustrated by the high proportion of people with advanced stage of infection at the time of ART initiation. [ABSTRACT FROM AUTHOR]

Background: Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. Methods and findings: In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33–46 years) and median T-CD4 count was 199 cells/μl (IQR: 113–319 cells/μl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36–72 months) and the median baseline SI was 101 (IQR: 87–116). In multivariable analysis, factors associated with baseline SI were sex (β = -10.8 [-18.1,-3.5] for women), age (β = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (β = +0.8 [0.1,1.5] per unit of BMI), and study site (β = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. Conclusion: Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up. [ABSTRACT FROM AUTHOR]

Background: UNAIDS recently defined the 90-90-90 target as a way to end the HIV epidemic. However, the proportion of virological success following antiretroviral therapy (ART) may not be as high as the anticipated 90%, and may in fact be highly heterogeneous. We aimed to describe the proportion of virological success in sub-Saharan Africa and to identify factors associated with the proportion of virological success. Methods: We performed a systematic review and meta-analysis focusing on the proportion of patients in sub-Saharan Africa who demonstrate virological success at 12 and 24 months since ART initiation, as well as at 6 and 36 months, where possible. Programme factors associated with the proportion of virological success were identified using meta-regression. Analyses were conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches. Results: Eighty-five articles were included in the meta-analysis, corresponding to 125 independent study populations. Using an on-treatment approach, the proportions (95% confidence interval (CI)) of virological success at 12 (n = 64) and at 24 (n = 32) months since ART initiation were 87.7% (81.3–91.0) and 83.7% (79.8–87.6), respectively. Univariate analysis indicated that the proportion of virological success was not different by study design. Multivariate analysis at 24 months showed that the proportion of virological success was significantly larger in studies conducted in public sector sites than in other sites (p = 0.045). Using an ITT approach, the proportions (95% CI) of virological success at 12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8–69.1) and 56.8% (51.3–62.4), respectively. At 12 months, multivariate analysis showed that the proportion of success was significantly lower in cohort studies than in trials (63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that the proportion of success was also lower in cohorts. Discussion: Regardless of the time following ART initiation, and of the threshold, proportions of virological success were highly variable. Evidence from this review suggests that the new international target of 90% of patients controlled is not yet being achieved, and that in order to improve the virological outcome, efforts should be made to improve retention in care. [ABSTRACT FROM AUTHOR]

Objective: The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation. Methods: Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m2 (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4. Results: Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9–41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m2/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m2/year during TDF exposure versus 3 ml/min/1.73m2/year after TDF discontinuation; p = 0.01). Conclusions: The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood. [ABSTRACT FROM AUTHOR]

Background: Bone status in HIV-infected patients on antiretroviral treatment (ART) is poorly documented in resource-limited settings. We compared bone mineral density between HIV-infected patients and control subjects from Dakar, Senegal. Methods: A total of 207 (134 women and 73 men) HIV-infected patients from an observational cohort in Dakar (ANRS 1215) and 207 age- and sex-matched controls from the general population were enrolled. Bone mineral density was assessed by quantitative ultrasound (QUS) at the calcaneus, an alternative to the reference method (i.e. dual X-absorptiometry), often not available in resource-limited countries. Results: Mean age was 47.0 (±8.5) years. Patients had received ART for a median duration of 8.8 years; 45% received a protease inhibitor and 27% tenofovir; 84% had undetectable viral load. Patients had lower body mass index (BMI) than controls (23 versus 26 kg/m², P<0.001). In unadjusted analysis, QUS bone mineral density was lower in HIV-infected patients than in controls (difference: -0.36 standard deviation, 95% confidence interval (CI): -0.59;-0.12, P = 0.003). Adjusting for BMI, physical activity, smoking and calcium intake attenuated the difference (-0.27, CI: -0.53;-0.002, P = 0.05). Differences in BMI between patients and controls explained a third of the difference in QUS bone mineral density. Among patients, BMI was independently associated with QUS bone mineral density (P<0.001). An association between undetectable viral load and QUS bone density was also suggested (β = 0.48, CI: 0.02;0.93; P = 0.04). No association between protease inhibitor or tenofovir use and QUS bone mineral density was found. Conclusion: Senegalese HIV-infected patients had reduced QUS bone mineral density in comparison with control subjects, in part related to their lower BMI. Further investigation is needed to clarify the clinical significance of these observations. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level. Design: We conducted a systematic review and meta-regression of available data. Data Sources: Electronic and paper records on subject area ever produced up to February 2008. Review Methods: We searched for population-based studies reporting on the prevalence of epilepsy in communities for which onchocerciasis prevalence was available or could be estimated. Two authors independently assessed eligibility and study quality and extracted data. The estimation of point prevalence of onchocerciasis was standardized across studies using appropriate correction factors. Variation in epilepsy prevalence was then analyzed as a function of onchocerciasis endemicity using random-effect logistic models. Results: Eight studies from west (Benin and Nigeria), central (Cameroon and Central African Republic) and east Africa (Uganda, Tanzania and Burundi) met the criteria for inclusion and analysis. Ninety-one communities with a total population of 79,270 individuals screened for epilepsy were included in the analysis. The prevalence of epilepsy ranged from 0 to 8.7% whereas that of onchocerciasis ranged from 5.2 to 100%. Variation in epilepsy prevalence was consistent with a logistic function of onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence. Conclusion: These results give further evidence that onchocerciasis is associated with epilepsy and that the disease burden of onchocerciasis might have to be re-estimated by taking into account this relationship. Author Summary: Epilepsy is particularly common in tropical areas. One main reason is that many endemic infections have neurological consequences. In addition, the medical, social and demographic burden of epilepsy remains substantial in these countries where it is often seen as a contagious condition and where the aetiology is often undetermined. For several decades, field researchers had reported some overlapping between the geographical distributions of epilepsy and onchocerciasis, a parasitic disease caused by the filarial worm Onchocerca volvulus which afflicts some 40 million persons worldwide. Here, we conducted a statistical analysis of all the data available on the relationship between the two conditions to determine whether the proportion of people suffering from epilepsy in a community could be related to the frequency of onchocerciasis. The combined results of the eight studies carried out in west, central and east Africa indicate a close epidemiological association between the two diseases. Should a causative relationship be demonstrated, onchocerciasis, which is known as "river blindness" because of its most serious sequela and the distribution of its vectors, could thus also be called "river epilepsy". More research is needed to determine the mechanisms explaining this association and to assess the burden of onchocerciasis-associated epilepsy. [ABSTRACT FROM AUTHOR]