The impact of food insecurity on HIV outcomes in Senegal, West Africa: a prospective longitudinal study.

BACKGROUND: Understanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa. METHODS: HIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart review at enrollment, month 6, and month 12. Logistic regression was used to determine the association between food insecurity and HIV outcomes. RESULTS: Among the 207 participants in this study, 70% were female and the median age was 37 years. The majority (69%) were food insecure at enrollment, 29% were severely food insecure, and 38% were undernourished. Nearly a third (32%) had no formal education, 23% practiced agriculture, and 40% owned livestock. The median daily food expenditure per person was $0.58. The median round trip transportation time to clinic was 90 min (IQR 30-240). The median cost of transportation to clinic was $1.74. At month 12, 69% were food insecure, 23% were severely food insecure, and 14% were undernourished. At month 12, 43% had not disclosed their HIV status; food insecurity was associated with non-disclosure of HIV-status due to fear of stigmatization and feelings of shame. Severe food insecurity was a strong predictor of loss to follow-up (OR 3.13 [1.08-9.06]) and persistent severe food insecurity was associated with virologic failure (OR 5.14 [1.01-26.29]) and poor adherence to ART 8.00 [1.11-57.57]. Poor nutritional status was associated with poor immunologic recovery (OR 4.24 [1.56-11.47]), virologic failure (OR 3.39 [1.13-10.21]), and death (OR 3.35 [1.40-8.03]). CONCLUSION: Severity and duration of food insecurity are important factors in understanding the relationship between food insecurity and HIV outcomes. Our findings highlight the importance of nutritional status, socioeconomic opportunity, and self-stigmatization in the complex pathway between food insecurity and HIV outcomes. Interdisciplinary, multisectoral efforts are needed to develop and implement effective interventions to address food insecurity among people living with HIV.

The dimensions of food insecurity and malnutrition among people living with HIV in Senegal, West Africa.

An understanding of the factors contributing to food insecurity and malnutrition among people living with HIV (PLHIV) in Senegal is urgently needed in order to develop effective interventions. The goals of this study were to identify differences in the dimensions of food security among PLHIV in Dakar versus Ziguinchor, Senegal, to determine which of these dimensions are most predictive of severe food insecurity, and to identify factors associated with malnutrition. We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Interviews were conducted with ninety-five food insecure, HIV-infected subjects. Daily household income and daily food expenditure per household member were the strongest predictors of severe food insecurity. The practice of agriculture, livestock ownership, nutritional status, and HIV outcomes were not predictive of severe food insecurity. CD4 count <350/mm3 was the strongest predictor of malnutrition. Severe food insecurity, daily household income, daily food expenditure per household member, dietary diversity score, skipping meals, the practice of agriculture, livestock ownership, ART status, and adherence were not predictive of malnutrition. This is the first study to analyze the dimensions of food security among PLHIV in Senegal. We discovered important differences in food access, availability, stability, and utilization in Dakar versus Ziguinchor. We found that economic access was the strongest predictor of severe food insecurity and poorly controlled HIV was the strongest predictor of malnutrition. Our findings suggest that the interventions needed to address food insecurity differ from those necessary to target malnutrition, and that effective interventions may differ in Dakar versus Ziguinchor. Furthermore, this study highlights a need for a greater understanding of the relationship between HIV and malnutrition among individuals receiving ART in resource-limited settings.

[Smoking in People Living with HIV (PLHA) and followed up in the Outpatient Department of the Hospital Fann of Dakar]. / Le tabagisme chez les patients vivant avec le VIH (PvVIH) suivis au Centre de Traitement Ambulatoire de l'Hôpital Fann de Dakar.

INTRODUCTION: PLHA who smoke have twice the never-smoker mortality rate and have an increased risk of developing non-AIDS diseases. The prevalence of tobacco smoking is higher among PLHA than in the general population. The purpose of this study was to assess the prevalence of smoking among PLHA, to describe the clinical and spirometric features of smokers and ex-smokers and to assess their knowledge and attitudes toward smoking. METHODS: We conducted a cross-sectional, descriptive and analytical study among PLHA followed up in the Outpatient Department of the National University Hospital Center of Fann from 15 July to 15 December 2015. RESULTS: Three hundred (300) PLHA were included in the study. Sex ratio was 0.8. Out of the study population, 15% were smokers and 23.7% were ex-smokers. The average age of patients was 44.38±9.55 years. The quasi-totality of the smokers (91.1%) had already started smoking before the detection of the serological status and 35.6% of them had increased tobacco use after. Respiratory symptoms among smokers were dominated by respiratory distress (64.4%). Smokers who underwent spirometry had obstructive ventilatory impairment not improved by beta-2-mimetic agents (67%) and restrictive disease (28.1%). Out of ex-smokers, 40.8% reported that their serological status was the reason for smoking cessation. CONCLUSION: People may begin or increase smoking after knowledge of serological status. In PLHA, smoking causes cardiovascular and respiratory diseases as well as complications.

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

BACKGROUND: Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). METHODS: We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per µL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (< 50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059. FINDINGS: Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p<0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause). INTERPRETATION: After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients. FUNDING: Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study.

OBJECTIVES: To evaluate survival and investigate causes of death among HIV-1 infected adults receiving HAART in Senegal. DESIGN: An observational prospective cohort. METHODS: Mortality was assessed in the first patients enrolled between August 1998 and April 2002 in the Senegalese antiretroviral drug access initiative. First-line regimen combined two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The most likely causes of death were ascertained through medical records or post-mortem interviews (verbal autopsy). RESULTS: Four hundred and four patients (54.7% women) were enrolled in the study and were followed for a median of 46 months (interquartile range: 32-57 months) after HAART initiation. At baseline, 5% were antiretroviral therapy (ART) non-naive, 39 and 55% were respectively at CDC stage B and C, median age, CD4 cell count and viral load were 37 years, 128 cells/microl and 5.2 log cp/ml, respectively. Ninety-three patients died during follow-up and the overall incidence rate of death was 6.3/100 person-years [95% confidence interval (CI), 5.2-7.7]. During the first year after HAART initiation, 47 patients died and seven were lost to follow-up, yielding to a probability of dying of 11.7% (95% CI, 8.9-15.3%). The death rate, which was highest during the first year after HAART initiation, decreased with time yielding a cumulative probability of dying of 17.4% (95% CI, 13.9-21.5%) and 24.6% (95% CI, 20.4-29.4%) at 2 and 5 years. Causes of death were ascertained in 76 deaths. Mycobacterial infections, neurotropic infections and septicaemia were the most frequent likely causes of death. CONCLUSIONS: This study underlines the early mortality pattern after HAART initiation and highlights the leading role of mycobacterial infections in the causes of death.

Low rate of genotypic HIV-1 drug-resistant strains in the Senegalese government initiative of access to antiretroviral therapy.

OBJECTIVE: To monitor the prevalence of antiretroviral (ARV)-resistant HIV-1 viruses, and the genotypic mutations in patients enrolled in the Senegalese initiative for access to antiretroviral treatment (ART). METHODS: A total of 80 patients with a virological follow-up of at least 6 months were selected, 68 were ART-naive and 12 ART-experienced. Genotypic resistance to ARV was studied at baseline for a random subset of patients and at each rebound in plasma viral load during ART, by sequencing the protease and reverse transcriptase genes. RESULTS: At baseline, 66 patients received highly active antiretroviral therapy (HAART) [2 nucleoside reverse transcriptase inhibitors (NRTIs) +1 protease inhibitor (PI) (n = 64) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (n = 2)] and 14 patients (17.5%) started with a dual therapy because of ongoing antitubercular therapy or efficient previous bitherapy for the ART-experienced patients. The emergence of drug-resistant viruses (n = 13) during follow-up was more frequent in ART-experienced patients than in ART-naive patients, 41.7 versus 11.8%, resistant viruses emerged at comparable follow-up periods, a median of 17.8 and 18.3 months, respectively. In patients receiving zidovudine and lamivudine in their drug regimen, resistance to lamivudine was more frequent than to zidovudine. Two of the three patients, with viruses resistant to PIs, acquired mutations associated with cross-resistance. Strikingly, five (39%) of the 13 patients developed resistances to drugs that they had never received (n = 3) or that they received 18 or 36 months ago (n = 2). Didanosine/stavudine pressure had selected zidovudine-resistant viruses in four patients, and indinavir had selected a nelfinavir-resistant virus in one patient. CONCLUSION: In contrast to other reports from developing countries where patients had received ARVs in an uncontrolled manner, our study showed that implementation of HAART together with good clinical, biological and logistical monitoring can reduce the emergence of resistant strains in Africa.

The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study.

OBJECTIVE: To study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative. METHODS: A prospective observational cohort study started in Dakar in August 1998. Initial treatment consisted of two nucleoside reverse transcriptase inhibitors and one protease inhibitor. The patients attended monthly medical examinations. Plasma HIV-1 RNA and CD4 cell counts were determined at baseline and every 6 months. Intention-to-treat analyses were performed. RESULTS: Fifty-eight treatment-naive patients, mostly infected by HIV-1 strain CRF02-AG, were enrolled. Most were at an advanced stage of HIV disease (86.2% had AIDS). Adherence was good in 87.9% of patients and treatment was effective in most of them. Thus, HIV-1 RNA was undetectable in 79.6, 71.2, 51.4 and 59.3% of patients at months 1, 6, 12 and 18, respectively and the median viral load reduction was approximately 2.5 log10 copies/ml. The CD4 cell count rose by a median of 82, 147 and 180 x 106 cells/l at months 6, 12 and 18, respectively. At the same time points, the cumulative probability of remaining alive or free of new AIDS-defining events was 94.8, 85.0 and 82.3%. Most adverse effects (80.8%) were mild or moderate and only two cases of drug resistance occurred. CONCLUSION: This study shows that HAART is feasible and well tolerated in African patients. Clinical and biological results were comparable to those seen in western cohorts, despite differences in the HIV-1 subtype distribution and an advanced disease stage when the treatment was initiated. Contrary to other recent studies in Africa, viral resistance rarely emerged.

Evaluation of four tenofovir-containing regimens as first-line treatments in Cameroon and Senegal: the ANRS 12115 DAYANA Trial.

BACKGROUND: The aim of the present study was to determine appropriate tenofovir-based regimens meriting evaluation in large-scale randomized trials among sub-Saharan African patients. METHODS: This was a randomized open-label 96-week prospective pilot study evaluating four first-line regimens: tenofovir/emtricitabine/nevirapine (group 1), tenofovir/lopinavir/ritonavir (group 2), tenofovir/emtricitabine/zidovudine (group 3) and tenofovir/emtricitabine/efavirenz (group 4) in antiretroviral-naive, HIV-1-infected patients in Senegal and Cameroon. The primary end point was defined as an HIV-1 RNA viral load <50 copies/ml (study detection limit) at week 16 in ≥50% of patients using intention-to-treat analysis. RESULTS: At baseline, 119 patients included were 34% male, had a median plasma viral load of 5.4 log10 copies/ml and median CD4(+) T-cell count of 200 cells/mm(3) (range 53-358). The primary end point was achieved for groups 1, 3 and 4 (58% [n=31], 62% [n=29] and 53% [n=30], respectively), but not for group 2 (38% [n=29]). At week 96, undetectable HIV-1 RNA had been achieved in 74% of patients in group 1, 38% in group 2, 72% in group 3 and 73% in group 4. Patients with detectable HIV-1 RNA at week 16 were more likely to have baseline HIV-1 RNA≥100,000 copies/ml (adjusted OR 5.56, 95% CI 1.72, 16.67). HIV mutations associated with protease inhibitor resistance emerged in three patients, all of whom were in group 2. Anaemia occurred in two group 3 patients and was the only serious treatment-related adverse event. CONCLUSIONS: Three efficient and safe tenofovir-based triple regimens were identified; the two-drug regimen (tenofovir/lopinavir/ritonavir) did not achieve the protocol-defined virological threshold of efficacy.

Lipodystrophy and metabolic disorders in HIV-1-infected adults on 4- to 9-year antiretroviral therapy in Senegal: a case-control study.

OBJECTIVE: To assess adverse effects of long-term highly active antiretroviral therapy (HAART), that is, lipodystrophy and metabolic disorders, in a cohort of African patients. METHODS: One hundred eighty HIV-1-infected patients treated with HAART for 4-9 years in Dakar and 180 age-matched and sex-matched controls were enrolled. Regional subcutaneous fat changes were assessed by physicians, and fasting blood samples were drawn. Centralization of body fat was estimated using skinfold ratio, waist circumference, and waist to hip ratio (WHR). RESULTS: Mean duration of HAART was 5.4 years. Main drugs received were zidovudine, stavudine, and protease inhibitors. The prevalence of moderate-severe lipodystrophy was 31.1% (95% confidence interval: 24.3 to 37.9), with 13.3%, 14.5%, and 3.3% for lipoatrophy, lipohypertrophy, and mixed forms, respectively. Mild-severe lipodystrophy affected 65.0% (58.0; 72.0) of patients. Stavudine was the only independent risk factor (any vs. none: odds ratio = 2.8; 1.4 to 5.5). Patients had lower body mass index and skinfolds but greater centralization of body fat (WHR, P < 0.0001 and skinfold ratio, P < 0.001), fasting glucose (P < 0.0001), homeostasis model assessment insulin resistance, and triglyceride levels (P < 0.01 for both) than controls. Moderately-severely lipodystrophic patients had higher triglyceride and low-density lipoprotein cholesterol than other patients (P < 0.001 and P < 0.05, respectively). CONCLUSIONS: Moderate-severe lipodystrophy affected one third of West African patients on long-term HAART and was associated with a less favorable metabolic profile.

Change over time of mortality predictors after HAART initiation in a Senegalese cohort.

BACKGROUND: In 1998, Senegal was among the first sub-Saharan African countries to launch a Highly active anti-retroviral therapy (HAART) access program. Initial studies have demonstrated the feasibility and efficacy of this initiative. Analyses showed a peak of mortality short after starting HAART warranting an investigation of early and late mortality predictors. METHODS: 404 HIV-1-infected Senegalese adult patients were enrolled and data censored as of September 2005. Predictor effects on mortality were first examined over the whole follow-up period (median 46 months) using a Cox model and Shoenfeld residuals. Then, changes of these effects were examined separately over the early and late treatment periods; i.e., less and more than 6-month follow-up. RESULTS: During the early period, baseline body mass index and baseline total lymphocyte count were significant predictors of mortality (Hazard Ratios 0.82 [0.72-0.93] and 0.80 [0.69-0.92] per 200 cell/mm3, respectively) while baseline viral load was not significantly associated with mortality. During the late period, viro-immunological markers (baseline CD4-cell count and 6-month viral load) had the highest impact. In addition, the viral load at 6-month was a significant predictor (HR = 1.42 [1.20-1.66]). CONCLUSION: In this cohort, impaired clinical status could explain the high early mortality rate while viro-immunological markers were rather predictors of late mortality.