Efficacy and safety of three antiretroviral therapy regimens for treatment-naive African adults living with HIV-2 (FIT-2): a pilot, phase 2, non-comparative, open-label, randomised controlled trial.

BACKGROUND: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. METHODS: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per µL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. FINDINGS: Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. INTERPRETATION: The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. FUNDING: ANRS MIE.

Seroprevalence of SARS-CoV-2 IgG and associated factors among people living with HIV over the first 12 months following the outbreak of COVID-19 in Burkina Faso, a sub-Saharan African country.

OBJECTIVE: This study aimed to evaluate the seroprevalence of anti-SARS-CoV-2 IgG and factors associated with the infection among PLWHIV over the first 12 months following the outbreak of COVID-19 in Burkina Faso. DESIGN: A retrospective cross-sectional study of plasma samples collected from March 9, 2020, and March 8, 2021, at the outpatient HIV referral center, before the introduction of the SARS-CoV-2 vaccine in Burkina Faso. METHODS: Anti-SARS-CoV-2 IgG were detected in plasma using DS-ЕIA-ANTI-SARS-CoV-2-G (S) kit. Logistic regressions were used to compare SARS-CoV-2 specific immune responses between groups and within subgroups. RESULTS AND DISCUSSION: A total of 419 plasma were subjected to serological diagnosis. None of the participants was vaccinated against COVID-19 during the period of sample collection, and 130 samples were positive for anti-SARS-CoV-2 IgG, giving a prevalence of 31.0% (95% CI 26.6-35.7). The median CD4 cell count was 661 cells/µL (IQR,422-928). Retailers had half the risk of being infected compared to housemaids with an OR of 0.49 (p = 0.028, 95% CI 0.26-0.91). Likewise, the risk of infection was 1.69 times higher in patients on integrase inhibitors compared to that of patients on non-nucleoside reverse transcriptase inhibitors (p = 0.020, 95% CI 1.09-2.63). CONCLUSION: Our study reveals a high seroprevalence among PLWHIV to SARS-CoV-2 during the first year of the pandemic. In addition, PLWHIV on integrase inhibitors are 1.69 times more likely to be infected than PLWHIV on non-nucleoside inhibitors, and this observation remains an intriguing topic that still needs to be clarified.

Evaluation of the impact of COVID-19 in people coinfected with HIV and/or tuberculosis in low-income countries: study protocol for mixed methods research in Burkina Faso.

BACKGROUND: An issue of particular concern is the impact of the 2019 novel coronavirus (2019 nCOV) on the people coinfected with the Human Immuno-deficiency Virus (HIV) and/or tuberculosis (TB). Unfortunately, this interaction has not been well explored in African despite the large proportion of these risk populations living with HIV and/or patients and/or tuberculosis (TB) in the African region. This study aims to design a research protocol for assessment of the impact of coronavirus disease 2019 (COVID-19) on these risk populations in response to COVID-19 strategic plans in Burkina Faso by generating serological, epidemiological, virological, clinical and socio-anthropological evidence-based data. METHODS: A multidisciplinary research will be conducted in the city of Bobo-Dioulasso, Burkina Faso using mixed methods. Data will be collected from a cohort of people living with HIV and/or TB patients in the city (i) to determine the proportion of people with specific antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using retrospective data ; (ii) to determine the proportion of people infected with Covid-19 and the dynamics of viral loads and antibodies in these people based on prospective data; (iii) to identify circulating SARS-COV-2 variants and novel biomarkers using prospective data ; (iv) to analyze perceptions, community experiences and response strategies during the public health emergencies imposed by COVID-19 through a qualitative study. DISCUSSION: This study will generate factual and comprehensive data that will contribute in improving response strategies to COVID-19 and the other possible emerging diseases with keen interest on the risk populations living with HIV and/or TB infected patients.

Future of HIV2 and HIV2 + 1 Infected Patients Treated with Antiretrovirals Followed at the Day Hospital HIV Care Unit from 2011 to 2015.

Introduction: HIV2 is endemic in West Africa. In Burkina Faso, its prevalence was estimated at 2%. The aim of this work was to evaluate the follow-up of patients and also to contribute to the availability of data. Methods: We involved 18 years or older. Infection was screened according to the national algorithm. A cross- sectional study from first June 2017 to 31 December 2017 was performed. For each patient, sociodemographic, clinical, biological, therapeutic and evolution data were collected and analyzed. Results: The proportion of patients infected with HIV2 (n = 48; 1.7%) and HIV2 + 1 (n = 67; 2.4%) was 4.3%. The sex rat mean age was 50.3 ± 8.5 years. The combination of 2INTI + LPV/r was the most prescribed (n = 73; 63.5%). The average gain of LTCD4 has evolved from + 236 cells/mm3 in 2011 to + 364 cells/mm3 in 2015. The retention rate at grade 5 was about 70%. Conclusion: The immunological and clinic response of the patients was satisfactory. More than half of the patients remained in the continuum of care after five years of follow-up.

APOL1 Renal Risk Variants and Kidney Function in HIV-1-Infected People From Sub-Saharan Africa.

Introduction: APOL1 G1 and G2 alleles have been associated with kidney-related outcomes in people living with HIV (PLHIV) of Black African origin. No APOL1-related kidney risk data have yet been reported in PLHIV in West Africa, where high APOL1 allele frequencies have been observed. Methods: We collected clinical data from PLHIV followed in Burkina Faso (N = 413) and in the ANRS-12169/2LADY trial (Cameroon, Senegal, Burkina Faso, N = 369). APOL1 G1 and G2 risk variants were genotyped using TaqMan assays, and APOL1 high-risk (HR) genotype was defined by the carriage of 2 risk alleles. Results: In West Africa (Burkina Faso and Senegal), the G1 and G2 allele frequencies were 13.3% and 10.7%, respectively. In Cameroon (Central Africa), G1 and G2 frequencies were 8.7% and 8.9%, respectively. APOL1 HR prevalence was 4.9% in West Africa and 3.4% in Cameroon. We found no direct association between APOL1 HR and estimated glomerular filtration rate (eGFR) change over time. Nevertheless, among the 2LADY cohort participants, those with both APOL1 HR and high baseline viral load had a faster eGFR progression (ß = -3.9[-7.7 to -0.1] ml/min per 1.73 m2 per year, P < 0.05) than those with low-risk (LR) genotype and low viral load. Conclusion: Overall, the APOL1 risk allele frequencies in PLHIV were higher in the West African countries than in Cameroon, but much lower than previously reported in some Nigeria ethnic groups, which strongly advocates for further investigation in the African continent. This study suggested that the virological status could modulate the APOL1 impact on kidney function, hence reinforcing the need for early therapeutic interventions.

Assessment of Recovery Time, Worsening, and Death among Inpatients and Outpatients with COVID-19, Treated with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso.

OBJECTIVES: Our study aimed to assess the statistical relationship between the use of chloroquine phosphate or hydroxychloroquine plus azithromycin (CQ/HCQ + AZ) and virological recovery, disease worsening, and death among out- and inpatients with COVID-19 in Burkina Faso. METHODS AND DESIGNS: This was a retrospective observational study that compared outcomes in terms of time to recovery, worsening, and death in patients who received CQ/HCQ + AZ and those who did not using a multivariable Cox or Poisson model before and after propensity matching. RESULTS: Of the 863 patients included in the study, about 50% (432/863) were home-based follow-up patients and 50% were inpatients. Of these, 83.3% (746/863) received at least 1 dose of CQ/HCQ + AZ and 13.7% (118/863) did not. There were no significant differences in associated time to recovery for patients receiving any CQ/HCQ + AZ (adjusted HR 1.44; 95% CI 0.76-2.71). Similarly, there was no significant association between CQ/HCQ + AZ use and worsening (adjusted IRR 0.80; 95% CI 0.50-1.50). However, compared with the untreated group, the treated group had a lower risk of death (adjusted HR 0.20; 95% CI 0.10-0.44). CONCLUSIONS: The study provided valuable additional information on the use of CQ/HCQ in patients with COVID-19 and did not show any harmful outcomes of CQ/HCQ + AZ treatment.

Prevalence of human leukocyte antigen HLA-B*57:01 in individuals with HIV in West and Central Africa.

BACKGROUND: The presence of the human leukocyte antigen HLA-B*57:01 is associated with the development of a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*57:01 prevalence in individuals with HIV-1 in Africa. This study aimed to estimate HLA-B*57:01 prevalence in individuals with HIV-1 in West and Central Africa. METHODS: A cross-sectional study was conducted in four countries in West and central Africa (Burkina-Faso, Côte d'Ivoire, Gabon, and Togo) from January 2016 to February 2020 to determine the status of HLA-B*57:01 in adults with HIV-1. The presence of HLA-B*57:01 was determined by using Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) in blood samples. Prevalence rates were stratified based on country. RESULTS: A total of 4016 (69.8% women) individuals with HIV were enrolled. Their median age was 45, and the interquartile range was 38-52. We included 500 (12.4%) patients in Burkina-Faso, 1453 (36.2%) in Côte d'Ivoire, 951 (23.7%) in Gabon, and 1112 (27.7%) in Togo. The overall HLA-B*57:01 prevalence was 0.1% [95% CI: 0.0-0.2%]. The prevalence of HLA-B*57:01 was similar according to the four countries. Only one case was reported in each country except Togo, with no cases. CONCLUSIONS: HLA-B*57:01 prevalence is low in individuals with HIV in West and central Africa, and there is no difference among countries. This study does not confirm the utility of HLA-B*57:01 allele testing for abacavir use in this region.

[High incidence of asymptomatic myocardial ischemia in a population of HIV-infected patients in Bobo-Dioulasso, Burkina Faso]. / Fréquence élevée de l´ischémie myocardique asymptomatique dans une population de patients infectés par le VIH à Bobo-Dioulasso, Burkina Faso.

INTRODUCTION: cardiovascular complications have become the 3th cause of death and the 4th reason for hospitalization in HIV-infected patients. The purpose of this study was to determine the frequency of asymptomatic myocardial ischemia in HIV-infected patients on antiretroviral therapy. METHODS: we conducted a descriptive cross-sectional study in November 2015. Asymptomatic HIV-1-infected patients on ARV treatment and followed up in the Day Hospital Unit of the Department of Infectious Diseases of the University Hospital Sanon Sourou of Bobo-Dioulasso were included in the study. Among enrolled patients data on cardiovascular risk factors were collected as well as two sitting blood pressure measurements after 10 minutes of rest were taken during consultations and resting 12-lead electrocardiogram (ECG) was performed. RESULTS: a total of 123 HIV-1-infected patients with a median age of 42 years (IQR: 36-50), among whom 79% were female subjects, were included in the study. Cardiovascular risk factors included: PAH (31.7%), obesity (33%), dyslipidemia (10.57%), active smoking (0.8%) and diabetes (0.8%). All patients with hypertension (5.7%) were insufficiently treated. The median duration of ARV treatment was 5.3 years (IQR: 3-7.7). Repolarization disorders were found in 26 cases (21.13%). They were divided into subepicardial ischaemia in 20 cases (16.26%), subendocardial damage in 2 cases (1.63%) and sequelae of necrosis in 4 cases (3.25%). Left ventricular hypertrophy (LVH) was found in 12 cases (9.76%) and, in particular, in hypertensive patients. Prolonged QTc interval was found in 7 patients (5.69%) regardless of the ARV drugs given. CONCLUSION: this study of HIV-1-infected patients highlights that asymptomatic myocardial ischemia is common. Screening programmes should be improved through more effective ischemia tests in order to better determine its severity in this sub-population with increased cardiovascular risk.

Predictors of severe hypoxemia among COVID-19 patients in Burkina Faso (West Africa): Findings from hospital based cross-sectional study.

INTRODUCTION: COVID-19 is one of the world's major health crises. The objective of this study was to determine the predictive factors of severe hypoxemia in patients hospitalized in COVID-19 health facilities in Burkina Faso. PATIENTS AND METHOD: This study was a hospital-based cross-sectional study. The data collected relate to the period of the first wave of the epidemic (March 9 to June 30, 2020). All patients hospitalized for COVID-19 in the requisitioned health facilities of Ouagadougou were included in this study. Predictors of severe hypoxemia were identified using a multivariate logistic regression model. RESULTS: During the study period, 442 patients were included, representing 45.7% of the total number of positive patients in the entire country. The most common co-morbidities were diabetes (55; 12.4%) and arterial hypertension (97; 21.9%). Severe hypoxemia (SpO2 < 90%) was observed in 64 patients (14.5%). Age over 65 years (OR = 8.24; 95% CI: 2.83-24.01) and diabetes (OR = 2.43; 95% CI: 1.17-5.06) were the predictors for occurrence of severe hypoxemia in multivariate analysis. CONCLUSION: The predictive factors of COVID-19 are similar in African and Caucasian populations. The surveillance of COVID-19 in risk groups should be strengthened to reduce their morbidity and mortality.

Severe dengue in adults and children, Ouagadougou (Burkina Faso), West Africa, October 2015-January 2017.

Introduction: Although dengue is the most common arbovirus infection worldwide, studies of severe dengue in Africa are lacking, and risk factors for severe dengue have been insufficiently described. This study was conducted in the context of the 2016 dengue epidemic in Burkina Faso to determine the prevalence of severe dengue, identify factors associated with severe dengue, and perform mapping of dengue cases in the country's capital, Ouagadougou. Methods: This cross-sectional study was conducted from November 2015 to January 2017. Data were collected in 15 public and private health centres, and included sociodemographic, clinical and patient outcome variables. Dengue was diagnosed using SD Bioline Dengue Duo rapid diagnostic tests. Data were analysed using Epi-Info Version 7. Logistic regression was used to identify predictors of severe dengue. P<0.05 was considered significant. Dengue case mapping was performed using Geographic Information System software (ArcGIS). Results: Of the 811 patients who tested positive for dengue, 609 (75%) had early dengue (AgNS1 positive) and 272 (33.5%) had severe dengue. Patient age ranged from 1 to 83 years (median 30.5 years) and 393 (48.3%) were female. Renal failure (13.1%) and severe bleeding (10.6%) were the most common signs of severe dengue. Risk factors for severe dengue included age, male sex, haemoglobin S, diabetes, hypertension, and primary dengue. Dengue cases were more concentrated  in sectors located in the centre of the city and close to the health centres. Conclusion: Dengue is increasingly common in Africa and factors associated with severity should be sought systematically as soon as a patient tests positive. Additional studies are needed to determine if the factors found to be associated with severity can be used to identify patients at risk for dengue-related complications, and to provide early and specialized management to reduce morbidity and mortality related to dengue in Africa.

Prevalence and Molecular Characterization of Extended Spectrum ß-Lactamase, Plasmid-Mediated Quinolone Resistance, and Carbapenemase-Producing Gram-Negative Bacilli in Burkina Faso.

The spreading of carbapenemase-producing gram-negative bacilli (GNB) must be considered as an "urgent" threat. The aim of this study was to determine the prevalence of extended spectrum ß-lactamase (ESBL), plasmid-mediated quinolone resistance (PMQR), and carbapenemase-producing GNB and to characterize the supporting genes in GNB specimens isolated from patients and healthy volunteers in Burkina Faso. From April to June 2016, carbapenemase-producing GNB screening was performed in 1,230 consecutive clinical specimens, and 158 fecal samples from inpatients and healthy volunteers without digestive pathology at Souro Sanou University Hospital, Bobo Dioulasso. Strains were identified by matrix-assisted laser desorption ionization-time of flight and antimicrobial susceptibility was tested with the disk diffusion method on Müller-Hinton agar. The presence of carbapenemase, ESBL, and PMQR genes was assessed by multiplex PCR. The molecular epidemiological study was performed using multilocus sequence typing analysis. From the 1,230 clinical samples, 443 GNB strains were isolated among which 4 (0.9%) were carbapenemase-producing isolates (Escherichia coli, n = 1; Acinetobacter baumannii, n = 3). Among the 158 fecal samples tested for carbapenemase-producing Enterobacteriaceae carriage, 13 (8.2%) were carbapenemase-producing isolates (E. coli, n = 4; Klebsiella pneumoniae, n = 6; A. baumannii, n = 2; Acinetobacter nosocomialis, n = 1; Acinetobacter bereziniae, n = 1). The strains from the two groups were resistant to broad-spectrum cephalosporins (100% for both), gentamicin (100% and 64.3%), levofloxacin (100% and 85.7%), and to amikacin (0% and 7.1%). The carbapenemase-encoding genes blaNDM-1, blaOxa-58, blaOxa-181, and blaVIM-2 were detected in clinical and in fecal samples. The majority (10/11) of the enterobacterial strains carried also blaCTX-M-15. The majority of the strains belonged to ST692 for E. coli, to ST147 for K. pneumoniae and to ST2 for A. baumannii. This study confirms the presence of carbapenemase-producing GNB in samples from patients and healthy volunteers. More effective active surveillance activities are needed.

[Description of a new epidemic focus of cutaneous Leishmaniasis major in western Burkina Faso]. / Description d'un nouveau foyer épidémique de leishmaniose cutanée à Leishmania major à l'Ouest du Burkina Faso.

INTRODUCTION: in Burkina Faso, the only epidemic focus of cutaneous leishmaniasis confirmed in the literature by lab tests was in Ouagadougou. We report the epidemiological, clinical and biological results of the assessment of a new epidemic focus in Larama in western Burkina Faso. METHODS: camps were used to receive patients. Sociodemographic and clinical data were collected using a questionnaire. Confirmation was based on microscopy and polymerase chain reaction (PCR). RESULTS: a total of 108 suspected cases have been identified in Larama, reflecting an attack rate of 5.8%. Sex ratio was 1.08. The patients were most often farmers (35.2%) and traders (33.3%). The working population (15-49 years old) accounted for 51.9%. The number of lesions varied between 1 and 5 in 91.7% of the cases. The lesions manifested as raised and infiltrated ulcerative lesions on the limbs (87%) with evolution ranging from 1 to 5 months in 96.3% of the cases. Samples were collected from two patients; microscopy showed leishmanias and PCR confirmed Leishmania major. CONCLUSION: our results confirm the presence of a cutaneous leishmaniasis major outbreak in the western part of the country. Additional surveys are needed to clarify the burden of leishmaniasis in Burkina Faso.

Dengue infection during pregnancy in Burkina Faso: a cross-sectional study.

BACKGROUND: Dengue fever is prevalent in the world; in recent years, several outbreaks occurred in West Africa. It affects pregnant women. We aimed to assess the consequences of dengue fever on pregnant women and their fetuses during dengue epidemic in Burkina Faso. METHODS: We conducted a cross-sectional study from November 1, 2015 to January 31, 2017 in 15 public and private health facilities in Ouagadougou, using secondary data. Immunochromatographic rapid test Duo detecting specific antibodies, immunoglobin M/G and /or dengue non structural antigen1 virus was used to diagnose dengue cases. RESULTS: Out of 399 (48%) women registered during the study period, 25 (6%) were pregnant. The average age of pregnant women was 30 years, with 18 and 45 years as extremes. The main symptoms were fever (92%) and headache (92%). Nine patients (36%) had severe dengue characterized by bleeding (16%), neurological symptoms (16%) and acute respiratory distress (8%). Eight (32%) of the 25 women had early miscarriage and 8 (32%) women gave birth to viable fetuses. Among those with viable babies, 5 (20%) presented post-partum hemorrhage and 3 (12%) presented early delivery. The main fetal complications included 3 cases of acute fetal distress (12%). One case of maternal death (4%) and 4 cases of neonatal mortality (44.5%) were notified. CONCLUSION: Dengue fever occurring during pregnancy increases maternal and neonatal mortality. Its severe complications require specific monitoring of pregnant women until delivery.

Implementation of an intensive adherence intervention in patients with second-line antiretroviral therapy failure in four west African countries with little access to genotypic resistance testing: a prospective cohort study.

BACKGROUND: The decision about whether to switch to third-line antiretroviral therapy (ART) in patients with treatment failure on second-line therapy is difficult in settings with little access to genotypic resistance testing. In this study, we used a standardised algorithm including a wide range of adherence-enhancing interventions followed by a new viral load measurement to decide whether to switch to third-line therapy in this situation. The decision, made on the basis of effectiveness of the adherence reinforcement to drive viral resuppression, did not use genotypic resistance testing. METHODS: In this prospective cohort study, adults in four west African countries with treatment failure of a boosted protease inhibitor ART regimen were offered nine adherence reinforcement interventions, and followed up for 64 weeks. We measured viral load at week 12 and used the results to decide ART treatment at week 16: if successful resuppression (plasma HIV-1 RNA <400 copies per mL or had decreased by ≥2 log10 copies per mL compared with baseline), patients continued the same second-line regimen; otherwise they switched to a third-line regimen based on ritonavir-boosted darunavir and raltegravir. The primary endpoint was virological success at week 64 (plasma HIV-1 RNA <50 copies per mL). After study termination we did genotypic resistance testing on frozen plasma samples collected at baseline, and retrospectively determined the appropriateness of the week 16 decision on the basis of the baseline genotypic susceptibility score. FINDINGS: Between March 28, 2013, and May 11, 2015, of the 198 eligible participants, five died before week 16. Of the 193 remaining, 130 (67%) reached viral resuppression and continued with second-line ART, and 63 (33%) switched to third-line ART at week 16. Post-study genotypic resistance testing showed that the baseline genotypic susceptibility score was calculable in 166 patients, of whom 57 (34%) had a score less than 2. We retrospectively concluded that the week 16 decision was appropriate in 145 (75%) patients. At week 64, four patients (2%) were lost to follow-up, ten (5%) had died, and 101 (52%) had a viral load less than 50 copies per mL. INTERPRETATION: Poor adherence is the first problem to tackle in patients for whom second-line ART is failing when resistance tests are not routinely available and is effectively a manageable problem. Lack of access to genotypic resistance testing should not be an obstacle to the prescription of third-line ART in patients who do not achieve viral resuppression after adherence reinforcement. FUNDING: French Agency for Research on AIDS and Viral Hepatitis.

Chronic kidney disease and HIV in the era of antiretroviral treatment: findings from a 10-year cohort study in a west African setting.

BACKGROUND: It has been reported that people living with HIV in West Africa exhibited the highest risks for chronic kidney disease (CKD) in the world. Here, we aimed at determining the CKD frequency and changes in kidney function during antiretroviral treatment (ART) in a large cohort of HIV-patients followed in Burkina Faso. METHODS: We included ART-naive adults who initiated ART at the Day Care Unit of the Souro Sanou University Hospital between 01/01/2007 and 12/31/2016. We assessed the estimated glomerular filtration rate (eGFR) by serum creatinine using the Modification of Diet in Renal Disease (MDRD) equation. Following the K/DOQI recommendations, CKD was defined as eGFR < 60 ml/min/1.73m2 at two consecutive measurements at least 3 months apart. The factors associated with eGFR decline or CKD were identified by mixed linear regression and Cox regression, respectively. RESULTS: Three thousand, one hundred and thirty-eight patients (72% women) were followed for a median (IQR) of 4.5(2.2-6.9) years. At baseline, median eGFR (IQR) was 110.7(94.4-128.4) ml/min/1.73m2 and 93 (3%) patients exhibited eGFR < 60 ml/min/1.73m2. The lowest-performing progressions of eGFR during the first year of ART were observed in patients with 40-49 yr. age range (- 8.3[- 11.7;-5.0] ml/min/1.73m2, p < 0.001), age ≥ 50 yr. (- 6.2[- 10.7;-1.8] ml/min/1.73m2, p = 0.006) and high blood pressure (HBP) (- 28.4[- 46.9;-9.9] ml/min/1.73m2, p = 0.003) at ART initiation. Regarding the ART exposure in patients with normal baseline eGFR, zidovudine (AZT) with protease inhibitor (PI) (- 4.7[- 7.7;-1.6] ml/min/1.73m2, p = 0.002), tenofovir (TDF) + PI (- 13.1[- 17.4;-8.7] ml/min/1.73m2, p < 0.001), TDF without PI (- 3.2[- 5.0;-1.4] ml/min/1.73m2, p < 0.001), stavudine (d4T) + PI (- 8.5[- 14.6-2.4] ml/min/1.73m2, p = 0.006) and d4T without PI (- 5.0[- 7.6-2.4] ml/min/1.73m2, p < 0.001) were associated with poorer eGFR progression. The prevalence of CKD was 0.5% and the incidence was 1.9 [1.3; 2.7] cases/1000 person-years. The risk of CKD was higher in patients with HBP (4.3[1.8;9.9], p = 0.001), 40-49 yr. patients (4.2[1.6;11.2], p = 0.004), ≥50 yr. patients (4.5[1.5;14.1], p = 0.009) and patients exposed to abacavir (ABC) or didanosine (ddI) based ART (13.1[4.0;42.9], p < 0.001). CONCLUSIONS: Our findings do not confirm the high risk of CKD reported in previous studies of West Africans with HIV, but support the recommendations for early initiation of ART and close kidney function monitoring in patients with HBP or aged ≥40 yr.

Evaluation de la satisfaction des patients hospitalisés dans les services du département de Médecine du Centre hospitalier universitaire Souro Sanou (CHUSS) de Bobo-Dioulasso, Burkina Faso

La satisfaction des usagers des établissements sanitaires fait partie de l'appréciation de la qualité des soins. L'objectif était d'étudier la satisfaction des patients hospitalisés dans les services du département de médecine du Centre hospitalier universitaire Souro Sanou (CHUSS) de Bobo-Dioulasso, Burkina Faso. Il s'est agi d'une étude transversale à visée analytique conduite en 8 mois. Les domaines de satisfaction ont été calculés selon le modèle SAPHORA (version 7). Des 294 patients éligibles, 250 (85,0 %) patients ont été retenus dont 42,0 % de femmes. L'âge moyen des patients était de 47,1 (± 17,9) ans. Les domaines à score faible étaient : niveau global de satisfaction, accueil, communication avec le personnel, restauration et organisation de la sortie. Les patients plus âgés et ceux à durée d'hospitalisation plus longue étaient plus satisfaits. Les 94,0 % des patients sans assurance maladie étaient moins satisfaits.Les scores des domaines de satisfaction par service et le score global de satisfaction étaient inférieurs à 50,0 %. Les différences entre les services étaient en lien avec : accueil, qualité humaine du personnel, soins médicaux, hôtellerie, restauration, coûts, et niveau global de satisfaction. L'amélioration de la satisfaction des patients hospitalisés requiert le respect des besoins fondamentaux des patients et une réorganisation des services avec un personnel engagé, pour l'offre de soins et services de santé de qualité

Impact of alternative treatment approach for cerebral toxoplasmosis among HIV/AIDS patients from a resource-poor setting in Burkina Faso

Cerebral toxoplasmosis is caused by the protozoan Toxoplasma gondii because of reactivation of latent tissue cysts in the Acquired Immunodeficiency Syndrome (AIDS) patients with severe immunosuppression. The objective of this study was to evaluate the benefit of co-trimoxazole in presumptive and prevention of cerebral toxoplasmosis in Human Immunodeficiency Virus (HIV)/AIDS patients at Bobo-Dioulasso Hospital in Burkina Faso from June 2012 to October 2014. ELISA and ELFA were performed on serum for the quantitative determination of IgG and IgM anti-T. gondii, respectively. The seroprevalence of toxoplasmosis was 29.3%. No IgM antibodies for T. gondii were found. Six patients with Toxoplasma-specific antibodies presented cerebral toxoplasmosis. All patients were infected by HIV-1 with the median of CD4+ T lymphocytes at 141 cells/µl. No patient was under antiretroviral therapy. No case of cerebral toxoplasmosis was noted in patients receiving co-trimoxazole in prevention. Presumptive treatment of cerebral toxoplasmosis with co-trimoxazole was effective in all patients with a significant clinical improvement in 83.3%. These results attest the benefit of cotrimoxazole in cerebral toxoplasmosis treatment in countries where drug resources are limited when sulfadiazine is not available. Ours finding highlight the importance of establishing toxoplasmosis chemoprophylaxis to HIV with severe immunosuppression patients and positive Toxoplasma serology.

TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study.

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 (ß = -10.8 [-18.1,-3.5] for women), age (ß = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (ß = +0.8 [0.1,1.5] per unit of BMI), and study site (ß = +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.

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.

Getting pregnant in HIV clinical trials: women's choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials.

INTRODUCTION: Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless pregnancies are often observed. Reproductive choices during clinical trials should be understood to adapt interventions to the level of risk for mother and baby safety. Our goal was to describe the reproductive behavior and pregnancy outcomes among HIV-infected women on second-line antiretroviral treatment enrolled in two clinical trials and to compare them with those of HIV-positive women in non-research settings. METHODS: The number and outcomes of pregnancies were recorded among 281 non menopausal women enrolled in the ANRS 12169-2LADY and ANRS 12286-MOBIDIP clinical trials in Cameroon, Senegal and Burkina Faso. All participants had agreed to use a least one contraceptive method (barrier or non-barrier) which was provided for free during the study. Data were collected through revision of pregnancy notification forms and by data extraction from the study database, regularly updated and checked during the study. RESULTS: Sixty-six women had 84 pregnancies between January 2010 and July 2015 resulting in a pregnancy rate of 8.0 per 100 women-years (WY) (95% CI 6.5-9.9) which is similar to the ones observed in cohort studies in Sub-Saharan Africa (varying from 2.5 to 9.4 pregnancies per 100 WY). Among 60 live births, 10 (16.6%) were born prematurely and 9 (15%) had a low birth weight. Sixteen miscarriages/stillbirths occurred (19.5%). This percentage is comparable to the one expected in the seronegative population which is reassuring for HIV-positive women considering pregnancy on ART. Only one minor birth defect was diagnosed. In univariate and multivariate analysis, miscarriages/stillbirths were not associated either with age, nadir of CD4 count, duration of ART, CD4 count, or viral load at the beginning of pregnancy. CONCLUSION: HIV-positive women participating in clinical trials conducted in Sub-Saharan Africa tend to get pregnant as often as seropositive women who received medical care in non-research settings. It is therefore essential to adopt a pragmatic approach by re-evaluating the relevance of the criteria for exclusion of pregnant women according to the risk associated with exposure and to seek more effective and innovating contraceptive strategies when using potentially teratogenic molecules.