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.

Factors associated with verbal fluency in older adults living with HIV in West Africa: A longitudinal study.

OBJECTIVE: Verbal fluency decline, observed both in aging and HIV infection, has been related to lower quality of life. This study aimed to evaluate the factors associated with categorical fluency in people living with HIV (PLHIV) aged ≥60 years living in West Africa. METHODS: In this longitudinal study, PLHIV aged ≥60 years, on antiretroviral therapy (ART) for ≥6 months were included in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. Categorical fluency was evaluated with the Isaacs Set Test at 60 s at baseline and 2 years later. Factors associated with verbal fluency baseline performance and annual rates of changes were evaluated using multivariate linear regression models. RESULTS: Ninety-seven PLHIV were included with 41 of them (42%) having a 2-year follow-up visit. The median age was 64 (62-67), 45.4% were female, and 89.7% had an undetectable viral load. The median annual change in categorical fluency scores was -0.9 (IQR: -2.7 to 1.8). Low baseline categorical fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline categorical fluency performance but not with its decline. Categorical fluency decline was also associated with marital status and hypertension. CONCLUSIONS: Among older West African PLHIV, usual socio-demographic variables and hypertension were the main factors associated with low categorical fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV.

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.

Prevalence and factors associated with physical function limitation in older West African people living with HIV.

Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the older people receiving antiretroviral treatment (ART) and living in sub-Saharan Africa (SSA). PLHIV aged ≥50 years old and on ART since ≥6 months were included (N = 333) from three clinics (two in Côte d'Ivoire, one in Senegal) participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Physical function was measured using the Short Physical Performance Battery (SPPB), the unipodal balance test and self-reported questionnaires. Grip strength was also assessed. Logistic regression was used to identify the factors associated with SPPB performance specifically. Median age was 57 (54-61) years, 57.7% were female and 82.7% had an undetectable viral load. The mean SPPB score was 10.2 ±1.8. Almost 30% had low SPPB performance with the 5-sit-to-stand test being the most altered subtest (64%). PLHIV with low SPPB performance also had significantly low performance on the unipodal balance test (54.2%, p = 0.001) and low mean grip strength (but only in men (p = 0.005)). They also showed some difficulties in daily life activities (climbing stairs, walking one block, both p<0.0001). Age ≥60 years (adjusted OR (aOR) = 3.4; CI95% = 1.9-5.9,), being a female (aOR = 2.1; CI95% = 1.1-4.1), having an abdominal obesity (aOR = 2.1; CI95% = 1.2-4.0), a longer duration of HIV infection (aOR = 2.9; CI95% = 1.5-5.7), old Nucleoside reverse transcriptase inhibitors (NRTIs) (i.e., AZT: zidovudine, ddI: didanosine, DDC: zalcitabine, D4T: stavudine) in current ART (aOR = 2.0 CI95% = 1.1-3.7) were associated with low SPPB performance. As in western countries, physical function limitation is now part of the burden of HIV disease complications of older PLHIV living in West Africa, putting this population at risk for disability. How to screen those impairments and integrate their management in the standards of care should be investigated, and specific research on developing adapted daily physical activity program might be conducted.

Prevalence and factors associated with severe depressive symptoms in older west African people living with HIV.

BACKGROUND: Depression is one of the most common psychiatric disorders in people living with HIV (PLHIV). Depression has a negative impact on both mental and physical health and is mainly associated with suboptimal HIV treatment outcomes. To encourage successful aging and the achievement of the 3 × 90 objectives in older PLHIV, the psychological domain must not be neglected. In this context and as data are scarce in West Africa, this study aimed to evaluate the prevalence and the factors associated with severe depressive symptoms in older PLHIV living in this region of the world. METHODS: Data from PLHIV aged ≥50 years and on ART since ≥6 months were collected in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. The severity of depressive symptoms was measured using the Center for Epidemiological Studies Depression scale (CES-D), and associated factors were identified using logistic regressions. RESULTS: The median age of the 334 PLHIV included in the study was 56.7 (53.5-61.1), 57.8% were female, and 87.1% had an undetectable viral load. The prevalence of severe depressive symptoms was 17.9% [95% Confidence Interval (95% CI): 13.8-22.0]. PLHIV with severe depressive symptoms were more likely to be unemployed (adjusted Odd Ratio (aOR) = 2.8; 95% CI: 1.4-5.7), and to be current or former tobacco smokers (aOR = 2.6; 95% CI: 1.3-5.4) but were less likely to be overweight or obese (aOR = 0.4; 95% CI: 0.2-0.8). CONCLUSIONS: The prevalence of severe depressive symptoms is high among older PLHIV living in West Africa. Unemployed PLHIV and tobacco smokers should be seen as vulnerable and in need of additional support. Further studies are needed to describe in more details the reality of the aging experience for PLHIV living in SSA. The integration of screening and management of depression in the standard of care of PLHIV is crucial.

Prevalence of malaria and clinical profile of febrile HIV infected patients in three HIV clinics in Ivory Coast.

BACKGROUND: To determine the prevalence and clinical profile of malaria among febrile HIV-infected patients followed up in three HIV clinics in Ivory Coast. MATERIALS AND METHODS: A cross-sectional multicentre study was conducted between 2009 and 2010 in the Pneumology Department of Cocody Teaching Hospital in Abidjan, Medical Esperance Centre and the Regional Hospital in San-Pedro. Patients of all ages presenting with fever (rectal or axillary temperature >37,5°C) or a medical history of fever within 72 hrs prior to consultation were included. Parasitological diagnostic methods used were microscopy by blood smear (BS) for search malaria parasite and parasite density. Haemoglobin levels were assessed to assess anaemia. RESULTS: Over the study period, 530 people living with HIV consulted for fever. The 476 patients included were predominantly female (n=280, 59%), with a median age of 34 (range 3-74 yrs), a mean of 38 ± 8.3 (SD) yrs, infected with HIV-1 (n=409, 86%), on antiretroviral therapy (n=376, 79%), and cotrimoxazole prophylaxis (n=381, 80%). Only 73 (15%) patients were using LLINs. Malaria prevalence was 10% (n=47). Plasmodium falciparum was the only species identified with a mean density of 15 900 trophozoites/µl. Malaria was more common among patients with a CD4 count of <200/mm3 (p<0.001) neither on cotrimoxazole prophylaxis (p<0.001) nor on antiretroviral therapy (ART) (p<0.001). Uncomplicated malaria accounted for 32 (68%) of the cases. The signs of severe malaria (n=15, 32%,) were dominated by severe anaemia (n= 12, 25.5%). CONCLUSION: Our study revealed that malaria prevalence appears to be low in HIV clinics for people living with HIV on HAART and cotrimoxazole prophylaxis. Uncomplicated malaria is predominant when consultation is early. Signs of severe malaria were dominated by severe anaemia.

Plasmodium falciparum malaria in northern Côte d'Ivoire: prevalence in the general hospital of Tanda sanitary district.

Background: Until about 2010, the majority of data collected on malaria in Côte d'Ivoire were based on presumptive cases, particularly in the northern part of the country, where parasitological research had rarely been carried out. Recently, WHO recommended restricting treatment to confirmed malaria cases only. Thus, the purpose of this study determine the actual malaria prevalence amongst presumptive cases admitted to one of the general hospitals in the Northern part of the country, where malaria diagnosis is suboptimal. Materials and methods: A cr oss-sectional study was conducted in the general medicine, maternity and paediatric wards between January and August 2010. Patients of all ages, suspected of having malaria, were included after giving their informed oral consent. Several parameters were investigated: the presence of Plasmodium using thick blood film, HIV/ Plasmodium co-infection, signs of severity, aspects of malaria treatment and other associated factors. Results: Of 379 patients included, with a median age of 4 yrs [range 1 month - 71 yrs], 9% were HIV-positive, 74% were ≤ 15 yrs of age, 60% were urbanised and 23% were using long-lasting insecticide-treated nets. Malaria prevalence was 67.5% and was significantly associated with the rainy season (p < 0.001), age ≤ 5 yrs (p = 0.004) and no cotrimoxazole chemoprophylaxis in HIV-infected patients (p = 0.04). Only P. falciparum was detected, with a mean density of 12,523 trophozoites/µl of blood, but with 12,610 trophozoites/µl of blood in HIV-positive patients and 7,055 trophozoites/µl of blood in HIV-negative patients (p < 0.001). Severe malaria accounted for 77% of cases. Prescribed antimalarial drugs were: IM artemether (56%), quinine (28%), artemether + lumefantrine (10%) and artesunate + amodiaquine (6%). Apyrexia and parasite clearance were observed at day 2-3 post treatment in 87% of patients. Adverse events were reported among 60 patients (17%). The outcome was marked by: a healing rate of 90%, a rate of 5% lost to follow-up and a 7% lethality for severe malaria, significantly associated with the age ≤ 5 yrs (p=0.02), hyperparasitaemia >20% (p=0.004), neurological disorders (p < 0.001) and respiratory distress (p=0.007). Conclusions: Malaria prevalence in the general hospital of Tanda remains high, with a predominance of sever e malaria affecting children under the age of 5 yrs.

Metabolic disorders and cardiovascular risk in treatment-naive HIV-infected patients of sub-saharan origin starting antiretrovirals: impact of westernized lifestyle.

In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk.