Effect of cotrimoxazole prophylaxis on malaria occurrence among HIV-infected adults in West Africa: the MALHIV Study.

INTRODUCTION: Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm3 according to 2006 WHO guidelines. We assessed the impact of CTX prophylaxis on the risk of malaria episodes in HIV-1-infected adults from four West African countries with different patterns of malaria transmission. METHOD: Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm3 or were at WHO clinical stage ≥2. For patients who did not start CTX at enrolment (non-CTX group) and started CTX afterwards, follow-up was censored at CTX initiation. We used Cox's proportional hazard model to compare the risk of malaria between CTX groups. RESULTS: A total of 514 participants (median CD4 count 238 cells/mm3 ) were followed for a median of 15 months. At enrolment, 347 started CTX, and 261 started ART. During the follow-up, 28 started CTX. The incidence of malaria was 8.7/100 PY (95%CI 6.3-11.5) overall, 5.2/100 PY (95%CI 3.1-8.3) in the CTX group and 15.5/100 PY (95%CI 10.3-22.1) in the non-CTX group. In multivariate analysis, CTX led to a 69% reduction in the risk of malaria (aHR 0.31, 95%CI 0.10-0.90). CONCLUSION: Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region.

Prevalence of severe cardiovascular abnormalities amongst West African HIV-infected patients on antiretroviral therapy followed at a referral HIV centre.

BACKGROUND: With success and effective long-term antiretroviral treatment (ART), HIV-infected patients live longer and frequently developed non-communicable diseases (NCDs). Few studies have been conducted in low-income countries, particularly in West Africa. METHODS: We carried out a cross-sectional study in the referral HIV centre of the Service des Maladies Infectieuses et Tropicales (SMIT) in Abidjan. From April to September 2015, we consecutively included HIV-1 infected patients aged 18 years and older, and on ART for a minimum of 12 months. Data were collected using a structured questionnaire, and entered into the centre's computerised HIV database. Clinical assessment, laboratory tests, electrocardiogram, transthoracic echocardiography and vascular Doppler ultrasound were performed. The main outcome was the prevalence of patients with severe cardiovascular abnormalities (SCA). Univariate and multivariate logistic regressions were used to identify factors associated with SCA. RESULTS: Out of 278 patients (median age 46 years, interquartile range [IQR: 41-52]), 74.5% were female. Overall, the median duration of ART was 84 months (IQR: 54-126). One hundred and ninety-nine (71.6%) patients were on first-line ART regimen and 229 (82.4%) were virologically suppressed with a median CD4 count of 511 cells/mm3 (IQR: 347-529). Basically, cardiovascular abnormalities were mainly non-obstructive carotid plaques (19.1%) followed with left ventricular diastolic dysfunction (16.5%). The overall prevalence of SCA in the study population was 7.6% (95% Confidence Interval [95% CI]: 4.7-11.3). The prevalence of SCA 7.6% (95% Confidence Interval [95% CI]: 4.7-11.3). In multivariate analysis, age > 50 years and nadir CD4 count > 200 cells/mm3 were significant predictors of SCA. CONCLUSION: The prevalence of SCA is high in West African HIV-treated patients. Given the high mortality associated with cardiovascular diseases in the general population, refining disease preventive strategies in HIV-positive subjects is essential to continue prolonging their life.

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.

[Thromboembolic manifestations in 36 HIV-infected patients in West Africa]. / Manifestations thromboemboliques chez 36 patients Ouest Africains infectés par le VIH.

In HIV-infected patients thromboembolic disease is a complication linked to heightened risk. In Ivory Coast no study has been conducted on HIV-infected patients treated in HIV Services. The aim of our study is to describe HIV-associated thromboembolic manifestations in patients treated or untreated with antiretroviral drugs whose data were collected in the Infectious and Tropical Diseases Service (ITDS). We conducted a retrospective study by reviewing the medical records of HIV-infected patients hospitalized with deep vein thrombosis (DVT), arterial thrombosis and/or pulmonary embolism over the period January 2005-July 2015. Diagnosis was based on Doppler ultrasound of vessels and/or on thoracic angioscanner. Diagnostic, therapeutic and evolutionary features of thromboembolic manifestations in these patients were analyzed. The medical records of 36 patients, including 23 women (64%), with a sex-ratio M/F of 0.57 and an average age of 43±12 years were selected. Deep venous thrombosis (DVT) was found in 26 (72.2%) patients, pulmonary embolism (PE) in 9 (25%) patients and arterial thrombosis in 1 patient (2.8%). DVT was unilateral in 81% of cases and predominantly left-sided in 77% of cases. PE was unilateral and right-sided in 100% of cases while arterial thrombosis was bilateral in 2.7% of cases. In patients with DVT, the femoral vein (39%) and the popliteal vein (35%) were most commonly affected by thrombosis. PE involved the pulmonary arteries in 77.8% of cases while arterial thrombosis involved the left and right internal carotid. The majority of patients was under antiretroviral treatment (69%). The most commonly associated opportunistic infections included oral candidiasis (31%) and tuberculosis (33%). Nine patients died (25%). This study highlights high rates of DVT in HIV-infected patients. Other studies are necessary to better understand the role of HIV in the occurrence of thromboembolic disease.

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.

OBJECTIVE: Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing. DESIGN: Randomized clinical trial. METHODS: We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses (800 mg o.d., 600 mg b.i.d., 1200 mg o.d.) versus ZDV (300 mg b.i.d.) in combination with lamivudine and efavirenz in HIV-infected, ART-naive patients from Tanzania and Côte d'Ivoire. The primary objective was to demonstrate virological efficacy after 24 weeks in intent-to treat and per-protocol analysis. Secondary endpoints included safety and pharmacokinetic outcomes. RESULTS: Of 119 participants included in the intent-to treat analysis, HIV RNA less than 50 copies/ml at 24 weeks was observed in 64 of 88 (73%) patients in the combined FZD arms versus 24 of 31 (77%) in the ZDV arm (RR 0.94, 95% confidence interval 0.75-1.18). In the per-protocol analysis, responses were 64 of 77 (87%) versus 23 of 29 (79%), respectively (RR 1.09, 95% confidence interval 0.89-1.34). Outcomes were similar between FZD arms. Overall, treatments were well tolerated. Severe or worse anaemia occurred in two cases (one related to FZD, one to ZDV), grade III/IV neutropenia was less frequent in FZD compared with ZDV arms (22 versus 42%, P = 0.035). Pharmacokinetic analysis supported o.d. administration of FZD. CONCLUSION: Virological 24-week efficacy was demonstrated in b.i.d. and o.d. administered FZD-based regimens. Reduced myelotoxicity of FZD needs to be confirmed in a larger trial.

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.