Meta-Analysis of Data from Four Clinical Trials in the Ivory Coast Assessing the Efficacy of Two Artemisinin-Based Combination Therapies (Artesunate-Amodiaquine and Artemether-Lumefantrine) between 2009 and 2016.

The combinations of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) are used as first-line treatments for uncomplicated malaria in the Ivory Coast. Different studies document the efficacy of two artemisinin-based combination therapies (ACTs) (AL and ASAQ) in the Ivory Coast. However, there is no meta-analysis examining the data set of these studies. The purpose of this work was to determine the prevalence of malaria treatment failure cases in randomized control trials with two artemisinin-based combination therapies (AL versus ASAQ) in the Ivory Coast between 2009 to 2016. This study is a meta-analysis of data from the results of four previous multicenter, open-label, randomized clinical trial studies evaluating the clinical and parasitological efficacy of artemether-lumefantrine and artesunate-amodiaquine conducted between 2009 and 2016 following World Health Organization (WHO) protocol at sentinel sites in the Ivory Coast. These drug efficacy data collected between 2009 and 2016 were analyzed. During these studies, to distinguish between recrudescence and new infection, molecular genotyping of genes encoding merozoite surface protein 1 and 2 was carried out using nested polymerase chain reaction (PCR). A total of 1575 patients enrolled in the four studies, including 768 in the AL arm and 762 in the ASAQ arm, which were fully followed either for 28 days or 42 days according to WHO protocol. The adequate clinical and parasitological response (ACPR) was higher than 95% in the two groups (intention to treat (ITT): AL = 96.59% and ASAQ = 96.81; Per Protocol (PP): AL = 99.48% and ASAQ = 99.61%) after PCR correction at day 28. Aggregate data analysis (2009-2016) showed that at day 28, the proportions of patients with recurrent infection was higher in the AL group (ITT: 3.79%, PP: 3.9%) than in the ASAQ group (ITT: 2.17%, PP: 2.23%). After PCR correction, most treatment failures were classified as new infections (AL group (ITT: 0.13%, PP: 0.13%); ASAQ group (ITT: 0.39%, PP: 0.39%). The recrudescent infections rate was high, at 0.39% compared to 0.13% for ASAQ and AL, respectively, for both ITT and PP, no significant difference. However, the Kaplan-Meier curve of cumulative treatment success showed a significant difference between the two groups after PCR from 2012-2013 (p = 0.032). Overall, ASAQ and AL have been shown to be effective drugs for the treatment of uncomplicated P. falciparum malaria in the study areas, 14 years after deployment of these drugs.

Safety of a fixed-dose combination of artesunate and amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in real-life conditions of use in Côte d'Ivoire.

BACKGROUND: In many malaria-endemic, sub-Saharan African countries, existing pharmacovigilance systems are not sufficiently operational to document reliably the safety profile of anti-malarial drugs. This study describes the implantation of a community-based pharmacovigilance system in Côte d'Ivoire and its use to document the safety of ASAQ Winthrop® (artesunate-amodiaquine). METHODS: This prospective, longitudinal, descriptive, non-comparative, non-interventional study on the use of artesunate-amodiaquine in real-life conditions of use was conducted in seven Community Health Centres of the Agboville district in Côte d'Ivoire. Twenty trained Health Centre employees and 70 trained community health workers were involved in data collection in the field. All patients with suspected uncomplicated falciparum malaria, seeking treatment at one of the participating Health Centres, and treated with artesunate-amodiaquine could be enrolled. Two visits were planned, one for inclusion at the Health Centre and a second at home, performed by a community health worker 3-10 days after the inclusion visit. Administration of artesunate-amodiaquine was unsupervised. Adverse events (AEs) were documented at the home visit or during any unexpected visit to the Health Centre or to the hospital and coded and adjudicated by a local pharmacovigilance committee. Symptoms suggestive of hepatic failure, severe neutropaenia, extrapyramidal disorders and retinopathy were considered a priori as AEs of special interest. RESULTS: Some 15,228 malaria episodes in 12,198 patients were evaluated; 2545 AEs were documented during 1978 malaria episodes (13.0%). The most frequently observed events were asthenia (682 cases), vomiting (482 cases) and somnolence (174 cases). Most reported AEs were of mild or moderate intensity and resolved without corrective treatment. One-hundred and five (105) AEs reported during 100 episodes (0.7%) were considered as serious. Three serious cases of transient extrapyramidal disorders, identified as AEs of special interest were reported in three patients. CONCLUSION: The fixed dose artesunate-amodiaquine combination ASAQ Winthrop® for the unsupervised treatment of uncomplicated falciparum malaria under real-life conditions of care in Côte d'Ivoire is well tolerated. The study emphasizes the interest of involving properly trained community health workers to collect pharmacovigilance data in the field in order to document rare AEs.

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.

[A plea for introduction of hepatitis B vaccination at birth in Côte d'Ivoire]. / Plaidoyer pour l?introduction du vaccin contre l?hépatite virale B à la naissance en Côte d?Ivoire.

The Côte d'Ivoire National Immunization Technical Advisory Group 2015 work plan included elaboration of an opinion on inclusion of hepatitis B vaccination at birth in the Expanded Program on Immunization (EPI) in Côte d'Ivoire. A task force was set up to conduct this assessment according to a systematized method. The task force analysed scientific articles on the burden of hepatitis B in Côte d'Ivoire, the burden of mother-child transmission, the impact of hepatitis B vaccination at birth in countries which have adopted this strategy, the efficacy and safety of hepatitis B vaccine in newborns, the cost-effectiveness of hepatitis B vaccination at birth, and the best strategy to introduce hepatitis B vaccination at birth in the EPI. The National Immunization Technical Advisory Group of Côte d'Ivoire finally recommended introduction of a dose of hepatitis B vaccine at birth in the context of the Expanded Program on Immunization with maintenance of three doses of pentavalent vaccine (DPT-HepB-Hib) at 6, 10, and 14 weeks of age.

Sustained Effectiveness of a Fixed-Dose Combination of Artesunate and Amodiaquine in 480 Patients with Uncomplicated Plasmodium falciparum Malaria in Côte d'Ivoire.

The objective of this study was to monitor the effectiveness of artesunate-amodiaquine fixed-dose combination tablets (ASAQ Winthrop®) in the treatment of uncomplicated Plasmodium falciparum malaria in Côte d'Ivoire. Two enrolment periods (November 2009 to May 2010 and March to October 2013) were compared using an identical design. Subjects with proven monospecific P. falciparum infection according to the WHO diagnostic criteria were eligible. 290 patients during each period received a dose of ASAQ Winthrop tablets appropriate for their age. The primary outcome measure was PCR-corrected adequate clinical and parasitological response at Day 28 in the per protocol population (255 in Period 1 and 240 in Period 2). This was achieved by 95.7% of patients during Period 1 and 96.3% during Period 2. Over 95% of patients were afebrile at Day 3 and complete parasite clearance was achieved at Day 3 in >99% of patients. Nineteen adverse events in nineteen patients were considered as possibly related to treatment, principally vomiting, abnormal liver function tests, and pruritus. There was no evidence for loss of effectiveness over the three-year period in spite of strong drug pressure. This trial was registered in the US Clinical Trials Registry (clinical.trials.gov) under the identifier number NCT01023399.

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.

Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis.

BACKGROUND: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa. METHODS: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics. FINDINGS: Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per µL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per µL). INTERPRETATION: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing. FUNDING: National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.

Cancer and HIV infection in referral hospitals from four West African countries.

The consequences of the HIV epidemic on cancer epidemiology are sparsely documented in Africa. We aimed to estimate the association between HIV infection and selected types of cancers among patients hospitalized for cancer in four West African countries. A case-referent study was conducted in referral hospitals of Benin, Côte d'Ivoire, Nigeria and Togo. Each participating clinical ward included all adult patients seeking care with a confirmed diagnosis of cancer. All patients were systematically screened for HIV infection. HIV prevalence of AIDS-defining and some non-AIDS defining cancers (Hodgkin lymphoma, leukemia, liver, lung, skin, pharynx, larynx, oral cavity and anogenital cancers) were compared to a referent group of cancers reported in the literature as not associated with HIV. Odds ratios adjusted on age, gender and lifetime number of sexual partners (aOR) and their 95% confidence intervals (CI) were estimated. Among the 1644 cancer patients enrolled, 184 (11.2%) were identified as HIV-infected. The HIV prevalence in the referent group (n=792) was 4.4% [CI 3.0-5.8]. HIV infection was associated with Kaposi sarcoma (aOR 34.6 [CI: 17.3-69.0]), non-Hodgkin lymphoma (aOR 3.6 [CI 1.9-6.8]), cervical cancer (aOR 4.3 [CI 2.2-8.3]), anogenital cancer (aOR 17.7 [CI 6.9-45.2]) and squamous cell skin carcinoma (aOR 5.2 [CI 2.0-14.4]). A strong association is now reported between HIV infection and Human Papillomavirus (HPV)-related cancers including cervical cancer and anogenital cancer. As these cancers are amenable to prevention strategies, screening of HPV-related cancers among HIV-infected persons is of paramount importance in this African context.

Socio-Demographic and Behavioral Factors Associated with the Desire to Procreate Among Patients Living with HIV in Gabon.

The desire to procreate in patients living with HIV (PLHIV) has been seldom investigated in Africa, particularly in Gabon. The aim of this transversal and descriptive study was to analyze the socio-demographic and behavioral factors associated with a desire to have children in a cohort of PLHIV. The study included 442 patients, predominantly females [79.9% (337/422)], and those with a secondary school education [64.2% 271/422)]. The highest prevalence of HIV was found in patients aged 30-39 years old (44.3%), of which 59% (249/422) were unemployed. The desire to have children was noted in 78% (329/422) of patients, of which 82.4% (271/329) were treated with antiretroviral drugs; this was significantly higher in subjects under 40 years versus those over 40 years old [81% (268/329) versus 19% (61/329), p<0.001]. Sero-discordant couples represented 33.4% (110/329) of patients. The frequency of patients with the desire to have a child was significantly higher when patients wanted to hold the status of parent of a child [77% (255/329) versus 23% (74/329), p<0.001]; this was influenced by the partner's desire [60% 197/329 versus 40% (132/329), p< 0.001], as well as by the absence of weight loss [56% (185/329) versus 44% (144/329), p<0.001]. The average number of children was significantly lower in patients with the desire to procreate compared to those with no desire to have children [1.7 versus 3.2, p<0.001]. These first observations in Gabon highlight the importance of the desire to have children in PLHIV and sero-discordant couples, and they show the level of interest in developing assistance methods for procreation and family planning programs to help this population, as well as to reduce the risk of mother-to-child HIV transmission.

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.

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

BACKGROUND: HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). METHODS: We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region. RESULTS: Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3). CONCLUSIONS: This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

The spectrum of cancers in West Africa: associations with human immunodeficiency virus.

BACKGROUND: Cancer is a growing co-morbidity among HIV-infected patients worldwide. With the scale-up of antiretroviral therapy (ART) in developing countries, cancer will contribute more and more to the HIV/AIDS disease burden. Our objective was to estimate the association between HIV infection and selected types of cancers among patients hospitalized for diagnosis or treatment of cancer in West Africa. METHODS: A case-referent study was conducted in referral hospitals in Côte d'Ivoire and Benin. Each participating clinical ward enrolled all adult patients seeking care for a confirmed diagnosis of cancer and clinicians systematically proposed an HIV test. HIV prevalence was compared between AIDS-defining cancers and a subset of selected non-AIDS defining cancers to a referent group of non-AIDS defining cancers not reported in the literature to be positively or inversely associated with HIV. An unconditional logistic model was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of the risk of being HIV-infected for selected cancers sites compared to a referent group of other cancers. RESULTS: The HIV overall prevalence was 12.3% (CI 10.3-14.4) among the 1,017 cancer cases included. A total of 442 patients constituted the referent group with an HIV prevalence of 4.7% (CI 2.8-6.7). In multivariate analysis, Kaposi sarcoma (OR 62.2 [CI 22.1-175.5]), non-Hodgkin lymphoma (4.0 [CI 2.0-8.0]), cervical cancer (OR 7.9 [CI 3.8-16.7]), anogenital cancer (OR 11.6 [CI 2.9-46.3]) and liver cancer (OR 2.7 [CI 1.1-7.7]) were all associated with HIV infection. CONCLUSIONS: In a time of expanding access to ART, AIDS-defining cancers remain highly associated with HIV infection. This is to our knowledge, the first study reporting a significant association between HIV infection and liver cancer in sub-Saharan Africa.

HIV treatment and care in resource-constrained environments: challenges for the next decade.

Many successes have been achieved in HIV care in low- and middle-income countries (LMIC): increased number of HIV-infected individuals receiving antiretroviral treatment (ART), wide decentralization, reduction in morbidity and mortality and accessibility to cheapest drugs. However, these successes should not hide existing failures and difficulties. In this paper, we underline several key challenges. First, ensure long-term financing, increase available resources, in order to meet the increasing needs, and redistribute the overall budget in a concerted way amongst donors. Second, increase ART coverage and treat the many eligible patients who have not yet started ART. Competition amongst countries is expected to become a strong driving force in encouraging the least efficient to join better performing countries. Third, decrease early mortality on ART, by improving access to prevention, case-finding and treatment of tuberculosis and invasive bacterial diseases and by getting people to start ART much earlier. Fourth, move on from WHO 2006 to WHO 2010 guidelines. Raising the cut-off point for starting ART to 350 CD4/mm(3) needs changing paradigm, adopting opt-out approach, facilitating pro-active testing, facilitating task shifting and increasing staff recruitments. Phasing out stavudine needs acting for a drastic reduction in the costs of other drugs. Scaling up routine viral load needs a mobilization for lower prices of reagents and equipments, as well as efforts in relation to point-of-care automation and to maintenance. The latter is a key step to boost the utilization of second-line regimens, which are currently dramatically under prescribed. Finally, other challenges are to reduce lost-to-follow-up rates; manage lifelong treatment and care for long-term morbidity, including drug toxicity, residual AIDS and HIV-non-AIDS morbidity and aging-related morbidity; and be able to face unforeseen events such as socio-political and military crisis. An old African proverb states that the growth of a deep-rooted tree cannot be stopped. Our tree is well rooted in existing field experience and is, therefore, expected to grow. In order for us to let it grow, long-term cost-effectiveness approach and life-saving evidence-based programming should replace short-term budgeting approach.

Short-term risk of anaemia following initiation of combination antiretroviral treatment in HIV-infected patients in countries in sub-Saharan Africa, Asia-Pacific, and central and South America.

BACKGROUND: The objective was to examine the short-term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV-infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration. METHODS: Anaemia was defined as haemoglobin of < 10 g/dL. Patients were included if they started cART with three or more drugs, had prior haemoglobin of > = 10 g/dL, and had one or more follow-up haemoglobin tests. Factors associated with anaemia up to 12 months were examined using Cox proportional hazards models and stratified by IeDEA region. RESULTS: Between 1998 and 2008, 19,947 patients initiated cART with baseline and follow-up haemoglobin tests (7358, 7289, 2853, 471, 1550 and 426 in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions, respectively). At initiation, anaemia was found in 45% of Western Africa patients, 29% of Eastern Africa patients, 21% of Southern Africa patients, 36% of Central Africa patients, 15% of patients in Asian-Pacific and 14% of patients in Caribbean and Central and South America. Among patients with haemoglobin of > = 10 g/dL at baseline (13,445), the risks of anaemia were 18.2, 6.6, 9.7, 22.9, 11.8 and 19.5 per 100 person-years in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian, and Caribbean and Central and South America regions, respectively. Factors associated with anaemia were female sex, low baseline haemoglobin level, low baseline CD4 count, more advanced disease stage, and initial cART containing zidovudine. CONCLUSIONS: In data from 34 cohorts of HIV-infected patients from sub-Saharan Africa, Central and South America, and Asia, the risk of anaemia within 12 months of initiating cART was moderate. Routine haemoglobin monitoring was recommended in patients at risk of developing anaemia following cART initiation.

Pharmacovigilance for antiretroviral drugs in Africa: lessons from a study in Abidjan, Cote d'Ivoire.

BACKGROUND: Although antiretroviral treatment (ART)-related adverse drug reactions (ADR) are documented in industrialised countries, there is no pre-existing surveillance system dedicated to ADR monitoring in most African countries. We assessed knowledge towards pharmacovigilance among ART prescribers and available capacity of HIV clinics to conduct ADR monitoring in Abidjan, Côte d'Ivoire. METHODS: A questionnaire was administered to ART prescribers to assess their knowledge towards the occurrence of ADRs. A retrospective ADR survey was also conducted based on a data query of treatment modification/interruptions in three HIV clinics. Clinical monitors went back to medical charts to review and validate the reasons of the treatment modification/interruptions. RESULTS: Of the 81 ART prescribers interviewed, 25 (31%) declared not grading ADRs and 12 (14.8%) declared notifying ADRs to the national regulatory authorities. Among 5252 adult ART-treated patients who attended the participating clinics in 2008, 599 treatment modifications were identified. Reasons for treatment modification/interruptions identified in the electronic database were documented in the medical charts in 554 cases (92.5%), ADR accounting for 273 cases (45.5%). Toxicity related to ART was graded in only 58 cases (21%) in the medical charts. DISCUSSION: This study describes challenges limiting the implementation of reliable pharmacovigilance activities in HIV clinics in Côte d'Ivoire. The lack of knowledge of ART prescribers concerning ADR grading does not support the spontaneous reporting of ADRs. Using treatment modification/interruptions for ADR monitoring appears feasible, but improvements are needed to respond to key questions related to drug toxicities in the context of ART scale-up in Africa.

[Malaria and HIV infection in subSaharan Africa: another match made in hell?]. / Paludisme et infection à VIH en Afrique subsaharienne: encore un couple maudit ?

Malaria and HIV are the most important infections in subSaharan Africa, in terms of the morbidity and mortality they cause. Current data suggest a possible interaction between the two diseases. Cellular immunodeficiency due to HIV infection might increase the frequency and severity of malaria, as local populations in endemic areas become less resistant. Likewise, the onset and repetition of malaria episodes might activate HIV replication and thus decrease the number of CD4 lymphocytes and accelerate the disease course. Despite their geographical coincidence, the epidemiological profiles of malaria and HIV differ considerably. The entanglement of these two diseases has epidemiological, clinical and therapeutic consequences in subSaharan Africa that raise concerns that HIV with malaria, as with tuberculosis, is a match made in Hell.

Low retention of HIV-infected patients on antiretroviral therapy in 11 clinical centres in West Africa.

OBJECTIVE: To study factors associated with the probability of retention in antiretroviral therapy (ART) programmes in West Africa. METHODS: The International epidemiologic Databases to Evaluate AIDS (IeDEA) in West Africa is a prospective, operational, observational cohort study based on collaboration between 11 cohorts of HIV-infected adult patients in Benin, Côte d'Ivoire, Gambia, Mali and Senegal. All patients aged 16 and older at ART initiation, with documented gender and date of ART initiation, were included. For those with at least 1 day of follow-up, Kaplan-Meier method and Weibull regression model were used to estimate the 12-month probability of retention in care and the associated factors. RESULTS: In this data merger, 14 352 patients (61% female) on ART were included. Median age was 37 (interquartile range (IQR): 31-44 years) and median CD4 count at baseline was 131 cells/mm(3) (IQR: 48-221 cells/mm(3)). The first-line regimen was NNRTI-based for 78% of patients, protease inhibitor-based for 17%, and three NRTIs for 3%. The probability of retention was 0.90 [95% confidence interval (CI): 0.89-0.90] at 3 months, 0.84 (95% CI: 0.83-0.85) at 6 months and 0.76 (95% CI: 0.75-0.77) at 12 months. The probability of retention in care was lower in patients with baseline CD4 count <50 cells/mm(3) [adjusted hazard ratio (aHR) = 1.37; 95% CI: 1.27-1.49; P < 0.0001] (reference CD4 > 200 cells/mm(3), in men (aHR = 1.17; 95% CI: 1.10-1.24; P = 0.0002), in younger patients (<30 years) (aHR = 1.10; 95% CI: 1.03-1.19; P = 0.01) and in patients with low haemoglobinaemia <8 g/dl (aHR = 1.33; 95% CI: 1.21-1.45; P < 0.0001). Availability of funds for systematic tracing was associated with better retention (aHR = 0.29; 95% CI: 0.16-0.55; P = 0.001). CONCLUSIONS: Close follow-up, promoting early access to care and ART and a decentralized system of care may improve the retention in care of HIV-infected patients on ART.

Alcohol use and non-adherence to antiretroviral therapy in HIV-infected patients in West Africa.

AIM: To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)-infected patients in sub-Saharan Africa. DESIGN AND SETTING: Cross-sectional survey conducted in eight adult HIV treatment centres from Benin, Côte d'Ivoire and Mali. Participants and measurements During a 4-week period, health workers administered the Alcohol Use Disorders Identification Test to HAART-treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow-up questionnaire. FINDINGS: A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32-45 years] and a median duration on HAART of 3 years (IQR 1-4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non-adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1-2.0], hazardous drinking (OR 4.7; 95% CI 2.6-8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5-0.9). CONCLUSIONS: Alcohol consumption and hazardous drinking is associated with non-adherence to HAART among HIV-infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking.

First-year lymphocyte T CD4+ response to antiretroviral therapy according to the HIV type in the IeDEA West Africa collaboration.

OBJECTIVE: To compare the lymphocyte T CD4+ (CD4) response to combinations of antiretroviral therapy (ART) in HIV-1, HIV-2 and dually positive patients in West Africa. DESIGN AND SETTING: Collaboration of 12 prospective cohorts of HIV-infected adults followed in Senegal (2), Gambia (1), Mali (2), Benin (1) and Côte d'Ivoire (6). SUBJECTS: Nine thousand, four hundred and eighty-two patients infected by HIV-1 only, 270 by HIV-2 only and 321 dually positive, who initiated an ART. OUTCOME MEASURES: CD4 change over a 12-month period. RESULTS: Observed CD4 cell counts at treatment initiation were similar in the three groups [overall median 155, interquartile range (IQR) 68; 249 cells/microl). In HIV-1 patients, the most common ART regimen was two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI; N = 7714) as well as for dually positive patients (N = 135). HIV-2 patients were most often treated with a protease inhibitor-based regimen (N = 193) but 45 of them were treated with an NNRTI-containing ART. In those treated with a NNRTI-containing regimen, the estimated mean CD4 change between 3 and 12 months was significantly lower in HIV-2 (-41 cells/microl per year) and dually positive patients (+12 cells/microl per year) compared to HIV-1 patients (+69 cells/microl per year, overall P value 0.01). The response in HIV-2 and dually positive patients treated by another regimen (triple NRTIs or protease inhibitor-containing ART) was not significantly different than the response obtained in HIV-1-only patients (all P values >0.30). CONCLUSION: An optimal CD4 response to ART in West Africa requires determining HIV type prior to initiation of antiretroviral drugs. NNRTIs are the mainstay of first-line ART in West Africa but are not adapted to the treatment of HIV-2 and dually positive patients.

Avascular osteonecrosis of the femoral head in three West African HIV-infected adults with heterozygous sickle cell disease.

Three men (aged 33, 44 and 45 years, CD4(+) T-cell nadir 86 cells/mm(3), 99 cells/mm(3) and 12 cells/mm(3), respectively) were admitted to the Department of Infectious Diseases (Treichville Hospital, Abidjan, Côte d'Ivoire) for hip pain and impaired mobility. Their last available CD4(+) T-cell counts were 243 cells/mm(3), 245 cells/mm(3) and 8 cells/mm(3), respectively. They had all received antiretroviral therapy for >4 years, including lopinavir/ritonavir for >8 months. The other risk factors were hypertriglyceridaemia (n=3), smoking addiction (n=2), alcohol consumption (n=2) and lipodystrophy (n=1). All three patients had heterozygous haemoglobin AS sickle cell disease (percentage of haemoglobin S 41%, 45% and 50%, respectively). The diagnosis of avascular osteonecrosis of the femoral head (unilateral n=2 and bilateral n=1) was documented by CT scan. Only one patient underwent surgical arthroplasty. In resource-limited settings, avascular osteonecrosis is uneasy to diagnose and unlikely to be appropriately treated. Physicians should be aware of its symptoms and risk factors, including HIV infection and antiretroviral therapy. Future studies should explore whether these risk factors might include haemoglobin AS sickle cell disease, a common trait in the West African general population.