Severe morbidity after antiretroviral (ART) initiation: active surveillance in HIV care programs, the IeDEA West Africa collaboration.

BACKGROUND: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities. METHODS: Within the International epidemiological Database to Evaluate AIDS (IeDEA)--West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever>38°5C, Karnofsky index<70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale. RESULTS: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study. CONCLUSIONS: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.

Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin.

BACKGROUND: Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies. METHODS: A cohort study was conducted in order to estimate the incidence rate and to determine the factors associated with malaria-related fever, as well as the maternal morbidity attributable to malaria in a high-transmission setting of South Benin among HIV-infected pregnant women. Four-hundred and thirty-two women who participated in a randomized trial testing strategies to prevent malaria in pregnancy were included and followed until delivery, with at least three scheduled visits during pregnancy. Confirmed malaria-related fever was defined as axillary temperature >37.5°C and a concomitant, positive, thick blood smear or rapid diagnostic test for Plasmodium falciparum. Suspected malaria-related fever was defined as an axillary temperature >37.5°C and the concomitant administration of an anti-malarial treatment in the absence of parasitological investigation. RESULTS: Incidence rate for confirmed malaria-related fever was of 127.9 per 1,000 person-year (PY) (95% confidence interval (CI): 77.4-211.2). In multivariate analysis, CD4 lymphocytes (Relative Risk (RR) for a 50 cells/mm3 variation = 0.82; CI: 0.71-0.96), antiretroviral treatment started before inclusion (RR = 0.34; CI: 0.12-0.98) and history of symptomatic malaria in early pregnancy (RR = 7.10; CI: 2.35-22.49) were associated with the incidence of confirmed or suspected malaria-related fever. More than a half of participants with parasitaemia were symptomatic, with fever being the most common symptom. The crude fraction of febrile episodes attributable to malaria was estimated at 91%. CONCLUSIONS: This work highlights that malaria is responsible for a substantial morbidity in HIV-infected pregnant women, with cellular immunodepression as a major determinant, and establishes the possible advantage offered by the early initiation of antiretroviral treatment. TRIAL REGISTRATION: PACOME Study has been registered under the number NCT00970879.

Incidence of lipodystrophy and metabolic disorders in patients starting non-nucleoside reverse transcriptase inhibitors in Benin.

BACKGROUND: The incidence and risk factors for lipodystrophy and metabolic disorders among patients in Africa on first-line combined antiretroviral treatment (cART) mostly containing non-nucleoside reverse transcriptase inhibitors is poorly documented. METHODS: This prospective cohort study recruited 88 HIV-infected patients initiating cART between October 2004 and June 2005 in Cotonou, Benin. Patients were followed for 24 months. The main outcomes were incidence of lipodystrophy and metabolic disorders. Multivariate Cox proportional hazards regression models were used to describe factors associated with progression to lipodystrophy. RESULTS: After a median follow-up of 23.2 months (interquartile range 22.3-23.7), 24 (30%) patients developed lipodystrophy (lipoatrophy 9%, lipohypertrophy 24% and mixed pattern 2.5%). The incidence rate for lipodystrophy was estimated to 1.72 per person-month (95% confidence interval [CI] 1.15-2.56) occurring after a median time of 11 months on cART. Metabolic syndrome (International Diabetes Federation definition) appeared in 10 (13%) patients after a median of 15 months with an estimated incidence rate of 0.62 per person-month (95% CI 0.33-1.16). It was more common in women (19.2% versus 3.1% in men; P=0.043). Diabetes (8%) and hypercholesterolaemia (35%) were also observed. After adjustment, gender, young age (hazard ratio [HR] 0.45 [95% CI 0.22-0.90]; P=0.025), high BMI at inclusion (HR 1.53 [95% CI 1.28-1.83]; P<0.0001) and smoking (HR 28.0 [95% CI 2.5-307.4]; P=0.006) were significantly associated with lipohypertrophy. CONCLUSIONS: Lipodystrophy and metabolic syndrome were commonly and rapidly observed in this cohort of sub-Saharan patients initiating cART.

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.

Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era.

OBJECTIVE: We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. METHOD: We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. RESULTS: Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women), 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm(3) (IQR: 25-177) and 48% had previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36%), cerebral toxoplasmosis (10%), cryptococcosis (9%) and sepsis (7%). Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. CONCLUSIONS: AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease conditions and optimize earlier diagnosis of HIV infection and initiation of ART.

Reasons for hospitalization in HIV-infected children in West Africa.

INTRODUCTION: Current knowledge on morbidity and mortality in HIV-infected children comes from data collected in specific research programmes, which may offer a different standard of care compared to routine care. We described hospitalization data within a large observational cohort of HIV-infected children in West Africa (IeDEA West Africa collaboration). METHODS: We performed a six-month prospective multicentre survey from April to October 2010 in five HIV-specialized paediatric hospital wards in Ouagadougou, Accra, Cotonou, Dakar and Bamako. Baseline and follow-up data during hospitalization were recorded using a standardized clinical form, and extracted from hospitalization files and local databases. Event validation committees reviewed diagnoses within each centre. HIV-related events were defined according to the WHO definitions. RESULTS: From April to October 2010, 155 HIV-infected children were hospitalized; median age was 3 years [1-8]. Among them, 90 (58%) were confirmed for HIV infection during their stay; 138 (89%) were already receiving cotrimoxazole prophylaxis and 64 children (40%) had initiated antiretroviral therapy (ART). The median length of stay was 13 days (IQR: 7-23); 25 children (16%) died during hospitalization and four (3%) were transferred out. The leading causes of hospitalization were WHO stage 3 opportunistic infections (37%), non-AIDS-defining events (28%), cachexia and other WHO stage 4 events (25%). CONCLUSIONS: Overall, most causes of hospitalizations were HIV related but one hospitalization in three was caused by a non-AIDS-defining event, mostly in children on ART. HIV-related fatality is also high despite the scaling-up of access to ART in resource-limited settings.

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.

Tolerability of mefloquine intermittent preventive treatment for malaria in HIV-infected pregnant women in Benin.

OBJECTIVE: To investigate the tolerability of mefloquine intermittent preventive treatment (MQ IPTp) for malaria in HIV-infected pregnant women compared with HIV-negative women. DESIGN: Prospective cohort study comparing samples of HIV-negative and HIV-infected pregnant women from 2 clinical trials conducted in Benin. METHODS: One hundred and three HIV-infected women from the ongoing PACOME trial were compared with 421 HIV-negative women from a former trial, both trials aiming to evaluate the efficacy and tolerability of MQ IPTp, administered at the dose of 15 mg/kg. Descriptive analysis compared the proportion of women reporting at least 1 adverse reaction, according to HIV status. Multilevel logistic regression identified factors associated with the probability of reporting an adverse reaction for each MQ intake. RESULTS: Dizziness and vomiting were the most frequent adverse reactions. Adverse reactions were less frequent in HIV-infected women (65% versus 78%, P = 0.009). In multilevel analysis, HIV infection [odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.08 to 0.61] decreased the risk for adverse reactions, whereas detectable viral load (OR = 2.46, 95% CI = 1.07 to 5.66), first intake (versus further intakes, OR = 5.26, 95% CI = 3.70 to 7.14), older age (OR = 1.62, 95% CI = 1.13 to 2.32), and higher education level (OR = 1.71, 95% CI = 1.12 to 2.61) increased the risk. Moderate and severe adverse reactions were more frequent when antiretrovirals were started concomitantly with a MQ intake. CONCLUSIONS: This study provides reassuring data on the use of MQ IPTp in HIV-infected pregnant women. However frequent, adverse reactions remained moderate and did not impair adherence to MQ IPTp. In this high-risk group, MQ might be an acceptable alternative in case sulfadoxine-pyrimethamine loses its efficacy for intermittent preventive treatment.