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Article Reference 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.
Article Reference The challenge of AIDS-related malignancies in sub-Saharan Africa
BACKGROUND With the lengthening of life expectancy among HIV-positive subjects related to the use of highly active antiretroviral treatments, an increased risk of cancer has been described in industrialized countries. The question is to determine what occurs now and will happen in the future in the low income countries and particularly in sub-Saharan Africa where more than two-thirds of all HIV-positive people live in the world. The objective of our paper is to review the link between HIV and cancer in sub-Saharan Africa, putting it in perspective with what is already known in Western countries. METHODS AND FINDINGS Studies for this review were identified from several bibliographical databases including Pubmed, Scopus, Cochrane, Pascal, Web of Science and using keywords "HIV, neoplasia, epidemiology and Africa" and related MesH terms. A clear association was found between HIV infection and AIDS-classifying cancers. In case-referent studies, odds ratios (OR) were ranging from 21.9 (95\% Confidence Interval (CI) 12.5-38.6) to 47.1 (31.9-69.8) for Kaposi sarcoma and from 5.0 (2.7-9.5) to 12.6 (2.2-54.4) for non Hodgkin lymphoma. The association was less strong for invasive cervical cancer with ORs ranging from 1.1 (0.7-1.2) to 1.6 (1.1-2.3), whereas ORs for squamous intraepithelial lesions were higher, from 4.4 (2.3-8.4) to 17.0 (2.2-134.1). For non AIDS-classifying cancers, squamous cell conjunctival carcinoma of the eye was associated with HIV in many case-referent studies with ORs from 2.6 (1.4-4.9) to 13.0 (4.5-39.4). A record-linkage study conducted in Uganda showed an association between Hodgkin lymphoma and HIV infection with a standardized incidence ratio of 5.7 (1.2-17) although OR in case-referent studies ranged from 1.4 (0.7-2.8) to 1.6 (1.0-2.7). Other cancer sites found positively associated with HIV include lung, liver, anus, penis, vulva, kidney, thyroid and uterus and a decreased risk of female breast cancer. These results so far based on a relatively small number of studies warrant further epidemiological investigations, taking into account other known risk factors for these tumors. CONCLUSION Studies conducted in sub-Saharan Africa show that HIV infection is not only strongly associated with AIDS-classifying cancers but also provided some evidence of association for other neoplasia. African countries need now to implement well designed population-based studies in order to better describe the spectrum of AIDS-associated malignancies and the most effective strategies for their prevention, screening and treatment.
Article Reference Pregnancy outcomes in women exposed to efavirenz and nevirapine: an appraisal of the IeDEA West Africa and ANRS Databases, Abidjan, Cote d'Ivoire
BACKGROUND An increasing number of HIV-infected women become pregnant while receiving efavirenz (EFV). We compared the pregnancy outcomes of women exposed to EFV and to nevirapine (NVP) during the first trimester. METHODS A retrospective study in 4 HIV care centers participating to clinical trials and international cohort collaboration. All HIV-infected pregnant women who conceived on EFV-based or NVP-based antiretroviral therapy (ART) between 2003 and 2009 were included. Pregnancy outcomes were as follows: abortion (voluntary termination), miscarriage [unwanted termination 20 weeks of amenorrhea (WA)], stillborn (death ≥ 20 WA), preterm delivery (live-birth 37 WA), and low birth weight (LBW) (2500 grams). RESULTS Overall, 344 HIV-infected pregnant women conceived on ART (213 on EFV and 131 on NVP). Median age was 29 years, and median CD4 count 217 cells per microliter at ART initiation. The overall proportion was 11.7\% for abortion, 5.2\% for miscarriage, 6.7\% for stillborn, 10.8\% for preterm delivery, and 20.2\% for LBW. There was no difference between EFV and NVP exposure, except for abortion (14.3\% vs 7.3\%; P = 0.05). No external and visible congenital malformation was observed neither in women exposed to EFV nor in women exposed to NVP. CONCLUSIONS Among women exposed to EFV, no significant increased risk of unfavorable pregnancy outcome was reported except for abortion.
Article Reference 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.
Article Reference 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.
Article Reference Tobacco use and its determinants in HIV-infected patients on antiretroviral therapy in West African countries
BACKGROUND Tobacco smoking is common in human immunodeficiency virus (HIV) infected patients from industrialised countries. In West Africa, few data concerning tobacco consumption exist. METHODS A cross-sectional survey of the International Epidemiological Database to Evaluate AIDS (IeDEA) network in West Africa was conducted. Health workers administered a questionnaire assessing tobacco and cannabis consumption among patients receiving antiretroviral treatment. Regular smokers were defined as current smokers who smoked 1 cigarette per day for or=1 year. RESULTS Overall, 2920 patients were enrolled in three countries. The prevalence of ever smokers and regular smokers were respectively 46.2\% (95\%CI 42.8-49.5) and 15.6\% (95\%CI 13.2-18.0) in men and 3.7\% (95\%CI 2.9-4.5) and 0.6\% (95\%CI 0.3-0.9) in women. Regular smoking was associated with being from Côte d'Ivoire or Mali compared to Benin (OR 4.6, 95\%CI 2.9-7.3 and 7.7, 95\%CI 4.4-13.6), severely impaired immunological status at highly active antiretroviral treatment initiation (OR 1.5, 95\%CI 1.1-2.2) and history of tuberculosis (TB; OR 1.8, 95\%CI 1.1-3.0). CONCLUSION There are marked differences in smoking prevalence among these West African countries. This survey approach also provides proof of the association between cigarette smoking and TB in HIV-infected patients, a major public health issue in this part of the world.
Article Reference Time trends in demographic and clinical characteristics of adult patients on HAART initiation in West Africa
Objective We studied the evolution of drug combinations used, as well as the clinical and immunological profile of patients at initiation of highly active antiretroviral therapy (HAART) between 1996 and 2006 in West Africa. Settings and Method IeDEA West Africa is a network of HIV care programs established in 2006. We analyzed data from 12 clinical centers treating adults in five countries: Benin, Cote d'Ivoire, Senegal, Gambia, and Mali. Patients 16 years of age or over were included in the study and the following was documented: sex, date of birth and date of initiation of HAART. RESULTS We included 14,496 adult patients having started HAART, among these 55 % had started HAART between 2005-2006. The proportion of HIV-infected women increased from 46 % in 1996-2000 to 63 % in 2005-2006. The median age at HAART initiation remained constant: 35 years for women and 40 years for men. The proportion of patients having started HAART with a CD4 count<200 cells/microl was 54 % in 1996-2000, and 64 % in 2005-2006. The most frequently prescribed HAART was: AZT/3TC (or d4T/DDI)/IDV (27 %) in 1996-2000; d4T (or AZT)/3TC/EFV (49 %) in 2003-2004, and d4T/3TC/NVP (49 %) in 2005-2006. Conclusion The first line HAART regimen recommended by WHO was initiated in 83 % of cases in 2005-2006. New approaches to an earlier initiation of ART should be explored to reduce mortality in HIV-infected patients on HAART.
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Article Reference Challenges in integrating cervical cancer screening in HIV care clinics in West Africa: a pilot study in Abidjan, Cote d’Ivoire
Background The ongoing scale-up of antiretroviral therapy (ART) in low-resource settings continues to improve the prognosis of HIV-infected individuals, necessitating a focus on long-term case management especially in women. Facing the particularly high burden of cervical cancer in sub-Saharan Africa, preventive measures are therefore becoming an integral component of a comprehensive approach to the management of patients. We describe here some of the operational aspects of a cervical cancer screening procedure based on visual inspection among HIV-positive women attending ART clinics in Abidjan. Methods A cross-sectional study is being conducted in two HIV clinics of Abidjan, since August 2009. A mobile team composed of three trained midwives and a senior gynecologist is in charge of proposing cervical screening based on visual inspection to all HIV-infected women attending participating clinics. Midwives are in charge to perform visual inspection of the cervix with acetic acid (IVA) and lugol’s iodine (IVL). Exclusion criteria are following: no previous cervical cancer or total hysterectomy, aged <25 or >59 years, pregnancy over 20 weeks. They refer positively screened women (IVA+ or IVL+), to a gynecologist in charge of the colposcopy examination (and biopsy if needed). Women with confirmed lesions are proposed an adapted treatment according to local available resources. Results Of the first 1,653 HIV-positive women, who attended the cervical screening consultations, 49 were not eligible and 103 were not assessable because of a prevalent cervical infection. The median age of the 1,501 screened women was 37 (IQR 32-43) years, and 1171 (78%) were on ART. 133 (9%) women were positively screened for cervical pre malignancy and referred for medical examination. 69 (4.6%, 95% CI 3.5-5.6) were confirmed by colposocopy and had histological investigation. Results of the 69 biopsy performed were as follows; 48 cervical intraepithelial neoplasia (CIN) of grade 1, 8 CIN grade 2 or 3, 2 invasive carcinoma and 10 nonmalignant findings. 22 patients were treated with cryotherapy, 16 were referred for surgical excision, and 31 were proposed a gynecological followup. Conclusion Several barriers were identified as limiting the ability of visual inspection used as a cervical screening method such as a high rate of cervical infection or a high rate of false-positive cervical lesions. Health care systems in West African countries cannot afford the financial and structural burdens of a conventional cervical screening program. Strategies adapted to HIV-infected women and relying on visual inspection appear feasible despite stated limitations and should be further evaluated.
Article Reference Scaling up antiretroviral therapy for HIV-infected children in Côte d’Ivoire: determinants of survival and loss to programme
Objective To investigate deaths and losses to follow-up in a programme designed to scale up antiretroviral therapy (ART) for HIV-infected children in Côte d’Ivoire. Methods Between 2004 and 2007, HIV-exposed children at 19 centres were offered free HIV serum tests (polymerase chain reaction tests in those aged < 18 months) and ART. Computerized monitoring was used to determine: (i) the number of confirmed HIV infections, (ii) losses to the programme (i.e. death or loss to follow-up) before ART, (iii) mortality and loss-to-programme rates during 12 months of ART, and (iv) determinants of mortality and losses to the programme. Findings The analysis included 3876 ART-naïve children. Of the 1766 with HIV-1 infections (17% aged < 18 months), 124 (7.0%) died, 52 (2.9%) left the programme, 354 (20%) were lost to follow-up before ART, 259 (15%) remained in care without ART, and 977 (55%) started ART (median age: 63 months). The overall mortality rate during ART was significantly higher in the first 3 months than in months 4–12: 32.8 and 6.9 per 100 child-years of follow-up, respectively. Loss-to-programme rates were roughly double mortality rates and followed the same trend with duration of ART. Independent predictors of 12-month mortality on ART were pre-ART weight-for-age z-score < –2, percentage of CD4+ T lymphocytes < 10, World Health Organization HIV/AIDS clinical stage 3 or 4, and blood haemoglobin < 8 g/dl. Conclusion The large-scale programme to scale up paediatric ART in Côte d’Ivoire was effective. However, ART was often given too late, and early mortality and losses to programme before and just after ART initiation were major problems.