A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

BACKGROUND: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. METHODS: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. FINDINGS: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. INTERPRETATION: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS)

Les hépatites virales B et C en Côte d'Ivoire : l'urgence d'une dynamisation de la lutte

En Côte d'Ivoire, malgré une prévalence d'environ 12% du VHB et 5% du VHC, le dépistage et la prise en charge des hépatites virales B et C demeurent très limités. Une étude qualitative a été menée en 2013 à Abidjan pour évaluer les modalités de dépistage et de prise en charge de ces infections. Les résultats révèlent la méconnaissance des hépatites tant dans la population générale que parmi les soignants non spécialistes. L'offre et la demande de dépistage sont restreintes et la formation insuffisante du personnel de santé engendre des occasions manquées. Seuls les donneurs de sang sont systématiquement dépistés, mais la prévention par la vaccination et la prise en charge sont peu effectives, faute de moyens financiers. Officiellement, les traitements sont disponibles, mais inaccessibles du fait de leur coût élevé, en l'absence de couverture maladie universelle. Le Programme National de Lutte contre les Hépatites Virales, créé en 2008, ne dispose pas du budget nécessaire pour pratiquer dépistage, prise en charge, prévention et campagnes de sensibilisation. L'absence de mobilisation financière internationale, comme celle qu'a connue l'épidémie de VIH, est vécue comme une injustice, tant par les médecins spécialisés qui ont les compétences pour traiter la maladie mais pas les moyens de les mettre au service des patients, que par les personnes porteuses d'une hépatite chronique B et/ou C. Il apparaît donc urgent de dynamiser et renforcer la lutte contre les hépatites B et C en Côte d'Ivoire

Troubles alimentaires ressentis par des adultes infectés par le virus de l'immunodéficience humaine à Abidjan (Côte d'Ivoire)

Les troubles du comportement alimentaire ont été évalués pour leur fréquence, leurs facteurs associés et leur évolution dans une cohorte de 330 adultes infectés par le VIH participant à un essai thérapeutique à Abidjan (Côte d'Ivoire). Après six mois de suivi, une anoréxie etait signalée par 28% des patients interrogés, une dysphagie par 9% et une aversion vis-à-vis de certains aliments par 28%. En analyse multivariée après ajustement sur l'activité professionnelle, les femmes (Odds Ratio (OR)=2,0 (Intervalle de confiance à 95% : 1,2-3,5) et les patients ayant moins de 200 lymphocytes CD4+/mm3 (OR=1,8 (1,0-3,0)) étaient les plus à risque de notifier une anoréxie. La dysphagie était plus fréquente chez les femmes que chez les hommes (OR=2.9 (1,2-7,4)) et l'aversion vis-à-vis de certains aliments plus fréquente chez les patients ayant moins de 200 lymphocytes CD4+/mm3 que chez ceux en ayant plus (OR=1,9 (1,2-3,1)). L'analyse de l'évolution de la proportion de patients notifiant ces troubles a montré une tendance à la diminution des cas d'anoréxie et de dysphagie au cours du suivi, tandis que les patients rapportant une aversion vis-à-vis de certains aliments tendaient à être plus nombreux. Les facteurs associés à l'évolution de la présence de troubles alimentaires entre la visite du 6e mois et celle du 12e mois étaient le sexe, le niveau de lymphocytes CD4+ et la prise de cotrimoxazole qui était le médicament évalué dans cet essai. Ces observations soulignent l'interêt pour les cliniciens en Afrique de s'informer sur le comportement alimentaire des adultes infectés par le VIH, pour dépister les troubles fréquemment rapportés par ces patients, et de leur dispenser de façon systématique des conseils nutritionnels, afin de prévenir la réduction des apports, l'un des facteurs de dénutrition associée au VIH en Afrique. (Résumé d'auteur

Troubles alimentaires ressentis par des adultes infectés par le virus de l'immunodéficience humaine à Abidjan (Côte d'Ivoire)

Les troubles du comportement alimentaire ont été évalués pour leur fréquence, leurs facteurs associés et leur évolution dans une cohorte de 330 adultes infectés par le VIH participant à un essai thérapeutique à Abidjan (Côte d'Ivoire). Après six mois de suivi, une anoréxie etait signalée par 28% des patients interrogés, une dysphagie par 9% et une aversion vis-à-vis de certains aliments par 28%. En analyse multivariée après ajustement sur l'activité professionnelle, les femmes (Odds Ratio (OR)=2,0 (Intervalle de confiance à 95% : 1,2-3,5) et les patients ayant moins de 200 lymphocytes CD4+/mm3 (OR=1,8 (1,0-3,0)) étaient les plus à risque de notifier une anoréxie. La dysphagie était plus fréquente chez les femmes que chez les hommes (OR=2.9 (1,2-7,4)) et l'aversion vis-à-vis de certains aliments plus fréquente chez les patients ayant moins de 200 lymphocytes CD4+/mm3 que chez ceux en ayant plus (OR=1,9 (1,2-3,1)). L'analyse de l'évolution de la proportion de patients notifiant ces troubles a montré une tendance à la diminution des cas d'anoréxie et de dysphagie au cours du suivi, tandis que les patients rapportant une aversion vis-à-vis de certains aliments tendaient à être plus nombreux. Les facteurs associés à l'évolution de la présence de troubles alimentaires entre la visite du 6e mois et celle du 12e mois étaient le sexe, le niveau de lymphocytes CD4+ et la prise de cotrimoxazole qui était le médicament évalué dans cet essai. Ces observations soulignent l'interêt pour les cliniciens en Afrique de s'informer sur le comportement alimentaire des adultes infectés par le VIH, pour dépister les troubles fréquemment rapportés par ces patients, et de leur dispenser de façon systématique des conseils nutritionnels, afin de prévenir la réduction des apports, l'un des facteurs de dénutrition associée au VIH en Afrique. (Résumé d'auteur

Prognostic value of cross-sectional anthropometric indices on short-term risk of mortality in human immunodeficiency virus-infected adults in Abidjan, Côte d'Ivoire

In sub-Saharan Africa where weight loss is very difficult to estimate, cross-sectional anthropometric indicators could be useful to predict human immunodeficiency virus (HIV)-associated mortality. The study objective was to look for threshold values of baseline body mass index, arm muscle circumference, and fat mass to predict the risk of death in HIV-infected adults included in a 1996-1998 trial of early cotrimoxazole chemoprophylaxis in Abidjan, Côte d'Ivoire (COTRIMO-CI-ANRS 059 trial). The authors graphically determined if consecutive anthropometric categories with the closest hazards ratios of the risk of death could be clustered to obtain a unique threshold that distinctly separated two categories. When the threshold values were determined, the authors estimated the hazards ratio of mortality of this two-category model. A significant increase of mortality was observed for a body mass index of < or =20.3 in men (hazards ratio = 2.6; 95% confidence interval (CI): 1.4, 5.0) and of < or =18.5 in women (hazards ratio = 2.2; 95% CI: 1.05, 4.5) and for a fat mass of < or =6% in men (hazards ratio = 4.6; 95% CI: 2.3, 9.4) and of < or =18% in women (hazards ratio = 2.4; 95% CI: 1.2, 4.9). No simple threshold could be identified for arm muscle circumference. In Côte d'Ivoire where chemoprophylaxis of opportunistic infections has recently been recommended to be widely initiated on clinical criteria, such thresholds may help to screen patients with higher risks of mortality.info:eu-repo/semantics/publishe

Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa

Abstract Background Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. Methods A medical chart review was conducted in large urban HIV treatment centers in Côte d’Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. Results Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4–14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02–4.79) had a confirmed HCV infection. Conclusions The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012

Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks

Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg remains a potential threat in blood safety. We investigated the actual prevalence, viral factors and genotype of OBI infections in Nigerian blood donors.Serum collected from two blood banks were reconfirmed as HBsAg seronegative by ELISA. Forty HBsAg positive samples were employed as controls. HBV-DNA was amplified from all donors and viral loads were determined using quantitative real-time PCR. Antibodies to the HBV core, surface and HBe antigen (anti-HBc,anti-HBs,HBeAg) were measured. The PreS/S and PreC/C regions of the HBV genome were sequenced.Of the 429 blood donors, 72(17%) were confirmed as OBI by DNA detection in different reference labs and excluded the concern of possible contamination. Of the 72 OBI samples, 48(67%) were positive for anti-HBc, 25(35%) positive for anti-HBs, and 2(3%) positive for HBeAg. Of the 72 OBI samples, 31(43%) were seropositive for either anti-HBc, anti-HBs or HBeAg, 21 (30%) positive for both anti-HBc and anti-HBs,one positive for both anti-HBc and HBeAg. None of the OBI samples were positive for all three serological markers. The viral load was <50copies/ml in the OBI samples and genotype E was predominant. The L217R polymorphism in the reverse transcriptase domain of the HBV polymerase gene was observed significantly higher in OBI compared with HBsAg positive individuals (P<0.0001).High incidence of OBI is relevant in high endemic areas worldwide and is a general burden in blood safety. This study signifies the high prevalence of OBI and proposes blood donor samples in Nigeria should be pre-tested for OBI by nucleic acid testing (NAT) and/or anti-HBc prior to transfusion to minimize the HBV infection risk