Impact of opportunistic diseases on chronic mortality in HIV-infected adults in Côte d'Ivoire

Objective: To estimate incidence rates of opportunistic diseases (ODs) and mortality for patients with and without a history of OD among HIV-infected patients in Côte d'Ivoire. Methods: Using incidence density analysis, we estimated rates of ODs and chronic mortality by CD4 count in patients in a cotrimoxazole prophylaxis trial in Abidjan before the highly active antiretroviral therapy (HAART) era. Chronic mortality was defined as death without a history of OD or death more than 30 days after an OD diagnosis. We used Poisson's regression to examine the effect of OD history on chronic mortality after adjusting for age, gender, and current CD4 count.Results: Two hundred and seventy patients (40% male, mean age 33 years, median baseline CD4 count 261 cells/µl) were followed up for a median of 9.5 months. Bacterial infections and tuberculosis were the most common severe ODs. Of 47 patients who died, 9 (19%) died within 30 days of an OD, 26 (55%) died more than 30 days after an OD, and 12 (26%) died with no OD history. The chronic mortality rate was 31.0/100 person-years for those with an OD history, and 11.1/100 person-years for those with no OD history (rate ratio (RR) 2.81, 95% confidence interval (CI): 1.43 - 5.54). Multivariate analysis revealed that OD history remained an independent predictor of mortality (RR 2.15, 95% CI: 1.07 - 4.33) after adjusting for CD4 count, age and gender.Conclusions: Before the HAART era, a history of OD was associated with increased chronic HIV mortality in Côte d'Ivoire, even after adjusting for CD4 count. These results provide further evidence supporting OD prophylaxis in HIVinfected patients.South African Medical Journal Vol. 96(6) 2006: 526-52

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.)

Impact of a Citywide Sanitation Program in Northeast Brazil on Intestinal Parasites Infection in Young Children

BACKGROUND: Sanitation affects health, especially that of young children. Residents of Salvador, in Northeast Brazil, have had a high prevalence of intestinal parasites. A citywide sanitation intervention started in 1996 aimed to raise the level of sewer coverage from 26% to 80% of households. OBJECTIVES: We evaluated the impact of this intervention on the prevalence of Ascaris lumbricoides, Trichuris trichuria, and Giardia duodenalis infections in preschool children. METHODS: The evaluation was composed of two cross-sectional studies (1998 and 2003-2004), each of a sample of 681 and 976 children 1-4 years of age, respectively. Children were sampled from 24 sentinel areas chosen to represent the range of environmental conditions in the study site. Data were collected using an individual/household questionnaire, and an environmental survey was conducted in each area before and after the intervention to assess basic household and neighborhood sanitation conditions. Stool samples were examined for the presence of intestinal parasites. The effect of the intervention was estimated by hierarchical modeling, fitting a sequence of multivariate regression models. FINDINGS: The prevalence ofA. lumbricoides infection was reduced from 24.4% to 12.0%, T. trichuria from 18.0% to 5.0%, and G. duodenalis from 14.1% to 5.3%. Most of this reduction appeared to be explained by the increased coverage in each neighborhood by the sewage system constructed during the intervention. The key explanatory variable was thus an ecological measure of exposure and not household-based, suggesting that the parasite transmission prevented by the program was mainly in the public (vs. the domestic) domain. CONCLUSION: This study, using advanced statistical modeling to control for individual and ecological potential confounders, demonstrates the impact on intestinal parasites of sanitation improvements implemented at the scale of a large population

Ten-year attrition and antiretroviral therapy response among HIV-positive adults: a sex-based cohort analysis from eight West African countries

INTRODUCTION: Sex differences have already been reported in sub-Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow-up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults. METHODS: We used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no-follow-up and 10-year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively. RESULTS: A total of 71,283 patients (65.8% women) contributed to 310,007 person-years of follow-up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10-year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow-up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10-year attrition throughout the 10-year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow-up, whereas men failed to reach it even at the end of the 10-year follow-up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%). CONCLUSIONS: In West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex-adapted are needed for patients in care to monitor attrition, detect early high-risk groups so that they can stay in care with a durably controlled infection

Association Between Nutritional Status and the Immune response in HIV + Patients under HAART: Protocol for a Systematic Review.

Over 850 million people worldwide and 200 million adults in Sub-Saharan Africa suffer from malnutrition. Countries most affected by HIV are also stricken by elevated rates of food insecurity and malnutrition. HIV infection and insufficient nutritional intake are part of a vicious cycle that contributes to immunodeficiency and negative health outcomes. However, the effect of the overlap between HIV infection and undernutrition on the immune response following antiretroviral initiation remains unclear. A possible explanation could be the lack of consensus concerning the definition and assessment of nutritional status. Our objectives are to investigate the existence of an association between undernutrition and immune response at antiretroviral treatment initiation and the following year in low- and middle-income countries where malnutrition is most prevalent. Our systematic review will identify studies originating from low- and middle-income countries (LMICs) published from 1996 onwards, through searches in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and grey literature. No language restrictions will be applied. We will seek out studies of any design investigating the association between the nutritional status (for example, undernourished versus well nourished) and the immune response, either in terms of CD4 count or immune failure, in seropositive patients initiating antiretroviral therapy or in their first year of treatment. Two reviewers will independently screen articles, extract data and assess scientific quality using standardized forms and published quality assessment tools tailored for each study design. Where feasible, pooled measures of association will be obtained through meta-analyses. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. This protocol has been registered in the PROSPERO database (registration number: CRD42014005961). Undernutrition and weight loss are prevalent amongst highly active antiretroviral therapy (HAART)-treated patients in LMICs and contribute to excess early mortality. A possible intermediate pathway could be poor immune reconstitution secondary to deficient nutritional status. In the face of limited access to second line treatments, raising HIV resistance and cut backs to HIV programs, it is crucial to identify the factors associated with suboptimal response and therapeutic failure in order to better customize the care strategies employed in LMICs

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)

Correcting Mortality for Loss to Follow-Up: A Nomogram Applied to Antiretroviral Treatment Programmes in Sub-Saharan Africa

Matthias Egger and colleagues present a nomogram and a web-based calculator to correct estimates of program-level mortality for loss to follow-up, for use in antiretroviral treatment programs

Cost-Effectiveness of Preventing Loss to Follow-up in HIV Treatment Programs: A Côte d'Ivoire Appraisal

Based on data from West Africa, Elena Losina and colleagues predict that interventions to reduce dropout rates from HIV treatment programs (such as eliminating copayments) will be cost-effective