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

IntroductionSex 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.MethodsWe 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.ResultsA 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%).ConclusionsIn 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.     

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/mm³ (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.     

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 subSaharan 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.     

Sexual behaviour after antiretroviral therapy initiation in female sex workers and HIV-positive patients from the general population,Cotonou, Benin

From September 2008 to December 2011, we enrolled and followed-up 247 HIV-negative, 88 untreated and 32 treated HIV-positive female sex workers (FSWs), as well as 238 untreated and 115 treated HIV-positive patients from the general population (GP) of Cotonou, Benin. We wanted to assess the effect of antiretroviral therapy (ART) on sexual risk-taking in FSWs and patients from the GP. We used multivariate log binomial regression models for repeated measures to compare risky behaviours reported during pre-ART and post-ART visits and we performed linear time-trend analyses to assess changes in condom use in all five groups. At 58.8% of pre-ART and 45.3% of post-ART visits (adjusted p-value=0.293), treated FSWs have reported ≥16 clients during the last week of work. Inconsistent condom use with clients over the same period decreased by more than 50% (from 20.7 to 10.0%, adjusted p-value=0.082). In treated patients from the GP, inconsistent condom use with regular partners during the last four months was reported at 52.8% of pre-ART and 53.5% of post-ART visits (p=0.778). Reported casual sex was stable (36.8% versus 38.7%, adjusted p-value=0.924). In linear time-trend analyses, there was a significant downward trend in inconsistent condom use at the early stage of the study and stability thereafter in all HIV-negative and HIV-positive FSWs. There was no negative alteration in sexual behaviour following ART initiation either inpatients from the GP or in FSWs. The results underscore the key role of concomitant sexual risk-reduction strategies.     

Stabilization of the maleate salt of a basic drug by adjustment of microenvironmental pH in solid dosage form

Tablet formulations of the maleate salt of a basic drug (I) showed a major loss in potency and a lack of mass balance upon storage under accelerated stability testing conditions. No such stability issues were observed in capsules that were compositionally similar, and even the tablet was stable when it was encapsulated in capsule shell. It was identified that the salt converts to its free base form in the microenvironment of the tablet formulation. Studies using radiolabeled drug substance showed that the free base formed in the tablet volatilized under test conditions used and was absorbed in the wall of plastic container. No mass loss was observed with encapsulated tablets since the capsule shell either protected the drug substance from volatilization or trapped any drug substance that volatilized. The conversion of the salt to free base could be related to the pH-solubility profile of the compound where the pH(max) (pH of maximum solubility) was 3.3-3.6, above which the salt would convert to base while no such conversion would occur below this pH. The microenvironmental pH of the tablet was found to be 4.3, favoring the salt-to-base conversion. A stable tablet formulation with shelf-life >3 years was successfully developed by lowering the microenvironemental pH of tablet from 4.3 to <3.0 by adding citric acid to the formulation.     

Predictive factors of human cytomegalovirus reactivation in newly diagnosed glioblastoma patients treated with chemoradiotherapy

Journal of NeuroVirology - The human cytomegalovirus (HCMV) is a ubiquitous herpes virus which infects 40 to 99% of the population. HCMV reactivation may occur in the context of immunosuppression...     

Measurement of surface pH of pharmaceutical solids: a critical evaluation of indicator dye-sorption method and its comparison with slurry pH method

Two methods for the measurement of surface pH of pharmaceutical solids, namely, the dye-sorption method and the slurry pH method, were compared. High purity drug substances, instead of excipients, were used as model solids, because acidic or basic impurities present in excipients could influence slurry pH. Solid test samples were prepared by sorption of methanol-water solutions of several indicator dyes, and their diffuse reflectance UV-visible spectra were measured. The solid surface pH values were estimated by comparing base-to-acid peak ratios of the diffuse reflectance UV-visible spectra of solid samples to the calibration plots of dye solutions in aqueous standard buffers of known pH. In the slurry pH method, pH values of concentrated slurries of the compounds in water were considered to represent solid surface pH. The agreement between the two methods was mixed and depended on the compound or the indicator used. It was concluded that in many cases calibration plots of indicator dye spectra in aqueous buffers were not applicable to the solid state, and, as a result, the reliability of the method was low. The slurry method provided a simple and reliable measurement of surface pH indicating that concentrated slurry may closely represent solid surface pH.     

Costing universal access of highly active antiretroviral therapy in Benin

The study aimed to estimate costs of provision and access to highly active antiretroviral therapy (HAART) in order to assist in planning and resource allocation regarding scaling up and sustainable access to HAART in Benin. A prospective study was carried out to collect data on costs of provision of care at the Outpatient Treatment Centre (OTC) of the National University hospital in Cotonou, Benin and on costs borne by people living with HIV/AIDS (PLWHA) and their families in accessing care. We used an Excel model, a macro costing approach and WHO guidelines for costing health services. Annual costs were subsequently extrapolated from a societal perspective over a 10-year time horizon. Sensitivity analysis was conducted on major cost categories. The study population was mostly of middle age (median age of 38, IQR 34-42), married (65%), working class (60%) with low literacy (70% primary education level or less). The main drivers of costs of HAART service provision were drugs (73%), biological monitoring (15%) and personnel (8%). Annual costs of provision of HAART and household costs borne by PLWHA and families in seeking care amounted to 1160 USD and 111 USD per PLWHA respectively. These household costs are respectively 40% and 14% of household health and education related costs and may represent catastrophic health expenditures for patients and families. The provision of drugs and biological monitoring, and household costs in accessing care, remain by far the main barriers to ensuring universal access to HAART.