Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring.
Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches.
A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/mL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity.
In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention.
"Although increased availability of first line HAART in LMICs has significantly reduced mortality and morbidity amongst people living with HIV/AIDS (PLA), undernutrition and weight loss persist [17,23,24]. Both act as strong predictors of excessive early mortality [35,37,40,41]; possibly through poor immune reconstitution secondary to deficient nutritional status in PLA. With the rapid scale-up of ART programs, concerns have also been growing about the sustainability and effectiveness of such programs . "
[Show abstract][Hide abstract] ABSTRACT: 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.Methods/design: 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.
"While various reasons are known, demonstrating associations between various variables and risk of becoming LTFU remains challenging. Reported reasons for LTFU in Malawi and elsewhere have included: food insecurity [13-15], financial constraints [14,16,17], religious and family influences [14,16,18,19], wanting to access traditional medicine , stigma and fear of disclosure of HIV status [10,19-22], living far from clinics and transport-related costs [10,14,18,20,23], and poor patient-provider relationships [10,14,20]. Treatment literacy (e.g., understanding the natural course of treatment and the need for adherence to ART) [24,25], experiencing an improvement in health and believing that treatment is no longer necessary  may also matter. "
[Show abstract][Hide abstract] ABSTRACT: Background
Retention in antiretroviral therapy (ART) programmes remains a challenge in many settings including Malawi, in part due to high numbers of losses to follow-up. Concept Mapping (CM), a mix-method participatory approach, was used to explore why patients on ART are lost to follow-up (LTFU) by identifying: 1) factors that influence patient losses to follow-up and 2) barriers to effective and efficient tracing in Zomba, Malawi.
CM sessions (brainstorming, sorting and rating, interpretation) were conducted in urban and rural settings in Zomba, Malawi. Participants included ART patients, ART providers, Health Surveillance Assistants, and health managers from the Zomba District Health Office. In brainstorming, participants generated statements in response to “A specific reason why an individual on ART becomes lost to follow-up is…” Participants then sorted and rated the consolidated list of brainstormed items. Analysis included inductive qualitative methods for grouping of data and quantitative cluster identification to produce visual maps which were then interpreted by participants.
In total, 90 individuals brainstormed 371 statements, 64 consolidated statements were sorted (participant n = 46), and rated on importance and feasibility (participant n = 69). A nine-cluster concept map was generated and included both patient- and healthcare-related clusters such as: Stigma and Fears, Beliefs, Acceptance and Knowledge of ART, Access to ART, Poor Documentation, Social and Financial Support Issues, Health Worker Attitudes, Resources Needed for Effective Tracing, and Health Worker Issues Related to Tracing. Strategies to respond to the clusters were generated in Interpretation.
Multiple patient- and healthcare focused factors influence why patients become LTFU. Findings have implications particularly for programs with limited resources struggling with the retention of ART patients.
BMC Health Services Research 06/2013; 13(1):210. DOI:10.1186/1472-6963-13-210 · 1.71 Impact Factor
" Unfortunately, early outcomes are generally worse, as a result of high mortality rates soon after treatment start. ,  Studies performed in RLS are typically set in urban areas. However, data from non-urban settings are limited. "
[Show abstract][Hide abstract] ABSTRACT: This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.
An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure.
Median duration of follow-up after switch to second-line treatment was 20 months [IQR 11-35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure.
Good virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring.
PLoS ONE 03/2013; 8(3):e58526. DOI:10.1371/journal.pone.0058526 · 3.23 Impact Factor
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