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Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa.

ABSTRACT: Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8 and 26% of patients die in the first year of antiretroviral treatment, with most deaths occurring in the first few months. Patients typically access antiretroviral treatment with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count less than 50 cells/mul and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by antiretroviral treatment programmes, but more fundamentally on how advanced disease is at programme enrollment and the quality of preceding healthcare. In addition to improving delivery of antiretroviral treatment and providing it free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of antiretroviral treatment. Health systems delays in antiretroviral treatment initiation must be minimized, especially in patients who present with advanced immunodeficiency.

SUBMITTER: Lawn SD

PROVIDER: S-EPMC3816249 | biostudies-other | 2008 Oct

REPOSITORIES: biostudies-other

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Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa.

Lawn Stephen D SD Harries Anthony D AD Anglaret Xavier X Myer Landon L Wood Robin R

AIDS (London, England) 20081001 15

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, ...[more]

PMID: 18784453

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Project description:BackgroundThe World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.Methods and findingsWe developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year.ConclusionsThe amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up.

Project description:BackgroundMortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa.Methods and findingsPatients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77).ConclusionsMortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Project description:BackgroundPrognostic models have been developed for patients infected with HIV-1 who start combination antiretroviral therapy (ART) in high-income countries, but not for patients in sub-Saharan Africa. We developed two prognostic models to estimate the probability of death in patients starting ART in sub-Saharan Africa.MethodsWe analysed data for adult patients who started ART in four scale-up programmes in Côte d'Ivoire, South Africa, and Malawi from 2004 to 2007. Patients lost to follow-up in the first year were excluded. We used Weibull survival models to construct two prognostic models: one with CD4 cell count, clinical stage, bodyweight, age, and sex (CD4 count model); and one that replaced CD4 cell count with total lymphocyte count and severity of anaemia (total lymphocyte and haemoglobin model), because CD4 cell count is not routinely measured in many African ART programmes. Death from all causes in the first year of ART was the primary outcome.Findings912 (8.2%) of 11 153 patients died in the first year of ART. 822 patients were lost to follow-up and not included in the main analysis; 10 331 patients were analysed. Mortality was strongly associated with high baseline CD4 cell count (>/=200 cells per muL vs <25; adjusted hazard ratio 0.21, 95% CI 0.17-0.27), WHO clinical stage (stages III-IV vs I-II; 3.45, 2.43-4.90), bodyweight (>/=60 kg vs <45 kg; 0.23, 0.18-0.30), and anaemia status (none vs severe: 0.27, 0.20-0.36). Other independent risk factors for mortality were low total lymphocyte count, advanced age, and male sex. Probability of death at 1 year ranged from 0.9% (95% CI 0.6-1.4) to 52.5% (43.8-61.7) with the CD4 model, and from 0.9% (0.5-1.4) to 59.6% (48.2-71.4) with the total lymphocyte and haemoglobin model. Both models accurately predict early mortality in patients starting ART in sub-Saharan Africa compared with observed data.InterpretationPrognostic models should be used to counsel patients, plan health services, and predict outcomes for patients with HIV-1 infection in sub-Saharan Africa.FundingUS National Institute of Allergy And Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute.

Project description:Introduction Programmes that merge management of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) aim to improve HIV/TB co-infected patients’ access to comprehensive treatment. However, several reports from sub-Saharan Africa (SSA) indicate suboptimal uptake of antiretroviral therapy (ART) even after integration of HIV and TB treatment. This study assessed ART uptake, its barriers and enablers in programmes integrating TB and HIV treatment in SSA. Method A systematic review was performed. Seven databases were searched for eligible quantitative, qualitative and mixed-methods studies published from March 2004 through July 2019. Random-effects meta-analysis was used to obtain pooled estimates of ART uptake. A thematic approach was used to analyse and synthesise data on barriers and enablers. Results Of 5139 references identified, 27 were included in the review: 23/27 estimated ART uptake and 10/27 assessed barriers to and/or enablers of ART uptake. The pooled ART uptake was 53% (95% CI: 42, 63%) and between-study heterogeneity was high (I2 = 99.71%, p < 0.001). WHO guideline on collaborative TB/HIV activities and sample size were associated with heterogeneity. There were statistically significant subgroup effects with high heterogeneity after subgroup analyses by region, guideline on collaborative TB/HIV activities, study design, and sample size. The most frequently described socioeconomic and individual level barriers to ART uptake were stigma, low income, and younger age group. The most frequently reported health system-related barriers were limited staff capacity, shortages in medical supplies, lack of infrastructure, and poor adherence to or lack of treatment guidelines. Clinical barriers included intolerance to anti-TB drugs, fear of drug toxicity, and contraindications to antiretrovirals. Health system enablers included good management of the procurement, supply, and dispensation chain; convenience and accessibility of treatment services; and strong staff capacity. Availability of psychosocial support was the most frequently reported enabler of uptake at the community level. Conclusions In SSA, programmes integrating treatment of TB and HIV do not, in general, achieve high ART uptake but we observe a net improvement in uptake after WHO issued the 2012 guidelines on collaborative TB/HIV activities. The recurrence of specific modifiable system-level and patient-level factors in the literature reveals key intervention points to improve ART uptake in these programmes. Systematic review registration: CRD42019131933. Supplementary Information The online version contains supplementary material available at 10.1186/s12981-021-00395-3.

Dataset Information

Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa.

Publications

Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa.

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