Project description:BACKGROUND:To meet global targets for the treatment of HIV, high-prevalence countries are launching or expanding differentiated models of service delivery (DSD) for antiretroviral therapy (ART). Ongoing studies report on metrics specific to individual models of care, but little is known about the overall scale, impact, costs, and benefits of widespread implementation of DSD. We will conduct a rapid review of recent literature on DSD currently in use in sub-Saharan Africa and identify gaps in the literature with respect to the description of delivery models, coverage, effectiveness, and cost. METHODS:We will use an adapted version of the preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P) for reporting. To avoid repeating earlier reviews, only sources reporting data on interventions conducted and/or patients starting antiretroviral treatment since 1 January 2016 will be included. Other inclusion criteria: must report on HIV-positive patients receiving antiretroviral therapy (ART) for the treatment of HIV/AIDS in sub-Saharan Africa; must describe an antiretroviral care intervention and identify the location, visit frequency, provider, patient group, and intervention intensity; and must report at least one of the following outcomes: population coverage, intervention uptake, treatment outcomes, cost or resource allocation, acceptability, or feasibility. EXCLUSION CRITERIA:receiving ART as part of prevention of mother-to-child transmission (PMTCT) program or receiving preventive ART (PEP or PrEP). This review will include peer-reviewed articles and conference abstracts. Publication databases to be searched include PubMed, EMBASE, and Web of Science. For analysis, where possible, we will group the DSD by key characteristics (e.g., population served, visit frequency, visit location) and then report means and/or medians of coverage and outcomes with confidence intervals or IQRs. We will also descriptively compare and contrast different models of care, implementation challenges, and other non-quantitative information. DISCUSSION:This review will provide an initial picture of the status quo for the implementation of DSD in sub-Saharan Africa and identify directions for research and implementation support in the future. This big-picture analysis will be useful for ministries of health, implementers, and donor agencies to inform decision-making on DSD scale-up. SYSTEMATIC REVIEW REGISTRATION:PROSPERO: CRD42019118230.

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: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. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects

Project description:In sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up.In a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05.Data from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4% had CD4+ T-cell counts <100 cells/μL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9% (established cumulative mortality = 2.3%, loss to follow-up = 24.6%), 5.6% were transferred to other service providers, and 67.5% were retained in care. A diagnosis of Kaposi's sarcoma (hazard ratio (HR) = 3.3, 95% CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95% CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95% CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95% CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10%; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status.Among HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

Project description:IntroductionDifferentiated service delivery (DSD) models for antiretroviral treatment (ART) for HIV are being scaled up in the expectation that they will better meet the needs of patients, improve the quality and efficiency of treatment delivery and reduce costs while maintaining at least equivalent clinical outcomes. We reviewed the recent literature on DSD models to describe what is known about clinical outcomes.MethodsWe conducted a rapid systematic review of peer-reviewed publications in PubMed, Embase and the Web of Science and major international conference abstracts that reported outcomes of DSD models for the provision of ART in sub-Saharan Africa from January 1, 2016 to September 12, 2019. Sources reporting standard clinical HIV treatment metrics, primarily retention in care and viral load suppression, were reviewed and categorized by DSD model and source quality assessed.Results and discussionTwenty-nine papers and abstracts describing 37 DSD models and reporting 52 discrete outcomes met search inclusion criteria. Of the 37 models, 7 (19%) were facility-based individual models, 12 (32%) out-of-facility-based individual models, 5 (14%) client-led groups and 13 (35%) healthcare worker-led groups. Retention was reported for 29 (78%) of the models and viral suppression for 22 (59%). Where a comparison with conventional care was provided, retention in most DSD models was within 5% of that for conventional care; where no comparison was provided, retention generally exceeded 80% (range 47% to 100%). For viral suppression, all those with a comparison to conventional care reported a small increase in suppression in the DSD model; reported suppression exceeded 90% (range 77% to 98%) in 11/21 models. Analysis was limited by the extensive heterogeneity of study designs, outcomes, models and populations. Most sources did not provide comparisons with conventional care, and metrics for assessing outcomes varied widely and were in many cases poorly defined.ConclusionsExisting evidence on the clinical outcomes of DSD models for HIV treatment in sub-Saharan Africa is limited in both quantity and quality but suggests that retention in care and viral suppression are roughly equivalent to those in conventional models of care.

Project description:BACKGROUND:Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. METHODS:A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. RESULTS:Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. CONCLUSION:In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

Dataset Information

Cost of Differentiated HIV Antiretroviral Therapy Delivery Strategies in Sub-Saharan Africa: A Systematic Review.

Publications

Cost of Differentiated HIV Antiretroviral Therapy Delivery Strategies in Sub-Saharan Africa: A Systematic Review.

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