Impact of HIV Drug Resistance on HIV/AIDS-Associated Mortality, New Infections, and Antiretroviral Therapy Program Costs in Sub-Saharan Africa.
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ABSTRACT:
SUBMITTER: Phillips AN
PROVIDER: S-EPMC5451603 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
Impact of HIV Drug Resistance on HIV/AIDS-Associated Mortality, New Infections, and Antiretroviral Therapy Program Costs in Sub-Saharan Africa.
Phillips Andrew N AN Stover John J Cambiano Valentina V Nakagawa Fumiyo F Jordan Michael R MR Pillay Deenan D Doherty Meg M Revill Paul P Bertagnolio Silvia S
The Journal of infectious diseases 20170501 9
To inform the level of attention to be given by antiretroviral therapy (ART) programs to HIV drug resistance (HIVDR), we used an individual-level model to estimate its impact on future AIDS deaths, HIV incidence, and ART program costs in sub-Saharan Africa (SSA) for a range of program situations. We applied this to SSA through the Spectrum-Goals model. In a situation in which current levels of pretreatment HIVDR are over 10% (mean, 15%), 16% of AIDS deaths (890 000 deaths), 9% of new infections ...[more]
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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.
| S-EPMC2667633 | biostudies-literature
Project description: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.
| S-EPMC3816249 | biostudies-other
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.
2014-02-20 | GSE52791 | GEO
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
2014-02-20 | E-GEOD-52791 | biostudies-arrayexpress
Project description:Based on epidemiological, clinical and experimental evidence, male circumcision (MC) could have a significant impact on the HIV epidemic in selected areas. We reviewed studies of the acceptability of MC in sub-Saharan Africa to assess factors that will influence uptake of circumcision in traditionally non-circumcising populations. Thirteen studies from nine countries were identified. Across studies, the median proportion of uncircumcised men willing to become circumcised was 65% (range 29-87%). Sixty nine percent (47-79%) of women favored circumcision for their partners, and 71% (50-90%) of men and 81% (70-90%) of women were willing to circumcise their sons. Because the level of acceptability across the nine countries was quite consistent, additional acceptability studies that pose hypothetical questions to participants are unnecessary. We recommend pilot interventions making safe circumcision services available in conjunction with current HIV prevention strategies and evaluating the safety and acceptability of circumcision.
| S-EPMC1847541 | biostudies-other
Project description:BackgroundSince the Start Free, Stay Free, and AIDS-Free launch, UNAIDS targets intended to promote interventions to prevent HIV transmission and promote access to ART among adolescents and children, of which none were achieved in 2020. In the sub-Saharan African region, the number of adolescents initiated on ART drugs remained consistently low, with approximately100 000 adolescents succumbing to AIDS-related causes in 2022. Although HIV prevalence among adolescents had been reduced, several HIV- positive adolescents died without being initiated on ART drugs. Therefore, this scoping review protocol aims to map factors influencing the initiation of ART drugs among adolescents living with HIV in sub-Saharan Africa.MethodsThe methodological framework for scoping reviews will guide this scoping protocol. A search strategy will be used to search literature in electronic databases, including EBSCOhost (PubMed/MEDLINE), Google Scholar, Science Direct, Scopus, BioMed Central, and the World Health Organization library for citations and literature using keywords and the Medical Subjects Heading (MeSH). The electronic databases will be supplemented by hand-searching references on the included studies. The search will be from Jan 01, 2012, to Dec 31, 2022. Articles will be searched and assessed for eligibility by two screeners uploaded on the Endnote software, and duplicates will be identified and removed before the abstract screening. The two screeners will assess the eligibility of the abstracts and the complete articles of the selected studies using the inclusion and exclusion criteria. A third screener will intervene when there is a lack of consensus between the two screeners. The selection process will be documented by following and using the PRISMA flow diagram (Fig 1). A thematic content analysis will present a narrative account of the extracted data.DiscussionThe results of this review will identify and describe factors influencing the initiation of Antiretroviral treatment among adolescents living with HIV in the Sub-Saharan African region. The findings will guide future research and inform tailored interventions and strategies for initiating ART among adolescents.Trial registrationOpen Science Framework. https://doi.org/10.17605/OSF.IO/RNF2T.
| S-EPMC10883572 | biostudies-literature
Project description:OBJECTIVE:HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression. METHODS:In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4/?L), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.0 microarrays at 0, 2, 4, 8, and 24 weeks after ART initiation. RESULTS:We identified 160 mRNA transcripts that were consistently down-regulated and 48 that were up-regulated after ART at each point over 24 weeks based on linear regression modeling (adjusted P < 0.05), Of these 208 transcripts, approximately half represent heretofore unrecognized ART-responsive genes and one-third have no known function. The down-regulated genes with known function encoded mediators of innate antiviral responses, including antiviral restriction factors, pattern recognition receptors, and interferon response proteins, and mediators of immune activation, cellular proliferation, and apoptosis. CONCLUSIONS:By using ART to block the viral stimulus, we identified transcripts involved in innate antiviral immunity, including antiviral restriction factors and pattern recognition receptors, that were not previously known to be induced by HIV infection.
| S-EPMC3159954 | biostudies-literature
Project description:ObjectiveTo review HIV testing services (HTS) costs in sub-Saharan Africa.DesignA systematic literature review of studies published from January 2006 to October 2020.MethodsWe searched ten electronic databases for studies that reported estimates for cost per person tested ($pptested) and cost per HIV-positive person identified ($ppositive) in sub-Saharan Africa. We explored variations in incremental cost estimates by testing modality (health facility-based, home-based, mobile-service, self-testing, campaign-style, and stand-alone), by primary or secondary/index HTS, and by population (general population, people living with HIV, antenatal care male partner, antenatal care/postnatal women and key populations). All costs are presented in 2019US$.ResultsSixty-five studies reported 167 cost estimates. Most reported only $pptested (90%), while (10%) reported the $ppositive. Costs were highly skewed. The lowest mean $pptested was self-testing at $12.75 (median = $11.50); primary testing at $16.63 (median = $10.68); in the general population, $14.06 (median = $10.13). The highest costs were in campaign-style at $27.64 (median = $26.70), secondary/index testing at $27.52 (median = $15.85), and antenatal male partner at $47.94 (median = $55.19). Incremental $ppositive was lowest for home-based at $297.09 (median = $246.75); primary testing $352.31 (median = $157.03); in the general population, $262.89 (median: $140.13).ConclusionWhile many studies reported the incremental costs of different HIV testing modalities, few presented full costs. Although the $pptested estimates varied widely, the costs for stand-alone, health facility, home-based, and mobile services were comparable, while substantially higher for campaign-style HTS and the lowest for HIV self-testing. Our review informs policymakers of the affordability of various HTS to ensure universal access to HIV testing.
| S-EPMC11348535 | biostudies-literature
Project description:BackgroundWomen account for over half of persons living with HIV/AIDS globally. We examined geographic variation in all-cause mortality after antiretroviral therapy (ART) for women living with HIV (WLWH) worldwide.MethodsWe pooled data from WLWH at least 18 years initiating ART 2000-2014 within COHERE (Europe) and IeDEA regions (East Africa, West Africa, South Africa, North America, Latin America/Caribbean). Mortality rates were calculated at 0-3, 3-6, 6-12, 12-24 and 24-48 months after ART, and mortality rate ratios were compared with European rates with piecewise exponential parametric survival models based on Poisson regression.FindingsOne hundred ninety thousand, one hundred and seventy-five WLWH (16% Europe, 47% East Africa, 13% West Africa, 19% South Africa, 1% South America, 3% North America and 2% Central America/Caribbean) were included. The highest death rates occurred 0-3 months after ART [1.51 (95% CI 1.25-1.82) per 100 person-years in Europe, 12.45 (11.30-13.73), 14.03 (13.12-15.02) and 9.44 (8.80-10.11) in East, West and South Africa, and 1.53 (0.97-2.43), 7.83 (5.44-11.27) and 17.02 (14.62-19.81) in North, South America and Central America/Caribbean, respectively] and declined thereafter. Mortality in Europe was the lowest, with regional differences greatest in the first 3 months and smaller at longer ART durations [adjusted rate ratios 24-48 months after ART: 3.63 (95% CI 3.04-4.33), 5.61 (4.84-6.51) and 3.47 (2.97-4.06) for East, West and South Africa; 2.86 (2.26-3.62), 2.42 (1.65-3.55) and 2.50 (1.92-3.26) for North, South America and Central America/Caribbean, respectively].ConclusionGlobal variations in short-term and long-term mortality among WLWH initiating ART may inform context-specific interventions.
| S-EPMC6948801 | biostudies-literature
Project description:BackgroundSignificant quantities of antiretroviral drugs (ARVs) to treat HIV/AIDS have been procured for Sub-Saharan Africa for the first time in their 20-year history. This presents a novel opportunity to empirically study the roles of brand and generic suppliers in providing access to ARVs.Methodology/principal findingsAn observational study of brand and generic supply based on a dataset of 2,162 orders of AIDS drugs for Sub-Saharan Africa reported to the Global Price Reporting Mechanism at the World Health Organization from January 2004-March 2006 was performed. Generic companies supplied 63% of the drugs studied, at prices that were on average about a third of the prices charged by brand companies. 96% of the procurement was of first line drugs, which were provided mostly by generic firms, while the remaining 4%, of second line drugs, was sourced primarily from brand companies. 85% of the generic drugs in the sample were manufactured in India, where the majority of the drugs procured were ineligible for patent protection. The remaining 15% was manufactured in South Africa, mostly under voluntary licenses provided by brand companies to a single generic company. In Sub-Saharan African countries, four first line drugs in the dataset were widely patented, however no general deterrent to generic purchasing based on a patent was detected.Conclusions/significanceGeneric and brand companies have played distinct roles in increasing the availability of ARVs in Sub-Saharan Africa. Generic companies provided most of the drugs studied, at prices below those charged by brand companies, and until now, almost exclusively supplied several fixed-dose combination drugs. Brand companies have supplied almost all second line drugs, signed voluntary licenses with generic companies, and are not strictly enforcing patents in certain countries. Further investigation into how price reductions in second line drugs can be achieved and the cheapest drugs can actually be procured is warranted.
| S-EPMC1805689 | biostudies-literature