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Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.

ABSTRACT: 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.

SUBMITTER: Boulware DR

PROVIDER: S-EPMC3159954 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.

Boulware David R DR Meya David B DB Bergemann Tracy L TL Williams Darlisha D Vlasova-St Louis Irina A IA Rhein Josh J Staddon Jack J Kambugu Andrew A Janoff Edward N EN Bohjanen Paul R PR

Journal of acquired immune deficiency syndromes (1999) 20101201 4

<h4>Objective</h4>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.<h4>Methods</h4>In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4/μL), we measured mRNA gene profiles in peripheral blood using Affy ...[more]

PMID: 20838227

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Project description:BackgroundLong-term retention of patients in Africa's rapidly expanding antiretroviral therapy (ART) programs for HIV/AIDS is essential for these programs' success but has received relatively little attention. In this paper we present a systematic review of patient retention in ART programs in sub-Saharan Africa.Methods and findingsWe searched Medline, other literature databases, conference abstracts, publications archives, and the "gray literature" (project reports available online) between 2000 and 2007 for reports on the proportion of adult patients retained (i.e., remaining in care and on ART) after 6 mo or longer in sub-Saharan African, non-research ART programs, with and without donor support. Estimated retention rates at 6, 12, and 24 mo were calculated and plotted for each program. Retention was also estimated using Kaplan-Meier curves. In sensitivity analyses we considered best-case, worst-case, and midpoint scenarios for retention at 2 y; the best-case scenario assumed no further attrition beyond that reported, while the worst-case scenario assumed that attrition would continue in a linear fashion. We reviewed 32 publications reporting on 33 patient cohorts (74,192 patients, 13 countries). For all studies, the weighted average follow-up period reported was 9.9 mo, after which 77.5% of patients were retained. Loss to follow-up and death accounted for 56% and 40% of attrition, respectively. Weighted mean retention rates as reported were 79.1%, 75.0% and 61.6 % at 6, 12, and 24 mo, respectively. Of those reporting 24 mo of follow-up, the best program retained 85% of patients and the worst retained 46%. Attrition was higher in studies with shorter reporting periods, leading to monthly weighted mean attrition rates of 3.3%/mo, 1.9%/mo, and 1.6%/month for studies reporting to 6, 12, and 24 months, respectively, and suggesting that overall patient retention may be overestimated in the published reports. In sensitivity analyses, estimated retention rates ranged from 24% in the worse case to 77% in the best case at the end of 2 y, with a plausible midpoint scenario of 50%.ConclusionsSince the inception of large-scale ART access early in this decade, ART programs in Africa have retained about 60% of their patients at the end of 2 y. Loss to follow-up is the major cause of attrition, followed by death. Better patient tracing procedures, better understanding of loss to follow-up, and earlier initiation of ART to reduce mortality are needed if retention is to be improved. Retention varies widely across programs, and programs that have achieved higher retention rates can serve as models for future improvements.

Project description:Antiretroviral therapy (ART) is efficacious in improving clinical outcomes among people living with HIV (PLWH) and reducing HIV transmission when taken regularly. Research examining modifiable factors associated with ART non-adherence is critical for informing novel intervention development in settings with high HIV prevalence. Alcohol use has been linked with ART non-adherence in studies in sub-Saharan Africa; however, no review has pooled estimates across studies. We reviewed studies of alcohol use and ART non-adherence conducted in sub-Saharan Africa. We searched PubMed, CINAHL, EMBASE, and PsycINFO through August 2019 with terms related to ART non-adherence, alcohol use, and sub-Saharan Africa. One author reviewed titles/abstracts (n = 754) and two authors reviewed full texts (n = 308) for inclusion. Discrepancies were resolved by group consensus. Studies were retained if they quantitatively measured associations between alcohol use and ART non-adherence or viral non-suppression. We defined ART non-adherence using the definitions from each parent study (e.g., patients with > 5% missed ART doses during the previous four, seven or 30 days were considered non-adherent). A random effects meta-analysis was conducted to pool associations and we conducted additional analyses to assess between-study heterogeneity and publication bias and sensitivity analyses to determine robustness of our results when considering only certain study designs, alcohol use or ART scales, or studies that used viral non-suppression as their primary outcome. Of 56 articles meeting our inclusion criteria, 32 articles were included in the meta-analysis. All studies measured alcohol use via self-report. ART non-adherence was assessed using self-report, pill counts, or pharmacy records and definition of non-adherence varied depending on the measure used. Individuals who used alcohol had twice the odds of ART non-adherence compared with those who did not use alcohol (34% non-adherence among alcohol users vs. 18% among non-users; pooled odds ratio: 2.25; 95% confidence interval: 1.87-2.69; p < 0.001). We found evidence of a high degree of heterogeneity between studies (Cochrane Q statistic: 382.84, p< 0.001; I2 proportion: 91.9%) and evidence of publication bias. However, the magnitude of our pooled odds ratio was consistent across a number of sensitivity analyses to account for heterogeneity and publication bias. In a secondary analysis with studies using viral non-suppression as their primary outcome, we also estimated a statistically significant pooled effect of alcohol use on viral non-suppression (pooled odds ratio: 2.47; 95% confidence interval: 1.58-3.87). Evidence suggests alcohol use is associated with ART non-adherence in Sub-Saharan Africa, potentially hindering achievement of the UNAIDS 90-90-90 HIV treatment targets.

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: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.

Dataset Information

Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.

Publications

Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.

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