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Unfavorable outcomes to second-line tuberculosis therapy among HIV-infected versus HIV-uninfected patients in sub-Saharan Africa: A systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Drug resistance is a key obstacle to the global target set to end tuberculosis by 2030. Clinical complexities in drug-resistant tuberculosis and HIV-infection co-management could worsen outcomes of second-line anti-tuberculosis drugs. A comprehensive estimate for risks of unsuccessful outcomes to second-line tuberculosis therapy in HIV-infected versus HIV-uninfected patients is mandatory to address such aspects in segments of the target set. Therefore, this meta-analysis was aimed to estimate the pooled risk ratios of unfavorable outcomes to second-line tuberculosis therapy between HIV-infected and HIV-uninfected patients in sub-Saharan Africa. METHODS:We conducted a literature search from PubMed/MEDLINE, EMBASE, SCOPUS and Google Scholar. We screened the retrieved records by titles and abstracts. Finally, we assessed eligibility and quality of full-text articles for the records retained by employing appraisal checklist of the Joanna Briggs Institute. We analyzed the data extracted from the included studies by using Review Manager Software, version 5.3 and presented our findings in forest and funnel plots. Protocol for this study was registered on PROSPERO (ID: CRD42020160473). RESULTS:A total of 19 studies with 1,766 from 4,481 HIV-infected and 1,164 from 3,820 HIV-uninfected patients had unfavorable outcomes. The risk ratios we estimated between HIV-infected and HIV-uninfected drug-resistant tuberculosis patients were 1.18 (95% CI: 1.07-1.30; I2 = 48%; P = 0.01) for the overall unfavorable outcome; 1.50 (95% CI: 1.30-1.74) for death; 0.66 (95% CI: 0.38-1.13) for treatment failure; and 0.82 (95% CI: 0.74-0.92) for loss from treatment. Variable increased risks of unfavorable outcomes estimated for subgroups with significance in mixed-age patients (RR: 1.22; 95% CI: 1.10-1.36) and eastern region of sub-Saharan Africa (RR: 1.47; 95% CI: 1.23-1.75). CONCLUSIONS:We found a higher risk of unfavorable treatment outcome in drug-resistant tuberculosis patients with death highly worsening in HIV-infected than in those HIV-uninfected patients. The risks for the unfavorable outcomes were significantly higher in mixed-age patients and in the eastern region of sub-Saharan Africa. Therefore, special strategies that reduce the risks of death should be discovered and implemented for HIV and drug-resistant tuberculosis co-infected patients on second-line tuberculosis therapy with optimal integration of the two programs in the eastern region of sub-Saharan Africa.

SUBMITTER: Edessa D

PROVIDER: S-EPMC7428180 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Unfavorable outcomes to second-line tuberculosis therapy among HIV-infected versus HIV-uninfected patients in sub-Saharan Africa: A systematic review and meta-analysis.

Edessa Dumessa D Sisay Mekonnen M Dessie Yadeta Y

PloS one 20200814 8

<h4>Background</h4>Drug resistance is a key obstacle to the global target set to end tuberculosis by 2030. Clinical complexities in drug-resistant tuberculosis and HIV-infection co-management could worsen outcomes of second-line anti-tuberculosis drugs. A comprehensive estimate for risks of unsuccessful outcomes to second-line tuberculosis therapy in HIV-infected versus HIV-uninfected patients is mandatory to address such aspects in segments of the target set. Therefore, this meta-analysis was a ...[more]

PMID: 32797110

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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:BackgroundIncreased second-line antiretroviral therapy (ART) failure rate narrows future options for HIV/AIDS treatment. It has critical implications in resource-limited settings; including sub-Saharan Africa (SSA) where the burden of HIV-infection is immense. Hence, pooled estimate for second-line HIV treatment failure is relevant to suggest valid recommendations that optimize ART outcomes in SSA.MethodsWe retrieved literature systematically from PUBMED/MEDLINE, EMBASE, CINAHL, Google Scholar, and AJOL. The retrieved studies were screened and assessed for eligibility. We also assessed the eligible studies for their methodological quality using the Joanna Briggs Institute's appraisal checklist. The pooled estimates for second-line HIV treatment failure and its associated factors were determined using STATA, version 15.0 and MEDCALC, version 18.11.3, respectively. We assessed publication bias using Comprehensive Meta-analysis software, version 3. Detailed study protocol for this review/meta-analysis is registered and found on PROSPERO (ID: CRD42018118959).ResultsA total of 33 studies with the overall 18,550 participants and 19,988.45 person-years (PYs) of follow-up were included in the review. The pooled second-line HIV treatment failure rate was 15.0 per 100 PYs (95% CI: 13.0-18.0). It was slightly higher at 12-18 months of follow-up (19.0/100 PYs; 95% CI: 15.0-22.0), in children (19.0/100 PYs; 95% CI: 14.0-23.0) and in southern SSA (18.0/100 PYs; 95% CI: 14.0-23.0). Baseline values (high viral load (OR: 5.67; 95% CI: 13.40-9.45); advanced clinical stage (OR: 3.27; 95% CI: 2.07-5.19); and low CD4 counts (OR: 2.80; 95% CI: 1.83-4.29)) and suboptimal adherence to therapy (OR: 1.92; 95% CI: 1.28-2.86) were the factors associated with increased failure rates.ConclusionSecond-line HIV treatment failure has become highly prevalent in SSA with alarming rates during the 12-18 month period of treatment start; in children; and southern SSA. Therefore, the second-line HIV treatment approach in SSA should critically consider excellent adherence to therapy, aggressive viral load suppression, and rapid immune recovery.

Project description:WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000?copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50?copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200?copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval -5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval -4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100?000?copies/ml (n?=?122) had a viral load below 50?copies/ml at week 48 (37.7 versus 75.4%; P?<?0.001).The three second-line regimens obtained similar and satisfactory virologic control and confirmed the WHO recommendation (TDF/FTC/LPVr) as a valid option. However, the suboptimal response for patients with high viral load warrants research for improved strategies.

Project description:Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

Project description:Novel tuberculosis (TB) prevention and control strategies are urgently required. Utilising specimens from the Improving Retreatment Success (NCT02114684) trial we assessed the associations between inflammatory markers, measured during active TB, with treatment response and disease severity in HIV-infected and uninfected individuals. Multiplex immunoassays and ELISA were used to measure plasma expression of 24 cytokines/chemokines. Cytokines were log transformed to adjust for skewness. We conducted a nested, un-matched, case (n= 31) - control (n=101) study with cases defined as those participants who failed to sputum culture convert within 8-weeks of TB treatment initiation. Additionally, we examined the association between the measured cytokines and time to culture conversion and presence of lung cavitation using cox proportional hazards and logistic regression models, respectively. Multivariable analyses adjusted for a wide range of baseline clinical and demographic variables. IP-10 expression during active TB was associated with increased odds of sputum culture conversion by 8-weeks overall (aOR 4.255, 95% CI 1.025 - 17.544, p=0.046)) and among HIV-infected individuals (OR 10.204, 95% CI 1.247 - 83.333, p=0.030). Increased MCP-3 (aHR 1.723, 95% CI 1.040 - 2.855, p=0.035) and IL-6 (aHR 1.409, 95% CI 1.045 - 1.899, p=0.024) expression was associated with a shorter time to culture conversion in the total cohort. Higher plasma expression of IL-6 (aHR 1.783, 95% CI 1.128 - 2.820, p=0.013), IL-1RA (aHR 2.595, 95% CI 1.136 - 5.926, p=0.024), IP-10 (aHR 2.068, 95% CI 1.034 - 4.137, p=0.040) and IL-1α (aHR 2.008, 95% CI 1.053 - 3.831, p=0.035) were significantly associated with shorter time to culture conversion among HIV-infected individuals. Increased IL-6 and IL-1RA expression was significantly associated with the presence of lung cavitation during active TB in the total cohort (OR 2.543, 95% CI 1.254 - 5.160, p=0.010), (OR 4.639, 95% CI 1.203 - 21.031, p=0.047) and in HIV-infected individuals (OR 2.644, 95% CI 1.062 - 6.585, p=0.037), (OR 7.795, 95% CI 1.177 - 51.611, p=0.033) respectively. Our results indicate that inflammatory cytokines/chemokines play an important role in TB disease outcome. Importantly, the observed associations were stronger in multivariable models highlighting the impact of behavioural and clinical variables on the expression of immune markers as well as their potential effects on TB outcome.

Dataset Information

Unfavorable outcomes to second-line tuberculosis therapy among HIV-infected versus HIV-uninfected patients in sub-Saharan Africa: A systematic review and meta-analysis.

Publications

Unfavorable outcomes to second-line tuberculosis therapy among HIV-infected versus HIV-uninfected patients in sub-Saharan Africa: A systematic review and meta-analysis.

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