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Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

ABSTRACT: INTRODUCTION:HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings. METHODS:We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months). RESULTS AND DISCUSSION:Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes. CONCLUSIONS:Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region.

SUBMITTER: Tenforde MW

PROVIDER: S-EPMC6970088 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

Tenforde Mark W MW Gertz Alida M AM Lawrence David S DS Wills Nicola K NK Guthrie Brandon L BL Farquhar Carey C Jarvis Joseph N JN

Journal of the International AIDS Society 20200101 1

<h4>Introduction</h4>HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings.<h4>Methods</h4>We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-co ...[more]

PMID: 31957332

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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:BackgroundUndernutrition is one of the most common problems among people living with HIV, contributing to premature death and the development of comorbidities within this population. In Sub-Saharan Africa (SSA), the impacts of these often inter-related conditions appear in a series of fragmented and inconclusive studies. Thus, this review examines the pooled effects of undernutrition on mortality and morbidities among adults living with HIV in SSA.MethodsA systematic literature search was conducted from PubMed, EMBASE, CINAHL, and Scopus databases. All observational studies reporting the effects of undernutrition on mortality and morbidity among adults living with HIV in SSA were included. Heterogeneity between the included studies was assessed using the Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger's and Begg's tests at a 5% significance level. Finally, a random-effects meta-analysis model was employed to estimate the overall adjusted hazard ratio.ResultsOf 4309 identified studies, 53 articles met the inclusion criteria and were included in this review. Of these, 40 studies were available for the meta-analysis. A meta-analysis of 23 cohort studies indicated that undernutrition significantly (AHR: 2.1, 95% CI: 1.8, 2.4) increased the risk of mortality among adults living with HIV, while severely undernourished adults living with HIV were at higher risk of death (AHR: 2.3, 95% CI: 1.9, 2.8) as compared to mildly undernourished adults living with HIV. Furthermore, the pooled estimates of ten cohort studies revealed that undernutrition significantly increased the risk of developing tuberculosis (AHR: 2.1, 95% CI: 1.6, 2.7) among adults living with HIV.ConclusionThis review found that undernutrition has significant effects on mortality and morbidity among adults living with HIV. As the degree of undernutrition became more severe, mortality rate also increased. Therefore, findings from this review may be used to update the nutritional guidelines used for the management of PLHIV by different stakeholders, especially in limited-resource settings.

Project description:BACKGROUND:Simple immune capture assays that detect mycobacterial lipoarabinomannan (LAM) antigen in urine are promising new tools for the diagnosis of HIV-associated tuberculosis (HIV-TB). In addition, however, recent prospective cohort studies of patients with HIV-TB have demonstrated associations between LAM in the urine and increased mortality risk during TB treatment, indicating an additional utility of urinary LAM as a prognostic marker. We conducted a systematic review and meta-analysis to summarise the evidence concerning the strength of this relationship in adults with HIV-TB in sub-Saharan Africa, thereby quantifying the assay's prognostic value. METHODS:We searched MEDLINE and Embase databases using comprehensive search terms for 'HIV', 'TB', 'LAM' and 'sub-Saharan Africa'. Identified studies were reviewed and selected according to predefined criteria. RESULTS:We identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44 %) tested positive for urinary LAM. After a variable duration of follow-up of between 2 and 6 months, overall case fatality rates among HIV-TB cases varied between 7 % and 53 %. Pooled summary estimates generated by random-effects meta-analysis showed a two-fold increased risk of mortality for urinary LAM-positive HIV-TB cases compared to urinary LAM-negative HIV-TB cases (relative risk 2.3, 95 % confidence interval 1.6-3.1). Some heterogeneity was explained by study setting and patient population in sub-group analyses. Five studies also reported multivariable analyses of risk factors for mortality, and pooled summary estimates demonstrated over two-fold increased mortality risk (odds ratio 2.5, 95 % confidence interval 1.4-4.5) among urinary LAM-positive HIV-TB cases, even after adjustment for other risk factors for mortality, including CD4 cell count. CONCLUSIONS:We have demonstrated that detectable LAM in urine is associated with increased risk of mortality during TB treatment, and that this relationship remains after adjusting for other risk factors for mortality. This may simply be due to a positive test for urinary LAM serving as a marker of higher mycobacterial load and greater disease dissemination and severity. Alternatively, LAM antigen may directly compromise host immune responses through its known immunomodulatory effects. Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB. Further research is warranted to elucidate the underlying mechanisms and to determine whether this vulnerable patient population may benefit from adjunctive interventions.

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Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

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Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

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