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BMC Public Health Jun 2024Owing to the introduction of highly active antiretroviral therapy (HAART), the trajectory of mortality and morbidity associated with human immunodeficiency virus (HIV)... (Meta-Analysis)
Meta-Analysis
Highly active antiretroviral therapy is necessary but not sufficient. A systematic review and meta-analysis of mortality incidence rates and predictors among HIV-infected adults receiving treatment in Ethiopia, a surrogate study for resource-poor settings.
BACKGROUND
Owing to the introduction of highly active antiretroviral therapy (HAART), the trajectory of mortality and morbidity associated with human immunodeficiency virus (HIV) infection has significantly decreased in developed countries. However, this remains a formidable public health challenge for people living with HIV in resource-poor settings. This study was undertaken to determine the pooled person-time incidence rate of mortality, analyze the trend, and identify predictors of survival among HIV-infected adults receiving HAART.
METHODS
Quantitative studies were searched in PubMed, Embase, Scopus, Google Scholar, African Journals Online, and Web of Science. The Joana Briggs Institute critical appraisal tool was used to assess the quality of the included articles. The data were analyzed using the random-effects Dersimonian-Laird model.
RESULTS
Data abstracted from 35 articles involving 39,988 subjects were analyzed. The pooled person-time incidence rate of mortality (all-cause) was 4.25 ([95% uncertainty interval (UI), 3.65 to 4.85]) per 100 person-years of observations. Predictors of mortality were patients aged ≥ 45 years (hazard ratio (HR), 1.70 [95% UI,1.10 to 2.63]), being female (HR, 0.82 [95% UI, 0.70 to 0.96]), history of substance use (HR, 3.10 [95% UI, 1.31 to 7.32]), HIV positive status non disclosure (HR, 3.10 [95% UI,1.31 to 7.32]), cluster of differentiation 4 + T cell - count < 200 cells/mm3 (HR, 3.23 [95% UI, [2.29 to 4.75]), anemia (HR, 2.63 [95% UI, 1.32 to 5.22]), World Health Organisation classified HIV clinical stages III and IV (HR, 3.02 [95% UI, 2.29 to 3.99]), undernutrition (HR, 2.24 [95% UI, 1.61 to 3.12]), opportunistic infections (HR, 1.89 [95% UI, 1.23 to 2.91]), tuberculosis coinfection (HR, 3.34 [95% UI, 2.33 to 4.81]),bedridden or ambulatory (HR,3.30 [95% UI, 2.29 to 4.75]), poor treatment adherence (HR, 3.37 [95% UI,1.83 to 6.22]), and antiretroviral drug toxicity (HR, 2.60 [95% UI, 1.82 to 3.71]).
CONCLUSION
Despite the early introduction of HAART in Ethiopia, since 2003, the mortality rate has remained high. Therefore, guideline-directed intervention of identified risk factors should be in place to improve overall prognosis and increase quality-adjusted life years.
Topics: Humans; HIV Infections; Antiretroviral Therapy, Highly Active; Ethiopia; Incidence; Adult; Female; Male
PubMed: 38943123
DOI: 10.1186/s12889-024-19268-1 -
Clinical Infectious Diseases : An... Oct 2023It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline...
BACKGROUND
It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year.
METHODS
We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded.
RESULTS
We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%).
CONCLUSIONS
ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence.
Topics: Humans; Randomized Controlled Trials as Topic; HIV Infections
PubMed: 37243351
DOI: 10.1093/cid/ciad308 -
Behavioural Neurology 2023Dementia is a severe neurodegenerative disorder and it is a group of acquired symptoms associated with impaired cognitive functions. In low-income settings particularly... (Review)
Review
BACKGROUND
Dementia is a severe neurodegenerative disorder and it is a group of acquired symptoms associated with impaired cognitive functions. In low-income settings particularly in Sub-Saharan Africa (SSA), it is often seen as part of normal aging. Environmental, behavioral, and lifestyle interventions have the potential to alter the disease course of dementia.
OBJECTIVE
This study is aimed to synthesize the literature/evidence(s) on the management practice and treatment outcomes of dementia in SSA.
METHOD
Comprehensive literature was searched in PubMed database, Cochrane Library, and Google Scholar. Eligibility has been set, and based on the criteria, initially, a total of 442 results were obtained, and from those around 183 articles were duplicated. After examining titles and abstracts of records 26 articles were identified. Finally, five randomized clinical trials (RCT) and three prospective cohort studies that were reported on the management practice and treatment outcome of dementia in SSA were eligible for analysis. RCT and prospective cohort studies were used to strengthen the quality of evidence. The quality of the included RCT studies was assessed by using the Cochrane Risk of Bias Tool.
RESULT
A total of 2781 patient data were included in the final analysis. Of these, 2354 patients were obtained from 5 RCTs and 427 patients from 3 prospective cohort studies, which were conducted in SSA countries. RCT studies were done on the feasibility and clinical effectiveness of cognitive stimulation therapy (CST) showed improvements in language memory domains and physical health. In addition, studies that focus on the management of human immunodeficiency virus-associated dementia (HIVAD) were reported to improve neurocognitively.
CONCLUSION
CST is applicable in low-resource settings and it shows improvements in cognitive function and quality of life. Early initiation of combination antiretroviral therapy in resource-limited settings has been associated with improvement in the cognitive function of HIVAD.
Topics: Humans; Cognition; Cognitive Behavioral Therapy; Treatment Outcome; Quality of Life; Dementia
PubMed: 37533682
DOI: 10.1155/2023/2307443 -
Reviews in Medical Virology May 2024Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We... (Meta-Analysis)
Meta-Analysis Review
Prevalence and factors associated with viral non-suppression in people living with HIV receiving antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.
Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We determined the prevalence and factors associated with VNS for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). This review, registered with PROSPERO (CRD42023470234), conducted an extensive search for evidence, focusing on PLHIV living in SSA on ART from the year 2000 to 19 October 2023, across databases including PubMed/MEDLINE, Embase, Web of Science, and Scopus. A total of 2357 articles were screened, from which 32 studies met the criteria for the final analysis, involving 756,620 PLHIV of all ages. The pooled prevalance for VNS was found to be 20.0% (95% CI: 15.43%-25.52%, I = 100%, p-value <0.01) Children and adolescents demonstrated the highest prevalence of VNS (viral load ≥1000 copies/mL) at 27.98% (95% CI: 21.91%-34.97%, I = 94%, p-value <0.01). The study revealed various factors associated with increased odds (risk) of VNS, p-value <0.05. These factors encompassed socio-demographics such as sex, age, education level, and marital status. Additionally, aspects related to HIV care, such as the facility attended, HIV status disclosure and adherence exhibited higher odds of VNS. Suboptimal ART adherence, longer duration on ART, socio-economic factors, lack of family and social support, presence of co-morbidities, advanced WHO HIV clinical stage, ART regimens, lower CD4+ count, abnormal body mass index, history of treatment interruptions, and progression of HIV illness were associated with VNS. Furthermore, behavioural/psychological factors including depression, substance use, negative perceptions towards ART, experiences of abuse, alcohol use, stigma, and certain patterns of sexual behaviour were also identified as factors for VNS. The occurrence of two VNS to every ten PLHIV on ART poses a threat to the progress made towards reaching the third 95% UNAIDS target in SSA. Additionally, these findings highlight the intricate interplay of various factors, encompassing patient characteristics, behavioural patterns, sociocultural influences, and pharmacological factors, all impacting VNS among PLHIV. Recognising its multifaceted nature, we recommend designing and implementing high impact interventions to effectively address VNS in SSA.
Topics: Humans; HIV Infections; Africa South of the Sahara; Prevalence; Viral Load; Anti-HIV Agents; Risk Factors; Adolescent; Female; Male; Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Child
PubMed: 38708846
DOI: 10.1002/rmv.2540 -
Journal of Investigative Medicine : the... May 2024Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney... (Review)
Review
Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney diseases cause morbidity and mortality in patients living with HIV (PLWH), though cART has permitted kidney transplants with acceptable post-transplant graft and patient survival. Risk of allograft rejection remains high, which may be related to interactions between cART, specifically protease inhibitors (PI), and immunosuppressants prescribed post-transplant. This systematic review evaluates renal transplant outcomes in PLWH treated with PI- vs non-PI-based cART. A search strategy was generated with terms related to renal transplant, HIV, and cART and run on PubMed, Embase, Scopus, and Cochrane. Studies were evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on Covidence by two reviewers and then evaluated for bias. Of 803 studies, 9 were included. Included papers were prospective or retrospective cohort studies or chart reviews of adult patients. Outcome measures included acute graft rejection, graft survival, and patient survival. One study had significant results demonstrating that PI-based therapy was correlated with increased graft rejection rates. Two studies demonstrated significant graft survival benefit to non-PI-based therapy, while one demonstrated significant benefit to PI-based therapy. Two studies found significant patient survival benefit to non-PI-based therapy. For each outcome measure, remaining data suggested improved outcomes with non-PI-based therapies without achieving statistical significance. The results demonstrate superior outcomes in PLWH taking non-PI-based cART, though the paucity of significant results suggests that PLWH who require PI-based cART for virological control may continue their regimen safely post-kidney transplant.
PubMed: 38666448
DOI: 10.1177/10815589241252595 -
Cureus Sep 2023Progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system (CNS), is most commonly associated with advanced HIV infection.... (Review)
Review
Progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system (CNS), is most commonly associated with advanced HIV infection. Although the severe neurological conditions - PML and progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS) - are linked to HIV, little is known about their characteristics in the era of established antiretroviral therapy (ART). The aim of this systematic review, which was performed by adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, was to determine the prognosis of PML in patients with HIV. We gathered and examined articles, including case-control and cohort studies, systematic reviews, and meta-analyses that were published between January 1, 2013, and May 2023. These articles were compiled from the following databases: Pubmed, Pubmed Central, Google Scholar, Wiley Library, and ScienceDirect. A total of 519 records were found from these databases for our systematic review after applying the proper filters. They were then further screened and put through quality appraisal tools, which ultimately led to the selection of 10 articles for the final analysis. This research offers crucial insights into the clinical consequences of PML in HIV patients receiving highly active antiretroviral therapy (HAART).
PubMed: 37842471
DOI: 10.7759/cureus.45155 -
Thrombosis Research Feb 2024Aim Although antiretroviral therapy (ART) is available, the rate of new HIV infections is alarming. With this trend, it is anticipated that the use of ART will continue... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Aim Although antiretroviral therapy (ART) is available, the rate of new HIV infections is alarming. With this trend, it is anticipated that the use of ART will continue to rise, potentially resulting in associated vascular disorders. Therefore, we aimed to examine the impact of ART on endothelial function in people living with HIV (PLHIV), a predictor of cardiovascular diseases.
METHOD
A comprehensive search for evidence was made on PubMed and Scopus on May 06, 2023, following the Preferred Reporting Items for Systematic Review and Meta-analysis. Cochrane and Newcastle-Ottawa quality assessment scales were used to evaluate quality, while the metaHun web tool and Review Manager version 5.4.1 were used for analysis. Subgroup, sensitivity, and publication bias were conducted for each outcome measure.
RESULTS
We identified 37 studies, including a sample size of 3700 with 2265 individuals on ART. The analyzed evidence showed a large significant effect of ART on vascular cell adhesion molecule-1, with a standardized mean difference (SMD) of -1.23 (95 % CI: -1.72, -0.74; p = 0.0013). Similarly, a significant medium effect of ART was observed on intercellular cell adhesion molecule-1 in PLHIV, with an SMD of -1.28 (95 % CI: -2.00, -0.56; p = 0.0231) compared to the control group. Furthermore, ART exhibited a significant but small effect on flow-mediated dilation (FMD) with an SMD of -0.40 (95 % CI: -0.62, -0.19, p = 0.0159).
CONCLUSION
Our findings show an improved endothelial function in PLHIV on ART, as demonstrated by reduced adhesion molecules; however, ART exhibited a small effect on FMD, thus suggesting PLHIV on ART may still be at risk of endothelial dysfunction and further cardiovascular diseases.
Topics: Humans; HIV Infections; Cardiovascular Diseases; Vascular Diseases; Cell Adhesion Molecules; Vascular Cell Adhesion Molecule-1
PubMed: 38211378
DOI: 10.1016/j.thromres.2023.12.011 -
AIDS (London, England) Aug 2023To identify types, evidence, and study gaps of alternative HIV preexposure prophylaxis (PrEP) care delivery models in the published literature.
OBJECTIVES
To identify types, evidence, and study gaps of alternative HIV preexposure prophylaxis (PrEP) care delivery models in the published literature.
DESIGN
Systematic review and narrative synthesis.
METHODS
We searched in the US Centers for Disease Control and Prevention (CDC) Prevention Research Synthesis (PRS) database through December 2022 (PROSPERO CRD42022311747). We included studies published in English that reported implementation of alternative PrEP care delivery models. Two reviewers independently reviewed the full text and extracted data by using standard forms. Risk of bias was assessed using the adapted Newcastle-Ottawa Quality Assessment Scale. Those that met our study criteria were evaluated for efficacy against CDC Evidence-Based Intervention (EBI) or Evidence-Informed Intervention (EI) criteria or Health Resources and Services Administration Emergency Strategy (ES) criteria, or for applicability by using an assessment based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework.
RESULTS
This review identified 16 studies published between 2018 and 2022 that implemented alternative prescriber ( n = 8), alternative setting for care ( n = 4), alternative setting for laboratory screening ( n = 1), or a combination of the above ( n = 3) . The majority of studies were US-based ( n = 12) with low risk of bias ( n = 11). None of the identified studies met EBI, EI, or ES criteria. Promising applicability was found for pharmacists prescribers, telePrEP, and mail-in testing.
CONCLUSIONS
Delivery of PrEP services outside of the traditional care system by expanding providers of PrEP care (e.g. pharmacist prescribers), as well as the settings of PrEP care (i.e. telePrEP) and laboratory screening (i.e. mail-in testing) may increase PrEP access and care delivery.
Topics: Humans; HIV Infections; Delivery of Health Care; Risk; Pre-Exposure Prophylaxis; Anti-HIV Agents
PubMed: 37199602
DOI: 10.1097/QAD.0000000000003601 -
BMJ Open Nov 2023As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate...
OBJECTIVES
As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation.
DESIGN
Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa.
DATA SOURCES
PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences.
ELIGIBILITY CRITERIA
Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure.
DATA EXTRACTION AND SYNTHESIS
We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature.
RESULTS
Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret.
CONCLUSIONS
The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%-50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure.
PROSPERO REGISTRATION NUMBER
CRD42022324136.
Topics: Humans; Adult; Anti-HIV Agents; HIV Infections; Anti-Retroviral Agents; Health Services Accessibility; Africa South of the Sahara
PubMed: 37984944
DOI: 10.1136/bmjopen-2022-071283 -
Atherosclerosis Plus Mar 2024Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable... (Review)
Review
Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.
Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.
PubMed: 38379882
DOI: 10.1016/j.athplu.2024.01.003