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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 -
American Journal of Preventive Medicine Feb 2024HIV preexposure prophylaxis (PrEP) is highly effective when taken as prescribed. Digital health adherence interventions have been identified as effective for improving... (Review)
Review
INTRODUCTION
HIV preexposure prophylaxis (PrEP) is highly effective when taken as prescribed. Digital health adherence interventions have been identified as effective for improving antiretroviral therapy adherence among people with HIV, but limited evidence exists for PrEP adherence interventions among people without HIV. The purpose of this Community Guide systematic review was to present the characteristics and effectiveness of digital PrEP adherence interventions.
METHODS
The author searched the CDC HIV Prevention Research Synthesis cumulative database for digital health interventions with PrEP adherence outcomes published in peer-reviewed journals from 2000 to 2022. Studies with comparison arms or pre-post data evaluating interventions in high-income countries were included. Two reviewers independently screened citations, extracted data, conducted risk of bias assessment, and resolved discrepancies through discussion. Summary effect estimates were calculated using median and interquartile interval.
RESULTS
Nine studies were included and all focused on gay, bisexual, and other men who have sex with men. Eight studies were U.S.-based while the other was conducted in the Netherlands. Five were randomized control trials and four were pre-/post studies. All studies showed improved adherence in the intervention arms compared with comparison groups or preintervention data. One study also reported improvement in PrEP care retention.
DISCUSSION
Digital health adherence interventions with different strategies to improve PrEP and HIV-related outcomes were identified. The small number of studies identified is a limitation. Findings from this review served as the basis for the Community Preventive Services Task Force recommendation to use these interventions to increase PrEP adherence to prevent HIV infection.
PubMed: 38367928
DOI: 10.1016/j.amepre.2024.02.009 -
Frontiers in Immunology 2024In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial.
METHODS
We conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, and reporting CD4/CD8 ratio or CD8+ counts. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5. (CRD42020170931).
FINDINGS
We identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher mortality risk (OR 3.65; 95% CI 3.04 - 4.35; I2 = 0.00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term.
CONCLUSIONS
Our results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0.5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.
Topics: Humans; Prognosis; HIV Infections; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; CD4 Lymphocyte Count
PubMed: 38361925
DOI: 10.3389/fimmu.2024.1343124 -
Drug Development Research Feb 2024Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as... (Review)
Review
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as different combinations of NNRTIs have been used on clinically approved combining highly active antiretroviral therapy (HAART) to resist the growth of HIV-1 and decrease the mortality rate of HIV/AIDS. Although the feeble strength against the drug-resistant mutant strains and the long-term damaging effects have been reducing the effectiveness of HAART, it could be a crucial challenge to develop novel Anti-HIV leads with a vital mode of action and the least side effects. The extensive chemical reactivity and the diverse chemotherapeutic applications of the 1,3,5-triazine have provided a wide scope of research in medicinal chemistry via a structural modification. In this review, we focused on the Anti-HIV profile of the tri-substituted s-triazine derivatives with structure-based features and also discussed the active mode of action to evaluate the significant findings. The tri-substituted 1,3,5-triazine derivatives have been found more promising to inhibit the growth of the drug-sensitive and drug-resistant variants of HIV-1, especially HIV-1 wild-type, HIV-1 K103N/Y181C, and HIV-1 Tyr181Cys. It has been observed that these derivatives have interacted with the enzyme protein residues via a significant - interaction and hydrogen bonding to resist the proliferation of the viral genomes. Further, the SAR and the active binding modes are critically described and highlight the role of structural variations with functional groups along with the binding affinity of targeted enzymes, which may be beneficial for rational drug discovery to develop highly dynamic Anti-HIV agents.
Topics: Triazines; HIV-1; Reverse Transcriptase Inhibitors; Chemistry, Pharmaceutical; Drug Discovery
PubMed: 38349259
DOI: 10.1002/ddr.22154 -
PloS One 2024cute kidney injury(AKI) is a rapid loss of the kidney's excretory function, resulting in an accumulation of end products of nitrogen metabolism. The causes of AKI in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
cute kidney injury(AKI) is a rapid loss of the kidney's excretory function, resulting in an accumulation of end products of nitrogen metabolism. The causes of AKI in HIV-positive patients are not well investigated, but it may be associated with antiretroviral drug side effects and HIV itself. Even though there were studies that reported the prevalence of AKI among HIV-positive patients in Africa, their findings were inconsistent across the studies.
METHODS
We searched on PubMed, Embas, Ebsco, OVID, Cochrane Library, and other supplementary search engines, including Google and Google Scholar. Articles published upto July 2023 were included in this review study. The quality of the study was assessed using the Newcastle-Ottawa Scale for cross-sectional, case-control, and cohort studies. The data were extracted using a Microsoft Excel spreadsheet and exported to Stata version 14 for analysis. A random effect meta-analysis model was used to estimate the pooled prevalence of AKI among HIV-positive patients. Heterogeneity was evaluated using Cochrane Q statistics and I squared (I2). Furthermore, the graphic asymmetric test of the funnel plot and/or Egger's tests were computed to detect publication bias. Sensitivity analysis was computed to see the effect of a single study on the summary effects. To treat the publication bias, a trim and fill analysis was carried out. The protocol of this review has been registered in an international database, the Prospective Register of Systematic Reviews (PROSPERO),with reference number CRD42023446078.
RESULTS
A total of twenty-four original articles comprising 7913HIV-positive patients were included in the study. The pooled prevalence of AKI among HI-positive patients was found to be 23.35% (95% CI: 18.14-28.56%, I2 = 97.7%, p-value <0.001). Low hemoglobin (Hgb <8mg/dl) was found to be the determinant factor for AKI among HIV-positive patients (AOR = 2.4; 95% CI:1.69-3.4, I2 = 0.0%, p-value = 0.40). In meta-regression analysis, sample size was the possible source of variation among the included studies (AOR = 3.11, 95%CI: 2.399-3.83).
CONCLUSIONS
The pooled prevalence of AKI among HIV-positive patients was high. HIV-positive patients with low hemoglobin levels are at risk of developing AKI. Hence, regular monitoring of kidney function tests is needed to prevent or delay the risk of AKI among HIV-positive patients. Healthcare workers should provide an integrated healthcare service to HIV-positive patients on the prevention, treatment, and reduction of the progression of AKI to advanced stages and complications.
Topics: Humans; Cross-Sectional Studies; Africa; Prevalence; HIV Infections; Acute Kidney Injury; Hemoglobins; Ethiopia
PubMed: 38335171
DOI: 10.1371/journal.pone.0298302 -
Drug Safety Apr 2024Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus (HIV) epidemic, people living with HIV have represented most cases for more than a decade. With the diffusion of highly active antiretroviral therapy, this group progressively decreased in favor of patients undergoing treatment with targeted therapy/immunomodulators. In this systematic review and meta-analysis, the objective was to assess which drugs are most frequently related to PML development, and report the incidence of drug-induced PML through a meta-analytic approach.
METHODS
The electronic databases MEDLINE, EMBASE, ClinicalTrials.gov, Web of Science and the Canadian Agency for Drugs and Technologies in Health Database (CADTH) were searched up to May 10, 2022. Articles that reported the risk of PML development after treatment with immunomodulatory drugs, including patients of both sexes under the age of 80 years, affected by any pathology except HIV, primary immunodeficiencies or malignancies, were included in the review. The incidence of drug-induced PML was calculated based on PML cases and total number of patients observed per 100 persons and the observation time. Random-effect metanalyses were conducted for each drug reporting pooled incidence with 95% confidence intervals (CI) and median (interquartile range [IQR]) of the observation time. Heterogeneity was measured by I statistics. Publication bias was examined through funnel plots and Egger's test.
RESULTS
A total of 103 studies were included in the systematic review. In our analysis, we found no includible study reporting cases of PML during the course of treatment with ocrelizumab, vedolizumab, abrilumab, ontamalimab, teriflunomide, daclizumab, inebilizumab, basiliximab, tacrolimus, belimumab, infliximab, firategrast, disulone, azathioprine or danazole. Dalfampridine, glatiramer acetate, dimethyl fumarate and fingolimod show a relatively safe profile, although some cases of PML have been reported. The meta-analysis showed an incidence of PML cases among patients undergoing rituximab treatment for multiple sclerosis (MS) of 0.01 cases/100 persons (95% CI - 0.08 to 0.09; I = 20.4%; p = 0.25) for a median observation period of 23.5 months (IQR 22.1-42.1). Treatment of MS with natalizumab carried a PML risk of 0.33 cases/100 persons (95% CI 0.29-0.37; I = 50%; p = 0.003) for a median observation period of 44.1 months (IQR 28.4-60) and a mean number of doses of 36.3 (standard deviation [SD] ± 20.7). When comparing data about patients treated with standard interval dosing (SID) and extended interval dosing (EID), the latter appears to carry a smaller risk of PML, that is, 0.08 cases/100 persons (95% CI 0.0-0.15) for EID versus 0.3 cases/100 persons (95% CI 0.25-0.34) for SID.
CONCLUSIONS
A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents.
Topics: Male; Female; Humans; Aged, 80 and over; Natalizumab; Leukoencephalopathy, Progressive Multifocal; Canada; Immunologic Factors; Multiple Sclerosis; HIV Infections
PubMed: 38321317
DOI: 10.1007/s40264-023-01383-4 -
BMC Infectious Diseases Feb 2024The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active... (Meta-Analysis)
Meta-Analysis
The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10‑1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76‑1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.
Topics: Humans; Adult; Antiretroviral Therapy, Highly Active; C-Reactive Protein; HIV; HIV Infections; Cardiovascular Diseases; Lipids
PubMed: 38308222
DOI: 10.1186/s12879-024-09050-4 -
PLOS Global Public Health 2024Mental health problems, particularly depression and anxiety, are common in women and young girls living with HIV/ AIDS particularly in low- and middle-income (LMICs)...
Mental health problems, particularly depression and anxiety, are common in women and young girls living with HIV/ AIDS particularly in low- and middle-income (LMICs) countries where women's vulnerability to psychiatric symptoms is heightened due to the prevalent intersectional stressors such as stigma and intimate partner violence. However, no synthesized evidence exists on the mental health burden of females living with HIV/AIDS (FLWHA) in Africa. This systematic review aimed to synthesize the current evidence on the mental health burden among FLWHA in sub-Saharan Africa. A systematic literature review of articles published from 2013-2023 was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Five electronic databases; PubMed, MEDLINE with full text, Scopus, Academic Search Complete, and Health Source: Nursing Academic Edition were searched for articles published in English. Nineteen articles (15 quantitative, 3 qualitative, and 1 case study) from over 7 African countries met the inclusion criteria. The majority of the studies' quality was determined to be moderate. The prevalence of depression ranged from 5.9 to 61% and anxiety from 28.9 to 61%. Mental health burden was a logical outcome of HIV diagnosis. Predictors of mental health outcomes in the context of HIV/AIDS were identified as intimate partner violence (IPV), stigma, childhood traumas, sexual abuse, poverty, unemployment, and social isolation. Social support and resilience were identified as protective factors against mental illness in FLWHA. Mental illness had a deleterious effect on viral suppression rates among FLWHA, resulting in delayed initiation of antiretroviral therapy treatment and increased mortality but had no impact on immune reconstitution in the face of ART adherence. Given the high prevalence rates of depression and anxiety and their relationship with HIV progression, it is crucial that mental health care services are integrated into routine HIV care.
PubMed: 38300927
DOI: 10.1371/journal.pgph.0002767 -
AIDS and Behavior Feb 2024Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to... (Meta-Analysis)
Meta-Analysis
Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.
Topics: Humans; HIV Infections; Noncommunicable Diseases; Hypertension; Diabetes Mellitus; Africa South of the Sahara
PubMed: 38300475
DOI: 10.1007/s10461-023-04248-0 -
ClinicoEconomics and Outcomes Research... 2024The World Health Organization (WHO) recommends dolutegravir (DTG), a human immunodeficiency virus (HIV) medicine, as the first- and second-line treatment for all... (Review)
Review
The World Health Organization (WHO) recommends dolutegravir (DTG), a human immunodeficiency virus (HIV) medicine, as the first- and second-line treatment for all populations because, when compared to an efavirenz (EFV) regimen, plus two nucleoside reverse transcriptase inhibitors (NRTIs) has demonstrated significant effectiveness in HIV suppression in persons. This study aims to review evidence of the cost-effectiveness of DTG in combination with tenofovir and lamivudine compared with the standard of care for HIV therapy. The systematic review involved searching electronic databases for articles published between January 2018 and May 2022. Electronic database sources include PubMed, ScienceDirect, and EBSCO for articles on DTG in combination with tenofovir and lamivudine as subjects with cost-effectiveness outcomes. The inclusion criteria in this systematic review were studies about the cost-effectiveness analysis (CEA) of DTG in combination with tenofovir and lamivudine, written in English. A total of 145 articles were identified from three databases. After removing nine duplicates, 142 articles were screened by title and abstract, excluding 123 articles. After a full-text screening of 19 articles, five articles were selected for further analysis. Five articles reviewed in sub-Saharan Africa, India, and China implemented different modelling methods for CEA but produced similar results. The results of these studies demonstrate that it is more cost-effective than standard care for HIV treatment. The study conducted in sub-Saharan Africa from 2018 to 2020 showed a cost-effective result with disability-adjusted life years averted (DALY averted) by 83%; in India, it resulted in incremental cost-effectiveness ratio (ICER) $130 per year of live-saved (YLS); and a study in China found that dolutegravir plus tenofovir and lamivudine led to 0.006 incremental quality-adjusted life years (QALYs) with cost savings of $64. The DTG regimen is cost-effective and recommended for HIV therapy in all studies that provide results.
PubMed: 38293254
DOI: 10.2147/CEOR.S439725