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Viruses Feb 2024There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques.
METHODS
For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the 'meta' package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS.
RESULTS
A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58-2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations.
CONCLUSION
In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS.
Topics: Humans; HIV-1; Anti-HIV Agents; HIV Infections; Genotype; Drug Resistance, Viral; HIV Seropositivity; High-Throughput Nucleotide Sequencing; Prevalence; Mutation
PubMed: 38400015
DOI: 10.3390/v16020239 -
Journal of Public Health in Africa Oct 2023There has been significant progress with regards to winning the fight against HIV globally, particularly due to the introduction of antiretroviral therapy (ART)....
There has been significant progress with regards to winning the fight against HIV globally, particularly due to the introduction of antiretroviral therapy (ART). COVID-19 threatened to derail gains in the fight against HIV. As we have started to see with studies on COVID-19 and HIV, there is a need to 'provide an in-depth view' in understanding the dynamics between the two epidemics, especially in sub-Saharan Africa. We, therefore, undertook a systemic review of existing literature to synthesize the effects of COVID-19 on the utilization of HIV services in sub-Saharan Africa, the literature on the risks associated with HIV during the COVID-19 pandemic, and lastly, the innovations and strategies adopted to continue receiving treatment in sub-Saharan Africa. We conducted a systematic review of studies published between 2020 and April 2022. We searched for relevant sub-Saharan studies in the following databases: PubMed, Google Scholar, J-STOR, and Science Direct. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search identified 647 papers, and after screening, 41 were in line with the inclusion criteria and were included in the review. There was evidence of the negative effects of COVID-19 on reducing HIV testing, ART treatment, and HIV prevention services. There is evidence pointing to the need for people living with HIV to be prioritized for COVID-19 vaccinations. Innovations and strategies implemented to mitigate the effects of COVID-19 on HIV services include community-based ART distribution, multi-month ART dispensing, the use of digital technologies, and the use of the already existing HIV infrastructure to fight COVID-19. It is still imperative that future studies explore the predictors of utilization of HIV services in the advent of COVID-19.
PubMed: 37908391
DOI: 10.4081/jphia.2023.2658 -
Frontiers in Medicine 2024Integrase strand transfer inhibitor (INSTI) dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended by World Health Organisation as preferred first-line...
BACKGROUND
Integrase strand transfer inhibitor (INSTI) dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended by World Health Organisation as preferred first-line regimen in pregnant women living with human immunodeficiency virus (HIV) (WLHIV). Non-nucleoside reverse transfer inhibitor (NNRTI)-based ART and protease inhibitor (PI)-based ART are designated as alternative regimens. The impact of different ART regimens on perinatal outcomes is uncertain. We aimed to assess the comparative risk of adverse perinatal outcomes in WLHIV receiving different classes of ART.
MATERIALS AND METHODS
A systematic literature review was conducted by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between Jan 1, 1980, and July 14, 2023. We included studies reporting on the association of pregnant WLHIV receiving different classes of ART with 11 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Pairwise random-effects meta-analyses compared the risk of each adverse perinatal outcome among WLHIV receiving INSTI-ART, NNRTI-ART, PI-ART, and nucleoside reverse transfer inhibitor (NRTI)-based ART, and compared specific "third drugs" from different ART classes. Subgroup and sensitivity analyses were conducted based on country income status and study quality.
RESULTS
Thirty cohort studies published in 2006-2022, including 222,312 pregnant women, met the eligibility criteria. Random-effects meta-analyses found no evidence that INSTI-ART is associated with adverse perinatal outcomes compared to NNRTI-ART and PI-ART. We found that PI-ART is associated with a significantly increased risk of SGA (RR 1.28, 95% confidence interval (95% CI) [1.09, 1.51], = 0.003) and VSGA (RR 1.41, 95% CI [1.08, 1.83], = 0.011), compared to NNRTI-ART. Specifically, lopinavir/ritonavir (LPV/r) was associated with an increased risk of SGA (RR 1.40, 95% CI [1.18, 1.65], = 0.003) and VSGA (RR 1.84, 95% CI [1.37, 2.45], = 0.002), compared to efavirenz, but not compared to nevirapine. We found no evidence that any class of ART or specific "third drug" was associated with an increased risk of PTB.
CONCLUSION
Our findings support the recommendation of INSTI-ART as first-line ART regimen for use in pregnant WLHIV. However, the increased risks of SGA and VGSA associated with PI-ART, compared to NNRTI-ART, may impact choice of second- and third-line ART regimens in pregnancy.: https://www.crd.york.ac.uk/prospero/, identifier CRD42021248987.
PubMed: 38476445
DOI: 10.3389/fmed.2024.1323813 -
Reviews in Medical Virology May 2024Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that... (Review)
Review
Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28-73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one-third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.
Topics: Humans; HIV Infections; HIV-1; Plasma; RNA, Viral; Treatment Outcome; Viral Load
PubMed: 38578230
DOI: 10.1002/rmv.2536 -
PloS One 2024Dyslipidemia is a common public health problem in people living with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy and increases the risk... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Dyslipidemia is a common public health problem in people living with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy and increases the risk of cardiovascular disease. Although evidence indicates that the prevalence of dyslipidemia is high, estimated pooled data are not well documented. Therefore, we aimed to estimate the pooled prevalence of dyslipidemia in adult people living with HIV receiving antiretroviral therapy in Ethiopia.
METHOD
We conducted a systematic review and meta-analysis of the literature. The following databases and grey literature were searched: PubMed, WorldCat, ScienceDirect, DOAG, African Journals Online, Google Scholar, and African Index Medicine. We included all comparative epidemiological studies that reported the prevalence of high concentration of total cholesterol, triglycerides, and low density lipoprotein, and low concentration of high density lipoprotein cholesterol that were published between January 2003 and July 2023. The random effects model was used to pool the outcome of interest. Additionally, subgrouping, sensitivity analyses, and funnel plots were performed. R software Version 4.2.1 was used for statistical analysis.
RESULT
Seventeen studies with a total of 3929 participants were included in the meta-analysis. The pooled prevalence of dyslipidemia, high total cholesterol, high triglyceride, elevated level of low density lipoprotein and low level of high density lipoprotein cholesterol were 69.32% (95% CI: 63.33, 74.72), 39.78% (95%CI: 32.12, 47.96), 40.32% (95%CI: 34.56, 46.36), 28.58% (95%CI: 21.81, 36.46), and 36.17% (95%CI: 28.82, 44.24), respectively. Age and body mass index were associated with high total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels.
CONCLUSION
The authors concluded that the prevalence of dyslipidemia in Ethiopia is high in people living with HIV receiving antiretroviral therapy. Early detection of dyslipidemia and its integration into treatment are essential for preventing cardiovascular disease.
TRIAL REGISTRATION
Protocol registered with PROSPERO (CRD42023440125).
Topics: Humans; Dyslipidemias; Ethiopia; HIV Infections; Body Mass Index; Adult; Prevalence; Age Factors; Triglycerides
PubMed: 38722964
DOI: 10.1371/journal.pone.0298525 -
BMC Public Health Nov 2023Substance use remains a robust predictor of HIV infection and a serious impediment to HIV care continuum progression for people living with HIV. The primary research...
Promoting HIV care continuum outcomes among people who use drugs and alcohol: a systematic review of randomized trials evaluating behavioral HIV care interventions published from 2011 to 2023.
BACKGROUND
Substance use remains a robust predictor of HIV infection and a serious impediment to HIV care continuum progression for people living with HIV. The primary research question of this systematic review is focused on understanding the extent to which behavioral HIV care interventions have been efficacious in helping people who live with HIV and who use substances along the HIV care continuum.
METHODS
Using PubMed and ProQuest databases, we performed a systematic review of randomized trials of behavioral HIV care continuum interventions among people who use substances published from 2011 to August 2023, since the beginning of the treatment-as-prevention era.
RESULTS
We identified 11 studies (total participants: N = 5635), ten intentionally targeting substance-using populations. Four studies involved samples using ≥ 1 substance (e.g., alcohol, opioids, stimulants, marijuana); four involved injection drug use; one involved methamphetamine use; and one involved alcohol use. One study targeted a population with incidental substance use (i.e., alcohol, injection drug use, non-injection drug use reported in most participants). Each study defined one or more HIV care outcomes of interest. Viral suppression was an outcome targeted in 9/11 studies, followed by uptake of antiretroviral therapy (ART; 7/11), ART adherence (6/11), retention in care (5/11), and linkage to care (3/11). While most (nine) of the studies found significant effects on at least one HIV care outcome, findings were mostly mixed. Mediated (2/11) and moderated (2/11) effects were minimally examined.
CONCLUSIONS
The results from this systematic review demonstrate mixed findings concerning the efficacy of previous HIV care interventions to improve HIV care continuum outcomes among people who use substances. However, heterogeneity of study components (e.g., diversity of substances used/assessed, self-report vs. objective measures, attrition) prevent broad deductions or conclusions about the amenability of specific substance-using populations to HIV care intervention. More coordinated, comprehensive, and targeted efforts are needed to promote and disentangle intervention effects on HIV care continuum outcomes among substance-using populations.
Topics: Humans; HIV Infections; Randomized Controlled Trials as Topic; Continuity of Patient Care; Behavior Therapy; Substance-Related Disorders; Ethanol
PubMed: 37936103
DOI: 10.1186/s12889-023-17113-5 -
Revista Paulista de Pediatria : Orgao... 2023To investigate the impact of tenofovir disoproxil fumarate on bone mineral density and bone mineral content in children and adolescents infected with the human...
OBJECTIVE
To investigate the impact of tenofovir disoproxil fumarate on bone mineral density and bone mineral content in children and adolescents infected with the human immunodeficiency virus.
DATA SOURCE
The search procedure was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. The search was carried out until April 2022 in Medical Literature Analysis and Retrieval System Online (Medline), Embase, Cochrane Central, Latin American and Caribbean Health Sciences Literature, Web of Science, Scopus, and MedRxiv. The combination of terms used was: (Children OR Youth OR Teenagers) AND HIV AND (Tenofovir OR "Antiretroviral therapy") AND ("Bone density" OR Osteoporosis OR Osteopenia). The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022312851).
DATA SYNTHESIS
The initial searches resulted in 1156 papers. After the exclusion of duplicate studies, three blinded reviewers analyzed the title and abstract of 563 papers, of which 57 remained to be read in full. Only nine papers met the eligibility criteria and were included in descriptive and risk-of-bias analyses. Regarding study design, four were cross-sectional, three were longitudinal before-after studies without a control group, and two were prospective cohorts. Among these nine papers, seven showed no significant association between tenofovir disoproxil fumarate use and reduced bone mass in young people. However, these papers did not have high methodological quality.
CONCLUSIONS
Although most of the selected papers found no harmful effect of tenofovir disoproxil fumarate on bone mass, further primary research with higher methodological quality is needed so robust scientific evidences can be obtained.
Topics: Adolescent; Humans; Child; Tenofovir; Bone Density; HIV; Adenine; HIV Infections
PubMed: 37971172
DOI: 10.1590/1984-0462/2024/42/2023042 -
BMC Public Health Jan 2024To assess the adherence to option B + antiretroviral therapy (ART) and associated factors in pregnant and breastfeeding women in Sub-Saharan Africa (SSA). (Meta-Analysis)
Meta-Analysis
Adherence to option B + antiretroviral therapy and associated factors in pregnant and breastfeeding women in Sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
To assess the adherence to option B + antiretroviral therapy (ART) and associated factors in pregnant and breastfeeding women in Sub-Saharan Africa (SSA).
METHODS
We conducted a comprehensive search from 01 January 2012 to 03 October 2022, across four databases: PubMed, Scopus, Proquest Central, and Index Medicus Africain, to identify studies focused on pregnant and/or breastfeeding women living with HIV and receiving option B+ ART in SSA. Studies reporting adherence data were included in the meta-analysis. Were excluded studies published before 01 January 2012, grey literature, systematic reviews, and meta-analysis studies. Articles selection and data extraction were performed independently by two reviewers. We evaluated pooled adherence and pooled association between various factors and adherence using a random-effects model.
RESULTS
Overall, 42 studies involving 15,158 participants across 15 countries contributed to the meta-analysis. The overall pooled adherence was 72.3% (95% CI: 68.2-76.1%). Having high education level (pooled odds ratio (OR): 2.25; 95% CI: 1.57-3.21), living in urban area (pooled OR: 1.75; 95% CI: 1.10-2.81), disclosing status to a family/partner (pooled OR: 1.74; 95% CI: 1.27-2.40), having a support system (pooled OR: 3.19; 95% CI: 1.89-5.36), receiving counseling (pooled OR: 3.97; 95% CI: 2.96-5.34), initiating ART at early clinical HIV stage (pooled OR: 2.22; 95% CI: 1.08-4.56), and having good knowledge on PMTCT/HIV (pooled OR: 2.71; 95% CI: 1.40-5.25) were factors significantly associated with adherence to option B + ART.
CONCLUSIONS
Despite the implementation of option B+ ART, the level of adherence among pregnant and breastfeeding women in SSA falls short of meeting the critical thresholds for viral load suppression as outlined in the 95-95-95 objectives set for 2025. These objectives are integral for achieving HIV elimination, and in turn, preventing HIV mother-to-child transmission. To bridge this gap, urgent tailored interventions based on individual and structural factors are essential to enhance adherence within these subgroups of women. This targeted approach is crucial in striving towards the HIV elimination target in SSA.
Topics: Female; Humans; Pregnancy; Africa South of the Sahara; Breast Feeding; Educational Status; HIV Infections; Infectious Disease Transmission, Vertical; Anti-Retroviral Agents
PubMed: 38183014
DOI: 10.1186/s12889-023-17004-9 -
BMC Infectious Diseases Aug 2023Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with... (Meta-Analysis)
Meta-Analysis
Prevalence and trends of advanced HIV disease among antiretroviral therapy-naïve and antiretroviral therapy-experienced patients in South Africa between 2010-2021: a systematic review and meta-analysis.
BACKGROUND
Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022.
METHODS
We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I statistic and publication bias using the Egger and Begg's test.
RESULTS
We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1-46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution.
CONCLUSION
Despite HIV's evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART.
Topics: Humans; HIV; South Africa; Prevalence; HIV Infections; CD4 Lymphocyte Count
PubMed: 37608300
DOI: 10.1186/s12879-023-08521-4 -
JMIR MHealth and UHealth Apr 2024In the past few years, a burgeoning interest has emerged in applying gamification to promote desired health behaviors. However, little is known about the effectiveness... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the past few years, a burgeoning interest has emerged in applying gamification to promote desired health behaviors. However, little is known about the effectiveness of such applications in the HIV prevention and care continuum among men who have sex with men (MSM).
OBJECTIVE
This study aims to summarize and evaluate research on the effectiveness of gamification on the HIV prevention and care continuum, including HIV-testing promotion; condomless anal sex (CAS) reduction; and uptake of and adherence to pre-exposure prophylaxis (PrEP), postexposure prophylaxis (PEP), and antiretroviral therapy (ART).
METHODS
We comprehensively searched PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and the Journal of Medical Internet Research and its sister journals for studies published in English and Chinese from inception to January 2024. Eligible studies were included when they used gamified interventions with an active or inactive control group and assessed at least one of the following outcomes: HIV testing; CAS; and uptake of and adherence to PrEP, PEP, and ART. During the meta-analysis, a random-effects model was applied. Two reviewers independently assessed the quality and risk of bias of each included study.
RESULTS
The systematic review identified 26 studies, including 10 randomized controlled trials (RCTs). The results indicated that gamified digital interventions had been applied to various HIV outcomes, such as HIV testing, CAS, PrEP uptake and adherence, PEP uptake, and ART adherence. Most of the studies were conducted in the United States (n=19, 73%). The most frequently used game component was gaining points, followed by challenges. The meta-analysis showed gamification interventions could reduce the number of CAS acts at the 3-month follow-up (n=2 RCTs; incidence rate ratio 0.62, 95% CI 0.44-0.88). The meta-analysis also suggested an effective but nonstatistically significant effect of PrEP adherence at the 3-month follow-up (n=3 RCTs; risk ratio 1.16, 95% CI 0.96-1.38) and 6-month follow-up (n=4 RCTs; risk ratio 1.28, 95% CI 0.89-1.84). Only 1 pilot RCT was designed to evaluate the effectiveness of a gamified app in promoting HIV testing and PrEP uptake. No RCT was conducted to evaluate the effect of the gamified digital intervention on PEP uptake and adherence, and ART initiation among MSM.
CONCLUSIONS
Our findings suggest the short-term effect of gamified digital interventions on lowering the number of CAS acts in MSM. Further well-powered studies are still needed to evaluate the effect of the gamified digital intervention on HIV testing, PrEP uptake, PEP initiation and adherence, and ART initiation in MSM.
Topics: Male; Humans; United States; Homosexuality, Male; Gamification; HIV Infections; Sexual and Gender Minorities; Continuity of Patient Care
PubMed: 38623733
DOI: 10.2196/49509