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Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.JMIR Public Health and Surveillance Jul 2023HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
OBJECTIVE
This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
RESULTS
We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
CONCLUSIONS
LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.
Topics: Humans; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Tenofovir
PubMed: 37498645
DOI: 10.2196/46767 -
AIDS (London, England) Jul 2016Preexposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Preexposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.
DESIGN
Rigorous systematic review and meta-analysis.
METHODS
A comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.
RESULTS
Eighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared with placebo. Trials with PrEP use more than 70% demonstrated the highest PrEP effectiveness (risk ratio = 0.30, 95% confidence interval: 0.21-0.45, P < 0.001) compared with placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.
CONCLUSION
PrEP is protective against HIV infection across populations, presents few significant safety risks, and there is no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV risk.
Topics: Administration, Oral; Adult; Anti-HIV Agents; Chemoprevention; Female; HIV Infections; Humans; Male; Placebos; Pre-Exposure Prophylaxis; Tenofovir; Young Adult
PubMed: 27149090
DOI: 10.1097/QAD.0000000000001145 -
Lancet (London, England) Aug 2023The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications,...
BACKGROUND
The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications, especially in resource-limited settings that use alternatives to plasma-based viral load testing. This Article summarises the evidence related to sexual transmission of HIV at varying HIV viral load levels to inform messaging for people living with HIV, their partners, their health-care providers, and the wider public.
METHODS
We conducted a systematic review and searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Conference Proceedings Citation Index-Science, and WHO Global Index Medicus, for work published from Jan 1, 2010 to Nov 17, 2022. Studies were included if they pertained to sexual transmission between serodiscordant couples at various levels of viraemia, the science behind undetectable=untransmittable, or the public health impact of low-level viraemia. Studies were excluded if they did not specify viral load thresholds or a definition for low-level viraemia or did not provide quantitative viral load information for transmission outcomes. Reviews, non-research letters, commentaries, and editorials were excluded. Risk of bias was evaluated using the ROBINS-I framework. Data were extracted and summarised with a focus on HIV sexual transmission at varying HIV viral loads.
FINDINGS
244 studies were identified and eight were included in the analysis, comprising 7762 serodiscordant couples across 25 countries. The certainty of evidence was moderate; the risk of bias was low. Three studies showed no HIV transmission when the partner living with HIV had a viral load less than 200 copies per mL. Across the remaining four prospective studies, there were 323 transmission events; none were in patients considered stably suppressed on ART. Among all studies there were two cases of transmission when the index patient's (ie, patient with previously diagnosed HIV infection) most recent viral load was less than 1000 copies per mL. However, interpretation of both cases was complicated by long intervals (ie, 50 days and 53 days) between the transmission date and the most recent index viral load result.
INTERPRETATION
There is almost zero risk of sexual transmission of HIV with viral loads of less than 1000 copies per mL. These data provide a powerful opportunity to destigmatise HIV and promote adherence to ART through dissemination of this positive public health message. These findings can also promote access to viral load testing in resource-limited settings for all people living with HIV by facilitating uptake of alternative sample types and technologies.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Humans; HIV Infections; Anti-HIV Agents; Prospective Studies; Viremia; Viral Load
PubMed: 37490935
DOI: 10.1016/S0140-6736(23)00877-2 -
AIDS (London, England) Feb 2019: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on...
: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral therapy (cART). Importantly, growing evidence shows that the central nervous system (CNS) may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Although there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain. In many resource-limited settings, antiretrovirals considered second or third line in the United States, which carry substantial neurotoxicity, remain mainstays of treatment, and patients continue to present with severe immunosuppression and CNS opportunistic infections. Despite this, increased global access to cART has coincided with an aging HIV-positive population with cognitive sequelae, cerebrovascular disease, and peripheral neuropathy. Further neurological research in low-income and middle-income countries (LMICs) is needed to address the burden of neurological complications in HIV-positive patients, particularly regarding CNS viral reservoirs and their effects on eradication.
Topics: AIDS Dementia Complex; Adult; Aged; Aged, 80 and over; Aging; Anti-HIV Agents; Child; Child, Preschool; Global Health; HIV Infections; Humans; Middle Aged
PubMed: 29547440
DOI: 10.1097/QAD.0000000000001796 -
Bulletin of the World Health... Jan 2015To assess the association between the employment status of human immunodeficiency virus (HIV)-infected individuals and adherence to antiretroviral therapy (ART). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the association between the employment status of human immunodeficiency virus (HIV)-infected individuals and adherence to antiretroviral therapy (ART).
METHODS
We searched the Medline, Embase and Cochrane Central Register of Controlled Trials databases for studies reporting ART adherence and employment status published between January 1980 and September 2014. Information from a wide range of other sources, including the grey literature, was also analysed. Two independent reviewers extracted data on treatment adherence and study characteristics. Study data on the association between being employed and adhering to ART were pooled using a random-effects model. Between-study heterogeneity and sources of bias were evaluated.
FINDINGS
The meta-analysis included 28 studies published between 1996 and 2014 that together involved 8743 HIV-infected individuals from 14 countries. The overall pooled odds ratio (OR) for the association between being employed and adhering to ART was 1.27 (95% confidence interval, CI: 1.04-1.55). The association was significant for studies from low-income countries (OR: 1.85, 95% CI: 1.58-2.18) and high-income countries (OR: 1.33, 95% CI: 1.02-1.74) but not middle-income countries (OR: 0.94, 95% CI: 0.62-1.42). In addition, studies published after 2011 and larger studies showed less association between employment and adherence than earlier and small studies, respectively.
CONCLUSION
Employed HIV-infected individuals, particularly those in low- and high-income countries, were more likely to adhere to ART than unemployed individuals. Further research is needed on the mechanisms by which employment and ART adherence affect each other and on whether employment-creation interventions can positively influence ART adherence, HIV disease progression and quality of life.
Topics: Anti-HIV Agents; Developed Countries; Developing Countries; Employment; HIV Infections; Humans; Medication Adherence
PubMed: 25558105
DOI: 10.2471/BLT.14.138149 -
AIDS (London, England) Sep 2015As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following ART in resource-limited (RLS) and developed settings.
DESIGN
Systematic review and meta-analysis.
METHODS
We searched publications reporting growth [weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z scores] in HIV-infected children following ART through August 2014. Inclusion criteria were as follows: younger than 18 years; ART; at least 20 patients; growth at ART; and post-ART growth. Standardized and overall weighted mean differences were calculated using random-effects models.
RESULTS
A total of 67 articles were eligible (RLS = 54; developed settings = 13). Mean age was 5.8 years, and comparable between settings (P = 0.90). Baseline growth was substantially lower in RLS vs. developed settings (WAZ -2.1 vs. -0.5; HAZ -2.2 vs. -0.9; both P < 0.01). Rate of weight but not height reconstitution during 12 and 24 months was higher in RLS (12-month WAZ change 0.84 vs. 0.17, P < 0.01). Growth deficits persisted in RLS after 2 years ART (P = 0.04). Younger cohort age was associated with greater growth reconstitution. Protease inhibitor and nonnucleoside reverse-transcriptase inhibitor regimens yielded comparable growth. Adjusting for age and setting, cohorts with nutritional supplements had greater growth gains (24-month rate difference: WAZ 0.55, P = 0.03; HAZ 0.60, P = 0.007). Supplement benefits were attenuated after adjusting for baseline cohort growth.
CONCLUSION
RLS children had substantial growth deficits compared with developed settings counterparts at ART; growth shortfalls in RLS persisted despite reconstitution. Earlier age and nutritional supplementation at ART may improve growth outcomes. Scant data on supplementation limit evaluation of impact and underscores need for systematic data collection regarding supplementation in pediatric ART programmes/cohorts.
Topics: Adolescent; Anthropology; Anti-Retroviral Agents; Biostatistics; Child; Child Development; Child, Preschool; Developed Countries; Developing Countries; Dietary Supplements; Female; HIV Infections; Humans; Infant; Infant, Newborn; Male
PubMed: 26355573
DOI: 10.1097/QAD.0000000000000783 -
AIDS Care Apr 2017Data on antiretroviral therapy (ART) adherence among prison inmates are limited and not previously synthesized in a systematic manner. The objective of this study was to... (Meta-Analysis)
Meta-Analysis Review
Data on antiretroviral therapy (ART) adherence among prison inmates are limited and not previously synthesized in a systematic manner. The objective of this study was to provide accurate and up-to-date ART adherence estimates among prison inmates. We searched electronic databases for all studies reporting adherence as a primary or secondary outcome among prison inmates. A random-effects model was used to pool adherence rates; sensitivity, heterogeneity and publication bias were assessed. Eleven studies involving 2895 HIV-infected prison inmates were included. The studies were carried out between 1992 and 2011 and reported between 1998 and 2013. A pooled analysis of all studies indicated a pooled estimate of 54.6% (95% confidence interval 48.1-60.9%) of prison inmates had adequate (≥95%) ART adherence. The adherence estimates were significantly higher among cross-studies and studies that used self-reported measures. In summary, our findings indicate that optimal adherence remains a challenge among prison inmates. It is crucial to monitor ART adherence and develop appropriate interventions to improve adherence among these population.
Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Medication Adherence; Prisoners
PubMed: 27582186
DOI: 10.1080/09540121.2016.1223799 -
Journal of Acquired Immune Deficiency... Sep 2015There are data to suggest that infection with HIV or use of highly active antiretroviral therapy increases the risk of hypertensive disorders in pregnancy. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are data to suggest that infection with HIV or use of highly active antiretroviral therapy increases the risk of hypertensive disorders in pregnancy. This systematic review and meta-analysis aims to provide an overview of the research hitherto.
METHODS
A systematic review of EMBASE, PubMed, and The Cochrane Library databases was conducted to obtain articles about the association between HIV in pregnancy and/or HIV therapy and the risk of developing pregnancy-induced hypertension (PIH), pre-eclampsia, eclampsia, or Hemolysis Elevated Liver enzymes Low Platelet count syndrome. Quality of articles was evaluated with an adapted Cochrane Collaboration bias assessment tool. Relative risks (RRs) were pooled with a random-effects meta-analysis weighted by the inverse of their variance.
RESULTS
Of the 2136 articles screened, 28 studies were eligible for inclusion; 15 studies reported on the association with PIH, 16 on pre-eclampsia, 5 on eclampsia, and 3 articles on HIV therapy regimens. All articles had a high risk of bias, and between-study heterogeneity was considerable. Based on the meta-analysis, there does not seem to be an association between HIV and PIH [RR 1.26, 95% confidence interval (CI): 0.87 to 1.83, I = 78.6%], pre-eclampsia (RR 1.01, 95% CI: 0.87 to 1.18, I = 63.9%), or eclampsia (RR 1.61, 95% CI: 0.14 to 18.68, I = 97.0%). A meta-analysis of the association with HIV therapy and risk of hypertensive disorders in pregnancy could not be performed.
CONCLUSIONS
This meta-analysis shows no significant association between HIV positivity and PIH, pre-eclampsia, or eclampsia. However, the high risk of bias within most studies limits the strength of conclusions and well-designed studies are necessary to confirm or refute these findings.
Topics: Anti-Retroviral Agents; Eclampsia; Female; HELLP Syndrome; HIV Infections; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Risk Assessment
PubMed: 26322669
DOI: 10.1097/QAI.0000000000000686 -
AIDS and Behavior Feb 2021Childhood sexual abuse (CSA) has been shown to be more prevalent among populations living with HIV. Antiretroviral therapy (ART) adherence is crucial for populations...
Childhood sexual abuse (CSA) has been shown to be more prevalent among populations living with HIV. Antiretroviral therapy (ART) adherence is crucial for populations living with HIV as it significantly increases the likelihood of attaining and maintaining viral suppression. Previous findings on the association between CSA and ART adherence have been mixed. The current mixed-methods systematic review aimed to identify quantitative and qualitative studies from CINAHL, PsycInfo, PubMed, and Web of Science examining the relationship between CSA and ART adherence. Authors were also contacted if relevant data were unpublished. Studies had to be published from January 1, 2000 to April 1, 2019, written in English, and examined CSA as an exposure and ART adherence as an outcome. Four domains were combined: (1) childhood sexual abuse; (2) child; (3) antiretroviral; and (4) adherence. Eight quantitative and two qualitative studies were retained. The results showed that four quantitative studies found no association while the other four found factors such as timing of victimization, mental health and gender influenced the association between CSA and ART adherence. Themes emerging from the qualitative studies included use of ART evoking memories of CSA; CSA impacting mental health; and mental health treatment improving ART adherence. Mixed insights included the intricate links between CSA and ART adherence and the role of external factors on the relationship. ART adherence intervention programs may be needed for people who have experienced CSA. However, future studies are needed that will examine the association between CSA and ART adherence and include subgroup analyses.
Topics: Anti-Retroviral Agents; Child; Child Abuse, Sexual; HIV Infections; Humans; Medication Adherence; Sex Offenses; Sexual Trauma
PubMed: 32844336
DOI: 10.1007/s10461-020-03009-7 -
Epidemiology and Health 2021This meta-analysis investigated the risk of congenital anomalies among infants of human immunodeficiency virus-infected pregnant women who were exposed to antiretroviral... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis investigated the risk of congenital anomalies among infants of human immunodeficiency virus-infected pregnant women who were exposed to antiretroviral therapy (ART).
METHODS
Cohort studies, case-control studies, randomized controlled trials, and controlled clinical trials were reviewed by searching MEDLINE/PubMed, Embase, Web of Science, Scopus, AIDSLINE, CINAHL, Cochrane Library, and Google/Google Scholar. Methodological quality was assessed using the GRADE evaluation. A DerSimonian and Laird random-effects model was used. Subgroup analyses and meta-regression were used to investigate heterogeneity.
RESULTS
The electronic searches yielded 765 items. After quality assessment and grading, 30 studies were suitable for metaanalysis. In total, 1,461 congenital anomalies were found among 53,186 births. Children born to women receiving combined antiretroviral therapy (cART) had an approximately 10% higher risk of developing congenital anomalies (relative risk [RR], 1.09; 95% confidence interval [CI], 1.04 to 1.14). A subgroup analysis found no significant difference in the risk of congenital anomalies between cART and efavirenz users. However, zidovudine and protease inhibitor (RR, 1.09; 95% CI, 1.00 to 1.19) users were found to have a 10% increased risk of congenital anomalies, and integrase inhibitor users had a 60% increase in risk (RR, 1.61; 95% CI, 1.60 to 2.43). The subgroup results should be interpreted cautiously because of the moderate heterogeneity (I2 =58%).
CONCLUSIONS
The use of protease inhibitors, integrase inhibitors, zidovudine, and newer drugs should be carefully considered in pregnant women. Further studies are needed to address environmental, nutrition, and adherence factors related to ART. Establishing a congenital anomalies surveillance system is recommended.
Topics: Abnormalities, Drug-Induced; Anti-Retroviral Agents; Female; HIV Infections; Humans; Infant; Pregnancy; Pregnancy Complications, Infectious; Prenatal Exposure Delayed Effects; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 33541012
DOI: 10.4178/epih.e2021008