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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 -
BMJ Open May 2022To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to... (Meta-Analysis)
Meta-Analysis
Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.
OBJECTIVE
To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.
METHODS
Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for 'HIV' were combined with terms for 'PrEP' or 'tenofovir/emtricitabine'. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.
RESULTS
Of 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) -0.03, 95% CI -0.01 to -0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD -0.01, 95% CI -0.01 to -0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD -0.00, 95% CI -0.00 to -0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.
CONCLUSIONS
PrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.
PROSPERO REGISTRATION NUMBER
CRD42017065937.
Topics: Anti-HIV Agents; Emtricitabine; Female; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Tenofovir; Treatment Outcome
PubMed: 35545381
DOI: 10.1136/bmjopen-2020-048478 -
The Lancet. HIV Dec 2019Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a...
Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017.
BACKGROUND
Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980-2017 and forecast these estimates to 2030 for 195 countries and territories.
METHODS
We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package-a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections.
FINDINGS
Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87-2·04) and has since decreased to 0·95 million deaths (0·91-1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79-3·67) and since then have gradually decreased to 1·94 million (1·63-2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8-39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets.
INTERPRETATION
Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact.
FUNDING
Bill & Melinda Gates Foundation, National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH.
Topics: Cause of Death; Forecasting; Global Burden of Disease; HIV Infections; History, 20th Century; History, 21st Century; Humans; Incidence; Prevalence; Risk Factors; Seroepidemiologic Studies
PubMed: 31439534
DOI: 10.1016/S2352-3018(19)30196-1 -
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 -
Clinical Infectious Diseases : An... Apr 2022A panel of experts generated 5 "key questions" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed...
A panel of experts generated 5 "key questions" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these questions. Available data suggest no clinical benefit to >1 dose of benzathine penicillin G for early syphilis in human immunodeficiency virus (HIV)-infected patients. While penicillin remains the drug of choice to treat syphilis, doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There are very limited data regarding the impact of additional antibiotic doses on serologic responses in serofast patients and no data on the impact of additional antibiotic courses on long-term clinical outcomes. In patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, a diagnostic cerebrospinal fluid (CSF) examination is not necessary, because up to 40% and 90% of patients, respectively, would have no CSF abnormalities. Based on the results of 2 studies, repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis. Finally, several important gaps were identified and should be a priority for future research.
Topics: Adult; Anti-Bacterial Agents; Centers for Disease Control and Prevention, U.S.; HIV Infections; Humans; Neurosyphilis; Penicillin G Benzathine; Syphilis; United States
PubMed: 35416969
DOI: 10.1093/cid/ciac060 -
Parkinsonism & Related Disorders Sep 2023The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH). (Review)
Review
BACKGROUND
The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH).
OBJECTIVES AND METHODS
We conducted a systematic review on the spectrum of movement disorders in PLH using standard terms for each of the phenomenologies and HIV.
RESULTS
Movement disorders in PLH were commonly attributed to opportunistic infections (OI), dopamine receptor blockade reactions, HIV-associated dementia (HAD), presented during seroconversion, developed due to drug reactions or antiretroviral therapy (ART) itself and lastly, movement disorders occurred as a consequence of the HIV-virus. Parkinsonism in ART naïve PLH was associated with shorter survival, however when Parkinsonism presented in PLH on ART, the syndrome was indistinguishable from Idiopathic Parkinson's disease and responded to therapy. Tremor was often postural due to HAD, drugs or OI. Generalized chorea was most frequent in HIV encephalopathy and toxoplasmosis gondii caused most cases of hemichorea. Ataxia was strongly associated with JCV infection, ART efavirenz toxicity or due to HIV itself. Dystonia was reported in HAD, secondary to drugs and atypical facial dystonias. Both cortical/subcortical and segmental/spinal origin myoclonus were noted mainly associated with HAD. In patients with HIV related opsoclonus-myoclonus-ataxia-syndrome, seroconversion illness was the commonest cause of followed by IRIS and CSF HIV viral escape phenomenon.
CONCLUSIONS
Aetiology of movement disorders in PLH depend on the treatment state. Untreated, PLH are prone to develop OI and HAD and movement disorders. However, as the number of PLH on ART increase and survive longer, the frequency of ART and non-AIDS related complications are likely to increase.
Topics: Humans; HIV; Myoclonus; Movement Disorders; HIV Infections; Parkinson Disease; Parkinsonian Disorders; Ataxia
PubMed: 37532621
DOI: 10.1016/j.parkreldis.2023.105774 -
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 -
Cost Effectiveness and Resource... Aug 2021Achieving global targets of adherence to treatment, retention in care, and treatment success remains a challenge. Health system investment to make antiretroviral therapy... (Review)
Review
BACKGROUND
Achieving global targets of adherence to treatment, retention in care, and treatment success remains a challenge. Health system investment to make antiretroviral therapy services more responsive to patients' needs and values could address these impediments. Appropriate resource allocation to implement differentiated HIV treatment services demands research evidence. This study aimed to provide an overview of the patients' preferences for antiretroviral therapy service delivery features.
METHODS
Electronic databases (PubMed, Web of Science, Embase, and CINAHL) and search engines (Google and Google Scholar) were searched. This review has followed a convergent segregated approach to synthesis and integration. Data from the included studies were systematically extracted, tabulated, and summarised in a narrative review. Studies that analysed preferences for antiretroviral therapy regardless of the method used and published in the English language in any year across the world and HIV positive clients who were 15 years and above on 4th February 2021 were included for this review. The quality of the included studies was assessed using the mixed methods appraisal tool. A thematic synthesis of the data from the findings section of the main body of the qualitative study was undertaken. ATLAS.ti software version 7 was used for qualitative synthesis.
RESULTS
From the 1054 retrieved studies, only 23 studies (16 quantitative, three qualitative, and four mixed-methods) fulfilled the inclusion criteria. The median number of attributes used in all included quantitative studies was 6 (Inter Quartile Range 3). In this review, no study has fulfilled the respective criteria in the methodological quality assessment. In the quantitative synthesis, the majority of participants more valued the outcome, whereas, in the qualitative synthesis, participants preferred more the structure aspect of antiretroviral therapy service. The thematic analysis produced 17 themes, of which ten themes were related to structure, three to process, and four to outcome dimension of Donabedian's quality of care model. The findings from individual quantitative and qualitative syntheses complement each other.
CONCLUSIONS
In this review, participants' value for antiretroviral therapy service characteristics varied across included studies. Priorities and values of people living with HIV should be incorporated in the policy, practice, research, and development efforts to improve the quality of antiretroviral therapy service hence avoid poor patient outcomes.
PubMed: 34461939
DOI: 10.1186/s12962-021-00310-7 -
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