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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 -
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 -
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 -
Viruses Aug 2023Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced... (Review)
Review
Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced the mortality rate and incidence of acquired immunodeficiency syndrome (AIDS). However, despite the remarkable efficacy of ART, virologic failure remains a challenge in the long-term management of HIV-infected individuals. Virologic failure refers to the persistent detectable viral load in patients receiving ART, indicating an incomplete suppression of HIV replication. It can occur due to various factors, including poor medication adherence, drug resistance, suboptimal drug concentrations, drug interactions, and viral factors such as the emergence of drug-resistant strains. In recent years, extensive efforts have been made to understand and address virologic failure in order to optimize treatment outcomes. Strategies to prevent and manage virologic failure include improving treatment adherence through patient education, counselling, and supportive interventions. In addition, the regular monitoring of viral load and resistance testing enables the early detection of treatment failure and facilitates timely adjustments in ART regimens. Thus, the development of novel antiretroviral agents with improved potency, tolerability, and resistance profiles offers new options for patients experiencing virologic failure. However, new treatment options would also face virologic failure if not managed appropriately. A solution to virologic failure requires a comprehensive approach that combines individualized patient care, robust monitoring, and access to a range of antiretroviral drugs.
Topics: Humans; Acquired Immunodeficiency Syndrome; HIV Infections; Anti-Retroviral Agents; Medication Adherence; Treatment Failure
PubMed: 37632074
DOI: 10.3390/v15081732 -
Journal of Infection in Developing... Jun 2023Human immunodeficiency virus type 1 (HIV-1) causes various diseases in different age groups. Neurological manifestations of HIV are common and add to morbidity and... (Review)
Review
Human immunodeficiency virus type 1 (HIV-1) causes various diseases in different age groups. Neurological manifestations of HIV are common and add to morbidity and mortality. It was previously thought that the central nervous system (CNS) was involved only in the advanced stages of the disease. However, recent evidence supports pathological involvement of the CNS from initial viral entry. Some of the CNS manifestations in children share similarities to neurologic disorders of HIV-infected adult patients, while others are unique to the pediatric population. Many HIV-related neurologic complications seen in adults are rarely encountered in children with AIDS and vice versa. However, with recent advances in the treatment, more HIV-infected children are surviving into adulthood. A systematic review of the available literature was performed to study the manifestations, causes, outcomes, and treatment of primary neurologic disorders in children with HIV. Online databases (Ovid Medline, Embase and PubMed), websites from the World Health Organization, commercial search engines, including Google, and chapters on HIV in standard textbooks of pediatrics and medicine were reviewed. HIV-associated neurological syndromes can be classified into four types: primary HIV neurological diseases, treatment-related neurological diseases, adverse neurological effects of antiretroviral therapy and secondary/opportunistic neurological illness. These conditions are not mutually exclusive and may co-exist in a given patient. This narrative review will focus mainly on the primary neurological manifestations of HIV in children.
Topics: Child; Humans; HIV Infections; HIV-1; Nervous System Diseases
PubMed: 37406063
DOI: 10.3855/jidc.17645 -
Cellular and Molecular Neurobiology Oct 2023HIV-related neuropathic pain (HRNP) is a neurodegeneration that gradually develops during the long-term course of acquired immune deficiency syndrome (AIDS) and... (Review)
Review
HIV-related neuropathic pain (HRNP) is a neurodegeneration that gradually develops during the long-term course of acquired immune deficiency syndrome (AIDS) and manifests as abnormal sock/sleeve-like symmetrical pain and nociceptive hyperalgesia in the extremities, which seriously reduces patient quality of life. To date, the pathogenesis of HRNP is not completely clear. There is a lack of effective clinical treatment for HRNP and it is becoming a challenge and hot spot for medical research. In this study, we conducted a systematic review of the progress of HRNP research in recent years including (1) the etiology, classification and clinical symptoms of HRNP, (2) the establishment of HRNP pathological models, (3) the pathological mechanisms underlying HRNP from three aspects: molecules, signaling pathways and cells, (4) the therapeutic strategies for HRNP, and (5) the limitations of recent HRNP research and the future research directions and prospects of HRNP. This detailed review provides new and systematic insight into the pathological mechanism of HRNP, which establishes a theoretical basis for the future exploitation of novel target drugs. HIV infection, antiretroviral therapy and opioid abuse contribute to the etiology of HRNP with symmetrical pain in both hands and feet, allodynia and hyperalgesia. The pathogenesis involves changes in cytokine expression, activation of signaling pathways and neuronal cell states. The therapy for HRNP should be patient-centered, integrating pharmacologic and nonpharmacologic treatments into multimodal intervention.
Topics: Humans; Animals; Hyperalgesia; HIV Infections; HIV; Therapeutic Human Experimentation; Quality of Life; Neuralgia; Disease Models, Animal
PubMed: 37470889
DOI: 10.1007/s10571-023-01389-7 -
PLOS Global Public Health 2023Maintaining a high level of adherence to antiretroviral therapy (ART) is critical to limiting rapid viral replication, drug resistance, and viral transmission. However,...
Maintaining a high level of adherence to antiretroviral therapy (ART) is critical to limiting rapid viral replication, drug resistance, and viral transmission. However, ART adherence remains a major challenge in HIV/AIDS treatment success. This systematic review and meta-analysis was aimed to synthesize available evidence on adherence to ART among HIV/AIDS patients in Ghana.This review followed the preferred reporting item for systematic review and meta-analysis (PRISMA) criteria. A comprehensive literature search was done using five online databases (PubMed, Google Scholar, Medline, Africa Index Medicus, and Willey Online Library) from 25th- 30th April 2023 to identify potential studies. In addition, references of related articles were manually searched to further identify relevant studies. Search records were managed in Endnote library where duplicates were removed prior to screening. Studies were eligible for inclusion if they were conducted in Ghana, designed as an observational or experimental study, and explicitly measured adherence to ART, either as a primary or secondary outcome. Studies were excluded if the proportion or prevalence of adherence to ART was not reported.A total number of 126 potential studies were identified from the literature search. Of these, 14 met the inclusion criteria and were included in the Meta-analysis. The studies involved a total number of 4,436 participants. The pooled estimate of adherence to ART was 70% (CI: 58-81%). In subgroup analysis, adolescents and young adults had a lower adherence rate (66%, CI: 46-84%) compared with adults (70%; CI: 58-81%). Publication bias was not observed among studies. The pooled estimate of optimal adherence to ART among HIV patients in Ghana was lower than is recommended (≥95%) to achieve viral suppression. Adherence was lower among young persons living with HIV/AIDS. To achieve the United Nation's Sustainable development goals and the UNAIDS "95-95-95" targets, there is a need to focus on improving adherence interventions among persons living with HIV/AIDS, especially among the younger cohort.
PubMed: 37910452
DOI: 10.1371/journal.pgph.0002448 -
Cureus Oct 2023With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging... (Review)
Review
With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging the lifespan of people living with HIV (PLHIV). This has resulted in an increased non-AIDS-related morbidity in the HIV-infected population. Our aim is to study the role of contemporary ART in tackling the risk of atherosclerosis and cardiovascular disease (CVD) in PLHIV. We searched through the databases of PubMed, PubMed Central, and Cochrane Library for pertinent articles using the medical subject headings (MeSH) "HIV infection", "Atherosclerosis", and "Antiretroviral agents". The articles published in the past five years were retrieved, screened for relevance, and assessed for quality before being included in the review. This review was performed following the PRISMA 2020 guidelines. The results indicate that the incidence of dyslipidemia with integrase strand transfer inhibitors (INSTIs) is greater than with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and lesser than with protease inhibitors (PIs). INSTIs are indispensably associated with weight gain and obesity. High triglyceride (TG) and oxidized low-density lipoproteins to low-density lipoproteins (oxLDL/LDL) ratio levels and low high-density lipoprotein (HDL) levels are seen in patients taking PIs. A higher incidence of hypertension and metabolic syndrome (MetS) was noticed with INSTIs compared to NNRTIs. PI intake for >5 years increases the risk of subclinical atherosclerosis. Increased risk of myocardial infarction with INSTIs was observed in a study, while another study reported decreased risk. HIV infection independently increases the risk for atherosclerosis and CVD. Although contemporary ART decreases this enhanced risk, it inherently increases the risk for abnormal lipid profile, MetS, weight gain, and obesity. Further research into the risk of atherosclerosis and CVD with newer ART drugs is essential for decoding the underlying mechanisms and preventing adverse cardiac outcomes in PLHIV.
PubMed: 38021858
DOI: 10.7759/cureus.47730 -
International Journal of Nursing Studies Dec 2023Many people living with HIV reported poor quality of life, which was primarily due to HIV-related stigma and the lack of social support. Compared with face-to-face... (Meta-Analysis)
Meta-Analysis Review
The effectiveness of e-health on reducing stigma, improving social support and quality of life among people living with HIV: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Many people living with HIV reported poor quality of life, which was primarily due to HIV-related stigma and the lack of social support. Compared with face-to-face interventions, e-health interventions are reported to have potential to help people living with HIV improve their adherence to antiretroviral therapy, promote their management of HIV and depressive symptoms. However, in the literature, the effectiveness of e-health interventions in helping people living with HIV reduce stigma, improve social support and quality of life is unclear.
OBJECTIVE
To examine the effectiveness of e-health interventions in reducing stigma and improving social support and quality of life among people living with HIV.
DESIGN
This study is a systematic review and meta-analysis of randomized controlled trials following the Cochrane Handbook guidelines and PRISMA2020.
METHODS
A comprehensive search was conducted from inception to 1st December 2022 in six databases: PubMed, CINAHL Plus with Full Text, PsycINFO (Ovid), Embase, Web of Science, and CENTRAL (Ovid), and an updated search took place on 11st June 2023. Two authors independently screened the studies and extracted the data. Cochrane's bias risk tool for randomized controlled trials was used to examine the methodological quality of the included studies. The intervention effect was estimated by calculating the standardized mean difference (SMD) and 95 % confidence interval (CI) using Review Manager 5.3. A sensitivity analysis was conducted to test the rigor of the pooled results using one-study-out method. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
RESULTS
Nine studies met eligibility criteria and were included in this review. The results of the meta-analysis showed that e-health interventions could statistically significantly reduce stigma (SMD: -0.29, 95 % CI: [-0.48, -0.10], p = 0.002) and improve quality of life (SMD = 0.49, 95 % CI: [0.30, 0.68], P < 0.001), but had no significant effects on social support (SMD = -0.01, 95 % CI: [-0.48, 0.46] P = 0.96).
CONCLUSIONS
E-health interventions could reduce stigma and improve quality of life among people living with HIV. More studies are needed to further explore if e-health interventions can improve the social support for people living with HIV and investigate how to integrate e-health interventions into the existing health models to help people living with HIV treat and manage HIV/AIDS.
REGISTRATION
The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42022373299).
Topics: Humans; Quality of Life; Randomized Controlled Trials as Topic; Social Support; HIV Infections; Telemedicine
PubMed: 37801937
DOI: 10.1016/j.ijnurstu.2023.104606 -
Digital Health in Enhancing Antiretroviral Therapy Adherence: A Systematic Review and Meta-Analysis.AIDS Patient Care and STDs Nov 2023Adherence to antiretroviral therapy (ART) is essential in determining successful treatment of human immunodeficiency virus (HIV). The adoption of digital health is... (Meta-Analysis)
Meta-Analysis
Adherence to antiretroviral therapy (ART) is essential in determining successful treatment of human immunodeficiency virus (HIV). The adoption of digital health is suggested to improve ART adherence among people living with HIV (PLHIV). This study aimed to systematically determine the effect of digital health in enhancing ART adherence among PLHIV from published studies. The systematic search was conducted on Scopus, Web of Science (WoS), PubMed, Ovid, EBSCOHost, and Google Scholar databases up to June 2022. Studies utilized any digital health as an intervention for ART adherence enhancement and ART adherence status as study's outcome was included. Digital health refers to the use of information and communication technologies to improve health. Quality assessment and data analysis were carried out using Review Manager (RevMan) version 5.4. A random-effects model computed the pooled odds ratio between intervention and control groups. The search produced a total of 1864 articles. Eleven articles were eligible for analysis. Digital health was used as follows: six studies used short message service or text message alone, three studies used mobile applications, and two studies used combination method. Four studies showed statistically significant impacts of digital health on ART adherence, while seven studies reported insignificant results. Results showed studies conducted using combination approach of digital health produced more promising outcome in ART adherence compared to single approach. New innovative in combination ways is required to address potential benefits of digital health in promoting ART adherence among PLHIV.
Topics: Humans; HIV Infections; Medication Adherence; Anti-Retroviral Agents; Text Messaging; Communication
PubMed: 37956244
DOI: 10.1089/apc.2023.0170