Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. METHODS: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. RESULTS: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. DISCUSSION: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Managing Advanced HIV Disease in a Public Health Approach.

In 2017, the World Health Organization (WHO) published guidelines for the management of advanced human immunodeficiency virus (HIV) disease within a public health approach. Recent data suggest that more than a third of people starting antiretroviral therapy (ART) do so with advanced HIV disease, and an increasing number of patients re-present to care at an advanced stage of HIV disease following a period of disengagement from care. These guidelines recommend a standardized package of care for adults, adolescents, and children, based on the leading causes of morbidity and mortality: tuberculosis, severe bacterial infections, cryptococcal meningitis, toxoplasmosis, and Pneumocystis jirovecii pneumonia. A package of targeted interventions to reduce mortality and morbidity was recommended, based on results of 2 recent randomized trials that both showed a mortality reduction associated with delivery of a simplified intervention package. Taking these results and existing recommendations into consideration, WHO recommends that a package of care be offered to those presenting with advanced HIV disease; depending on age and CD4 cell count, the package may include opportunistic infection screening and prophylaxis, including fluconazole preemptive therapy for those who are cryptococcal antigen positive and without evidence of meningitis. Rapid ART initiation and intensified adherence interventions should also be proposed to everyone presenting with advanced HIV disease.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis.

Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods: We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results: Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). Conclusions: The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL.

The Role of ARV Associated Adverse Drug Reactions in Influencing Adherence Among HIV-Infected Individuals: A Systematic Review and Qualitative Meta-Synthesis.

Poor adherence remains a major barrier to achieving the clinical and public health benefits of antiretroviral drugs (ARVs). A systematic review and qualitative meta-synthesis was conduct to evaluate how ARV adverse drug reactions may influence ARV adherence. Thirty-nine articles were identified, and 33 reported that ARV adverse drug reactions decreased adherence and six studies found no influence. Visually noticeable adverse drug reactions and psychological adverse reactions were reported as more likely to cause non-adherence compared to other adverse drug reactions. Six studies reported a range of adverse reactions associated with EFV-containing regimens contributing to decreased adherence. Informing HIV-infected individuals about ARV adverse drug reactions prior to initiation, counselling about coping mechanisms, and experiencing the effectiveness of ARVs on wellbeing may improve ARV adherence.

Stable patients and patients with advanced disease: consensus definitions to support sustained scale up of antiretroviral therapy.

OBJECTIVE: As guidelines are evolving towards recommending starting antiretroviral therapy (ART) in all HIV-positive individuals irrespective of clinical and immunological status, HIV programmes will be challenged to manage an increasingly diverse set of patient needs. To support global guideline recommendations for differentiated service delivery, WHO developed consensus definitions for two distinct patient populations: patients presenting with advanced disease and patients who are stable on ART. METHODS: An expert panel consisting of 73 respondents from 28 countries across all six WHO regions supported the development of these definitions. The panel included clinicians, researchers, programme managers, technical advisors and patient group representatives. RESULTS: Patients presenting with advanced disease at presentation to care were defined as CD4 count <200 CD4 cells/mm(3) or WHO Stage III & IV defining illness. Patients stable on ART were defined as those who were receiving ART for at least 1 year with no adverse drug reactions requiring regular monitoring, no current illnesses or pregnancy, a good understanding of lifelong adherence, and evidence of treatment success. Treatment success was defined as two consecutive undetectable viral load measures or, in the absence of viral load monitoring, rising CD4 counts or CD4 counts above 200 cells/mm(3) and an objective adherence measure. CONCLUSIONS: Patients who are stable on ART should be offered a less intensive care package that can lead to improved outcomes while saving resources, including less frequent clinic visits, out-of-clinic drug refills and reduced laboratory monitoring. This will allow for clinic resources to be directed towards reducing morbidity and mortality among patients presenting with advanced disease.

Implications of prioritizing HIV cure: new momentum to overcome old challenges in HIV.

BACKGROUND: Curing HIV is a new strategic priority for several major AIDS organizations. In step with this new priority, HIV cure research and related programs are advancing in low, middle, and high-income country settings. This HIV cure momentum may influence existing HIV programs and research priorities. DISCUSSION: Despite the early stage of ongoing HIV cure efforts, these changes have directly influenced HIV research funding priorities, pilot programs, and HIV messaging. The building momentum to cure HIV infection may synergize with strategic priorities to better identify adults and infants with very early HIV infection. Although HIV cure represents a new goal, many existing programs and research techniques can be repurposed towards an HIV cure. HIV messages focused on engaging communities towards an HIV cure need to be careful to promote ARV adherence and retention within the HIV continuum of care. An increased emphasis within the AIDS field on finding an HIV cure has several important implications. Strengthening connections between HIV cure research and other areas of HIV research may help to catalyze research and facilitate implementation in the future.

Choice of antiretroviral drugs for postexposure prophylaxis for adults and adolescents: a systematic review.

BACKGROUND: The choice of preferred regimens for human immunodeficiency virus postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data have become available regarding the safety and tolerability of newer antiretroviral drugs. We undertook a systematic review to assess the safety and efficacy of antiretroviral options for PEP to inform the World Health Organization guideline revision process. METHODS: Four databases were searched up to 1 June 2014 for studies reporting outcomes associated with specific PEP regimens. Data on PEP completion and discontinuation due to adverse events was extracted and pooled estimates were obtained using random-effects meta-analyses. RESULTS: Fifteen studies (1830 PEP initiations) provided evaluable information on 2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10 studies (1755 initiations) provided evaluable information on the third drug, which was usually a protease inhibitor. The overall quality of the evidence was rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95% confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP discontinuation due to an adverse event was lower among people taking TDF-based PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For the 3-drug comparison, PEP completion rates were highest for the TDF-based regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+ lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%). CONCLUSIONS: The findings of this review provide evidence supporting the use of coformulated TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will depend on setting; for resource-limited settings, LPV/r is a reasonable choice, pending the improved availability of better-tolerated drugs with less potential for drug-drug interactions.

Systematic review and meta-analysis: Patient and programme impact of fixed-dose combination antiretroviral therapy.

OBJECTIVES: To compare the advantages to patients and to programmes between fixed-dose combination (FDC) antiretroviral therapy and separate tablet regimens. METHODS: Three electronic databases and two conference abstract sites were searched from inception to 01 March 2013 without geographical, language or date limits. Studies were included if they reported data on clinical outcomes, patient-reported outcomes and programme-related outcomes that could be related to pill burden for adult and adolescent patients on ART. For the primary outcomes of adherence and virological suppression, relative risks and 95% confidence intervals were calculated, and these were pooled using random effects meta-analysis. RESULTS: Twenty-one studies including information on 27,230 subjects were reviewed. Data from randomised trials showed better adherence among patients receiving FDCs than among patients who did not (relative risk 1.10, 95%CI 0.98-1.22); these findings were consistent with data from observational cohorts (RR 1.17, 95% CI 1.07-1.28). There was also a tendency towards greater virological suppression among patients receiving FDCs in randomised trials (RR 1.04, 95%CI 0.99-1.10) and observational cohort studies (RR 1.07, 95% CI 0.97-1.18). In all studies reporting patient preference, FDCs were preferred. The overall quality of the evidence was rated as low. CONCLUSIONS: Fixed-dose combinations appear to offer multiple advantages for programmes and patients, particularly with respect to treatment adherence.

Antiretroviral therapy response among HIV-2 infected patients: a systematic review.

BACKGROUND: Few data are available on antiretroviral therapy (ART) response among HIV-2 infected patients. We conducted a systematic review on treatment outcomes among HIV-2 infected patients on ART, focusing on the immunological and virological responses in adults. METHODS: Data were extracted from articles that were selected after screening of PubMed/MEDLINE up to November 2012 and abstracts of the 1996-2012 international conferences. Observational cohorts, clinical trials and program reports were eligible as long as they reported data on ART response (clinical, immunological or virological) among HIV-2 infected patients. The determinants investigated included patients' demographic characteristics, CD4 cell count at baseline and ART received. RESULTS: Seventeen reports (involving 976 HIV-2 only and 454 HIV1&2 dually reactive patients) were included in the final review, and the analysis presented in this report are related to HIV-2 infected patients only. There was no randomized controlled trial and only two cohorts had enrolled more than 100 HIV-2 only infected patients. The median CD4 count at ART initiation was 165 cells/mm3, [IQR; 137-201] and the median age at ART initiation was 44 years (IQR: 42-48 years). Ten studies included 103 patients treated with three nucleoside reverse transcriptase inhibitors (NRTI). Protease inhibitor (PI) based regimens were reported by 16 studies. Before 2009, the most frequent PIs used were Nelfinavir and Indinavir, whereas it was Lopinavir/ritonavir thereafter. The immunological response at month-12 was reported in six studies and the mean CD4 cell count increase was +118 cells/µL (min-max: 45-200 cells/µL). CONCLUSION: Overall, clinical and immuno-virologic outcomes in HIV-2 infected individuals treated with ART are suboptimal. There is a need of randomized controlled trials to improve the management and outcomes of people living with HIV-2 infection.

The UN Decade of Healthy Ageing (2021-30) for people living with HIV.

The Decade of Healthy Ageing (2021-30; the Decade), proclaimed by the UN in 2020, is a global initiative aimed at fostering collaborations to transform the world into a better place to live and grow older in. The Decade presents a positive vision of ageing, discarding the stereotypes of diseases and disabilities and promoting focus on capacities and abilities. This approach will help to foster a more inclusive world and, consequently, care systems, which value the dignity of each individual. Although the initiative represents a resource for the global population, the Decade also provides a unique opportunity for the large community of people living with HIV in terms of increased visibility and long-term solutions for their specific ageing-related health issues. This Personal View focuses on the relevance of the Decade in improving the lives of people in the HIV community, the rationale for a stronger engagement of people living with HIV in this initiative, and the potential to reduce global disparities between the HIV community and the general population and among different global regions.

The importance of the "how": the case for differentiated service delivery of long-acting and extended delivery regimens for HIV prevention and treatment.

INTRODUCTION: Long-acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access. DISCUSSION: The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment-the vast majority on a daily fixed-dose combination oral pill that is largely available, affordable and well-tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre-exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self-management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re-initiation. CONCLUSIONS: To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical.

COVID-19 and health systems in Brazil and around the world: effects on the working conditions and health of health workers. / COVID-19 e os sistemas de saúde do Brasil e do mundo: repercussões das condições de trabalho e de saúde dos profissionais de saúde.

This article discusses the impacts of the COVID-19 pandemic on health systems and its effects on the working conditions and mental health of health professionals and invisible health workers. It presents data on deaths among health professionals, highlighting the need for better and safer working conditions and improvements in public management. We emphasize WHO/PAHO recommendations and the need for equitable vaccine distribution, including poor countries and vulnerable populations. We also highlight the impacts of interrupting essential health services, such as the treatment of chronic conditions and infectious disease prevention, and the damage caused by the dissemination of fake news, stressing the need to improve access to correct and safe health information.

Este artigo apresenta os impactos da pandemia nos sistemas de saúde e as repercussões nas condições de trabalho e saúde mental dos profissionais de saúde e trabalhadores invisíveis da saúde no contexto da COVID-19. Apresenta a mortalidade entre os profissionais da saúde destacando a necessidade de melhores condições de trabalho e de segurança para os trabalhadores da saúde e melhora da gestão pública. Enfatiza as recomendações da OMS/OPAS, a necessidade de vacinação equânime, incluindo os países mais pobres e as populações mais vulneráveis. Relata os impactos da interrupção dos serviços essenciais em saúde, como para as doenças crônicas e infecciosas, e os prejuízos causados pela disseminação de informações falsas pela rede social, e lembra da necessidade de veiculação de informações corretas e seguras na saúde.

A Systematic Review of COVID-19 Vaccine Antibody Responses in People With HIV.

HIV infection is a significant independent risk factor for severe coronavirus disease 2019 (COVID-19) disease and death. We summarize COVID-19 vaccine responses in people with HIV (PWH). A systematic literature review of studies from January 1, 2020, to March 31, 2022, of COVID-19 vaccine immunogenicity in PWH from multiple databases was performed. Twenty-eight studies from 12 countries were reviewed. While 22 (73%) studies reported high COVID-19 vaccine seroconversion rates in PWH, PWH with lower baseline CD4 counts, CD4/CD8 ratios, or higher baseline viral loads had lower seroconversion rates and immunologic titers. Data on vaccine-induced seroconversion in PWH are reassuring, but more research is needed to evaluate the durability of COVID-19 vaccine responses in PWH.

Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy - a systematic literature review and network meta-analysis.

Background: This systematic review aimed to compare body weight gain associated outcomes over time between dolutegravir (DTG)-based antiretroviral (ART) regimens to other ART regimens, to compare tenofovir alafenamide (TAF)-based regimens, and to evaluate the associated prognostic factors. Methods: Systematic searches of MEDLINE, Embase, and CENTRAL for RCTs and observational studies comparing ART regimens were conducted on 13 September 2021. Outcomes of interest included: change in body weight, body mass index (BMI), waist circumference; and risk of hyperglycaemia and diabetes. Network meta-analyses were conducted at 12, 24, 48, 96 and 144 weeks using two networks differentiated by 3rd agents and backbone agents. Findings: The review identified 113 publications reporting on 73 studies. DTG-based regimens led to statistically higher weight gains than efavirenz-based regimens at all time points (mean difference: 1·99 kg at 96 weeks; 95% credible interval: 0·85-3·09) and was higher over time than low-dose efavirenz-, elvitegravir-, and rilpivirine-based regimens. They were comparable to raltegravir-, bictegravir- and atazanavir-based regimens. For backbones, TAF led to higher weight gain relative to tenofovir disoproxil fumarate (TDF), abacavir, and zidovudine. Prognostic factor analysis showed both low CD4 cell count and high HIV RNA viral load at baseline were consistently associated with higher weight gain, while sex was an effect modifier to African origins. Interpretation: DTG-based regimens lead to larger average weight gains than some other ART regimens and TAF leads to larger average weight gains than all other backbone antiretrovirals. Further research is needed to better understand long-term outcomes and their relationship to other metabolic outcomes. Funding: The WHO Global HIV, Hepatitis and Sexually Transmitted Infections Programmes.

Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus.

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.

What we have learned from antiretroviral treatment optimization efforts over the last 5 years?

Progression in the development of antiretroviral therapy has been remarkable, with new agents continuing to appear as options for modern regimens, including in low-and-middle income countries where the HIV epidemic is concentrated. Here, we reflect on progress made in guiding regimen changes to public health programmes, and the challenges facing selection of newer agents.

HIV infection in Eastern and Southern Africa: Highest burden, largest challenges, greatest potential.

BACKGROUND: The burden of HIV is especially concerning for Eastern and Southern Africa (ESA), as despite expansion of test-and-treat programmes, this region continues to experience significant challenges resulting from high rates of morbidity, mortality and new infections. Hard-won lessons from programmes on the ground in ESA should be shared. OBJECTIVES: This report summarises relevant evidence and regional experts' recommendations regarding challenges specific to ESA. METHOD: This commentary includes an in-depth review of relevant literature, progress against global goals and consensus opinion from experts. RESULTS: Recommendations include priorities for essential research (surveillance data collection, key and vulnerable population education and testing, in-country testing trials and evidence-based support services to improve retention in care) as well as research that can accelerate progress towards the prevention of new infections and achieving ambitious global goals in ESA. CONCLUSION: The elimination of HIV in ESA will require continued investment, commitment to evidence-based programmes and persistence. Local research is critical to ensuring that responses in ESA are targeted, efficient and evaluated.

Psychosocial interventions for improving engagement in care and health and behavioural outcomes for adolescents and young people living with HIV: a systematic review and meta-analysis.

INTRODUCTION: Adolescents and young people comprise a growing proportion of new HIV infections globally, yet current approaches do not effectively engage this group, and adolescent HIV-related outcomes are the poorest among all age groups. Providing psychosocial interventions incorporating psychological, social, and/or behavioural approaches offer a potential pathway to improve engagement in care and health and behavioural outcomes among adolescents and young people living with HIV (AYPLHIV). METHODS: A systematic search of all peer-reviewed papers published between January 2000 and July 2020 was conducted through four electronic databases (Cochrane Library, PsycINFO, PubMed and Scopus). We included randomized controlled trials evaluating psychosocial interventions aimed at improving engagement in care and health and behavioural outcomes of AYPLHIV aged 10 to 24 years. RESULTS AND DISCUSSION: Thirty relevant studies were identified. Studies took place in the United States (n = 18, 60%), sub-Saharan Africa (Nigeria, South Africa, Uganda, Zambia, Zimbabwe) and Southeast Asia (Thailand). Outcomes of interest included adherence to antiretroviral therapy (ART), ART knowledge, viral load data, sexual risk behaviours, sexual risk knowledge, retention in care and linkage to care. Overall, psychosocial interventions for AYPLHIV showed important, small-to-moderate effects on adherence to ART (SMD = 0.3907, 95% CI: 0.1059 to 0.6754, 21 studies, n = 2647) and viral load (SMD = -0.2607, 95% CI -04518 to -0.0696, 12 studies, n = 1566). The psychosocial interventions reviewed did not demonstrate significant impacts on retention in care (n = 8), sexual risk behaviours and knowledge (n = 13), viral suppression (n = 4), undetectable viral load (n = 5) or linkage to care (n = 1) among AYPLHIV. No studies measured transition to adult services. Effective interventions employed various approaches, including digital and lay health worker delivery, which hold promise for scaling interventions in the context of COVID-19. CONCLUSIONS: This review highlights the potential of psychosocial interventions in improving health outcomes in AYPLHIV. However, more research needs to be conducted on interventions that can effectively reduce sexual risk behaviours of AYPLHIV, as well as those that can strengthen engagement in care. Further investment is needed to ensure that these interventions are cost-effective, sustainable and resilient in the face of resource constraints and global challenges such as the COVID-19 pandemic.