key: cord-0771864-p1uhabw5
authors: Laurenzi, Christina A; du Toit, Stefani; Ameyan, Wole; Melendez‐Torres, GJ; Kara, Tashmira; Brand, Amanda; Chideya, Yeukai; Abrahams, Nina; Bradshaw, Melissa; Page, Daniel T; Ford, Nathan; Sam‐Agudu, Nadia A; Mark, Daniella; Vitoria, Marco; Penazzato, Martina; Willis, Nicola; Armstrong, Alice; Skeen, Sarah
title: 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
date: 2021-08-02
journal: J Int AIDS Soc
DOI: 10.1002/jia2.25741
sha: 5b2e2c5340e773f2d13821b6ef190423f619921d
doc_id: 771864
cord_uid: p1uhabw5

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.

Adolescents living with HIV are unlikely to meet the necessary milestones to end the AIDS epidemic by 2030. In 2019, an estimated 1.7 million (1.1 to 2.4 million) adolescents between ages 10 and 19 were living with HIV [1] . Adolescents and young people comprise a growing proportion of new infections globally, and especially in sub-Saharan Africa, with a decline in mother-to-child transmission coupled with persistent HIV incidence [2] [3] [4] [5] [6] . Furthermore, adolescents globally experience gaps in achieving testing, treatment and retention goals, all of which are critical to ending the epidemic [7] .

Adolescence and young adulthood is a time characterized by identity exploration, experimentation, risk-taking and increased vulnerability, during which many lifelong health behaviours become established [8] . For adolescents and young people living with HIV (AYPLHIV), this life stage brings increasing individual responsibilities, for example in managing their own HIV medication, as well as novel and distinct risks to their physical and emotional health. Many AYPLHIV face additional psychosocial challenges during this transitional time, including stigmatization, isolation and fears of rejection [9, 10] . For AYPLHIV who enter romantic and sexual relationships, learning to navigate issues of disclosure and safe sexual practices becomes particularly important [11] . Youth newly diagnosed with HIV, or who have been newly disclosed to, may also face challenges with accepting their status, which can be stressful and result in familial conflict, especially if young people blame their parents for their illness [12] . AYPLHIV have also been found to have poorer outcomes than other age groups in areas such as retention in care [13, 14] , treatment adherence [15] , HIV knowledge [16] and engagement in care [17] . As the global scale-up of antiretroviral therapy (ART) has been implemented, AYPLHIV are the only age group with increasing mortality rates [18, 19] .

These mortality rates reflect gaps in adolescent HIV care, including low rates of retention in care [7, 17, 20, 21] , poor adherence to ART [7, 20, [22] [23] [24] , incomplete linkage to care [7, 20, 25, 26] and sexual risk behaviours [27, 28] . In high-income countries, linkage to and retention in care are lowest among adolescents [20] . Importantly, these care-related outcomes are related: for example barriers in linking to and being retained in care have downstream effects on adolescents' ability to adhere to treatment. Barriers to linkage to care may include challenges in accessing health facilities; lack of adolescentfriendly health services and personnel [29, 30] and inadequate testing and counselling capacity.

In low-and middle-income countries, adolescent disengagement from care presents a major challenge. In these settings, barriers to retention in care include perceived and enacted stigma, fear of disclosure of HIV status to the adolescent or others and poor mental health [20, 31] . Furthermore, studies suggest that adherence to ART may be influenced by age, access to healthcare, intersecting vulnerabilities and comorbidities, policies surrounding risk behaviours and mental health [32] . Specifically, younger adolescent age and a history of mental health challenges are significantly associated with poor adherence [33] . The transition between paediatric and adult services has also been highlighted as a particular barrier to retention in care [34] . Current policies are structured towards the needs of adult populations; these must undergo a paradigm shift to comprehensively address the unique needs of adolescent populations [32] .

An increased propensity for risk-taking is a common phenomenon during adolescence [35] ; however, for AYPLHIV, these risks may be associated with greater vulnerability due to a number of linked factors [36, 37] . In sub-Saharan Africa, this group's vulnerability to high-risk behaviour may be exacerbated by social and environmental factors including household poverty, orphanhood, gender inequality, stigma and poor accessibility to social or health services [38] [39] [40] [41] [42] . These are the predominant risks studied to date in the quantitative literature; however, a broader set of factors, including intimate partner violence and adolescent sexuality, has emerged from qualitative studies [43] . Moreover, growing evidence suggests that underlying physiological conditions such as HIVassociated neurocognitive disorders [44] , anxiety, and depression [45, 46] increase susceptibility to risk-taking among AYPL-HIV.

Psychosocial interventions are one potential pathway to improve engagement in care and health and behavioural outcomes among AYPLHIV. Psychosocial interventions incorporate psychological, social, and/or behavioural approaches and may include activities, techniques or strategies delivered through interpersonal or information means [47] . These interventions may be broad-based, targeting multiple outcomes linked to health and wellbeing, or more targeted and directed at specific mechanisms. The implementation of psychosocial interventions may serve as a platform to address underlying health issues for AYPLHIV, and may elicit greater gains than individual treatment options [48, 49] . In addition to targeting specific psychosocial issues, behavioural interventions derived from mental health practice may also contribute to adherence to ART [50] . These types of interventions have been implemented across a range of settings to improve adherence to treatment [51] , promote mental health and wellbeing [52, 53] and reduce sexual risk behaviours [54, 55] . However, evidence and experience in applying these interventions to AYPLHIV is needed.

This review investigated the effectiveness of psychosocial interventions for improving engagement in care and health and behavioural outcomes (including clinical HIV outcomes and sexual risk behaviours) for AYPLHIV.

This systematic review and meta-analysis was developed to inform the 2020 WHO Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection, which included a section on service delivery under which this review falls. As part of the WHO guidelines development process, external evidence reviews including systematic reviews and meta-analyses are commissioned to provide evidence for the group's deliberations. Our review's focus was based on the review question set out by the working group coordinating this specific guideline. We followed the standardized systematic review methodology as described in the WHO Handbook for Guidelines Development, Second Edition [56] . The systematic review protocol was prospectively registered on PROSPERO (CRD42020197452) and adheres to PRISMA standards of reporting.

We included studies published in peer-reviewed journals between 1 January 2000 and 1 July 2020. Searches were conducted on 1 July 2020; the review itself was completed from 1 July to 1 October 2020. To be eligible, studies had to evaluate psychosocial interventions, defined as interventions using a social, psychological or behavioural approach, or a combination of these two. We aimed to include studies of interventions interpersonal or informational activities, techniques or strategies that targeted behavioural, psychological, interpersonal or social factors with the aim of improving health outcomes [57, 58] . Studies eligible for inclusion could include evaluations conducted as randomized controlled trials, crossover trials, cluster randomized trials or factorial trials. There was no exclusion based on language or geographical region.

We included studies with participants who were male or female adolescents and young people living with HIV/AIDS, between 10 and 24 years of age. When studies had age ranges that extended beyond this limit, they were included if the mean age of the participants was within the specified age range. Interventions could be implemented in an individual, group or combined context. While adolescents and/or young people living with HIV were the main target group, we also included intervention studies with additional participants, such as caregivers. Interventions aimed at improving adolescents' socioeconomic status, such as through the use of cash transfers, were only included when interventions combined these strategies with a psychosocial component.

The primary comparator for the studies included in this review was cared as usual. In a number of instances, a timematched alternative healthcare intervention was used as the control group. Studies comparing two active interventions were not included.

Relevant studies were identified by using a set of predetermined search terms to systematically search numerous academic databases, including Cochrane Library, PsycINFO, PubMed and Scopus (see Table S1 for search strategies by the database). A trained information specialist developed and ran the searches, and the search terms were adapted for each database. All identified studies were exported to Covidence [59] where all duplicates were removed. Reviewers, working in pairs, independently reviewed all abstracts. Following the removal of excluded studies, we obtained full-text versions of relevant studies from academic databases. Two reviewers independently evaluated each paper to determine its eligibility. In cases of disagreement, articles were adjudicated by a senior team member.

We used a standardized data extraction form to organize data extraction from each included study. Two review team members independently extracted key study characteristics, intervention content and delivery, risk of bias and study quality and control group type. Publications that were linked to the same study were merged as one study record. A senior review team member reviewed all discrepancies on a rolling basis.

Outcome data were also extracted in duplicate by two independent reviewers, with all discrepancies discussed and changes and corrections to the extracted data recorded. During the extraction process, reviewers identified distinct differences between types of outcomes reported within the domains of sexual risk and adherence to ART. In order to provide a more accurate analysis of the effectiveness of the intervention on a given outcome, sexual risk was divided into two categories for analysis (sexual risk behaviour, sexual risk knowledge) as was adherence (adherence to ART, ART knowledge). For the meta-analysis, viral load outcomes were divided into three distinct categories to ensure alignment of measures and to capture outcomes as reported by the studies: level of viral load was captured as a continuous variable; viral suppression was captured as a binary variable (<1000 copies/mL), as was undetectable viral load (<200 copies/mL). The final outcomes of interest included: adherence to ART, ART knowledge, retention in care, sexual risk behaviours, sexual risk knowledge, linkage to care, viral load (level), viral suppression, undetectable viral load and improved transitioning to adult services. Outcomes, as reported by study authors, could include self-report data, biological data (e.g. for viral load), and/or other clinical records. Definitions of outcomes are available in Table S2 .

We used the Cochrane Risk of Bias tool to assess the risk of bias according to the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias [60] . For studies that were assessed as cluster randomized controlled trials, four additional areas were assessed: recruitment bias, baseline imbalance, loss of clusters and incorrect analysis.

We classified effect estimates from included studies according to the outcome domain they represented and length of follow-up. Effects were measured by extracting data from all reported timepoints. Effect estimates were transformed into standardized mean differences (SMD), preferring Cohen's d. Where binary outcomes were reported, we converted odds ratios to Cohen's d using the logit transformation. Each of these transformations were conducted independently by two reviewers.

Meta-analyses were undertaken using robust variance estimation with random effects in order to account for multiple dependent effect estimates by study. In many cases, one study contributed several effect estimates to one outcome domain.

We assumed an intercorrelation of 0.8 within studies. We described heterogeneity in terms of s² adjusted for clustering and I². Meta-regression included categorical predictors to describe intervention and population characteristics that may account for heterogeneity in effectiveness. Meta-regressions were described using the regression coefficient, residual I² and residual s 2 The primary analysis compared treatment versus control group. Finally, we used GRADEPro GDT software to determine the certainty of the evidence and followed methodology as described by the GRADE Handbook and the mhGAP guidelines [61, 62] .

We identified 30 relevant studies for inclusion in this review ( Figure 1 ).

The majority of studies were conducted in the United States (n = 18, 60%), with the remainder of studies done in Uganda (n = 4) [63] [64] [65] [66] [67] , Thailand (n = 3) [68] [69] [70] [71] , Zimbabwe (n = 2) [72, 73] , Nigeria (n = 1) [74] , South Africa (n = 1) [75] and Zambia (n = 1) [76] . Most studies (n = 26, 86.7%) used an individually randomized controlled trial design to evaluate the intervention, whereas fewer (n = 4, 13.3%) used cluster randomization with families or clinic sites as the unit of randomization (Table 1) [63, 67, 71, 72, 77] .

The majority of studies recruited both male and female participants, with one study including only male participants [78] and two studies recruiting only female participants [79, 80] . The total sample size per study ranged from n = 12 to n = 702 participants (mean = 135.17, SD = 154.7), and a total of n = 4055 participants were included in the review. Participants' mean age, reported across 26 of the 30 studies, was 19.33 years (SD = 3.76). Other studies provided age ranges or median age. Most studies targeted individuals who were 15 years and older (n = 22, 73.3%), whereas others targeted younger participants (n = 4, 13.3%) [63, 67, 68, 73, 75] or a broader range of ages.

Clinic-based interventions comprised half of the studies (n = 15). A further six interventions were delivered in a clinical setting combined with another location or strategy (e.g. digital) [64, [72] [73] [74] 81, 82] . Other in-person interventions utilized homebased (n = 1) [83] , university-based (n = 1) [80] and community-centre settings (n = 1) [78] . Four studies took place completely digitally [65, 66, 84, 85] , and one study was implemented telephonically [86, 87] . One study used a combination of these settings and strategies to deliver their intervention.

Health providers were used to deliver the interventions in one-third of studies (n = 10), including three by nurses [64, 71, 83] , one by a social worker [78] and others by clinicians or mental health professionals [69, 77, [88] [89] [90] [91] [92] . Four studies involved peer implementers, in some cases relying on professional support to implement interventions [72, 73, 76, 93] . Five interventions were delivered by lay counsellors or facilitators [74, 79, 86, 87, 94, 95] . Additionally, five interventions had no delivery personnel involved and were delivered by digital means only (one of these was delivered in a hybrid clinicaldigital setting as described above) [65, 66, 82, 84, 85] . Four interventions were delivered using a combination of personnel, and two studies did not specify the intervention implementers.

Over a third of studies included interventions that had a remote delivery component (n = 11, digital, SMS and telephonic calls). Sixteen studies specified total contact time, which ranged from 30 minutes to 36 hours.

All included studies were targeted toward AYPLHIV. Certain studies targeted specific groups, including: AYPLHIV struggling with treatment adherence (n = 3, 10%) [71, 81, 84] , those newly diagnosed with HIV (n = 2, 6.7%) [82, 93] , those engaged in risky behaviours (n = 2, 6.7%) [88, 89, 96] , those diagnosed with a mental disorder (n = 1, 3.3%) [77] and young Black men who have sex with men and transgender women (n = 1, 3.3%) [78] .

AYPLHIV participated in discussions around the development, design and/or implementation of the intervention-or participated in actually implementing the intervention as peer facilitators-in over half of studies (n = 16, 53.3%). Six interventions were designed to include parental or caregiver participation, engaging them along with their children, or in less direct engagement (20.0%) [63, 67, 68, 73, 75, 76, 83 ].

Interventions were broadly categorized into interpersonal or informational [97] . Interpersonal interventions included counselling, motivational interviewing or cognitive-behavioural therapeutic techniques. Informational interventions, instead, employed predominantly one-way information delivery and/or messaging. Within our sample, 86.7% of studies (n = 26) involved interpersonal interventions, with the remainder utilizing informational interventions [65, 66, 84, 95] . Of the 30 included studies, most interventions (n = 25, 83.3%) were based on a designated theoretical approach or orientation. A smaller number (n = 5, 16.7%) of studies evaluated interventions that could be classified as non-specific, as they utilized strategies that were more generic to psychosocial interventions [63, 65, 67, 72, 73, 76] . Interventions included those based on principles of motivational interviewing (n = 7, 23.3%) [69, 70, 81, 88, 89, 91, 92, 96, 98] , cognitive-behavioural therapeutic techniques (n = 2, 6.7%) [64, 77] and social action theory (n = 2, 6.7%) [68, 75] . Other studies used theoretical principles such as economic empowerment, peer support, mindfulness and behavioural economics. Additionally, some studies used a combination of theoretical principles.

Overall, studies were assessed as having a low risk of bias in domains of selective reporting and other bias (see Figure S1 ). Most studies were assessed as having an unclear risk of bias for random sequence generation (n = 18, 60.0%) and allocation concealment (n = 23, 76.7%) due to poor reporting. Over one-quarter of studies were assessed as having a high risk of bias for performance bias (n = 8, 26.7%); the majority of the remaining studies were at unclear risk (n = 18, 60.0%), predominantly due to poor reporting combined with a strong likelihood of unblinding. Only five studies were at high risk for detection bias, mostly due to self-reported outcomes by unblinded participants, but half of the studies (n = 15) were at unclear risk of detection bias. Nearly a quarter of studies reported high attrition, with insufficient information or inappropriate approaches to handling missing data, leading to a high risk of bias judgments (n = 7, 76.7%), whereas only four studies in the attrition domain were judged as unclear (13.3%). For cluster-randomized trials, the additional risk of bias criteria was applied; baseline imbalance and loss of clusters presented a low risk of bias, whereas high risk of bias for recruitment bias and incorrect analysis techniques were identified in two studies each. low certainty evidence) and level of viral load (SMD = À0.2607, 95% CI À04518 to À0.0696, n = 1566, very low certainty evidence). For adherence to ART, substantial significant heterogeneity was identified with an I² of 80%. For viral load, heterogeneity was below the pre-specified threshold, at 60%. Retention in care (very low certainty evidence) showed non-significant results, as did sexual risk behaviours (very low certainty evidence) and sexual risk knowledge (low certainty evidence). The confidence intervals for viral suppression and undetectable viral load findings, dichotomized and converted to odds ratios, were wide and spanned unimportant benefit as well as large, important benefit; this made these outcomes less conclusive than viral load measured as a continuous variable. All three of these outcomes had very low certainty evidence. Finally, ART knowledge was statistically significant with high certainty of evidence, but its effect size was not clinically relevant (SMD = 0.1263, 95% CI 0.1131 to 0.1395). Linkage to care and improved transitioning to adult services were not included in the meta-analysis due to insufficient data. Table 2 shows these findings. Forest plots for all outcomes are available in Table S3 .

In this review, we synthesized and meta-analysed randomized controlled trials assessing the effect of psychosocial interventions on engagement in care and health and behavioural outcomes for AYPLHIV. While a growing body of research has attempted to understand drivers of adolescent engagement in HIV care [99] [100] [101] , as well as effective modes of improving health outcomes and reducing sexual risk behaviours in this age group [102, 103] , our systematic review and meta-analysis represents an important step toward establishing evidence for the effectiveness of psychosocial interventions to improve these outcomes for AYPLHIV.

Our findings showed that intervention participants demonstrated better adherence to ART and reductions in viral load among intervention participants when compared to controls. These types of interventions may be able to encourage positive behavioural and psychosocial changes in AYPLHIV, especially in regard to HIV treatment outcomes. The psychosocial interventions that we identified tended to rely on evidencebased approaches that have also been shown to be effective at improving adherence among adults living with HIV, including community-based adherence support and digital platforms [104] . These changes may also stem from high levels of support and investment from study team members, enabling adolescents living in resource-limited communities to engage more fully with the intervention than they would have been able to do within the standard of care, as well as from reporting bias, specifically in self-reported measures [105] .

While psychosocial interventions showed promise in improving HIV-specific outcomes, other outcomes related to engagement in care and behavioural outcomes were not found to be affected by these interventions. These types of outcomes, however, may be important to consider when aiming for longer-term, sustained improvements in health and health service engagement, and should be carefully considered in the design and implementation of this type of intervention. It is possible, for instance that these outcomes may require bolstering by multiple, complementary approaches. Retention in care is one example, where AYPLHIV may require a broader set of supports alongside individual skills to improve and sustain engagement in care. Some interventions included members of the participant's social network, including family members, to support retention in care [73, 106, 107] . Longer follow-up periods may also enable more accurate measures of retention in care, whereas many of these evaluations only followed participants for a short period following the end of the intervention.

Our meta-analysis showed limited effectiveness for improving outcomes related to sexual risk behaviours and knowledge. This is an important finding, especially given the intertwined risks of early, unintended pregnancy and secondary HIV transmission, especially in sub-Saharan Africa [108, 109] . Sexual risk behaviours in AYPLHIV have been found to be driven by a combination of individual, relationship, family, community and structural factors [110, 111] . Although a number of psychosocial interventions delivered content focused on influencing decision making about sexual risk behaviours and sexual negotiation skills [79] , the overall aim of these studies was not linked specifically to sexual health or mitigating associated risk behaviours. It may be that adolescents require more specific skills related to sexual risk and sexual and reproductive health, such as information and/or education about condom use and contraception, as well as supports such as caregiver engagement to improve communication, which has been found to work in more general adolescent populations [112] . For AYPL-HIV, psychosocial interventions may require more targeted attention to sexual risk, in lieu of more broad-based theoretical approaches such as motivational interviewing and goalsetting. Some outcomes were rarely or not reported, and our findings point to the need for additional research areas with populations of AYPLHIV. Only one study investigated linkage to care, and no studies measured improved transitioning to adult services. Linkage to care is important along the entire HIV continuum of care, from prevention of mother-to-child transmission along to adult-focused testing, counselling and treatment [113] [114] [115] [116] , and should be included as an outcome of interest for psychosocial interventions in studies with all ages. Interventions to improve transitioning to adult services are critically important for AYPLHIV and must be examined to leverage the potential role of psychosocial support in maintaining service engagement for young people.

This review elicits two critical, intertwined considerations for implementing interventions for AYPLHIV where they are most needed-adapting psychosocial interventions for both demographic/age group and geographical setting. The first consideration relates to the adaptation of interventions developed for adult populations. A substantial number of the studies detailed consultative processes with adolescents and young people, such as youth advisory groups [82] , preliminary interviews with AYPLHIV [107, 117, 118] , focus groups and workshops [74, [119] [120] [121] , youth-designed personalized content [122] and involvement of peer mentors [72, 73, 78, 81, 123] . These processes are vital to ensure that interventions are implemented with full consideration of what works best for younger HIV-affected populations [124] . Notably, some sub-groups of AYPL-HIV were not specifically targeted by the studies we found, including pregnant adolescents and young women, young people living with disabilities and young people engaged in sex work and transactional sex.

Secondly, while interventions were distributed across a number of countries-including sub-Saharan Africa, where the burden of HIV among young people is greatest-our review showed that these interventions are still most commonly implemented in the United States. Our final study subset reflected nearly double the number of studies in the United States as compared to all other countries, although these studies often engaged high-adversity sub-populations. More intervention efficacy and effectiveness research with AYPLHIV should be conducted in the regions with the highest burden of HIV, in particular in Eastern and Southern Africa, as well as in other countries with more limited resources and specific HIV-affected populations of young people [100, 111] . In low-resource, high-burden settings in particular, cost-effectiveness research and other forms of cost-related data are needed to ensure policy buy-in, and to build evidence on what works for this growing population [72] . Specifically, investigating costs related to integrating psychosocial interventions with existing HIV services is much-needed, in order to establish evidence that might add fewer additional costs but contribute to greater downstream effects on the wellbeing of AYPLHIV. While implementing interventions adapted from high-income settings may be a more feasible way to translate the best evidence to new settings, it is also imperative that adaptations allow for locally appropriate contextual input, to ensure that core content can be effectively delivered and received [125] [126] [127] . Moreover, considering the stark socioeconomic inequities many AYPLHIV may confront, it is important to note that psychosocial interventions alone may not adequately address the challenges this population faces. It is likely that a combination of different kinds of support at different levels may be required to meet the needs of AYPLHIV [128, 129] . Researchers developing and testing interventions in the near future could also consider adopting family-and peer-based intervention models, as well as relationship safety interventions, to provide additional structural supports.

Overall, given the very low certainty of evidence we found, more high-quality research in this area is needed. This is particularly important considering the significant burden of poor HIV-linked outcomes in this population. Furthermore, to facilitate comparability of findings across settings, future research should use standard definitions.

Our review also elicits a set of implications for policy and practice related to HIV programming. Lay health counsellors with specific HIV-focused training have been leveraged to positive effect among adult populations in resource-constrained settings [74] , and may be a feasible cadre to deliver support to younger populations living with HIV [72, 73] . Where lay workers have been deployed with adult populations, they are often trained in counselling skills [50] , and may be employed as part of government health systems. They also tend to come from the general communities in which interventions are implemented [130] . Addressing some of the broader challenges facing AYPLHIV through focusing on strengthening interpersonal skills for implementers of all types may be one way to deliver more holistic, responsive interventions at low cost.

In order to improve the health outcomes of AYPLHIV during their transition to adulthood, and equip them with skills and knowledge to manage their own health and wellbeing, psychosocial interventions need to respond to adolescents' specific needs. Many of the studies included in this review were attuned to this need, and involved AYPLHIV at various stages of the design, refinement, implementation and evaluation of these interventions. This approach should be emphasized in the process of introducing and implementing psychosocial interventions with adolescent and young populations, who are likely to respond more favourably to interventions that are co-designed and adapted [131] . In programming as well as in research, representation of more at-risk subgroups of AYPLHIV is also necessary. Importantly, in the context of the COVID-19 pandemic, new approaches to reaching AYPLHIV may be required. This population is facing marked disruptions in accessing healthcare, and also encountering additional challenges related to the social and economic impact of COVID-19 and periods of extended lockdowns [132, 133] . While these challenges have been explored in the immediate emergency response, it is also critical to consider the pandemic's longer term impact on how vulnerable populations of adolescents are reached and retained in supportive interventions [134] . Our review presents evidence that psychosocial interventions can benefit adherence and viral load outcomes, but might be bolstered by additional considerations around mechanisms by which they can retain their effectiveness and be integrated into other settings that are COVID-responsive. Digitally based interventions, which were well-represented among our sample in both high-and low-income settings, are one avenue for expanding the reach of interventions while managing the challenges posed by COVID-19, including the need for physical distancing and limited travel [135] . Digital interventions may have other benefits such as mitigating fear of unintended disclosure or stigma among AYPL-HIV, and may also present attractive and more innovative formats for engaging youth [135, 136] . Similarly, digital interventions are increasingly accessible through mobile phones, enabling rapid and effective reach while upholding safety precautions. It is worth noting that data, airtime and electricity for charging phones have a cost, and COVID-19 has placed many families in dire financial circumstances where these means may be less accessible than before. It may also be important to consider how to strengthen sexual risk elements of psychosocial interventions, especially within digitally based interventions, for those adolescents and young people who are unable to easily access clinical services, or who may benefit more from alternative approaches to education and care [136] [137] [138] .

Although we did not place a language restriction on our search, the final studies examined were all in English. The studies we identified had fewer behavioural outcomes (such as sexual and reproductive health) than HIV-specific outcomes, and more research with such outcomes is required. Additionally, our findings should be considered in the context of the included studies, which do not accurately represent the geographic distribution of HIV infection among adolescents and young people globally. Despite these limitations, we feel that the studies included in this review reflect a range of diverse psychosocial interventions and ages, making it a valuable addition to the expanding evidence about adolescents living with HIV.

This review found that psychosocial interventions for AYPL-HIV resulted in small-to-moderate beneficial effects on adherence to ART and viral load. More research is needed to understand the long-term impacts of these types of interventions, especially in light of persistent rates of HIV infection in this age group. Interventions designed with and for adolescents and young people, and implemented in the highest burden regions, are also needed to increase the accuracy and relevance of the evidence base. To this end, cost-effective solutions, and research accompanying them, are urgently needed. Finally, it is critical to assess the emergent consequences of the COVID-19 pandemic on how AYPLHIV can access and engage in care and achieve optimal health and wellbeing while navigating the transition to adulthood. Institute of Human Virology and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA; 7 Paediatric Adolescent Treatment Africa, Cape Town, South Africa; 8 Africaid, Harare, Zimbabwe; 9 UNICEF Eastern and Southern Africa Regional Office, Nairobi, Kenya

The authors have declared no conflict of interest.

CAL conceptualized and drafted the manuscript. SS led the review research team, and CAL, SDT, TK, YC, NA, MB and DTP contributed as members of the core research team to running searches, screening articles, extracting data and preparing data for analysis, as well as contributing to drafting specific sections of the manuscript. AB conducted all risk of bias assessments and led the GRADE process. GJMT conducted all statistical analyses. WA, NF, MP and MV were primarily responsible for defining the review question and contributing to the guidelines development protocol and final guidelines process. DM, NW, NASA and AA contributed to the protocol, discussion and provision of supporting resources. All authors contributed to reviewing, finalizing and approving the final manuscript.

ART, antiretroviral therapy; AYP, adolescents and young people; AYPLHIV, adolescents and young people living with HIV; CI, confidence interval; HIV, human immunodeficiency virus; SMD, standardized mean difference.

The authors thank Joy Oliver, Linda-Gail Bekker, Roger Chou and Cindy Amaiza for their contributions to this work along with all members of the World Health Organization Adolescent Service Delivery Working Group.

This review was funded by the World Health Organization.

Additional information may be found under the Supporting Information tab for this article. Table S1 . Search strategy Table S3 . Forest plots for all outcomes Figure S1 . Risk of bias diagram

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Epidemiology of HIV and AIDS among adolescents: current status, inequities, and data gaps

The adolescent and young adult HIV cascade of care in the United States: exaggerated health disparities

Living and dying to be counted: What we know about the epidemiology of the global adolescent HIV epidemic

Retention and adherence: global challenges for the long-term care of adolescents and young adults living with HIV

High attrition before and after ART initiation among youth (15-24 years of age) enrolled in HIV care

Toward an AIDS-free generation

Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges

The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection

Rates and correlates of antiretroviral therapy use and virologic suppression among perinatally and behaviorally infected HIV+ youth linked to care in the United States

Barriers and facilitators to linkage to ART in primary care: a qualitative study of patients and providers in

Building our youth for the future

Sexual behaviour among adolescents living with the human immunodeficiency virus in Zimbabwe: educational implications

Linking HIV-positive adolescents to care in 15 different clinics across the United States: creating solutions to address structural barriers for linkage to care

A qualitative study of the barriers and facilitators to retention-in-care among HIVpositive women in the rural southeastern United States: implications for targeted interventions

Psychosocial support interventions for improved adherence and retention in ART care for adolescents and young people living with HIV: a scoping review

An urgent need for research on factors impacting adherence to and retention in care among HIVpositive youth and adolescents from key populations

Longitudinal antiretroviral adherence among adolescents infected with human immunodeficiency virus

Optimizing HIV transition services for young adults

A social neuroscience perspective on adolescent risk-taking

Colebunders R. Sexual risk reduction needs of adolescents living with HIV in a clinical care setting

Children and adolescents living with HIV positive parents: emotional and behavioural problems

From affected to infected? Orphanhood and HIV risk among female adolescents in urban Zimbabwe

Predictors of HIV-related stigma among young people living with HIV

Early marriage and HIV risks in sub-Saharan Africa. Stud Family Plan

A qualitative study of barriers to enrollment into free HIV care: perspectives of never-in-care HIV-positive patients and providers in Rakai

My mother told me that I should not": a qualitative study exploring the restrictions placed on adolescent girls living with HIV in Zambia

Neurocognitive impairment and HIV risk factors: a reciprocal relationship

No change in health risk behaviors over time among HIV infected adolescents in care: role of psychological distress

Health risk behaviour among adolescents living with HIV in sub-Saharan Africa: a systematic review and meta-analysis

Efficacy of group psychotherapy to reduce depressive symptoms among HIV-infected individuals: a systematic review and meta-analysis

An Index of multiple psychosocial, syndemic conditions is associated with antiretroviral medication adherence among HIV-positive youth

Integrating mental health in global initiatives for HIV/AIDS

Psychosocial interventions enhance HIV medication adherence: a systematic review and meta-analysis

The benefits of psychosocial interventions for mental health in people living with HIV: a systematic review and meta-analysis

HIV and depression-a systematic review of interventions

An international systematic review and meta-analysis of multisession psychosocial interventions compared with educational or minimal interventions on the HIV sex risk behaviors of people who use drugs

Effective methods to change sex-risk among drug users: a review of psychosocial interventions

World Health Organization. WHO handbook for guideline development

Where the heart is: Meeting the psychosocial needs of young children in the context of HIV/AIDS. The Hague, The Netherlands: Bernard van Leer Foundation

Psychosocial interventions for mental and substance use disorders: A framework for establishing evidence-based standards

Veritas Health Innovation. Covidence systematic review software

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

GRADEpro guideline development tool

World Health Organization. mhGAP intervention guide for mental, neurological and substance use disorders in non-specialized health settings: mental health Gap Action Programme (mhGAP). Geneva: World Health Organization

Does economic strengthening improve viral suppression among adolescents living with HIV? Results from a cluster randomized trial in Uganda

Efficacy of a culturally adapted intervention for youth living with HIV in Uganda

Text messaging for improving antiretroviral therapy adherence: no effects after 1 year in a randomized controlled trial among adolescents and young

A randomized controlled trial study of the acceptability, feasibility, and preliminary impact of SITA (SMS as an Incentive To Adhere): a mobile technology-based intervention informed by behavioral economics to improve ART adherence among youth in Uganda

The long-term effects of a family based economic empowerment intervention (Suubi+Adherence) on suppression of HIV viral loads among adolescents living with HIV in southern Uganda: Findings from 5-year cluster randomized trial

pilot randomized control trial of a family-based psychosocial intervention for perinatally HIV-infected early

Motivational interviewing targeting risk behaviors for youth living with HIV in Thailand

Motivational interviewing targeting risky sex in HIV-positive young thai men who have sex with men

Effect of an empowerment intervention on antiretroviral drug adherence in Thai youth

Effect of a differentiated service delivery model on virological failure in adolescents with HIV in Zimbabwe (Zvandiri): a cluster-randomised controlled trial. The Lancet Global Health

Effectiveness of community adolescent treatment supporters (CATS) interventions in improving linkage and retention in care, adherence to ART and psychosocial well-being: a randomised trial among adolescents living with HIV in rural Zimbabwe

A social media-based support group for youth living with HIV in Nigeria (SMART Connections): randomized controlled trial

The VUKA family program: piloting a family-based psychosocial intervention to promote health and mental health among HIV infected early adolescents in South Africa

Project YES! Youth Engaging for Success: a randomized controlled trial assessing the impact of a clinic-based peer mentoring program on viral suppression, adherence and internalized stigma among HIV-positive youth (15-24 years

Effective treatment of depressive disorders in medical clinics for adolescents and young adults living with HIV

Project nGage: results of a randomized controlled trial of a dyadic network support intervention to retain young black men who have sex with men in HIV care

Young women living with HIV: outcomes from a targeted secondary prevention empowerment pilot trial

Fischl MA Adolescent girls and young women living with HIV: preconception counseling strategies

Using technology to improve adherence to HIV medications in transitional age youth: research reviewed, methods tried, lessons learned

Motivational enhancement system for adherence (MESA): pilot randomized trial of a brief computer-delivered prevention intervention for youth initiating antiretroviral treatment

Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention

A randomized controlled trial of personalized text message reminders to promote medication adherence among HIV-positive adolescents and young adults

Enhancing health among youth living with HIV using an iPhone game

The use of cell phone support for non-adherent HIV-infected youth and young adults: an initial randomized and controlled intervention trial

The impact of cell phone support on psychosocial outcomes for youth living with HIV nonadherent to antiretroviral therapy

A clinic-based motivational intervention improves condom use among subgroups of youth living with HIV

Positive strategies to enhance problem-solving skills (STEPS): a pilot randomized, controlled trial of a multicomponent, technology-enhanced, customizable antiretroviral adherence intervention for HIV-infected adolescents and young adults

Healthy choices: motivational enhancement therapy for health risk behaviors in HIVpositive youth

Brief report: maintenance of effects of motivational enhancement therapy to improve risk behaviors and HIV-related health in a randomized controlled trial of youth living with HIV

Project ACCEPT: evaluation of a group-based intervention to improve engagement in care for youth newly diagnosed with HIV

Rotheram-Borus MJ. Crystal clear with active visualization: understanding medication adherence among youth living with HIV

Prevention for substance-using HIV-positive young people

Interactive health communication applications for people with chronic disease

A Multisite randomized trial of a motivational intervention targeting multiple risks in youth living with HIV: initial effects on motivation, self-efficacy, and depression

Adolescents and young people at the centre: global perspectives and approaches to transform HIV testing, treatment and care

Improving retention in HIV care among adolescents and adults in lowand middle-income countries: a systematic review of the literature

Recent interventions to improve retention in HIV care and adherence to antiretroviral treatment among adolescents and youth: a systematic review

Systematic review: a review of adolescent behavior change interventions [BCI] and their effectiveness in HIV and AIDS prevention in sub-Saharan Africa

A Systematic review of hiv interventions for young women in Sub-Saharan Africa

Interventions to improve antiretroviral therapy adherence among adolescents in low-and middle-income countries: a systematic review of the literature

Project nGage: results of a randomized controlled trial of a dyadic network support intervention to retain young black men who have sex with men in HIV care

pilot randomized control trial of a family-based psychosocial intervention for perinatally HIV-infected early adolescents

HIV-infected adolescent mothers and their infants: low coverage of HIV services and high risk of HIV transmission in

Reproductive aspirations, contraception use and dual protection among adolescent girls and young women: the effect of motherhood and HIV status

Behavioral factors contributing to the transmission of HIV and AIDS amongst young women of Mbabane in Swaziland

Sex in the shadow of HIV: a systematic review of prevalence, risk factors, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa

A systematic review of sexual and reproductive health interventions for young people in humanitarian and lower-and-middle-income country settings

Effective interventions to improve young adults' linkage to HIV care in Sub-Saharan Africa: a systematic review

Linkage to and retention in care following healthcare transition from pediatric to adult HIV care

Tracking the transition of adolescents into adult HIV care: a global assessment

Adolescents, young people, and the 90-90-90 goals: a call to improve HIV testing and linkage to treatment

Positive strategies to enhance problem-solving skills (STEPS): a pilot randomized, controlled trial of a multicomponent, technology-enhanced, customizable antiretroviral adherence intervention for hiv-infected adolescents and young adults

Enhancing health among youth living with HIV using an iPhone game

Young women living with HIV: outcomes from a targeted secondary prevention empowerment pilot trial

Efficacy of a culturally adapted intervention for youth living with HIV in Uganda

Text messaging for improving antiretroviral therapy adherence: no effects after 1 year in a randomized controlled trial among adolescents and young adults

A randomized controlled trial of personalized text message reminders to promote medication adherence among HIV-positive adolescents and young adults

Project YES! youth engaging for success: a randomized controlled trial assessing the impact of a clinic-based peer mentoring program on viral suppression, adherence and internalized stigma among HIV-positive youth (15-24 years

Wingood GM, DiClemente RJ. The ADAPT-ITT model: a novel method of adapting evidence-based HIV Interventions

Adapting evidence-based behavioral interventions for new settings and target populations

Adapting evidence-informed complex population health interventions for new contexts: a systematic review of guidance

Factors associated with adherence to antiretroviral therapy among adolescents living with HIV/AIDS in low-and middle-income countries: a systematic review

The role of community health workers in improving HIV treatment outcomes in children: lessons learned from the ZENITH trial in Zimbabwe

Nothing about us without RIGHTS-meaningful engagement of children and youth: from research prioritization to clinical trials, implementation science, and policy

Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource-constrained settings during the COVID-19 pandemic

The effect of technology-based programmes on changing health behaviours of adolescents: systematic review. Compr Child Adolesc Nurs

Targeted client communication via mobile devices for improving sexual and reproductive health

Clients' perceptions and experiences of targeted digital communication accessible via mobile devices for reproductive, maternal, newborn, child, and adolescent health: a qualitative evidence synthesis