IntroductionAdolescents are a unique and sometimes neglected group in the planning of healthcare services. This is the case in many parts of sub-Saharan Africa, where more than eight out of ten of the world's HIV-infected adolescents live. Although the last decade has seen a reduction in AIDS-related mortality worldwide, largely due to improved access to effective antiretroviral therapy (ART), AIDS remains a significant contributor to adolescent mortality in sub-Saharan Africa. Although inadequate access to ART in parts of the subcontinent may be implicated, research among youth with HIV elsewhere in the world suggests that suboptimal adherence to ART may play a significant role. In this article, we summarize the epidemiology of HIV among sub-Saharan African adolescents and review their adherence to ART, emphasizing the unique challenges and factors associated with adherence behaviour.MethodsWe conducted a comprehensive search of online databases for articles, relevant abstracts, and conference reports from meetings held between 2010 and 2014. Our search terms included “adherence,” “compliance,” “antiretroviral use” and “antiretroviral adherence,” in combination with “adolescents,” “youth,” “HIV,” “Africa,” “interventions” and the MeSH term “Africa South of the Sahara.” Of 19,537 articles and abstracts identified, 215 met inclusion criteria, and 148 were reviewed.DiscussionAdolescents comprise a substantial portion of the population in many sub-Saharan African countries. They are at particular risk of HIV and may experience worse outcomes. Although demonstrated to have unique challenges, there is a dearth of comprehensive health services for adolescents, especially for those with HIV in sub-Saharan Africa. ART adherence is poorer among older adolescents than other age groups, and psychosocial, socio-economic, individual, and treatment-related factors influence adherence behaviour among adolescents in this region. With the exception of a few examples based on affective, cognitive, and behavioural strategies, most adherence interventions have been targeted at adults with HIV.ConclusionsAlthough higher levels of ART adherence have been reported in sub-Saharan Africa than in other well-resourced settings, adolescents in the region may have poorer adherence patterns. There is substantial need for interventions to improve adherence in this unique population.

We sought to describe virologic and clinical retention outcomes among a group of HIV-infected adolescents and young adults (AYA) newly established in an adult HIV clinic compared with matched HIV-infected adults. AYA demonstrated lower rates of HIV-1 virologic suppression and higher rates of HIV-1 viral rebound and loss to follow-up compared with adults. African American AYA had the lowest rates of virologic suppression and the highest rates of viral rebound. Adult providers should consider HIV-infected AYA, particularly African American HIV-infected AYA, to potentially be at high risk for poor clinical outcomes in adult care.

A goal of HIV therapy is to sustain suppression of the plasma viral load below the detection limits of clinical assays. However, widely followed treatment guidelines diverge in their interpretation and recommended management of persistent viremia of low magnitude, reflecting the limited evidence base for this common clinical finding. Here, we review the incidence, risk factors, and potential consequences of low-level HIV viremia (LLV; defined in this review as a viremia level of 50 to 500 copies/ml) and verylow-level viremia (VLLV; defined as a viremia level of <50 copies/ml detected by clinical assays that have quantification cutoffs of <50 copies/ml). Using this framework, we discuss practical issues related to the diagnosis and management of patients experiencing persistent LLV and VLLV. Compared to viral suppression at <50 or 40 copies/ml, persistent LLV is associated with increased risk of antiretroviral drug resistance and overt virologic failure. Higher immune activation and HIV transmission may be additional undesirable consequences in this population. It is uncertain whether LLV of <200 copies/ml confers independent risks, as this level of viremia may reflect assay-dependent artifacts or biologically meaningful events during suppression. Resistance genotyping should be considered in patients with persistent LLV when feasible, and treatment should be modified if resistance is detected. There is a dearth of clinical evidence to guide management when genotyping is not feasible. Increased availability of genotypic assays for samples with viral loads of <400 copies/ml is needed.

Outcomes following healthcare transition (HCT) from pediatric to adult HIV care are not well described. We sought to describe clinical outcomes following HCT within our institution among young adults with behavioral-acquired (N = 31) and perinatally-acquired (N = 19) HIV. We conducted a retrospective cohort study among HIV-infected adults who attempted transition from pediatric to adult HIV care within our institution. The primary end point was retention in care, defined as the completion of at least two visits over 12 months following linkage to adult care. Additional end points include time to linkage to adult care, and changes in CD4 + T cell count and HIV RNA across time. Outcomes were compared between perinatal and behavioral HIV cohorts. Binary data were analyzed using the Fisher exact test and continuous data were analyzed using the Mann-Whitney test. Forty-three (86%) of 50 patients were successfully linked to adult care. The median time to linkage was 98 days. Fifty percent of patients achieved full retention in care at 12 months post-linkage. Though those with behavioral-acquired HIV attempted transfer at an older age, the groups did not differ in rates of linkage and retention in adult care. CD4 + T cell counts and rates of viral suppression did not differ between pre- and post-HCT periods. Despite high rates of successful linkage to adult care in our study population, rates of retention in adult HIV care following HCT were low. These results imply that challenges remain in the adult HIV care setting toward improving the HCT process.

Introduction: The transition from paediatric to adult care poses risks to the health of young adults living with HIV if unsuccessful, including interruptions in care and poor health outcomes. Evolving best practices in HIV healthcare transition should ideally be informed by real-world qualitative and quantitative clinical healthcare transition outcomes. There has been a recent proliferation of HIV healthcare transition outcome research, largely from Europe and North America.Methods: A literature search was undertaken using the online databases PubMed, Web of Science, and Google Scholar. Medical subject and text word searches were combined for terms relating to HIV, paediatric transition outcomes, and internal and external factors were used to identify peer-reviewed articles.Results: In this paper, we review data on HIV healthcare transition outcomes in North America and Europe. Internal and external factors which may impact the success of HIV healthcare transition are examined. We describe ongoing research efforts to capture transition outcomes in the North America and Europe. Clinical, operational, and implementation science research gaps that exist to date are highlighted. Efforts to improve HIV healthcare transition research through country-level surveillance networks and large multicentre cohorts, including data integration and linkage between paediatric and adult cohorts are discussed.Conclusions: We identified the need for a comprehensive approach to implementing empirically supported protocols to support healthcare transition for ALHIV. While there is limited prospective longitudinal cohort data available at this time, cohorts linking the paediatric and adolescent with ongoing surveillance into adulthood are being developed. Through a review of existing qualitative and quantitative healthcare transition outcomes studies, we identify emerging areas of consensus surrounding healthcare transition research implementation. Successful healthcare transition programmes in Europe and North America often share several characteristics, including implementation of a youth friendly multidisciplinary approach, consistent communication and integration between paediatric and adult care teams, and an individualized approach which is attuned the adolescent’s transition readiness. Moving forward, the voices of youth and young adults living with HIV should be included in the development and evaluation of healthcare transition protocols to ensure that the definition of successful transition reflects all of the stakeholders in the transition process.

Objectives: This study's primary objective was to characterize attitudes to long-acting antiretrovirals (LAARV), among youth aged 13 to 24 years living with perinatally-and nonperinatally-acquired HIV (PHIV and NPHIV, respectively). Secondary objectives included: assessing whether those with detectable HIV RNA PCR viral load had higher enthusiasm for LAARV compared to those with suppressed viral load, and examining characteristics associated with LAARV enthusiasm.

HIV-infected patients are living longer as a result of potent antiretroviral therapy. Immuno-inflammatory phenomena implicated in the normal aging process, including immune senescence, depreciation of the adaptive immune system, and heightened systemic inflammation are also pathophysiologic sequelae of HIV infection, suggesting HIV infection can potentiate the biological mechanisms of aging. Aging HIV-infected patients manifest many comorbidities at earlier ages, and sometimes with more aggressive phenotypes compared to seronegative counterparts. In this review, we describe relevant biologic changes shared by normal aging and HIV infection and explore the growing spectrum of clinical manifestations associated with the accelerated aging phenotype in HIV-infected individuals.

Objective To address the need for nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens, we explored the virologic and pharmacokinetic characteristics of maraviroc plus ritonavir-boosted darunavir in a single-arm, open-label, 96-week study. Methods 24 antiretroviral-naïve R5 HIV-1-infected participants received maraviroc 150 mg and DRV/r 800/100 mg (MVC/DRV/r) once-daily. The primary outcome was virologic failure (VF) = confirmed viral load (VL) >50 copies/mL at week 24 in the modified intent-to-treat population. To determine viral dynamics, participant-specific first- and second-phase empirical Bayes estimates were compared to decay rates from efavirenz plus lopinavir/ritonavir, lopinavir/ritonavir plus 2NRTIs and efavirenz plus 2NRTIs. Maraviroc plasma concentrations were determined at weeks 2, 4,12, 24 and 48. Results Baseline median (Q1, Q3) CD4 count and VL were 455 (299, 607) cells/mm3 and 4.62 (4.18, 4.80) log10 copies/mL, respectively. VF occurred in 3/24 participants (12.5 % [95% CI 2.7, 32.4]) at week 24. One of these resuppressed, yielding a week 48 VF rate of 2/24 (8.3 % [95% CI 1.0, 27.0]). The week 48 failures were 2 of the 4 (50%) participants with baseline VL >100,000 copies/mL. Week 96 VF rate was 2/20 (10 % [95% CI 1.2, 31.7]). Phase 1 decay was faster with MVC/DRV/r than reported for ritonavir-boosted lopinavir plus 2 NRTIs (p=0.0063) and similar to efavirenz-based regimens. Individual maraviroc trough concentrations collected between 20–28 hours post dose (n=59) was 13.7 to 130 ng/mL (Q1, 23.4 ng/mL; Q3, 46.5 ng/mL), and modeled steady-state concentration was 128 ng/mL. Conclusion MVC/DRV/r 150/800/100 mg once-daily has potential for treatment-naïve patients with R5 HIV-1.