FREDERICK L. ALTICE, M.D., MA Professor Of Medicine, Epidemiology and Public Health Yale University Special Populations

 All PLWHA are “special populations”.  Treatment of a stigmatized and complex medical and social conditions associated with poor outcomes is challenging even in the best of circumstances.  The additional challenges of incarceration, poverty, food and housing instability, and psychiatric and substance use disorders further complicate adherence and often require specialized interventions to optimize treatment outcomes.

Special Populations  Pregnant women  Children and adolescents  Substance use disorders (SUDs)  Mental health disorders (MHDs)  Incarcerated populations  Homeless and marginally housed populations

Special Populations and Syndemics Pregnant Women Children & Adolescents Substance Use Disorders Mental Health Disorders Incarceration Unstable Housing Sex Workers Migrants

Pregnant Women  More than 50% of HIV+ women are of child-bearing age  Most current data are from resource-poor countries and address short-term PMTCT and not treatment adherence throughout and after pregnancy  Targeted PMTCT treatment (including HIV testing and serostatus awareness) improves adherence to ART for PMTCT and is recommended over untargeted approaches (treatment without HIV testing) in high HIV prevalence settings (IIIB).

Pregnant Women  Zambian RCT of universal SD NVP vs targeted HIV testing & treatment demonstrated higher NVP uptake in universal group, but adherence was lower among women who were illiterate and unaware of their HIV status.  Labor ward-based PMTCT adherence services are recommended for women who are not ART before labor (IIB).  Cluster RCT in 12 Zambian delivery centers found that VCT + ART training in the labor ward was feasible and improved SD NVP coverage and adherence.

Pregnant Women – Future Research  Investigation of specific ART adherence barriers related to pregnancy status  Well-controlled studies to understand adherence barriers for pregnant women and to improve ART adherence antenatally and post-partum

Children and Adolescents  PLWHA between birth and 24 are developmentally diverse, including perinatally and behaviorally infected.  Perinatal infection: adherence mostly related to caregivers and medication-associated problems include problems swallowing, “bad” taste and timing around meals or other activities.  Transition from childhood to adolescence then adulthood is challenging, resulting in deteriorations in adherence, loss of comprehensive services and health insurance.  Adolescents and young adults transition to poor retention, lower ART prescription and poor outcomes.

Children and Adolescents  Intensive youth-focused case management is recommended for adolescents and young adults living with HIV to improve entry into and retention in care (IVB).  Two observational studies showed (1) 174 HIV+ youth had increased appointment attendance after self-efficacy focused CM introduced and (2) 61HIV+ newly diagnosed or intermittently engaged gay youth improved clinic attendance and increased intensive CM intervention was associated with increased likelihood of ART prescription.

Children and Adolescents  Pediatric- and adolescent-focused therapeutic support interventions using problem-solving approaches and addressing psychosocial context are recommended (IIIB).  Two RCTs, one cohort and two pilot studies showed supportive, yet either mixed or non-significant findings with regard to short-term adherence and VL outcomes.  Pill-swallowing training is recommended and may be helpful for younger patients (IVB).  Adherence improved in 23 patients with swallowing difficulties after change from liquid to pills.

Children and Adolescents  DAART improves short-term outcomes and may be considered (IVC).  Three cohort studies of DAART showed CD4 improvements; CD4 gains were sustained in 2 of the 3 studies after DAART discontinuation. In the Cambodian study, the cost was $60 per child/year.  Research gaps: better understanding and appropriate intervention development for heterogeneous groups of children and adolescents; interventions that focus on the transition from child to adolescent to adult; and use of mobile technologies.

Substance Use Disorders  SUDs are associated with reduced linkage, retention, prescription of ART, ART adherence and virologic failure.  Offering buprenorphine or methadone for HIV+ patients with opioid dependence is recommended (IIA).  One RCT and 4 cohort studies support increased ART prescription, increased retention in care and immunological improvements. ART adherence and VL outcomes variable, but generally favor improvements.  DAART is recommended for those with SUDs (IB), confirmed by 4 RCTs and 3 cohort studies; 1 RCT suggests non- durable treatment outcomes.

Substance Use Disorders  Integration of DAART into methadone maintenance programs for individuals with opioid dependence is recommended (IIB).  One RCT and 3 longitudinal studies suggest improved adherence and higher levels of viral suppression.  Future Research: Interventions with ART-naïve patients and transitional interventions that sustain persistence from current EBIs. Inclusion of individuals with SUDs into trials of existing EBIs beneficial for non-drug users, peer-driven, contingency management, family support and electronic device interventions are needed. THPE606: Rose, RCT of SBIRT associated with reductions in drug use and increased VS.

Mental Health Disorders  A meta-analysis of 95 studies in resource rich and poor countries correlated depression with ART non-adherence.  Screening, management and treatment for depression and other mental illnesses in combination with adherence counseling is recommended (IIA).  Several RCTs, including among MSM and women, show CBT + ART adherence counseling improves depressive symptoms and ART adherence. One RCT of stress management w/o ART adherence did not improve adherence. Pharmacological treatment for depression improves ART adherence & outcomes.

Mental Health – Future Research  Interventions for other psychiatric disorders, including PTSD and bipolar and personality disorders.  Examination of relationship of MHDs to ART adherence and development of interventions in LMICs are needed.  Investigations of systematic MH screening and mechanisms through which MHDs negatively influence, including symptoms, influence ART adherence and treatment outcomes. WEPDD0102: Reif, Pilot study of 40 HIV+s with serious mental illness received home-based MH services showed MH improvements and reductions in missed doses.

Incarceration  Compared to the general population, HIV is several-fold greater among the incarcerated globally, including LMICs.  Incarceration negatively impacts continuity of HIV care and adherence and post-release outcomes remain dismal.  DAART is recommended during incarceration (IIIB) and may be considered upon release to the community (IIC).  Within prison, one comparative and one small RCT confirmed higher adherence and viral suppression.  After release, one RCT of 154 HIV+ prisoners showed higher adherence and viral suppression among those receiving DAART.

Incarceration  ART distribution and adherence strategies and outcomes in LMICs are needed.  Better studies needed to determine if DAART is the optimal strategy within prisons and duration needed post-release.  Studies examining if treatment for underlying SUDs, MHDs and/or provision of housing on improvements in post- release outcomes.  Studies of medication-assisted therapies post-release.  Structural interventions on reducing incarceration itself and police harassment on detention are needed. WEPE330: Springer, Retention on BPN increased adherence and MVS among released HIV+ prisoners after 6 months. WEPE617: Kang-Dufour, 2-month outcomes of Peer Navigation after jail release showed decreased drug use. WEPE330: Springer, Retention on BPN increased adherence and MVS among released HIV+ prisoners after 6 months. WEPE617: Kang-Dufour, 2-month outcomes of Peer Navigation after jail release showed decreased drug use.

Homeless and Marginally Housed  Often experience multiple overlapping medical, psychiatric and social co-morbidities.  Homelessness often disrupts daily routines, including taking medications, and can make medication storage difficult.  Case management is recommended to mitigate multiple adherence barriers (IIIB), based on 1observational study.  Pillbox organizers are recommended (IIA), based on one large observational study associated with improved adherence and viral suppression among homeless people with multiple adherence barriers.

Homeless and Marginally Housed  Future Research  Better strategies to assess adherence and detect lapses to individually tailor support to functional adherence challenges.  Studies on the effectiveness of DAART, adherence tools, ICM and medical outreach for the homeless and marginally housed.