Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV

Dyke, Russell B. Van; Patel, Kunjal; Kagan, Ron M.; Karalius, Brad; Traite, Shirley; Meyer, William A.; Tassiopoulos, Katherine; Seage, George R.; Seybolt, Lorna M.; Burchett, Sandra; Hazra, Rohan; Lurie, Robert H.; Yogev, Ram; Sanders, Margaret Ann; Malee, Kathleen; Shearer, William T.; Paul, Mary E.; Cooper, Norma; Harris, Lynnette; Purswani, Murli; Baig, Mahboobullah; Cintron, Anna; Puga, Ana María Méndez; Navarro, Sandra; Garvie, Patricia A.; Blood, James; Kammerer, Betsy; Wiznia, Andrew; Burey, Marlene; Nozyce, Molly; Dieudonne, Arry; Bettica, Linda; Adubato, Susan; Chen, Janet; Bulkley, Maria Garcia; Ivey, Latreaca; Grant, Mitzie; Knapp, Katherine M.; Allison, Kim; Wilkins, Megan L.; Acevedo-Flores, Midnela; Rios, Heida; Olivera, Vivian; Silio, Margarita; Jones, Medea; Sirois, Patricia A.; Spector, Stephen A.; Norris, Kim; Nichols, Sharon L.; McFarland, Elizabeth J.; Katai, Alisa; Dunn, Jennifer; Paul, Suzanne; Scott, Gwendolyn B.; Bryan, Patricia; Willen, Elizabeth J.

doi:10.1093/cid/ciw213

Cited by 23 publications

(22 citation statements)

References 12 publications

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“…Older PHIVY had greater early exposure to mono- or dual-regimens compared to younger PHIVY; the lack of viral suppression among those PHIVY prescribed cART is more likely related to poor medication adherence or acceptance, as resistance to newer ARVs, such as integrase inhibitors, is uncommon. 35 Older youth also spent more time with CD4 counts <200/μL. Data from PHIVY aged 6–17 suggest that having CD4 counts <200/μL is associated with lower quality of life, psychiatric symptoms, and poor cognitive, academic, and social functioning, and data from adults suggest high risks of OIs and death.…”

Section: Discussionmentioning

confidence: 98%

“…Complications potentially related to long-term antiretroviral therapy, including anemia, pancreatitis, hepatitis, peripheral neuropathy, and metabolic and bone abnormalities, were documented infrequently, likely reflecting use of less toxic ARVs over time. 35,51 …”

Section: Discussionmentioning

confidence: 99%

“…53–61 The 35% of person-time spent with VL ≥400 copies/mL in our study raises critical concerns not only for individual patient outcomes, but also for the HIV epidemic among US youth. 30,35,62 Youth who are viremic despite being engaged in care are more likely to have resistant virus and to report lower condom use than non-viremic youth, and thus are at risk of secondary horizontal or vertical transmission. 63–65 …”

Section: Discussionmentioning

confidence: 99%

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Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus–Infected Youth

et al. 2017

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IMPORTANCE As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. OBJECTIVE To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status. DESIGN, SETTING, AND PARTICIPANTS Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (<200, 200-499, and Ն500/μL), and a combined measure of VL and ARV status (VL <400 or Ն400 copies/mL; ARV therapy or no ARV therapy). A total of 1562 participants in the PHACS Adolescent Master Protocol and IMPAACT P1074 were eligible, and 1446 PHIVY from 41 ambulatory sites in the 12 US states, including Puerto Rico were enrolled. The dates of analysis were March 2015 through January 2017. MAIN OUTCOMES AND MEASURES Clinical event rates stratified by person-time in age, CD4 cell count, and VL and ARV categories. RESULTS A total of 1446 PHIVY participated in the study (mean [SD] age, 14.6 [4.6] years; 759 female [52.5%]; 953 black [65.9%]). During a mean (SD) follow-up of 4.9 (1.3) years, higher incidences of CDC-B events, CDC-C events, and mortality were observed as participants aged. Older PHIVY (aged 13-17 and 18-30 years) spent more time with a VL of 400 copies/mL or more and with a CD4 cell count of less than 200/μL compared with 7-to 12-year-old participants (30% and 44% vs 22% of person-time with a VLՆ400 copies/mL; 5% and 18% vs 2% of person-time with CD4 cell count <200/μL; P < .001 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 cell counts, as expected. The mortality rate among older PHIVY was 6 to 12 times that among the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 cell counts after adjusting for age. CONCLUSIONS AND RELEVANCEOlder PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ARV therapy adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus–Infected Youth

et al. 2017

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“…4 Among PHIV youth in both high-and low-and-middleincome countries, mental health problems are common, and some PHIV youth engage in high-risk behaviors, [4][5][6][7] including substance use, sexual risk-taking, and inconsistent condom use. [8][9][10] ART adherence rates among PHIV adolescents are also lower than among adults and younger children living with HIV, 11 increasing risk to individual health and of HIV transmission to others.…”

Section: Introductionmentioning

confidence: 99%

CHAMP+ Thailand: Pilot Randomized Control Trial of a Family-Based Psychosocial Intervention for Perinatally HIV-Infected Early Adolescents

Nestadt

Saisaengjan

McKay

et al. 2019

AIDS Patient Care and STDs

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Within Asia, HIV prevalence is highest in Thailand, including thousands of children and adolescents. Care for children born with HIV [perinatal transmission of HIV (PHIV)] will need to focus on adolescents for the foreseeable future. Thai PHIV adolescents experience significant mental health and psychosocial challenges, including treatment adherence. Yet, few, if any, comprehensive interventions for them exist. CHAMP+, an evidence-based intervention adapted for Thailand, was evaluated with a pilot randomized control trial at four HIV clinics. Eighty-eight dyads of 9-to 14-year-old PHIV young adolescents/caregivers were randomized to CHAMP+ or standard of care (SOC). Eleven cartoon-based sessions were delivered over 6 months. Participants completed baseline, 6-month (postintervention), and 9-month surveys, measuring youth outcomes (e.g., mental health and adherence), contextual factors (e.g., demographics and caregiver factors), and selfand social-regulation factors (e.g., HIV knowledge and youth-caregiver communication). Multi-level modeling to account for clustering within individuals was used to assess longitudinal changes within and between groups. All families randomized to CHAMP+ completed the intervention. Although the study was not statistically powered to detect differences in treatment effects, the CHAMP+ group significantly improved at 6 months in youth mental health and adherence, HIV knowledge, youth-caregiver communication, internalized stigma, and HIV-related social support, with most improvements sustained at 9 months and significantly better improvements than the SOC group on a number of outcomes. High levels of baseline viral suppression highlight the importance of reaching these young PHIV adolescents at a period of lower risk before adherence and other challenges emerge. Designed to be delivered with limited cost/resources, CHAMP+ Thailand holds scale-up potential.

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“…Various studies from the USA and sub-Saharan Africa have found that PHIV+ youth, similar to same age peers, are engaging in substance use and sexual behaviors, and use condoms inconsistently (Bauermeister, Elkington, Robbins, Kang, & Mellins, 2012 ; Birungi, Mugisha, Obare, & Nyombi, 2009 ; Mellins et al., 2011 ; Tassiopoulos et al., 2013 ). Furthermore, PHIV+ adolescents and young adults have lower levels of medication adherence and higher levels of drug resistance relative to younger children and adults (Van Dyke et al., 2016 ), increasing risk of adverse medical outcomes and transmission of HIV to others.…”

mentioning

confidence: 99%

Resilience in perinatal HIV+ adolescents in South Africa

et al. 2016

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Increasing numbers of perinatally HIV (PHIV+)-infected youth are surviving into adulthood with better access to treatment. However, few studies examine positive outcomes in the face of adversity (resilience) for PHIV+ youth. Social Action Theory (SAT) provided the theoretical framework for this study of PHIV + youth in South Africa (SA), allowing examination of contextual, social, and self-regulatory factors that influence behavioral health. Data were from youth and caregiver baseline interviews, simply pooled from a pilot (N=66) and larger (n=111) randomized control trial (RCT) of the VUKA Family program. For this analysis, outcomes included emotional and behavioral functioning (total difficulties), and prosocial behaviors. Potential SAT correlates included socio-demographics; caregiver health and mental health; parent-child relationship factors; stigma, and child coping, support; and self-esteem. Regression analyses adjusted for age, gender, and study revealed significant associations at the contextual, social, and self-regulation level. Lower total child difficulties scores were associated with lower caregiver depression (β = 3.906,p < .001), less caregiver-reported communication about difficult issues (β = 1.882, p = .009) and higher youth self-esteem (β = -0.119, p = .020). Greater prosocial behaviors were associated with greater caregiver-reported communication (β = 0.722, p = .020) and child use of wishful thinking for coping (β = 5.532, p = .009). Less youth depression was associated with higher caregiver education (β =−0.399, p = .010), greater caregiver supervision (β = −1.261, p = .012), more social support seeking (β = −0.453, p = .002), higher youth self-esteem (β = −0.067, p < .001), lower internalized stigma (β = 0.608, p = .040), and child use of resignation for coping (β = 1.152, p = .041). Our data support evidence-based family interventions that also promote youth self-regulation skills to enhance the health and mental health of PHIV+ youth.

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Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV

Cited by 23 publications

References 12 publications

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus–Infected Youth

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus–Infected Youth

CHAMP+ Thailand: Pilot Randomized Control Trial of a Family-Based Psychosocial Intervention for Perinatally HIV-Infected Early Adolescents

Resilience in perinatal HIV+ adolescents in South Africa

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