Browsing by Author "Abzug, Mark J."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth
    (Lippincott, Williams & Wilkins, 2017-06-01) Bellavia, Andrea; Williams, Paige L.; DiMeglio, Linda A.; Hazra, Rohan; Abzug, Mark J.; Patel, Kunjal; Jacobson, Denise L.; Van Dyke, Russell B.; Geffner, Mitchell E.; International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P219/219C Study; Pediatric HIV/AIDS Cohort Study (PHACS); Pediatrics, School of Medicine
    OBJECTIVE: To evaluate the association between HIV infection and sexual maturation, and mediation of this association by HIV effects on growth. DESIGN: Pooled data were analyzed from two longitudinal cohort studies, the International Maternal Pediatric Adolescent AIDS Clinical Trials P219/219C Study (1993-2007) and the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (2007-2015), including perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youths. METHODS: We evaluated age at sexual maturity among 2539 PHIV and PHEU adolescents based on annual physician-assessed pubertal staging measures. Interval-censored regression models were used to evaluate associations of HIV infection with age at maturity. Mediation analyses accounting for height and BMI Z-scores at specific ages were used to estimate direct and indirect effects of HIV infection on age at sexual maturity. RESULTS: Mean ages at sexual maturity for PHIV girls (n = 1032) were 15.5 years for both female breast and pubic hair and 15.9 and 15.8 years for PHIV boys (n = 1054) for genitalia and pubic hair, respectively. PHIV youths matured approximately 6 months later on average than PHEU (n = 221 girls and 232 boys), and this difference persisted after adjustment for race/ethnicity and birth cohort. BMI and height Z-scores mediated the association between HIV infection and later maturation in girls, accounting for up to 74% of the total HIV effect. Only height Z-scores mediated the effect of HIV on male age at maturity, accounting for up to 98% of the HIV effect. CONCLUSION: PHIV youths attain sexual maturity later on average than PHEU youths. Much of this difference may be attributable to deficient growth, suggesting directions for future interventions.
  • Thumbnail Image
    Item
    Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis
    (Wiley, 2022) Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration; Jesson, Julie; Crichton, Siobhan; Quartagno, Matteo; Yotebieng, Marcel; Abrams, Elaine J.; Chokephaibulkit, Kulkanya; Le Coeur, Sophie; Aké-Assi, Marie-Hélène; Patel, Kunjal; Pinto, Jorge; Paul, Mary; Vreeman, Rachel; Davies, Mary-Ann; Ben-Farhat, Jihane; Van Dyke, Russell; Judd, Ali; Mofenson, Lynne; Vicari, Marissa; Seage, George, III.; Bekker, Linda-Gail; Essajee, Shaffiq; Gibb, Diana; Penazzato, Martina; Collins, Intira Jeannie; Wools-Kaloustian, Kara; Slogrove, Amy; Powis, Kate; Williams, Paige; Matshaba, Mogomotsi; Thahane, Lineo; Nyasulu, Phoebe; Lukhele, Bhekumusa; Mwita, Lumumba; Kekitiinwa-Rukyalekere, Adeodata; Wanless, Sebastian; Goetghebuer, Tessa; Thorne, Claire; Warszawski, Josiane; Galli, Luisa; van Rossum, Annemarie M.C.; Giaquinto, Carlo; Marczynska, Magdalena; Marques, Laura; Prata, Filipa; Ene, Luminita; Okhonskaya, Lyuba; Navarro, Marisa; Frick, Antoinette; Naver, Lars; Kahlert, Christian; Volokha, Alla; Chappell, Elizabeth; Pape, Jean William; Rouzier, Vanessa; Marcelin, Adias; Succi, Regina; Sohn, Annette H.; Kariminia, Azar; Edmonds, Andrew; Lelo, Patricia; Lyamuya, Rita; Ogalo, Edith Apondi; Odhiambo, Francesca Akoth; Haas, Andreas D.; Bolton, Carolyn; Muhairwe, Josephine; Tweya, Hannock; Sylla, Mariam; D'Almeida, Marceline; Renner, Lorna; Abzug, Mark J.; Oleske, James; Purswani, Murli; Teasdale, Chloe; Nuwagaba-Biribonwoha, Harriet; Goodall, Ruth; Leroy, Valériane; Medicine, School of Medicine
    Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. Results: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.
  • Thumbnail Image
    Item
    Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration
    (Elsevier, 2019-02) Collins, Intira J.; Wools-Kaloustian, Kara; Goodall, Ruth; Smith, Colette; Abrams, Elaine J.; Ben-Farhat, Jihane; Balkan, Suna; Davies, Mary-Ann; Edmonds, Andrew; Leroy, Valériane; Nuwagaba-Biribonwoha, Harriet; Patel, Kunjal; Paul, Mary E.; Pinto, Jorge; Conejo, Pablo Rojo; Sohn, Annette; Van Dyke, Russell; Vreeman, Rachel; Maxwell, Nicky; Timmerman, Venessa; Duff, Charlotte; Judd, Ali; Seage, George, III; Williams, Paige; Gibb, Diana M.; Bekker, Linda-Gail; Mofenson, Lynne; Vicari, Marissa; Essajee, Shaffiq; Mohapi, Edith Q.; Kazembe, Peter N.; Hlatshwayo, Makhosazana; Lumumba, Mwita; Kekitiinwa-Rukyalekere, Adeodata; Wanless, Sebastian; Matshaba, Mogomotsi S.; Goetghebuer, Tessa; Thorne, Claire; Warszawski, Josiane; Galli, Luisa; Geelen, Sybil; Giaquinto, Carlo; Marczynska, Magdalena; Marques, Laura; Prata, Filipa; Ene, Luminita; Okhonskaia, Liubov; Noguera-Julian, Antoni; Naver, Lars; Rudin, Christoph; Jourdain, Gonzague; Volokha, Alla; Rouzier, Vanessa; Succi, Regina; Chokephaibulkit, Kulkanya; Kariminia, Azar; Yotebieng, Marcel; Lelo, Patricia; Lyamuya, Rita; Marete, Irene; Oyaro, Patrick; Boulle, Andrew; Malisita, Kennedy; Fatti, Geoffrey; Haas, Andreas D.; Desmonde, Sophie; Dicko, Fatoumata; Abzug, Mark J.; Levin, Myron; Oleske, James; Chernoff, Miriam; Traite, Shirley; Purswani, Murli; Teasdale, Chloe; Chadwick, Ellen; Pediatrics, School of Medicine
    Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22-3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations.