Association of risk of viremia, immunosuppression, serious clinical events, and mortality with increasing age in perinatally human immunodeficiency virus-infected youth

Anne M. Neilan, Brad Karalius, Kunjal Patel, Russell B. Van Dyke, Mark J. Abzug, Allison L. Agwu, Paige L. Williams, Murli Purswani, Deborah Kacanek, James M. Oleske, Sandra K. Burchett, Andrew Wiznia, Miriam Chernoff, George R. Seage, Andrea L. Ciaranello

Research output: Research - peer-reviewArticle

Abstract

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 ≥500/μL), and a combined measure of VL and ARV status (VL <400 or ≥400 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 VL≥400 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 RELEVANCE Older 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.

LanguageEnglish (US)
Pages450-460
Number of pages11
JournalJAMA Pediatrics
Volume171
Issue number5
DOIs
StatePublished - May 1 2017

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Viremia
Immunosuppression
HIV
Mortality
Centers for Disease Control and Prevention (U.S.)
CD4 Lymphocyte Count
Viral Load
Acquired Immunodeficiency Syndrome
Pediatrics
Therapeutics
Cohort Studies
Mothers
Clinical Trials
Incidence
Puerto Rico
Opportunistic Infections
Sexually Transmitted Diseases
Bacterial Infections
Multicenter Studies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Association of risk of viremia, immunosuppression, serious clinical events, and mortality with increasing age in perinatally human immunodeficiency virus-infected youth. / Neilan, Anne M.; Karalius, Brad; Patel, Kunjal; Van Dyke, Russell B.; Abzug, Mark J.; Agwu, Allison L.; Williams, Paige L.; Purswani, Murli; Kacanek, Deborah; Oleske, James M.; Burchett, Sandra K.; Wiznia, Andrew; Chernoff, Miriam; Seage, George R.; Ciaranello, Andrea L.

In: JAMA Pediatrics, Vol. 171, No. 5, 01.05.2017, p. 450-460.

Research output: Research - peer-reviewArticle

Neilan, AM, Karalius, B, Patel, K, Van Dyke, RB, Abzug, MJ, Agwu, AL, Williams, PL, Purswani, M, Kacanek, D, Oleske, JM, Burchett, SK, Wiznia, A, Chernoff, M, Seage, GR & Ciaranello, AL 2017, 'Association of risk of viremia, immunosuppression, serious clinical events, and mortality with increasing age in perinatally human immunodeficiency virus-infected youth' JAMA Pediatrics, vol 171, no. 5, pp. 450-460. DOI: 10.1001/jamapediatrics.2017.0141
Neilan, Anne M. ; Karalius, Brad ; Patel, Kunjal ; Van Dyke, Russell B. ; Abzug, Mark J. ; Agwu, Allison L. ; Williams, Paige L. ; Purswani, Murli ; Kacanek, Deborah ; Oleske, James M. ; Burchett, Sandra K. ; Wiznia, Andrew ; Chernoff, Miriam ; Seage, George R. ; Ciaranello, Andrea L./ Association of risk of viremia, immunosuppression, serious clinical events, and mortality with increasing age in perinatally human immunodeficiency virus-infected youth. In: JAMA Pediatrics. 2017 ; Vol. 171, No. 5. pp. 450-460
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author = "Neilan, {Anne M.} and Brad Karalius and Kunjal Patel and {Van Dyke}, {Russell B.} and Abzug, {Mark J.} and Agwu, {Allison L.} and Williams, {Paige L.} and Murli Purswani and Deborah Kacanek and Oleske, {James M.} and Burchett, {Sandra K.} and Andrew Wiznia and Miriam Chernoff and Seage, {George R.} and Ciaranello, {Andrea L.}",
year = "2017",
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doi = "10.1001/jamapediatrics.2017.0141",
volume = "171",
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TY - JOUR

T1 - Association of risk of viremia, immunosuppression, serious clinical events, and mortality with increasing age in perinatally human immunodeficiency virus-infected youth

AU - Neilan,Anne M.

AU - Karalius,Brad

AU - Patel,Kunjal

AU - Van Dyke,Russell B.

AU - Abzug,Mark J.

AU - Agwu,Allison L.

AU - Williams,Paige L.

AU - Purswani,Murli

AU - Kacanek,Deborah

AU - Oleske,James M.

AU - Burchett,Sandra K.

AU - Wiznia,Andrew

AU - Chernoff,Miriam

AU - Seage,George R.

AU - Ciaranello,Andrea L.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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 ≥500/μL), and a combined measure of VL and ARV status (VL <400 or ≥400 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 VL≥400 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 RELEVANCE Older 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.

AB - 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 ≥500/μL), and a combined measure of VL and ARV status (VL <400 or ≥400 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 VL≥400 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 RELEVANCE Older 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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