Improving Long-term Outcomes in Perinatally Infected Youth With HIV

Interventions aimed at improving patient adherence to antiretroviral therapy and optimizing care are key to improving long-term outcomes in perinatally HIV-infected youth, according to research published in JAMA Pediatrics.¹

Anne M. Neilan, MD, MPH, from the division of infectious diseases at Massachusetts General Hospital, and colleagues used data from 2 multicenter cohort studies — the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 — to identify clinical event rates in youth who were perinatally infected with HIV as they aged.

Primary study outcomes included mortality and first occurrence of either Centers for Disease Control and Prevention (CDC) stage C (CDC-C) and World Health Organization (WHO) stage 4 (WHO-4) events or CDC stage B (CDC-B) and WHO stage 3 (WHO-3) events. Secondary study outcomes included bacterial pneumonia; presumptive pelvic inflammatory disease (PID); and gastrointestinal, cardiac, or metabolic conditions, among others.

In total, 1446 perinatally HIV-infected youth participated (mean age: 14.6 years; 52.5% female; 65.9% black). Throughout the study period, 29 deaths were recorded (0.4 per 100 person-years); 23 total deaths occurred with CD4 cell counts <200/μL (3.5 per 100 person-years) while 24 total deaths occurred with a viral load of 400 copies/mL or higher. Additional mortality rates were 0.9 and 1.6 per 100 person-years, respectively, for nonsuppressive combination antiretroviral therapy and no antiretroviral drug use (P <.001 for trend). Mortality rates were 5.6-fold higher in patients between 15 and 19 years of age (95% CI, 2.8-11.1) and 12.3-fold higher in patients between 20 and 29 years of age (95% CI, 8.0-18.9).

Dr Neilan and colleagues recorded 86 CDC-C and WHO-4 events (1.4 per 100 person-years); higher rates of these events correlated with lower CD4 cell counts: 9.6 per 100 person-years for <200/μL, 1.0 per 100 person-years for 200-499/μL, and 0.4 per 100 person years for ≥500/μL; P <.001 for trend. Among the 20% of events occurring with CD4 cell counts lower than 500/μL, 2 were pulmonary tuberculosis and ocular toxoplasmosis; the remaining events were HIV-related kidney or cardiac diseases. Higher rates of CDC-C and WHO-4 events also correlated with higher viral load and older age (both P <.001 for trend).

Nearly 200 CDC-B and WHO-3 events were recorded. Higher rates were correlated with lower CD4 cell counts, higher viral load (both P <.001 for trend), and older age (P =.01 for trend). Higher event rates with lower CD4 cell counts and higher viral loads were also noted for both bacterial pneumonia and serious bacterial infections.

Additional events included high rates of presumptive PID, other sexually transmitted infections (STIs), and pregnancies — all more common with older age and viral loads >400 copies/mL; STIs and pregnancies were also associated with lower CD4 cell counts. Neurodevelopmental and mental health conditions were among the most frequently noted conditions (4.0 per 100 person-years), although no trend was noted based on age, CD4 cell count, viral load, or antiretroviral drug status.

“Serious clinical events…are rare in [perintatally HIV-infected youth] receiving suppressive ART, but viremia, lower CD4 cell counts, and rates of serious clinical events and mortality increase throughout adolescence and young adulthood,” the researchers concluded. “Interventions to improve ART adherence and optimize models of care…are urgently needed to improve long-term outcomes among this increasing and vulnerable population.”

Study Limitations

• Collection protocols for data in the cohorts may have affected estimates of incidence rates.
• Events prior to baseline were excluded, which may have resulted in overestimation of first event rates

Reference

Neilan AM, Karalius B, Patel K, et al; for the Pediatric HIV/AIDS Cohort Study and the International Maternal Adolescent and Pediatric AIDS Clinical Trials Network. Association of risk of viremia, immunosuppression, serious clinical events, and mortality with increasing age in perinatally human immunodeficiency virus-infected youth [published online March 27, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.0141