Osteonecrosis of the hip (Legg-Calvé-Perthes disease) in human immunodeficiency virus-infected children.
OBJECTIVE
Osteonecrosis of the hip has been reported in human immunodeficiency virus (HIV)-infected adults; whether this is related to HIV infection or its treatment is unknown. There has been 1 report of osteonecrosis among HIV-infected children. Specifically, avascular necrosis of the hip consistent with Legg-Calvé-Perthes disease (LCPD) was reported in 3 HIV-infected children with AIDS from Spain in 1992. We evaluated the prevalence and incidence of LCPD, the pediatric equivalent of adult osteonecrosis of the hip, in HIV-infected children participating in a prospective cohort study of long-term outcomes in HIV-infected and HIV-exposed children-Pediatric AIDS Clinical Trials Group (PACTG) protocol 219.


METHODS
PACTG 219 enrolled 2014 HIV-infected and 849 HIV-exposed, uninfected children between April 1993 and September 2000. Children had periodic examinations with collection of clinical and laboratory data. The database was reviewed for reports of LCPD and other bone disorders. A prevalent case was defined as LCPD diagnosis preceding PACTG 219 enrollment and an incident case had to have occurred between enrollment and September 2000. A case-control study (matching on age, gender, and race/ethnicity, which are known to be associated with risk of LCPD and HIV infection status) was performed to investigate factors possibly associated with LCPD.


RESULTS
Six cases of LCPD (4 prevalent cases reported at study entry; 2 diagnosed during 5837 person-years of follow-up) were observed; LCPD was seen only in children with perinatal HIV infection. LCPD prevalence was 199 per 100 000 compared with an estimated general pediatric population prevalence of 23 per 100 000. Based on age-adjusted general population rates, the expected number of prevalent cases at PACTG 219 study entry would have been 0.44; the age-adjusted LCPD prevalence rate ratio was 9.0 (95% confidence interval [CI]: 8.3-9.7) for HIV-infected children compared with the general population. LCPD incidence was 34 per 100 000 person-years (95% CI: 0.42-124) compared with the estimated general population incidence of 6 per 100 000 person-years (95% CI: 5-7). Based on age-adjusted general population rates, the expected incidence of LCPD in PACTG 219 would have been 0.42; the age-adjusted relative risk of LCPD in HIV-infected PACTG 219 children was 4.8 (95% CI: 0.56-10.4). No cases were observed in uninfected children during 1919 person-years of follow-up on PACTG 219; the age-adjusted expected number of cases was 0.09. Median onset age was 7 years; 67% were of Hispanic or black race/ethnicity and 33% were female. Four of the 6 LCPD cases had received antiretroviral therapy before diagnosis; treatment was primarily with nucleoside reverse transcriptase inhibitors, and 2 had received protease inhibitors. Three of the LCPD cases had corticosteroid exposure before the diagnosis, but only 1 child had systemic exposure and the remaining 2 had topical exposure exclusively. In the case-control study, antiretroviral and corticosteroid therapy, CD4 cell percentage, birth weight, height for age and gender percentile, and triglyceride levels were not significantly associated with LCPD. However, the case-control study had limited power to evaluate possible associations.


CONCLUSIONS
Similar to HIV-infected adults, children with perinatal HIV infection have an increased risk for osteonecrosis of the hip, and clinicians should be alert to this diagnosis when HIV-infected children present with limp or hip pain. Whether LCPD is attributable to HIV infection itself, HIV-associated complications that could predispose to hypercoagulopathy, HIV-related therapies, or to the growth abnormalities in HIV-infected children is unknown and deserves additional evaluation.
Gaughan
Denise M
DM
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA.
Mofenson
Lynne M
LM
Hughes
Michael D
MD
Seage
George R
GR
Ciupak
Gregory L
GL
Oleske
James M
JM
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007873:Legg-Calve-Perthes Disease / Q000453:epidemiology*; D008297:Male; D015995:Prevalence; D011446:Prospective Studies
D000305:Adrenal Cortex Hormones; D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors