749
Effect of ART Regimens on Selected Hematologic and Hepatic Parameters of HIV-1-uninfected African Infants
Taha Taha*1, G Kafulafula2, Q Li1, D Hoover3, M Thigpen4, N Kumwenda1, L Mipando2, M Fowler5, and L Mofenson6
1Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; 2Johns Hopkins Univ Coll of Med Res Project, Blatyre, Malawi; 3Rutgers Univ, Piscataway, NJ, US; 4Natl Ctr for HIV, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA, US; 5Makerere Univ-Johns Hopkins Univ Res Collaboration, Kampala, Uganda; and 6Natl Inst of Child Hlth and Human Devt, NIH, Rockville, MD, US
Background: Multiple infant ART regimens to prevent breast-milk HIV
transmission are under evaluation. Most infants exposed to these ART will not
become infected with HIV; thus safety monitoring during ART exposure is
critical, particularly in resource-limited settings where co-morbid illnesses
may be more common. We determined the longitudinal prevalence of anemia,
decreased absolute neutrophil count (ANC), and increased alanine
aminotransferase (ALT) among exposed, HIV-uninfected infants enrolled in a randomized
trial of infant ART prophylaxis to prevent postnatal transmission in Blantyre, Malawi.
Methods: Infants HIV-uninfected at birth were randomly
assigned to 3 regimens: A) single-dose nevirapine
(sd-NVP) + twice-daily zidovudine (ZDV) for 1 week; B) followed by NVP daily to
age 14 weeks; or C) followed by NVP+ZDV daily to age 14 weeks. Infant blood
samples were collected at birth and 1, 6, 9, and 14 weks and 6, 9, 12, 15, 18,
and 24 months. At these visits complete blood count and ALT were measured using
a hematology (Coulter) and chemistry analyzer. Infant HIV status was determined
by DNA polymerase chain reaction (PCR). We determined age-specific anemia
(hemoglobin <10 g/dL) and toxicity grade levels of ANC (103/µL)
and ALT (IU/L) based on the DAIDS Toxicity Table (grades 0 [normal], 1 [mild],
2 [moderate], 3 [severe], 4 [life-threatening]). Data are presented on the
first 600 infants to age 6 months.
Results: The prevalence of anemia was very low (<2%)
to age 3 weeks. At age 6 and 9 weeks the prevalence of anemia was significantly
higher in B and C (6 weeks: 6.8% in A,
14.4% in B, 12.3% in C [p = 0.02]; 9
weeks: 13.0% in A, 27.5% in B, 27.0% in
C [p <0.001]). Hemoglobin levels
recovered thereafter showed no differences noted by study arm and no long-term
sequelae resulting. ANC grades 0 to 4 were not significantly different by study
arm for infants <3 weeks or ≥6 weeks. At age 3 weeks grade 2 toxicity
was significantly higher in C (3.5% in A, 3.8% in B, and 11.6% in C; p <0.001). ALT levels were mostly (94
to 99%) within normal range from birth to 6 months in all arms; grade 1
toxicity from 1 week to 6 months ranged from 0.9% to 2.7%; only 1 case of grade
2 ALT was detected at age 6 months in C. There were no significant differences
in ALT between study arms at any age.
Conclusions: These data are reassuring and suggest that infant
exposure to ART for an extended period of 14 weeks does not increase safety
concerns in African infants.
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