High mortality in HIV-infected children diagnosed in hospital underscores need for faster diagnostic turnaround time in prevention of mother-to-child transmission of HIV (PMTCT) programs

Abstract

Background: Despite expanded programs for prevention of mother-to-child HIV transmission (PMTCT), HIV-infected infants may not be diagnosed until they are ill. Comparing HIV prevalence and outcomes in infants diagnosed in PMTCT programs to those in hospital settings may improve pediatric HIV diagnosis strategies.

Methods: HIV-exposed infants <12 months old were recruited from 9 PMTCT sites in public maternal child health (MCH) clinics or from an inpatient setting in Nairobi, Kenya and tested for HIV using HIV DNA assays. A subset of HIV-infected infants <4.5 months of age was enrolled in a research study and followed for 2 years. HIV prevalence, number needed to test, infant age at testing, and turnaround time for tests were compared between PMTCT programs and hospital sites. Among the enrolled cohort, baseline characteristics, survival, and timing of antiretroviral therapy (ART) initiation were compared between infants diagnosed in PMTCT programs versus hospital.

Results: Among 1,923 HIV-exposed infants, HIV prevalence was higher among infants tested in hospital than PMTCT early infant diagnosis (EID) sites (41% vs. 11%, p < 0.001); the number of HIV-exposed infants needed to test to diagnose one infection was 2.4 in the hospital vs. 9.1 in PMTCT. Receipt of HIV test results was faster among hospitalized infants (7 vs. 25 days, p < 0.001). Infants diagnosed in hospital were older at the time of testing than PMTCT diagnosed infants (5.0 vs. 1.6 months, respectively, p < 0.001). In the subset of 99 HIV-infected infants <4.5 months old followed longitudinally, hospital-diagnosed infants did not differ from PMTCT-diagnosed infants in time to ART initiation; however, hospital-diagnosed infants were >3 times as likely to die (HR = 3.1, 95% CI = 1.3-7.6).

Conclusions: Among HIV-exposed infants, hospital-based testing was more likely to detect an HIV-infected infant than PMTCT testing. Because young symptomatic infants diagnosed with HIV during hospitalization have very high mortality, every effort should be made to diagnose HIV infections before symptom onset. Systems to expedite turnaround time at PMTCT EID sites and to routinize inpatient pediatric HIV testing are necessary to improve pediatric HIV outcomes.

Figure 1

Testing yield, infant ages, and turnaround time for infant HIV testing at hospital and PMTCT. Infants were tested for HIV in PMTCT clinics and pediatric hospital wards as part of the parent clinical trial recruitment procedures. This figure shows the testing steps, test turnaround time, and infant age at testing among the two recruitment clinic types. Among HIV-exposed infants, HIV infection was more prevalent in hospital wards than in PMTCT clinics, infant age at testing was higher in hospital wards than in PMTCT clinics, and test turnaround time was shorter in hospital wards than in PMTCT clinics.

Figure 2

Comparison of survival overall and after ART initiation of HIV-infected infants, by place of diagnosis (hospital vs. Prevention of Mother-to-Child Transmission [PMTCT] site): Kaplan-Meier Survival Analysis. Infants enrolled in the parent clinical trial were followed prospectively; their mortality is compared in this graphic using Kaplan-Meier curves. Panel A: Overall mortality was significantly higher among the hospital-diagnosed infants than the PMTCT-diagnosed infants. Panel B: Differences in mortality persisted after ART initiation, with a trend towards significance.