R. J. Simonds

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV

Objectives:To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. Design:Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. Methods:The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. Results:The overall transmission risk was 18% [95% confidence interval (CI), 16–21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6–2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4–2.2), maternal CD4+ lymphocyte count < 500 × 106cells/l (RR, 1.7; 95% CI, 1.3–2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3–2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4–0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. Conclusions:Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Distinct Risk Factors for Intrauterine and Intrapartum Human Immunodeficiency Virus Transmission and Consequences for Disease Progression in Infected Children

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Prophylaxis against Pneumocystis carinii Pneumonia among Children with Perinatally Acquired Human Immunodeficiency Virus Infection in the United States

Background Pneumocystis carinii pneumonia (PCP) remains a common and often fatal opportunistic infection among children infected with the human immunodeficiency virus (HIV). HIV-infected infants between three and six months of age are particularly vulnerable. Current guidelines recommend prophylaxis in children from birth to 11 months old who have CD4+ counts below 1500 cells per cubic millimeter. Methods We used national surveillance data to estimate the annual incidence of PCP among children less than one year old. We reviewed the medical records of 300 children given a diagnosis of PCP between January 1991 and June 1993 to determine why treatment according to the 1991 guidelines for prophylaxis against PCP either was not given or failed to prevent the disease. Results In our study the incidence of PCP in the first year of life among infants born to HIV-infected mothers changed little between 1989 and 1992. Among 7080 children born to HIV-infected mothers in 1992, PCP developed in 2.4 percent. Of 300 ch...

Sensitivity and specificity of a qualitative RNA detection assay to diagnose HIV infection in young infants. Perinatal AIDS Collaborative Transmission Study.

OBJECTIVE To evaluate the sensitivity and specificity of an RNA detection assay for diagnosing perinatal HIV infection. METHODS Plasma and serum specimens taken during the first 3 months of life from HIV-infected and uninfected children enrolled in a cohort study were assayed for HIV RNA using the qualitative nucleic acid sequence-based amplification (NASBA) kit. Sensitivity, specificity, and predictive values were calculated. NASBA results from infected children were compared with DNA PCR results from the same blood samples. Autoantibody patterns of suspected false-positive specimens were compared with those of subsequent specimens from the same child to exclude specimen labelling errors. RESULTS Amongst 131 specimens from 105 HIV-infected children, the sensitivity of the qualitative NASBA assay was 13 out of 34 [38%; 95% confidence interval (CI), 22-56] at < 7 days, 56 out of 58 (97%; 95% CI, 88-100) at 7-41 days, and 37 out of 39 (95%; 95% CI, 83-99) at 42-93 days of life. Of 252 specimens from 206 uninfected children, six tested positive and one tested indeterminate by NASBA. Four of these positive specimens had discordant autoantibody patterns suggesting mislabelling; excluding these, the test specificity was 245 out of 248 (99%; 95% CI, 97-100). Amongst 128 paired specimens from infected children, NASBA results were more often positive than those from DNA PCR (103 versus 92; P=0.01). Amongst infants with specimens drawn in the first week of life, the proportion born after > 4 h of membrane rupture was greater amongst those testing negative (81%) than those testing positive (46%; P=0.05). CONCLUSIONS The qualitative NASBA RNA assay is highly specific and more sensitive than DNA PCR. Qualitative RNA assays may be useful for diagnosing and excluding perinatal HIV infection in children after the first week of life for such purposes as initiating antiretroviral therapy and other treatment, resolving parental uncertainty, determining timing of transmission, and providing endpoints for intervention trials.

Maternal characteristics associated with antenatal, intrapartum, and neonatal zidovudine use in four U.S. cities, 1994-1998

Objectives: To evaluate implementation of 1994 United States Public Health Service guidelines for zidovudine (ZDV) use in HIV‐infected women and their newborns by describing the prevalence of use of perinatal ZDV and other antiretrovirals and by investigating determinants of not receiving perinatal ZDV. Design/Methods: The Perinatal AIDS Collaborative Transmission Study is a prospective cohort study designed to collect information related to mother‐to‐child HIV transmission that was conducted in New York City (NY), Newark (NJ), Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to infants born between July 1994 and June 1998. Results: Utilization rates for antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4‐year period. Use of combination antiretrovirals increased from fewer than 2% of women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother‐infant pairs with the following characteristics were less likely to have received a complete 3‐part ZDV regimen: older maternal age, CD4 count >500 cells/μl, preterm birth, cocaine or heroin use during pregnancy, positive newborn drug screen test result, and smoking or alcohol use during pregnancy. By multivariate logistic regression adjusted for hospital and year of birth, cocaine or heroin use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6‐3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2‐0.8; comparing <200 with >500 cells/&mgr;l), and preterm birth (OR, 1.6; 95% CI, 1.1‐2.5) remained independently associated with not receiving the complete ZDV regimen. Conclusions: ZDV use by pregnant HIV‐infected women and their infants has increased dramatically since publication of the 1994 guidelines. Nevertheless, women who abuse substances, give birth preterm, or have less advanced immunosuppression, were at substantial risk of not receiving the complete ZDV regimen.