Mode of delivery and postpartum HIV-1 disease progression: the Women and Infants Transmission Study.

OBJECTIVE: To assess the relationship between mode of delivery and subsequent maternal HIV-1 disease progression. DESIGN AND METHODS: Changes in CD4+ lymphocyte percentage (CD4%) and plasma HIV-1 RNA concentration (HIV RNA), and time to progression to AIDS or death among HIV-1-infected women were compared according to mode of delivery [cesarean section before labor and ruptured membranes (SCS), cesarean section after labor and/or after ruptured membranes (NSCS), and vaginal delivery]. Generalized estimating equations were used to compare changes in adjusted mean CD4% and HIV RNA counts by mode of delivery. Cox proportional hazard models were used to assess differences in time to AIDS or death. RESULTS: In adjusted analyses, there were no clinically important differences in HIV-1 disease progression according to mode of delivery (SCS, n = 183; NSCS, n = 221; vaginal, n = 1087), as assessed by changes in CD4% and HIV RNA during the 18 months following delivery, and by progression to AIDS or death during a mean postpartum follow-up of 2.66 years. CONCLUSIONS: The present results suggest that, among HIV-1-infected women in North America, mode of delivery is not associated with subsequent HIV-1 disease progression.

Changing trends in clinical AIDS presentations and survival among HIV-1-infected women.

OBJECTIVES: To profile trends of clinical AIDS-defining illness (ADI) among a cohort of human immunodeficiency virus (HIV)-infected women over a 12-year period. METHODS: In a prospective evaluation of AIDS clinical presentation in the Women and Infants Transmission Study (WITS), 2255 subjects were enrolled and followed between December 1989 and June 2002 (total, 4993 person-years). Data on clinical AIDS presentation of 140 (6.2%) HIV-seropositive subjects were evaluated across three calendar periods corresponding to the use of different therapy regimens. Incidence rates (per 1000 woman-years) for AIDS and specific ADIs were compared between periods using Poisson regression methods. RESULTS: Incidence rates of AIDS, Mycobacterium tuberculosis, recurrent bacterial pneumonia, herpes simplex disease, esophageal/bronchial candidiasis, wasting syndrome, and neurological diseases have showed significant downward trends. Among women with ADI, the frequency of either esophageal or bronchial candidiasis as initial ADI showed an increasing trend (p(trend) = 0.03), whereas a decrease in proportion of cases with nontuberculosis mycobacterial infection (P(trend) = 0.05) was observed over the same periods. In the multivariate analysis, both the CD4+ lymphocyte count and HIV-1 RNA at the time of diagnosis were independently associated with survival after AIDS. Highly active antiretroviral therapy (HAART) was associated with a 70% reduction in progression to death following AIDS. CONCLUSIONS: Temporal changes in the incidence and clinical presentations in HIV-positive women in our cohort reflect an increased use of HAART that may have a differential effect on reduction in the risk of ADIs. These illnesses, although considerably less frequent in recent years, are still important contributors to morbidity in HIV-positive women.

Maternal neutralizing antibody and transmission of hepatitis C virus to infants.

To determine whether lower levels of hepatitis C virus (HCV)-specific neutralizing antibodies (nAb) are associated with an increased risk of mother-to-child transmission (MTCT) of HCV, HCV nAb titers were assessed in 63 mothers coinfected with HCV and human immunodeficiency virus (HIV) type 1. Of the mothers, 16 transmitted HCV to their infant, but no difference was detected between the ability of maternal plasma from transmitters and nontransmitters to neutralize heterologous HCV pseudoparticles (median nAb titer, 1:125 vs. 1:100; P = .23). In the setting of HIV/HCV coinfection, we found no evidence that HCV nAbs are associated with the prevention of MTCT of HCV.

Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy.

Data from 2543 HIV-infected women were analyzed to correlate antiretroviral therapy (ART) used during pregnancy with maternal and pregnancy outcomes. ART was analyzed according to class of agents used and according to monotherapy versus combination ART containing neither protease inhibitors (PIs) nor nonnucleoside reverse transcriptase inhibitors versus highly active ART. Timing of ART was classified according to early (recorded at or before 25-week gestation study visit) and late (recorded at 32-week gestation or delivery visit) use. Maternal outcomes assessed included hematologic, gastrointestinal, neurologic, renal, and dermatologic complications; gestational diabetes; lactic acidosis; and death. Adverse pregnancy outcomes assessed included hypertensive complications; pre-term labor or rupture of membranes; preterm delivery (PTD); low birth weight; and stillbirth. Logistic regression analyses controlling for multiple covariates revealed ART to be independently associated with few maternal complications: ART use was associated with anemia (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1-2.4), and late use of ART was associated with gestational diabetes (OR = 3.5, 95% CI: 1.2-10.1). Logistic regression analyses revealed an increase in PTD at <37 weeks for 10 women with late use of ART not containing zidovudine (ZDV; OR = 7.9, 95% CI: 1.4-44.6) and a decrease in adverse pregnancy outcomes as follows: late use of ART containing ZDV was associated with decreased risk for stillbirth and PTD at <37 weeks (OR = 0.06, 95% CI: 0.02-0.18; OR = 0.5, 95% CI: 0.3-0.8, respectively), and ART containing nucleoside reverse transcriptase inhibitors but not ZDV during early and late pregnancy was associated with decreased risk for PTD at <32 weeks (OR = 0.3, 95% CI: 0.2-0.7). Benefits of ART continue to outweigh observed risks.

Risk factors for in utero and intrapartum transmission of HIV.

OBJECTIVE: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000. METHODS: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age. RESULTS: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 (P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission. CONCLUSION: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.

Effect of hard-drug use on CD4 cell percentage, HIV RNA level, and progression to AIDS-defining class C events among HIV-infected women.

In vitro and animal studies suggest that cocaine and heroin increase HIV replication and suppress immune function, whereas epidemiologic studies are inconclusive regarding their effect on HIV infection progression. The authors prospectively examined the association between illicit-drug use and 4 outcome measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of HIV infection, and death) in a national cohort of HIV-infected women. Women enrolled between 1989 and 1995 were followed for 5 years and repeatedly interviewed about illicit ("hard")--drug use. Up to 3 periodic urine screens validated self-reported use. Outcomes were compared between hard-drug users (women using cocaine, heroin, methadone, or injecting drugs) and nonusers, adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard-drug use during pregnancy. In multivariate analyses, hard-drug use was not associated with change in CD4 cell percentage (P = 0.84), HIV RNA level (P = 0.48), or all-cause mortality (relative hazard = 1.10; 95% confidence interval, 0.61-1.98). Hard-drug users did, however, exhibit a higher risk of developing class C diagnoses (relative hazard = 1.65; 95% confidence interval, 1.00-2.72), especially herpes, pulmonary tuberculosis, and recurrent pneumonia. Hard-drug-using women may have a higher risk for nonfatal opportunistic infections.