Women who received no prenatal care were significantly more likely to transmit infection (16.3%, RR = 2.7, 95% confidence interval: 2.0–3.7) compared with women with 3 or more prenatal visits (6.1%; see Table 3).
Women with infants of low birth weight (1500–2499 g) and very low birth weight (<1500 g) were significantly more likely to transmit HIV. Women with infants of very low birth weight had the highest risk of transmission (17.6%, RR = 2.8, 95% confidence interval: 1.8–4.2; see Table 3).
Mode of Delivery
Vaginal delivery was associated with a higher rate of HIV transmission (9.0%) compared with elective cesarean delivery (3.2%, RR = 0.4, 95% confidence interval: 0.2–0.6). The transmission rate following nonelective cesarean section delivery was 8.2%, comparable to vaginal delivery (see Table 3).
The transmission rate was lowest among women who received prenatal combination ART with a protease inhibitor (2.5%, RR = 0.2, 95% confidence interval: 0.1–0.2) or without a protease inhibitor (2.3%, RR = 0.1, 95% confidence interval: 0.1–0.2) compared with no antiretroviral prophylaxis (16.7%). Prophylaxis with a single nucleoside analogue was also protective (5.8%, RR = 0.4, 95% confidence interval: 0.2–0.5) compared with no prophylaxis (see Table 3).
Timing of Perinatal Antiretroviral Prophylaxis
A 3-part antiretroviral regimen administered in the pre-natal, intrapartum, and newborn periods was associated with the lowest rate of transmission (3.3%, RR = 0.2, 95% confidence interval: 0.1–0.2) compared with other regimens. Abbreviated antiretroviral regimens were also associated with reductions in transmission (intrapartum/newborn period [9.4%, RR = 0.5, 95% confidence interval: 0.3–0.8] or only in the newborn period [11.9%, RR = 0.6, 95% confidence interval: 0.4–0.9]) compared with no therapy (19.4%; see Table 3).
Among the 38 infants who were HIV infected and who received abbreviated antiretroviral regimens, 37 received only ZDV (intrapartum/newborn or newborn only). One infant received only indinavir as a neonate.
Among 302 infants who were exposed to HIV and not infected and received abbreviated antiretroviral regimens, 133 of their 135 mothers received ZDV alone during the intrapartum period and 122 of 135 infants received only ZDV in the newborn period. Additional newborn regimens included ZDV/lamivudine (3TC; n = 7), ZDV/nevirapine (n = 2), nelfinavir (n = 1), and unknown antiretroviral treatment (n = 3).
Among 177 newborns who received only newborn ART, 157 received only ZDV, with the remaining receiving ZDV/3TC (n = 6), ZDV/nevirapine (n = 10), and an unknown antiretroviral (n = 4).
Multivariate Logistic Regression
A multivariate logistic regression model was developed to assess risks of vertical transmission while adjusting for other known or suspected risk factors. Factors related to the probability of HIV transmission at the bivariate level were used as independent variables in the model and included maternal demographics (age, race, and residence), the course of ART, the mode of delivery, and the infant’s birth weight. The number of prenatal visits and type of prenatal ART were omitted from the model due to a high correlation with the course of ART. Maternal age greater than 40 years (compared with women aged 20–29 years), white and Hispanic race/ethnicity (compared with black race/ethnicity), low or very low birth weight (compared with infants with normal birth weight), and residence in NYC compared with the rest of state were significantly associated with risk of vertical transmission. Abbreviated regimens of ART were also significantly associated with reductions in transmission compared with no treatment. Elective cesarean section delivery appeared to be associated with a lower probability of HIV transmission but was barely significant at the level of P < 0.05 (see Table 2).
This population-based observational study of 3492 HIV-infected pregnant women and their infants describes a substantial decline in perinatal HIV transmission in NYS over a 4-year period. A 1998 Institute of Medicine publication, Reducing the Odds Preventing Perinatal HIV Transmission, describes the steps on the pathway to perinatal HIV transmission and emphasizes the need for identification of women in the prenatal period, providing access to prenatal care, and access to ART. 8 In NYS, public health efforts have focused on intervening at all possible steps in the pathway to transmission so as to reduce perinatal transmission maximally by providing access to care for pregnant women, ensuring that they are offered testing and that providers are trained in the appropriate prophylaxis necessary to reduce transmission. Similarly, recent guidance from the Centers for Disease Control and Prevention calls for routine HIV testing of all pregnant women and for infants whose mother’s HIV infection status is unknown so as to decrease perinatal transmission. 9 Rapid HIV testing in the labor and delivery setting as well as in the postpartum setting if the mother is not previously tested is also an option.
Since 1994, when the PACTG 076 regimen became a standard of care, significant reductions in transmission have been reported in other studies and in well-defined populations. 10–12 These NYS data demonstrate that the reductions in transmission observed in research studies can be achieved on a population basis when women receive prenatal care and have access to appropriate ART in the prenatal, intrapartum, and newborn periods. NYS public health measures were instituted to ensure access to care, including HIV counseling and testing and ART prophylaxis if HIV infection was detected.
Since Public Health Service guidelines recommending treatment of the HIV-infected pregnant woman for her own health status were promulgated in 1998, the use of prenatal combination ART has increased. 13 The rates of transmission observed in our study among women receiving combination therapy are comparable to the transmission rates described in PACTG 367 (combination with a nucleoside reverse transcriptase inhibitor [0% vs. 2.9%] and combination with a protease inhibitor [1.8% vs. 2.7%]). 14 Similar rates were reported in the Woman-Infant Transmission Study (multiple antiretroviral agents [4.3%] and highly active ART [0%]). 15
Reductions in perinatal HIV transmission have occurred even when abbreviated regimens of ZDV were administered to the HIV-infected pregnant woman and her infant. In our previous analysis of NYS data, significant reductions in risk of perinatal HIV transmission were described among women initiating antiretroviral prophylaxis during the prenatal period, intrapartum period, and within the first 24 to 48 hours of a newborn’s life. 16 These findings were confirmed in this study, with significant reductions in transmission described even when antiretroviral prophylaxis was initiated in the intrapartum (9.0%) or newborn (11.9%) periods compared with no antiretroviral prophylaxis (19.3%). In other studies, decreased perinatal transmission has been described with prophylaxis administered in the intrapartum and newborn periods. 17,18 This study also describes reductions in transmission when ART was initiated in the newborn period. This finding is similar to that from a recent study from Malawi, where efficacy of ZDV/nevirapine administered in the newborn period was demonstrated. 19
The finding of higher transmission rates among white women compared with black women was unexpected. White women were more likely to receive prenatal care and were more likely to have 3 or more prenatal visits. White women were less likely to have low or extremely low birth weight infants. White women were also more likely to receive a 3-part regimen of ART and combination ART during the prenatal period. All these relationships were statistically significant. Black and white women did not differ significantly for age, receipt of any ART, mode of delivery, or when the woman found out that she was infected with HIV. The lower rates of HIV transmission in black women remain unexplained; indeed, the factors described would have been expected to decrease the transmission rate among white women. It is possible that black versus white women may have differed by other indicators that we were not able to account for adequately, including, for example, maternal viral load.
The finding of a higher rate of transmission among residents of NYC compared with the rest of the state may be explained in part by some additional risk factors. Women in NYS were less likely to have received prenatal care or to have had 3 or more prenatal visits. Women residing in NYC were as likely as women throughout the rest of the state to have received ART at some time during their pregnancy or in the newborn period. They were less likely to have received a full 3-part regimen of ART during the prenatal, intrapartum, and newborn periods, however. In addition, NYC women were less likely to deliver by cesarean section and were more likely to have delivered a low or extremely low birth weight infant. These findings would support the differences seen in transmission.
There are several limitations to this study. We did not have 100% ascertainment of infant infection status; however, the number was small and not expected to change results significantly. The study did not include maternal risk factors, plasma HIV RNA levels, or CD4 counts. Plasma HIV RNA levels may have identified women most at risk for transmission. Adherence to treatment regimens was not measured. In addition, because this was not a controlled clinical trial, dosage of medication, dosing intervals, and start dates during pregnancy may have varied. Because this was an observational study and not a clinical trial, there were many uncontrolled factors. Nevertheless, there were some important strengths. The study cohort was large and population based. Indeed, it was close to a universal cohort with complete information over 4 years.
NYS has taken major steps toward reducing perinatal HIV transmission. One benefit has been to dramatically increase the number of women being tested for HIV during prenatal care, when the full 3-part ART regiment can be given. Expedited delivery setting testing remains a critical “safety net” for women who are not tested perinatally, mostly because they did not receive prenatal care. Statutes and regulations with policies and programs have ensured access to prenatal care and receipt of ART to reduce the risk of perinatal HIV transmission. These factors coupled with clinical advances will continue to provide an environment for the lowest possible rates of transmission.
We are working to identify factors in the small number of residual transmissions that continue to occur. Lack of prenatal care remains a key issue preventing the administration of ART during pregnancy, intrapartum, and postpartum. The NYSDOH has embarked on an ambitious street level outreach targeting the highest risk women to help them navigate the medical and social service system, including accessing prenatal care. Finally, NYS is continuing a comprehensive educational program aimed at prenatal care providers and consumers to ensure that the community is knowledgeable about the most effective regimens for reducing perinatal transmission to the lowest possible levels. This combination of ongoing efforts will be necessary to sustain and further reduce the rate of perinatal HIV transmission to the lowest possible level.
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Keywords:© 2004 Lippincott Williams & Wilkins, Inc.
perinatal HIV transmission