(Last updated: August 6, 2015; last reviewed: August 6, 2015)
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
Basis for Current Recommendations
Scheduled cesarean delivery, defined as cesarean delivery performed before the onset of labor and before rupture of membranes, is recommended for prevention of perinatal transmission of HIV in women with HIV RNA levels >1000 copies/mL near delivery and for women with unknown HIV RNA levels.
This recommendation is based on findings from a multicenter, randomized clinical trial1 and from a large individual patient data meta-analysis.2 These two studies were conducted at a time when the majority of HIV-infected women received no antiretroviral (ARV) medications or zidovudine as a single drug and before the availability of viral load information. Study results have since been extrapolated to make current recommendations about the mode of delivery in an era when combination antiretroviral therapy (cART) during pregnancy is recommended and viral load information is readily available.
In the randomized clinical trial, 1.8% of infants born to women randomized to undergo cesarean delivery were HIV-infected compared with 10.5% of infants born to women randomized to vaginal delivery (P < .001). When adjusted for ARV use in pregnancy (zidovudine alone), scheduled cesarean delivery lowered risk of HIV transmission by 80%, although the results were no longer statistically significant (odds ratio [OR] 0.2; 95% CI, 0–1.7). The protective effect still remained for scheduled delivery (adjusted OR [AOR] 0.3; 95% CI, 0.1–0.8) but not for emergency cesarean delivery (AOR 1.0; 95% CI, 0.3–3.7) when the data were analyzed by actual mode of delivery rather than by the group to which women were allocated.1 Results from a large meta-analysis of individual patient data from 15 prospective cohort studies also demonstrated the benefit of scheduled cesarean delivery, with a 50% reduction in risk.2
HIV RNA Level of >1000 copies/mL as a Threshold for Recommendation of Scheduled Cesarean Delivery
The American College of Obstetricians and Gynecologists (ACOG) recommends that women with HIV RNA >1000 copies/mL be counseled regarding the potential benefits of scheduled cesarean delivery.3 Initially, the threshold of 1000 copies/mL was based largely on data from the Women and Infants Transmission Study, a large prospective cohort study that reported no HIV transmission among 57 women with HIV RNA levels less than 1000 copies/mL.4 Studies reported since then have demonstrated that HIV transmission can occur in infants born to women with low viral loads.
In an analysis of 957 women with plasma viral loads ≤1000 copies/mL, cesarean delivery (scheduled or urgent) reduced the risk of HIV transmission when adjusting for potential confounders including receipt of maternal ARV medications (AOR 0.30; P = 0.022); however, zidovudine alone was the regimen primarily used as prophylaxis.5 Among infants born to 834 women with HIV RNA ≤1000 copies/mL receiving ARV medications, 8 (1%) were HIV-infected. In a report from a comprehensive national surveillance system in the United Kingdom and Ireland, 3 (0.1%) of 2,309 and 12 (1.2%) of 1,023 infants born to women with HIV RNA levels <50 copies/mL and 50 to 999 copies/mL, respectively, were HIV infected.6
The recent studies demonstrate that transmission can occur even at very low HIV RNA levels. However, given the low rate of transmission in this group, it is unclear whether scheduled cesarean delivery confers any additional benefit in reducing transmission. Furthermore, there is evidence that complication rates for cesarean deliveries are higher in HIV-infected women compared with HIV-infected women.7 Therefore, decisions about mode of delivery for women receiving cART with HIV RNA levels ≤1000 copies/mL should be individualized based on discussion between the obstetrician and the mother.Women should be informed that there is no evidence of benefit for scheduled cesarean delivery performed solely for prevention of perinatal transmission in women receiving cART with HIV RNA ≤1000 copies/mL and that it is not routinely recommended in this group.
Scheduled Cesarean Delivery in the Combination Antiretroviral Therapy Era
In surveillance data from the United Kingdom and Ireland, pregnant women receiving cART (i.e., at least 3 drugs) had transmission rates of about 1%, unadjusted for mode of delivery.6 Given the low transmission rates achievable with use of maternal cART, the benefit of scheduled cesarean delivery is difficult to evaluate. Both the randomized clinical trial1 and meta-analysis2 documenting the benefits of cesarean delivery included mostly women who were receiving either no ARVs or zidovudine alone. However, other data partially address this issue.
In a report on births to HIV-infected women from the United Kingdom and Ireland between 2000 and 2011, perinatal transmission rates in women on cART with HIV RNA<1,000 copies/mL with planned cesarean delivery (13/3,814; 0.3%) were not significantly different than those in similar women with planned vaginal delivery (6/2,238; 0.3%).8 Similarly, data from the French Perinatal Cohort showed no difference in transmission rates between vaginal delivery and planned cesarean delivery among women on cART with suppressed viral loads, 0.3% in both. For preterm deliveries with HIV RNA <1,000 copies/mL, transmission rates were slightly higher among planned vaginal deliveries but the numbers were small and the differences were not statistically significant (1/9 [11.1%] vs. 1/17 [5.9%] for HIV RNA 400–1000 copies/mL; 1/39 [2.6%] vs. 1/56 [1.8%] for HIV RNA 50–400 copies/mL; 1/189 [0.5%] vs. 0/143 [0%] for HIV RNA <50 copies/mL, for planned vaginal deliveries and elective cesarean deliveries, respectively).9 Therefore, no evidence to date suggests any benefit from scheduled cesarean delivery in women who have been receiving cART for several weeks and who have achieved virologic supression.When the delivery method selected is scheduled cesarean delivery and the maternal viral load is >1000 copies/mL, a 1-hour loading dose followed by a continuous intravenous (IV) zidovudine infusion for 2 hours (3 hours total) before scheduled cesarean delivery should be administered. In a study of the pharmacokinetics of IV zidovudine in 28 pregnant women, the ratio of cord blood-to-maternal-zidovudine levels increased significantly in women who received IV zidovudine for 3 to 6 hours compared with <3 hours before delivery (1.0 vs. 0.55, respectively)10 This suggests that an interval of at least 3 hours may provide adequate time to reach equilibrium across the placenta, although the relationship between specific cord blood zidovudine levels or cord blood-to-maternal-zidovudine levels and efficacy in preventing perinatal transmission of HIV is unknown.
Women Presenting Late in PregnancyHIV-infected women who present late in pregnancy and are not receiving ARV drugs may not have HIV RNA results available before delivery. Without current therapy, HIV RNA levels are unlikely to be ≤1000 copies/mL at baseline. Even if cART was begun immediately, reduction in plasma HIV RNA to undetectable levels usually takes several weeks, depending on the kinetics of viral decay for a particular drug regimen.11-13 In this instance, scheduled cesarean delivery is likely to provide additional benefit in reducing the risk of perinatal transmission of HIV for women, unless viral suppression can be documented before 38 weeks’ gestation.
Timing of Scheduled Cesarean Delivery
For the general obstetric population, ACOG recommends that scheduled cesarean delivery not be performed before 39 weeks’ gestation because of the risk of iatrogenic prematurity.14,15 However, in cases of cesarean delivery performed to prevent transmission of HIV, ACOG recommends scheduling cesarean delivery at 38 weeks’ gestation in order to decrease the likelihood of onset of labor or rupture of membranes before delivery.3 In all women undergoing repeat cesarean delivery, the risk of any neonatal adverse event—including neonatal death, respiratory complications, hypoglycemia, newborn sepsis, or admission to the neonatal intensive care unit—is 15.3% at 37 weeks, 11.0% at 38 weeks, and 8.0% at 39 weeks.15 Gestational age should be determined by best obstetrical dating criteria, including last menstrual period and early ultrasound for dating purposes. Amniocentesis to document lung maturity should be avoided when possible in HIV-infected women and is rarely indicated before scheduled cesarean section for prevention of HIV transmission.
Among 1,194 infants born to HIV-infected mothers, 9 (1.6%) infants born vaginally had respiratory distress syndrome (RDS) compared with 18 (4.4%) infants born by scheduled cesearean delivery (P <0.001). There was no statistically significant association between mode of delivery and infant RDS in an adjusted model that included infant gestational age and birth weight.16 Although newborn complications may be increased in planned births <39 weeks’ gestation, the benefits of planned cesarean delivery at 38 weeks are generally thought to outweigh the risks if the procedure is performed for prevention of HIV transmission. When scheduled cesarean delivery is performed in HIV-infected women for an indication other than decreasing HIV transmission, cesarean delivery should be scheduled at 39 weeks, based on ACOG guidelines.
Risk of Maternal Complications
Management of Women Who Present in Early Labor or With Ruptured Membranes
Few data are available to address the question of whether performing cesarean delivery after the onset of labor or membrane rupture decreases risk of perinatal transmission of HIV. Most studies have shown a similar risk of transmission for cesarean delivery performed for obstetric indications after labor and membrane rupture as for vaginal delivery. In one study, the HIV transmission rate was similar in women undergoing emergency cesarean delivery and those delivering vaginally (1.6% vs. 1.9%, respectively).6 A meta-analysis of HIV-infected women, most of whom were on zidovudine as a single drug or receiving no ARV medications, demonstrated a 2% increased transmission risk for every additional hour of ruptured membranes.29 However, it is not clear how soon after the onset of labor or the rupture of membranes the benefit of cesarean delivery is lost.30 Because it is not clear whether cesarean delivery after rupture of membranes or onset of labor reduces the risk of perinatal HIV transmission, management of women originally scheduled for cesarean delivery who present with ruptured membranes or in labor must be individualized at the time of presentation. In these circumstances, consultation with an expert in perinatal HIV may be helpful. Because the delivery plan in the setting of labor or ruptured membranes must be made quickly, telephone consulation with a 24-hour, 7-day-a-week hotline (e.g., the National Perinatal HIV/AIDS Clinical Consultation Center (888) 448-8765) may be helpful in rapidly developing an individualized plan.
The ARV drug regimen should be continued and IV zidovudine initiated, if previously planned.
When membrane rupture occurs before 37 weeks’ gestation, decisions about timing of delivery should be based on best obstetrical practices, taking into account risks to the infant of prematurity and of HIV transmission. Steroids should be given, if appropriate, to accelerate fetal lung maturity because no data exist to suggest that these recommendations need to be altered for HIV-infected women. When the decision is made to deliver, route of delivery should be according to obstetrical indications.