Postpartum

A randomized controlled trial from 2005-2008 in Burkina Faso, Kenya and South Africa assessed both mothers’ health and mother-to-child transmission among HIV-positive women whose CD4 count was between 200 and 500. The study found that triple-antiretroviral treatment initiated during pregnancy and continued until six months postpartum reduced the risk of transmission to infants and improved HIV-free survival of infants compared to standard short- course antiretroviral therapy. At 12 months, 6.7% of the 402 infants whose mothers received triple-course antiretroviral treatment had died compared to 10.2% of the 403 infants whose mothers received short-course antiretroviral treatment. This effect was especially strong in women with CD4 counts between 200 and 350. At 12 months, the rate of transmission from mother to infant for triple-antiretroviral therapy was 5.5% compared to 9.5% for those who received short-course antiretroviral treatment. The infants whose mothers received triple-course antiretroviral therapy experienced a 42% risk reduction in HIV infections and a 37% risk reduction of death at 12 months, for a combined 36% risk reduction of either HIV infection or death. The study also found that triple-antiretroviral therapy had low toxicity for mothers and infants. All infants received single-dose nevirapine plus zidovudine in the first 72 hours and all mothers received counseling on replacement feeding or exclusive breastfeeding with weaning by six months. Formula was provided free of cost.

A study in Botswana (no date given) found a positive association between maternal viral load (in both plasma and breast milk) and mother-to-child transmission after one month in breastfed infants. 1,200 HIV-positive women at 4 sites were enrolled in the study and randomized to either exclusively breastfeed for 6 months in combination with infant zidovudine treatment or to exclusively formula feed. Mothers received antenatal zidovudine starting at 34 weeks of pregnancy along with intrapartum zidovudine and either single-dose nevirapine or a placebo at delivery. During the study HAART became available and women with CD4 counts below 200 cells/mm3 or AIDS defining illnesses were eligible for treatment either antenatally or postnatally. Infants received single-dose of nevirapine or a placebo at birth along with one month of zidovudine prophylaxis for formula fed infants and six months for breastfed infants. After 17 months the study protocol was changed so that all infants received single-dose nevirapine at birth. Of 1,116 infants alive and HIV- negative at birth, 1.1% of formula fed and 1.3% of breastfed infants tested HIV-positive after one month. Of 547 breastfed infants HIV-negative at one month, 4.4% tested HIV-positive before 2 years of age. Only 4 formula-fed infants tested HIV-positive after one month but before 2 years of age. For breastfed infants, the only predictors of mother-to-child transmission after one month of age were high maternal viral load and low maternal CD4 count. Infant prophylaxis with zidovudine was not a significant predictor of transmission. No transmission was observed in breastfeeding mothers who had started treatment with HAART before delivery. Similarly, no transmission was observed in breastfeeding mothers who had viral loads of less than 3,500 copies/mL. Maternal treatment with single-dose nevirapine at delivery did not predict mother-to-child transmission.

The Post-Exposure Prophylaxis of Infants (PEPI) trial in Malawi found that extended infant prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced breast-feeding acquired HIV-1 infection in 9-month-old infants. Between 2004 and 2007, 3016 breastfeeding infants were randomly assigned to one of three different drug regimens. The control group received single-dose nevirapine plus one week of zidovudine, the second group received the control regimen plus daily extended prophylaxis with nevirapine (extended nevirapine group) and the third group received the control regime plus nevirapine and zidovudine (extended dual prophylaxis group). At nine months (the primary end point in the study), the estimated rate of HIV-1 infection in the control group was 10.6%. The extended nevirapine group had an infection rate of 5.2% and the extended dual prophylaxis group had a rate of 6.4%. There were no significant differences between the two extended prophylaxis groups although the extended dual prophylaxis group had a significant increase in the number of adverse events which were thought related to a study drug. This study demonstrated a protective efficacy of more than 60% for the two extended prophylaxis groups at 14 weeks. Cumulative risk of postnatal infection between birth and 14 weeks was 8.4% in the control group and 2.8% in the extended prophylaxis groups. This net difference of approximately 5% continued at 24 months.

The Six Week Extended-Dose Nevirapine (SWEN) study combined study data from sites in Ethiopia, India and Uganda to assess whether daily nevirapine given to breastfed infants through six weeks of age would decrease HIV transmission from breastfeeding. HIV-positive women who were breastfeeding their infants were randomized to receive either single-dose nevirapine (during labor for the mother and after birth for the baby), or six week extended dose nevirapine (during labor for the mother and after birth for the baby) plus daily nevirapine doses for the baby from day 8 to 42. The primary goal of the study was to assess HIV-infection rates at six months of age for infants who were HIV PCR negative at birth. The study concluded that a six week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at six weeks of age but the lack of a significant reduction of HIV transmission at the study end point of six months of age suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective.^[13] (Six Week Extended-Dose Nevirapine (SWEN) Study Team, 2008)

^[13] Note: The three co-principal investigators of this study from India published a critique of this study write up in The Lancet in the same publication issue. These investigators disagree with the statistical analyses used in this study, express concern about the 40% of infants who experienced grade III or IV side effects during treatment and conclude that the recommendation to continue nevirapine beyond six weeks is “inappropriate.” The investigators suggest that a more prudent strategy is to “follow WHO/UNICEF guidelines for developed countries and to make formula feeding safe, sustainable, acceptable, and affordable for mothers in developing countries.”(Six Week Extended-Dose Nevirapine (SWEN) Study Team, 2008: 287).

A 2001-2003 study in Tanzania assessing 398 infants of HIV-positive women intending to breastfeed who were treated with zidovudine and lamivudine at antenatal clinics, found a 3.8% transmission rate of HIV from mother-to-child at week six and a 4.9% transmission rate after six months. The cumulative rate of HIV infection or death for infants was 8.5% at six months. Women were treated with zidovudine or lamivudine from 36 weeks gestation to one week post-delivery. Infants were treated with zidovudine and lamivudine for the first week of life and then lamivudine throughout six months of breastfeeding. Follow-up appointments included infant feeding counseling and occurred at weeks 1, 3 and 6 and months 3, 6, 9, 12, 15, 18, 21 and 24. Women were counseled to breastfeed exclusively and wean by six months. The infants were breastfed for a median of 18 weeks. Mothers reported 95% breastfeeding at six weeks, 86% after 12 weeks and 18% after 26 weeks. A total of 19 children became HIV-positive, 15 were considered early transmissions and 4 were considered late transmissions. CD4+ cell count and viral load were significantly associated with mother-to-child transmission. No infants suffered serious adverse outcomes due to antiretroviral treatment. The comparison group for this study was a historical study of the same cohort where mothers received the same antiretroviral regimen but infants were not treated throughout breastfeeding. In this earlier study, mothers reported 85% breastfeeding at six weeks, 77% at 12 weeks and 64% at 26 weeks. This study revealed a 5.4% transmission rate at six weeks and 11.9% transmission rate at six months. The cumulative risk for HIV acquisition or death was 8.7% at six weeks and 15.5% at six months, about 50% higher than the current study.

A study in Mozambique from 2005-2007 followed 313 HIV-positive mothers on HAART, who were counseled to breastfeed exclusively for six months and found that HAART reduced the risk of mother-to-child transmission by 93%. There were a total of 8 cases of HIV transmission, 4 of which were considered late postnatal transmission. Women with repeat pregnancies, who had previously received antenatal care and HAART through six months of breastfeeding, did not transmit HIV to their infants. HIV testing of infants was performed at 1, 6 and 12 months. Antiretroviral treatment began at 15 weeks of gestation and continued until six months after delivery. HAART was continued beyond six months if the mothers had CD4 cell counts that remained below 350. In combination with HAART, nutritional supplements to mother and infant, patient counseling to increase adherence to breastfeeding and a strong network of support within the community led to the marked reduction of maternal and infant deaths.

A study enrolling HIV-positive pregnant women receiving a single dose of nevirapine for preventing perinatal transmission of HIV during labor from 2003-2004 in Uganda found that nevirapine was detectable in breast milk, maternal plasma, and infant plasma for 2-3 weeks after a single dose of maternal nevirapine. Overall, 62 women were included in the study. Sixty-one women received a single dose of nevirapine at least 1.5 hours before delivery, and 53 women chose to breastfeed. All infants received a single dose of nevirapine syrup within 72 hours of birth. Samples of breast milk and plasma from both mothers and infants were taken 1, 2, and 6 weeks after maternal nevirapine treatment. Infant plasma levels of nevirapine at delivery were correlated with the timing of maternal nevirapine intake. Infant nevirapine levels were the highest approximately 4 hours after maternal nevirapine intake, after which infant treatment with nevirapine only slightly increased infant nevirapine plasma concentrations. Furthermore, nevirapine transferred from maternal plasma to breast milk rapidly, and nevirapine in breast milk was detectable before infants initiated breastfeeding. The long-term duration of nevirapine in breast milk was determined to be protective against postnatal transmission due to the effective suppression of HIV in breast milk for up to 3 weeks after maternal single dose nevirapine intake. However, the long-term duration of nevirapine also increases the risk for nevirapine resistance mutation development, and the acquisition of a resistant virus for infants. Because the risk of nevirapine resistance decreases over time, infants are most at risk for acquiring a resistant virus during the initial breastfeeding period. Extended antiretroviral treatment with zidovudine/lamivudine should therefore be considered to reduce the risk of nevirapine resistance . [See introduction of 9C-2. Treatment for discussion of nevirapine resistance]

Lower maternal CD4 count was associated with a significantly higher risk of transmission through breastfeeding , therefore HAART, by increasing CD4 counts can reduce transmission of HIV during breastfeeding (Abrams et al., 2007).

The Breastfeeding, Antiretroviral and Nutrition (BAN) Study is a randomized trial in Malawi that evaluated rates of post-natal HIV-1 transmission among mother infant pairs who received single dose nevirapine intrapartum and one week of twice-daily zidovudine/lamivudine followed by randomization into three ARV treatment groups. The dosing above served as the control group. Among 2637 mother-infant pairs, in utero transmission was estimated at 4.9% (measured at one week). Estimated risk of HIV transmission by 28 weeks among those infants who were negative at 1 week was: 6.4% in the control group, 3% in the second group receiving zidovudine, lamivudine, lopinar and ritonavir (MHAART) and 1.8% in the third group, in which infants received daily nevirapine (INVP). The estimated risk of HIV transmission or death at 28 weeks (breastfeeding stopped at 24 weeks) was 7.6% in the control group, 4.7% in the MHAART group and 2.9% in the INVP group. These results were statistically significant although the study was not powered to compare the two treatment groups. There was a trend favoring INVP prophylaxis (Abstract)

A quasi-experimental pre-post test study conducted from 2006 through 2007 of maternal health care interventions in Swaziland that provided care for all pregnant women, including HIV-positive women at several intervals (within the first six hours after delivery; an exam once per day postpartum while the woman was in the health facility; providing assessment, care and counseling, along with a specific appointment for the first postnatal visit upon being discharged from the facility and providing a postnatal visit at one week postpartum and a second visit at four to six weeks postpartum) increased contraceptive use and counseling on condom use. Over 60% of maternal deaths occur within 48 hours after childbirth , yet in Swaziland, mothers are usually discharged within 12 hours of delivery. The conventional recommendation for the first postnatal visit is at four to six weeks, by which time most of the postpartum deaths have already taken place. The study collected data on 114 HIV-positive women at the start of the study and from 136 HIV-positive women to evaluate the impact a year later. The intervention increased early postnatal visits by twenty-fold. Providers increased counseling of HIV-positive women on the need to regularly monitor CD4 counts for the mother from 41% to 74%. Following the intervention, 93% of mothers were assured of privacy. While at baseline, the provider asked the woman her preferred family planning only 32% of the time, by the end of the intervention, 82% did so. While at baseline, only 28% of clients received their preferred family planning method, at the end of the intervention, 70% did so. While at baseline, providers only counseled on condom use 16% of the time, by the end of the intervention, 25% did so. The percent of women on HAART increased from 4% to 15% and the mother tested for her CD4 count since giving birth increased from 4% to 26%. There was also a statistically significant increase in the proportion of postpartum women (88 to 98%) and their partners (from 28% to 56%) getting tested for HIV. Since the postnatal visit within one week of delivery did not exist anywhere in the country at the pre-intervention phase, conclusions following the introduction of the new timing of postnatal care could be assessed. Actual condom use was not measured (Mazia et al., 2009).

A study in Côte d’Ivoire with 546 HIV-positive women and 393 HIV-negative women who were tested for HIV prenatally and followed up for two years following delivery and were provided contraception as desired at each postpartum visit, resulting in high rates of contraception use after delivery and low pregnancy incidence. HIV-positive women had fewer unwanted pregnancies than HIV-negative women. At each postpartum visit, women received family planning counseling and free contraception. Between 6 and 24 months, proportion of women using modern contraception varied from 52 to 65% among HIV-positive women. Among HIV-positive women, pregnancy incidence for 100 women years at risk was 5.70 and unwanted pregnancy incidence was 1.07.

A pre-post test design with 356 postpartum women and 53 health care workers that instituted a one week post-delivery postpartum visit along with provider training in Swaziland from 2006 to 2007 found that the proportion of HIV-positive postpartum women not wanting another child increased from 77% to 83%. Provider training increased the woman being asked about her preferred contraceptive method, from 32% to 82% and receiving her preferred method, from 28% to 70%. Male partners who tested for HIV increased from 28% to 56%.

A study of 319 HIV-positive pregnant women who were followed postpartum for one year in a perinatal HIV transmission study in Kenya and were referred to local clinics for contraceptive counseling and management resulted in high rates of contraceptive use and dual method use, with 72% initiating hormonal contraceptive use and 61% of 231 hormonal contraceptive users reporting condom use in additional to hormonal contraceptives. Prior to this project, which had linked antenatal care with family planning, only 50% of the currently using 231 hormonal contraceptive users had a history of previous hormonal contraceptive use. Prior to this project, only 6 or 3% had used condoms. Of those using contraception, 44% used DMPA, 31% used oral contraception and 25% switching methods at follow up. Women were counseled antenatally to initiate contraception postpartum and dual contraception was encouraged. No particular method of contraception was given priority. Hormonal methods were the most popular contraceptive method, possibly because they are female controlled and available. Women who opted of formula feed their infants were counseled to initiate contraception four weeks after delivery, whereas those who opted to breastfeed were counseled to initiate contraception six weeks after delivery. Breastfeeding women who wanted oral contraception received progesterone only pills and non-breastfeeding women received combined oral contraceptive pills. DPMA was available for both breastfeeding and non-breastfeeding women. Median time to initiation of sexual activity was two months following delivery, ranging between one and 11 months, with 77% of women resuming sexual activity within three months of delivery. Partner notification and condom use were similar between those using and not using other forms of contraception besides condoms. . Other studies that did not provide contraceptive counseling in antenatal care found much lower rates of contraceptive use post partum (Nebrie et al., 2001; Desgrées-Du-Loû et al., 2002 cited in Balkus et al., 2007).

A study from Kenya enrolling HIV-positive mothers and their infants from 2006 to 2007 found that an integrated water safety and PMTCT program was effective in preventing MTCT in infants after 6 weeks of age. Women enrolled in the PMTCT program received HAART, either for prophylaxis or for the mother’s health, infant feeding counseling, safe water education, free infant formula for women choosing not to breastfeed, chlorine-based water disinfectant, a water storage container, and home visits by a community resource person. Of 144 mother-infant pairs included, 133 infants were tested for HIV at 6 weeks, 3 of whom tested positive. None of the 73 infants tested at 6 months of age were HIV-positive.

A review of clinical records from Rwanda enrolling HIV-positive mothers and their infants between 2005 and 2007 into an integrated PMTCT program combining clean water and formula provision, HIV and hygiene education, and healthcare services found low rates of postnatal HIV transmission and infant mortality after one year of follow-up. Replacement feeding was also monitored. Of 1,360 mother-infant pairs, 133 infants were enrolled at birth (without prior breastfeeding) and eligible for one year of follow-up. Two infants tested HIV-positive at birth and 4 died before one year. At one year of age, 92 infants were tested for HIV all of whom were HIV-negative.

A study in Zimbabwe from 1997 to 2000 of 2,060 infants born to HIV- positive mothers found that solid foods or animal milks given to infants prior to three months of age was associated with a fourfold greater risk of postnatal transmission of HIV at six months compared with exclusive breastfeeding. The protective effects of early exclusive breastfeeding were still significant at 18 months with a 61% reduction in postnatal transmission compared with mixed breastfeeding. Thus, the more strictly HIV-positive mothers are able to breastfeed exclusively, the lower the risks of HIV or death for their infants. More than two-thirds of all postnatal transmission of HIV occurred after six months. This is consistent with other studies from West Africa, South Africa and Tanzania and supports early cessation of breastfeeding among HIV-positive women. Lastly, women with CD4 counts less than 200 cells/ul were five times more likely to transmit HIV during breastfeeding compared with women with CD4 cell counts over 500 cells/ul, confirming the findings of other studies that postnatal transmission of HIV is highly correlated with immune suppression in the mother.

A study in Nigeria, which screened pregnant women for HIV-1 between 2004 and 2006, found that risk factors for mother-to-child transmission of HIV-1 differed by infant age. Infants at highest risk of acquiring HIV were those who had mothers with CD4 counts less than 200 and who received mixed feeding. The study analyzed 391 mothers and 371 infants, using follow-up visits 1 week after delivery and 1, 3, 6, and 12 months after delivery. A single-dose of nevirapine was given to each mother during delivery and to her infant within 48 hours of delivery. Women who chose replacement feeding were provided a 6-month supply of formula free of charge, as well as training and counseling on formula preparation, sterilization, and storage processes. Mothers who chose exclusive breastfeeding were provided counseling on the importance of weaning before 4-6 months. Exclusive breastfeeding was defined as only breast milk up until 6 months, with no other liquids or solids; replacement feeding as the use of formula only with no breast milk; and mixed feeding as a combination of breast milk and nonhuman milk or other solids before 6 months of age. For infants who were exclusively breastfed, 8.1% tested HIV-positive by 6-months of age compared to 9.5% of infants exclusively formula fed, and 29.2% of infants who received mixed feeding. After delivery, 71.7% of mothers chose replacement feeding while 28.3% chose to exclusively breastfeed. At 6-month follow-up, 71.1% of mothers who initially chose to breastfeed reported maintaining exclusive breastfeeding, 80.2% of mothers who initially chose formula feeding reported exclusive replacement feeding, and 82 mothers reported using mixed feeding. During the study period, 50 infants became infected with HIV-1, 34% in utero, 30% intrapartum or early postnatally, and 36% postnatally, with an overall transmission rate of 13.5%. For infants infected in utero, risk factors included maternal CD4 count of less than 200 and high maternal viral load. For infants infected during the intrapartum or early postnatal period, risk factors included high maternal viral load, gestational age of less than 37 weeks, and prolonged membrane rupture during delivery. Infants infected during the intrapartum or early postnatal period were at higher risk if they received mixed feeding compared to infants who were exclusively formula or breast-fed (12% compared to 2.2%). For infants infected during the postnatal period, mixed feeding and low birth weight increased the risk of HIV transmission. The risk of transmission for infants who were exclusively breastfed increased from 1.4% during the intrapartum/early postnatal period to 4.2% postnatally. The rate of transmission during all three infant-age periods for infants who were exclusively formula fed was similar. For mothers who initially chose to replacement feed but then switch to mixed feeding, stigma, pressure from family members, and no partner support were reported as reasons for not maintaining exclusive formula feeding.

A 2001-2005 South African intervention cohort study of 1,372 women and infants which examined the effect of breastfeeding by HIV-positive mothers found that exclusive breastfeeding leads to significantly lower rates of HIV transmission and higher rates of survival than does mixed feeding. “Infants who received formula milk in addition to breast milk, before or after 14 weeks of age, were nearly twice as likely” and “infants who were breastfed but also received solids were nearly 11 times” as likely to become infected than infants who were exclusively breastfed . HIV- positive women were provided during antenatal care, nevirapine, infant-feeding counseling, and no cost commercial infant formula. After delivery, clinic nurses and counselors provided mothers with breastfeeding and replacement feeding support, with infant-feeding counselors visiting mothers three to four times within the first two weeks after birth and once every two weeks until six months after birth. Independent field monitors who visited mothers once a week assessed infant feeding practices. The study defined “exclusive breastfeeding” as feeding a child with breast milk, providing no solid food, and not giving non-human milk or water for more than three days total. After delivery, 1,132 mothers began exclusive breastfeeding, and the median duration of breastfeeding of infants for whom HIV test results were available was 159 days. Of the mothers who decided to exclusively breastfeed, 82% exclusively breastfed for at least 6 weeks, 67% exclusively breastfed for at least three months, and 40% exclusively breastfed for 6 months. The study found that 22% of exclusively breastfed infants died or became HIV-infected, resulting in an overall Kaplan-Meier estimated HIV-free survival rate of 75.4% at six months. The risk of HIV transmission was associated with low maternal CD4-cell counts. The study found that the health of mothers was strongly correlated with PMTCT. “Infants exclusively breastfed by women with CD4-cell counts less than 200 µL were twice as likely to become infected and almost four times more likely to die before 6 months of age than were infants exclusively breastfed by women with CD4-cell counts above 500 µL” (Coovadia et al., 2007: 1115).

A study from Zambia (2001 to 2004) enrolling HIV-positive pregnant women from PMTCT programs, found that infants born to HIV-positive mothers who were exclusively breastfed up until at least 4 months were at least 50 percent less likely to acquire HIV through breastfeeding than infants fed any non-breast milk substances in addition to breast milk. Furthermore, the study found no difference in the rates of HIV transmission between infants weaned at 4 months and those who continued breastfeeding past 6 months. Overall, 734 infants who tested HIV-negative at 6 weeks of age and were still breastfeeding at 6 months of age were included in the study. Mothers were randomized into an intervention group in which women were counseled to exclusively breastfeed for 4 months and then wean abruptly, and a control group in which women were counseled to breastfeed for at least 6 months and then introduce complimentary foods while maintaining breastfeeding. At 4 months, 83.5 percent of mothers reported exclusively breastfeeding. The risk of acquiring HIV before 4 months of age was over 3 times higher for infants who were non-exclusively breastfed compared to those who received only breast milk. A maternal CD4 count of below 350 was a strong predictor of HIV transmission before 4 months of age, but a significant reduction in HIV transmission related to exclusive breastfeeding remained after controlling for CD4 count. For exclusively breastfed infants, the risk of acquiring HIV was greatest in the first 4 months and then declined thereafter. The rate of HIV transmission for non-exclusively breastfed infants was 2.4 percent per month compared to less than 1 percent per month for exclusively breastfed infants.

A 2001-2003 study that followed HIV-positive and HIV-negative pregnant women attending antenatal clinics in South Africa found that postnatal home visits offering infant feeding counseling significantly improved adherence to either exclusive breastfeeding or exclusive replacement feeding. The study followed 1,253 HIV-positive and 1,238 HIV-negative pregnant women who attended nine different clinics. Adherence was significantly associated with the number of antenatal feeding counseling home visits for both options. A breastfeeding counselor performed one antenatal home visit for every woman to discuss feeding options and three additional visits were available to those who chose to breastfeed. For women who chose to replacement feed, a specialist visited the home to teach methods of safe replacement feeding. The study also collected data on access to clean water, a refrigerator, fuel for boiling water and regular income for the mother, and found that only 3% of HIV- positive pregnant women had access to all four resources and 32.1% had access to all but regular income. “Of those who intended to replacement feed…few had the necessary resources to prepare infant formula safely” . Infant formula became available in 2002 for HIV-positive pregnant women (Bland et al., 2007).

A study from 1999 to 2000 that provided VCT for women attending maternal and child health clinics for their first postpartum or well-baby visit in Botswana found that 937 or 54% of 1,735 postpartum women accepted VCT. 30% of those who accepted VCT were HIV-positive (Thior et al. 2007).

In Ethiopia, while low numbers of women have institutional deliveries, more than 70% of children are immunized. A study found that of 1,430 women who brought their children to be immunized, 94% had not had an HIV test during antenatal care or delivery. When offered HIV testing at the clinic where their child was immunized, 80% accepted, of whom 5% were HIV-positive. All HIV- positive women and their children were enrolled in HIV care to receive antiretroviral treatment.

In a project in South Africa, maternal CD4 cell count was determined every six months during the infant’s immunization visit, with rapid referral for HAART for mothers with CD4 cell counts of less than 200/mm3.