Antenatal Care - Treatment
Good antenatal care is essential for safe motherhood. Clinical exams, rapid syphilis tests, tetanus toxoid, supplementation with iron and folic acid are all considered the standard of care for pregnant women (Villar et al., 2001). Of critical importance is to inform women, their partners, families and communities of the danger signs during pregnancy and ensure access to emergency obstetric care. Antenatal care is also an opportunity for HIV counseling and testing. Women who test HIV-negative still need information and support to remain HIV-negative. [See Chapter 3. Prevention for Women, Chapter 4. Prevention for Key Affected Populations, and Chapter 11. Strengthening the Enabling Environment] Women who test HIV-positive need to be informed of their treatment options, both for their own health and to prevent vertical transmission. Women who test HIV-positive also need information and counseling concerning infant feeding options. Improving quality of care in maternal health services can increase the likelihood that women will go to health facilities in case of obstetric emergencies, thus increasing the chances of positive maternal and infant health outcomes (Gay et al., 2003). Women living with HIV also need sexual and reproductive health services and treatment for critical co-infections. Further efforts are needed to screen and treat pregnant women for co-infections that potentially increase mortality for women and their infants. [See also Chapter 8. Meeting the Sexual and Reproductive Health Needs of Women Living With HIV and Chapter 10. Preventing, Detecting and Treating Critical Co-Infections]
Syphilis co-infection can be especially dangerous in pregnancy, particularly for HIV-positive pregnant women. There is some evidence that HIV-syphilis co-infection may increase the risk of perinatal HIV transmission. While numerous countries have policies to provide universal screening for syphilis for pregnant women, not enough women are actually screened and treated in practice. In 2007, WHO estimated that syphilis prevalence in pregnant women in Africa ranges from 4–15% (WHO, 2007d). As a result, infants are dying from syphilis despite access to ARVs for mothers and infants (Peeling et al., 2004). Universal screening and treatment for syphilis in pregnancy could prevent 492,000 syphilis-related stillbirths and perinatal deaths per year in sub-Saharan Africa (Saloojee et al., 2004). Syphilis testing and treatment in conjunction with HIV testing can prevent congenital syphilis and may reduce HIV transmission.
Antenatal care is also an opportunity to discuss with pregnant women and their partners the benefits of infant male circumcision, which may reduce HIV acquisition and transmission when the infant becomes sexually active. Male circumcision has now been shown in three randomized clinical trials to reduce the risk of HIV acquisition for men by 50–60% (Auvert et al., 2005; Bailey et al., 2007; and Gray et al., 2007). Male circumcision at birth as part of postnatal care could result, upon sexual initiation and for his lifetime, in a reduction in the risk of HIV acquisition and transmission (Weiss et al., 2009; Nagelkerke et al., 2007). [See also Chapter 3C. Prevention for Women: Male Circumcision]
Treatment
All women have a right to a safe pregnancy (Freedman et al., 2005), including women living with HIV. For pregnant women living with HIV there is no therapy or combination of therapies or medical procedures that can guarantee an HIV-negative infant (Anderson, 2005). However, there are proven strategies that improve the health of the mother during pregnancy and reduce the risk of mother-to-child transmission of HIV. The most important strategy is for the woman to access health care services where she can be evaluated for the use of antiretroviral drugs, either for the treatment of her own health or for prophylaxis to reduce the risk of mother-to-child transmission of HIV during pregnancy. “Antenatal care must include ‘fast-tracking’ HIV-infected women into programmes providing holistic care, including treatment with HAART…[with] HIV care to be integrated into routine antenatal care, and not [maintained] as a separate programme” (Sebitloane and Mhlanga, 2008: 496 and 498). Women who are on a HAART regimen [for their own health] have the least risk of perinatal transmission, estimated at 1% (Stek, 2008). In addition, women on HAART [for their own health] have a much greater likelihood of an expanded lifespan, which results in a better quality of life for the woman herself and reduces the likelihood of an intergenerational effect for orphans and vulnerable children. [See also Chapter 12B. Care and Support: Orphans and Vulnerable Children]
In 2007, only 12% of pregnant women identified as being HIV-positive during antenatal care were assessed to determine whether they were eligible to receive antiretroviral therapy for their own health, and only 9% of those HIV-positive women who received PMTCT services received HAART (UNAIDS, 2009e). “The best way to ensure that infants are not born with HIV or acquire it during breastfeeding is to provide HIV-positive women the care they need for their own disease” (ITPC, 2009: 11). The 900 new cases of HIV in babies in developing countries every day could be prevented (ITPC, 2009).[12] “…Each new pediatric HIV infection is considered a missed opportunity for prevention” (Abrams, 2007: 705).
Providers Should Consult the Most Recent Guidelines Regarding Medications’ Effect in Pregnancy
Currently, there is no evidence of a significant increased risk of birth defects associated with the appropriate antiretroviral treatment before conception or during the first trimester (Antiretroviral Pregnancy Registry Steering Committee, 2007 cited in Coll et al., 2008). Concerns remain about the use of efavirenz during the first trimester, however, (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2009) and health care providers should evaluate the most recent evidence when considering its use. A review of treatment options found that prophylaxis with co-trimoxazole is still advisable for persons with CD4 counts under 200, even if they are on HAART. Experts advise that once viral load is undetectable, co-trimoxazole is no longer required. While co-trimoxazole is potentially teratogenic, WHO recommends its use throughout pregnancy because the risk of life-threatening infection among women with low CD4 counts or symptomatic HIV infection may outweigh other risks (Watts and Mofenson, 2006). However, co-trimoxazole “should not be used as a substitute for the availability of HAART regimens for pregnant women with advanced disease but rather as an adjunct” (Watts and Mofenson, 2006: 1480). Health care providers should also check the most up-to-date literature on nevirapine resistance when using nevirapine for PMTCT (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2009).
Nevirapine Resistance Is a Concern in Future Treatment Options
The WHO states "if a woman receives AZT during pregnancy, daily nevirapine is recommended for her child from birth until the end of the breastfeeding period” (WHO, 2009b). While nevirapine may increase the numbers of infants with HIV-free survival, treatment with nevirapine may prejudice future treatment for the HIV-positive infant (Lockman et al., 2007; Coffie et al., 2008). For women who have received nevirapine already for PMTCT, and then access HAART, there are some concerns that prior use of nevirapine may hinder treatment. A study with 114 women in the U.S. found resistance rates of up to 43% in women who had pregnancy-limited antiretroviral treatment (Paredes et al., 2010). A study of 872 women in Zambia found that HAART was less effective among women who had been exposed to single dose nevirapine (Kuhn et al., 2009b). As of November 2009, the WHO no longer recommends single dose nevirapine for pregnant women living with HIV as a result of the potential to prejudice treatment options for mothers and transmit nevirapine resistance to their infants (Kiptoo et al., 2008).
Starting ARVs Early in Pregnancy Can Improve Pregnant Women’s Health and Reduce Vertical Transmission
In November 2009, the WHO released new recommendations for the use of ARVs in pregnant women. These guidelines recommend lifelong antiretroviral drug regimens for women who need ARVs to protect their own health (based on severe or advanced clinical disease or with the CD4 count at or below 350 cells/mm3, regardless of symptoms) and short-term prophylactic regimens to decrease the risk of HIV transmission to the baby during pregnancy, labor and delivery and throughout the breastfeeding period (based on CD4 cell counts above 350 or for women who do not require ARVs for their own health). Short-term prophylactic regimens delivered to the baby during delivery and the breastfeeding period (should the mother choose to breastfeed) are also recommended and will be discussed in the Delivery and Postpartum sections of this document. Of note, the recommendation for initiating ARV treatment for pregnant women has been raised from a CD4 count of <200 cells/mm3 to a CD4 count of <350 cells/mm3, regardless of clinical staging of disease (WHO, 2009b). For women who do not need ARV treatment for their own health, prophylaxis initiation to prevent mother-to-child transmission is now recommended at 14 weeks gestation instead of 28 weeks gestation (WHO, 2009b). The planned effect of these recommendations is to start more women on ARVs sooner, thus improving the health of HIV-positive pregnant women and decreasing the risk of mother-to-child transmission of HIV (WHO, 2009b).
Questions Remain About ARVs and Pregnancy
As stated above, according to these recent WHO guidelines (WHO, 2009b), women with CD4 counts below 350 should receive HAART for their own treatment needs. However, while consensus has been reached with the WHO November, 2009 recommendations that those with a CD4 count below 350 should initiate HAART, no conclusive studies have been conducted concerning the optimal time to initiate treatment for those people with HIV whose CD4 counts are above 350. [See also Chapter 7. Treatment] When a woman is on HAART with CD4 counts below 350, HAART will improve her own health and drastically reduce vertical transmission. When a woman has CD4 counts above 350, current recommendations are to have the woman go on ARVs during pregnancy, at labor and delivery or postpartum for the duration of breastfeeding. It is unknown at this time whether women who have CD4 counts above 350 and who go on HAART to prevent perinatal transmission should continue with HAART following pregnancy or breastfeeding or should stop HAART and resume HAART when their CD4 counts go below 350.
While it is clear that those who go on ARV therapy for their own treatment needs should not interrupt treatment (Fauci, 2009a, SMART Study Group, 2006), treatment interruption for women who are on HAART simply to prevent perinatal transmission rather than for their own health needs has never been evaluated. The new WHO guidelines represent the current consensus on best international practice for the use of ARVs in pregnant women in developing country settings for both the maintenance of the woman’s own health and the prevention of mother-to-child transmission of HIV (WHO, 2009b). Development of these guidelines proceeded according to the WHO GRADE procedure and included costing analyses of the different options under review (WHO, 2009b). Of course, many important questions remain under consideration, including the long-term effects on the health of women who initiate ARV therapy as prophylaxis to prevent mother-to-child transmission and then stop treatment (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2009). A study funded by NIH that started in January 2010 with results expected in 2015 should answer this vital question. The PROMISE Study (Promoting Maternal-Infant Survival Everywhere) is a multi-national clinical trial in 18 countries that is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group. It will examine the long-term effects on the health of women who initiate ARV therapy as prophylaxis to prevent vertical transmission and then stop treatment in addition to comparing the effectiveness of different drug combinations for the treatment of PMTCT (NIAID Web Bulletin, January 21, 2010).
WHO recommends pregnant women who access HAART with CD4 counts above 350 (i.e., for PMTCT prophylaxis) should continue “through the end of the breastfeeding period” (WHO, 2009b: 14); implying that women can stop HAART at the end of breastfeeding if their CD4 count remains above 350. Until the results from the PROMISE study are available, the question about what this might mean for the woman’s future treatment options remains.
Treatment Regimens for Preventing Vertical Transmission Vary Globally
It should be noted that the development of ARV regimens to treat pregnant women and prevent vertical transmission is evolving and implementation varies around the world. For instance, in Europe, the initiation of ARV therapy in pregnant women proceeds according to the same CD4 count measurements as are used to initiate therapy within the general population, with the goal of full suppression of HIV by the third trimester of pregnancy (European AIDS Clinical Society, 2009). By contrast, in the United States, ARV therapy is now recommended for all pregnant women, regardless of their CD4 counts (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2009).
It is important to note that the evidence base in this section does not yet reflect implementation of the November 2009 WHO guidelines. At the time of this writing, the final WHO guidelines, slated for publication in June 2010, remain pending (WHO, 2009b). The evidence presented in this section should thus be considered in light of the new WHO guidelines and pending research in the field.
[12] Note: UNAIDS statistics for 2009 are even higher – about 1,178 per day (UNAIDS, 2009d).