Antiretroviral therapy in pregnancy

To read about Anti-retroviral therapy, click here

Associate Editors-in-Chief: Ujjwal Rastogi, MBBS [mailto:urastogi@perfuse.org]

Overview
The risk of HIV transmission from mother to infant had declined to low levels with the use of ART in USA and Europe. The risk for perinatal HIV transmission can be reduced to <2% through the use of antiretroviral regimens and obstetrical interventions (i.e., zidovudine or nevirapine and elective cesarean section at 38 weeks of pregnancy) and by avoiding breastfeeding.

Therapeutic goals of ART in pregnancy

 * Reduction of perinatal transmission of infection.
 * Treatment of maternal HIV disease.

ART Regimen
Preferred agents include the following:
 * NRTI - Zidovudine, lamivudine.
 * NNRTI - Nevirapine.
 * Protease inhibitor - Lopinavir/ritonavir.

Salient features

 * Therapy should consist of 2 NRTI's with either an NNRTI or PI, guided by resistance testing.
 * Lopinavir/ritonavir in combination with zidovudine/lamivudine is preferred in most cases.
 * In a randomized control trial of 530 patients PI-based HAART has shown to increased preterm delivery (21.4% vs 11.8%, P = .003 with NRTI therapy); However ART regimen had no effect on infant hospitalizations and mortality.
 * In a randomized control trial involving patients from seven African countries, ritonavir-boosted lopinavir plus tenofovir–emtricitabine was found superior to nevirapine plus tenofovir–emtricitabine for initial ART in women with prior exposure to peripartum single-dose nevirapine.
 * Efavirenz should not be used during first trimester due to its teratogenic effect; while in second and third trimester, it should only be used, if it has clear benefits over other alternatives.
 * Nevirapine regimen has shown to cause hepatic failure and death in few patients.
 * Recommendations for Nevirapine:
 * Nevirapine-based regimens should be initiated in women with CD4 counts >250 cells/mm3only if the benefits clearly outweigh the risks because of the drug’s potential for causing hepatic toxicity/hypersensitivity reaction (AII).
 * Women who become pregnant while receiving nevirapine-containing regimens and who are tolerating the regimen well can continue on the therapy regardless of CD4 count (AII).
 * Rating of Recommendations: A = Strong; B = Moderate; C = Optional Rating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion.
 * Regardless of the antenatal ART regimen, zidovudine should be administered to mother and neonate as follows:
 * Mother : IV infusion during labor.
 * Neonate : Orally for 6 months following birth.

Factors influencing ART selection
Potential benefits and risks of therapy should be discussed with the patients by the health care provider. Following factors are taken into consideration for ART Selection:


 * Comorbidities.
 * Patient adherence and convenience of therapy.
 * Potential for adverse drug effects on the mother and drug interactions.
 * Pharmacokinetic changes in pregnancy
 * Results of genotypic resistance testing.
 * Potential teratogenic effects on the fetus and other adverse effects on the fetus or newborn.

ART for maternal health
Treatment of HIV infection is no different for the pregnant female than the nonpregnant patient. For effective viral suppression and immune recovery, three-drug combination therapy is needed.

ART prophylaxis for prevention of perinatal HIV transmission
Due to the use of appropriate ART prophylaxis which cause effective viral suppression, the risk of an infant becoming infected via perinatal transmission is currently estimated to be approximately 2 percent in USA and Europe.

Perinatal HIV infection can occur during the following conditions:
 * During pregnancy.
 * Labor and delivery.
 * During the breastfeeding period.

Recommendations for counselling of HIV-infected pregnant women
Pregnant women who are HIV-infected should be counseled concerning their options (either on-site or by referral), given appropriate antenatal treatment, and advised not to breastfeed their infants.

Centers for Disease Control and Prevention gives the following recommendations:
 * HIV-infected pregnant women should receive HIV prevention counseling as recommended. This counseling should include discussion of the risk for perinatal HIV transmission, ways to reduce this risk, and the prognosis for infants who become infected. HIV-infected pregnant women should also be told the clinical implications of a positive HIV antibody test result and the need for and benefit of HIV-related medical and other early intervention services, including how to access these services.
 * HIV-infected pregnant women should be counseled regarding antiretroviral therapy during pregnancy to improve their health and prevent perinatal transmission. Medical care and management of HIV-infected persons, especially pregnant women, can be complicated because of the need for combination therapy with multiple drugs, management of common side effects, careful monitoring of viral load and drug resistance, prophylaxis for and treatment of opportunistic infections, and monitoring of immune status. Health-care providers who are not experienced in the care of pregnant HIV-infected women are encouraged to obtain referral for specialty care from providers who are knowledgeable in this area.
 * HIV-infected pregnant women should receive information regarding all reproductive options. Reproductive counseling should be nondirective. Health-care providers should be aware of the complex concerns that HIV-infected women must consider when making decisions regarding their reproductive options and should be supportive of any decision.

Recommendations regarding treatment for HIV-Infected pregnant women


Although pregnancy is not an adequate reason to defer therapy for HIV infection, unique considerations exist regarding use of antiretroviral drugs during pregnancy, including the potential need to alter dosing because of physiologic changes associated with pregnancy, the potential for adverse short- or long-term effects on the fetus and infant, and the effectiveness in reducing the risk for perinatal transmission.
 * Obstetric providers should adhere to best obstetric practices, including offering scheduled cesarean section at 38 weeks to reduce risk for perinatal HIV transmission.


 * All pregnant women who require therapy for their own health should receive a combination antepartum antiretroviral (ART) drug regimen containing at least three drugs for treatment, which will also reduce the risk of perinatal transmission.


 * Combination antepartum drug regimens are also recommended for prevention of perinatal transmission in women who do not yet require therapy for their own health.


 * ART prophylaxis is more effective when given for a longer than a shorter duration. Therefore, ART drugs should be started as soon as possible in women who require treatment for their own health (AI), and without delay after the first trimester in women who do not require immediate initiation of therapy for their own health, although earlier initiation can be considered in these women as well.


 * In the absence of antepartum administration of ART drugs, ART drugs should be administered intrapartum in combination with infant ART prophylaxis to reduce the risk of perinatal transmission (AI); if antepartum and intrapartum ART drugs are not received, infant ART prophylaxis should be provided (see Infant Antiretroviral Prophylaxis) (AI).


 * Adding single-dose intrapartum/newborn nevirapine to the standard antepartum combination ART regimens used for prophylaxis or treatment in pregnant women in the United States is not recommended. This is because the drug does not appear to provide additional efficacy in reducing transmission and it may be associated with development of nevirapine resistance (AI).


 * To eliminate the risk for postnatal transmission, HIV-infected women in the United States should not breast-feed. Support services for use of appropriate breast milk substitutes should be provided when necessary. UNAIDS and World Health Organization recommendations for HIV and breast-feeding should be followed in international settings. Thus breastfeeding is not recommended for HIV-infected women in the United States—including those receiving combination antiretroviral therapy (ART)—because safe, affordable, and feasible alternatives are available (AII).


 * To optimize medical management, positive and negative HIV test results should be available to a woman's health-care provider and included on her confidential medical records and those of her infant. After informing the mother, maternal health-care providers should notify the pediatric-care providers of the impending birth of an HIV-exposed infant and any anticipated complications. If HIV is first diagnosed in the infant, health-care providers should discuss the implications for the mother's health and help her obtain care. Women should also be encouraged to have their other children tested for HIV. Children can be infected with HIV for many years before complications occur. Providers are encouraged to build supportive health-care relationships that promote discussion of pertinent health information. Confidential HIV-related information should be disclosed or shared only in accordance with prevailing legal requirements.
 * After receiving their test results, HIV-infected pregnant women should receive counseling, including assessment of the potential for negative effects (e.g., discrimination, domestic violence, psychological difficulties). Counseling should also include information on how to minimize these consequences, assistance in identifying supportive persons in their own social networks, and referral to appropriate psychological, social, and legal services. HIV-infected women should be counseled regarding the risk for transmission to others and ways to decrease this risk. They also should be told that discrimination based on HIV status or AIDS in housing, employment, state programs, and public accommodations (including physicians' offices and hospitals) is illegal.


 * Health-care providers should follow the Public Health Service Task Force recommendations for using antiretroviral drugs to treat pregnant HIV-1 infected women and reduce perinatal HIV-1 transmission in the United States, which address treating pregnant women who do not receive health care until near the time of delivery.

Recommendations for Postpartum follow-up of HIV infected women and perinatally exposed children

 * HIV-infected women should receive ongoing HIV-related medical care, including immune-function monitoring, recommended therapy, and prophylaxis for and treatment of opportunistic infections and other HIV-related conditions. HIV-infected women should receive gynecologic care, including regular Pap smears, reproductive counseling, information on how to prevent sexual and drug-related transmission of HIV, and treatment of gynecologic conditions according to published recommendations. Obstetrical providers should ensure that HIV-infected women are introduced or referred to another provider to continue their care after pregnancy.
 * HIV-infected women (or their children's guardians) should be informed of the importance of follow-up for their children. Children whose HIV infection status is unknown require early diagnostic testing and prophylactic therapy to prevent PCP pending determination of their status.
 * Infected children require follow-up care to determine the need for prophylactic therapy and antiretroviral treatment and to monitor disorders in growth and development that often occur before age 24 months.
 * Uninfected children who are exposed to antiretroviral therapy should be assessed for potential short- and long-term side effects.
 * Identification of an HIV-infected mother indicates that her family needs or will need medical and social services as her disease progresses. Thus, health-care providers should ensure that referrals to services address the needs of the entire family.