HIV in Pregnancy

Updated: Jan 15, 2015
  • Author: Teresa Marino, MD; Chief Editor: Thomas Chih Cheng Peng, MD  more...
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Overview

Overview

The reduction in mother-to-child transmission of human immunodeficiency virus (HIV) is regarded as one of the most effective public health initiatives in the United States. In the absence of treatment, the risk of vertical transmission of HIV is as high as 25-30%. With the implementation of HIV testing, counseling, antiretroviral medication, delivery by cesarean section prior to onset of labor, and discouraging breastfeeding, the mother-to-infant transmission has decreased to less than 2% in the United States.

Before the current treatment era, approximately 2000 babies were infected with HIV each year in the United States alone. Despite increasing HIV prevalence, that figure now stands at approximately 300 infants per year. [1]

The rapid clinical implementation of research findings directed toward decreasing perinatal transmission is credited as the key to this accomplishment. In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 demonstrated that the administration of zidovudine during pregnancy and labor and then to the newborn decreased the risk of perinatal transmission of HIV by 68%, from 25.5% to 8.3%. [2] In the late 1990s, the combined use of 3 or more antiretroviral medications was found to be highly successful at suppressing viral replication.

The exact mechanism of mother-to-child transmission of HIV remains unknown. Transmission may occur during intrauterine life, delivery, or breastfeeding. The greatest risk factor for vertical transmission is thought to be advanced maternal disease, likely due to a high maternal HIV viral load. [3] Unfortunately, about 30% of pregnant women are not tested for HIV during pregnancy, and another 15-20% receive no or minimal prenatal care, thereby allowing for potential newborn transmission. [4]

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Epidemiology

United States statistics

Early in the acquired immunodeficiency syndrome (AIDS) epidemic, women were rarely diagnosed with HIV or AIDS, but by 2005, women represented 27% of the estimated 45,669 new diagnosis of HIV/AIDS, with the greatest rise among young women. [5] About 80% of new cases in women in the United States are contracted through heterosexual intercourse, 20% by contaminated needles, and most of the remaining cases by maternal-child transmission. Testing of donated blood has essentially eliminated blood transfusions as a source of infection.

Of women with AIDS, 71% were diagnosed between the ages of 25 and 44, implying that many of them may have been infected as adolescents. In the United States, African American and Hispanic women represent 25% of the female population but account for 82% of the total number of women with AIDS. Furthermore, women of color account for 80% of newly diagnosed HIV/AIDS cases. [6]

International statistics

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has estimated that, in 2008, approximately 33.4 million people worldwide (1% of the global adult population aged 15-49 y) were infected with HIV, a decline from 2006 (39.5 million reported at that time); 67% of all people living with HIV worldwide live in sub-Saharan Africa, and 91% of all new infections among children occur there. [7]

More than 500,000 babies worldwide contract HIV from their mothers; 90% of these cases occur in developing countries. In 2005, AIDS claimed an estimated 2.4-3.3 million lives; more than 500,000 of which were children. One third of these deaths were in sub-Saharan Africa. [5]

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Prophylaxis and Pregnancy Outcome

The Antiretroviral Pregnancy Registry, where clinicians should report cases of exposure to antiviral therapy in pregnancy, contains approximately 5,000 reported exposures and notes no increase in the congenital malformation rate with exposure to antiretroviral medications, even in the first trimester, with the exception of efavirenz. Early exposure to efavirenz has been associated with neural tube defects.

Concern was raised that antiretroviral therapy may increase the incidence of adverse pregnancy outcomes. Several studies have shown that zidovudine monotherapy had no negative effect on pregnancy.

Although data from cohorts in the United States have not shown an increased risk of preterm birth with combination therapy, a European collaborative study showed an increased risk of preterm labor in women infected with HIV who were taking combination antiretroviral therapy, with an odds ratio for preterm birth of 1.8 for combination therapy without a protease inhibitor and 2.6 for combination therapy that included a protease inhibitor. [8]

In a US study of pregnant women infected with HIV, the overall rate of adverse pregnancy outcome, including prematurity, low birth weight, stillbirth, and abnormal Apgar scores, was similar in women who received antiretroviral therapy during pregnancy and those who did not. [9] Of the 2123 women in the study, 1590 received monotherapy, 396 received combination therapy without a protease inhibitor, and 137 received combination therapy with a protease inhibitor; 1143 did not receive antiretroviral therapy.

Rates of prematurity and extreme prematurity did not differ significantly according to antiretroviral regimen. Although the risk of low and very low birth weight was greater in the group receiving a protease inhibitor, the results did not reach statistical significance. Furthermore, this may be a reflection of higher viral load or advanced stage of disease rather than exposure to protease inhibitors. [9]

In a more recent retrospective study (2004-2012) that evaluated US infant growth patterns during their first year of life among those born to perinatally HIV-infected (PHIV) (32 infants, 25 mothers) and nonperinatally HIV-infected (NPHIV) mothers (120 infants, 99 mothers) who received care, infants of PHIV mothers had lower mean length-for-age z-scores (LAZ) that were associated with birth length. Other small-for-gestational age anthropometric parameter associations included those of birth weight and weight-for-age z-scores (WAZ) and those of both birth length and weight with weight-for-length z-scores (WLZ). The investigators also reported an association between delivery HIV RNA level below 400 copies/mL with increased WAZ and WLZ. [10]

A large meta-analysis that included articles from several countries between 1998 and 2006 showed that overall, highly active antiretroviral therapy (HAART) did not increase the risk of prematurity; however, the use of regimens with protease inhibitors seemed to increase prematurity slightly. [11]

A possible association exists between HAART and preeclampsia. [12]

The development of glucose intolerance may be more common in pregnant women with HIV. Originally thought to be associated with protease inhibitors, gestational diabetes appears to be somewhat increased regardless of the medication regimen. As such, during pregnancy, women should be screened and monitored for glucose intolerance. [13]

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HIV and Pregnancy Planning

Preliminary data suggest that women with HIV may suffer from subfertility. Conception in couples who have never conceived may occur in a median of 6 months with 2 acts of intercourse during the ovulatory period of the cycle. With each act, the risk of sexual transmission must be considered even in the presence of an undetectable viral load. Conducting testing and considering reproductive techniques in women infected with HIV may be worthwhile in an effort to reduce the risk of infection to a healthy partner.

In couples planning a pregnancy where only the male partner is infected, natural conception carries a risk of sexual transmission to the uninfected female. Counseling provided to such couples should include strategies to minimize HIV transmission. Options include adoption, sperm donation, and assisted reproduction techniques. While antiretroviral therapy can reduce viral load in the blood to undetectable levels, some reports have shown that men can still have a substantial viral concentration in semen in the presence of an undetectable plasma viral load.

When possible, confirmation of undetectable seminal plasma viral load may be considered. If HIV viral load cannot be suppressed, semen washing has been proposed and may decrease the HIV RNA and DNA to undetectable levels. After processing and rechecking for residual contamination, the spermatozoa can be used for intrauterine insemination or in vitro fertilization.

Pregnancy does not appear to influence the progression of HIV disease. [14, 15] A large cohort of French women with known seroconversion dates noted a pregnancy-adjusted relative risk of progression from HIV to AIDS of 0.7. [16] Furthermore, pregnancy does not seem to affect survival of women infected with HIV. [17]

For serodiscordant couples who want to conceive, the use of antiretroviral therapy (ART) is recommended for the HIV-infected partner, with the strength of the recommendation differing based on the CD4-cell count of the infected partner. Additionally, NIH guidelines include discussion regarding pre-exposure prophylaxis (PrEP) studies in heterosexual couples. New recommendations regarding periconception administration of antiretroviral PrEP for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission. The guidelines include information on counseling, laboratory testing, and monitoring of individuals on PrEP and the importance of reporting uninfected women who become pregnant on PrEP to the Antiretroviral Pregnancy Registry. [18, 19, 20]

HIV-infection risk-reduction strategies in conjunction with relatively inexpensive fertility awareness methods (FAMs) may be useful for counseling HIV-serodiscordant couples who want to conceive. [21] Such methods include use of accessible and highly sensitive, but poorly specific, strategies like the calendar method, basal body temperature measurements, and cervicovaginal mucus secretion features. Urinary luteinizing hormone testing has high specificity and cost with less sensensitivity. Timed condomless sex has low cost but necessitates understanding how to precisely predict the fertile period in a menstrual cycle. [21]

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Patient Education

Approximately 30% of women in the United States are not tested for HIV during pregnancy. Reasons for declining should be explored and patients counseled appropriately. Testing strategies also include reoffering screening in the third trimester to women who declined first-trimester screening or who are in high-risk groups. The Centers for Disease Control and Prevention (CDC) recommends routine third-trimester screening in women with high-risk behaviors or who exhibit signs or symptoms of the disease. [4]

Clinicians who care for women with HIV need to provide family planning services and counseling regarding optimizing health status. This includes encouraging compliance to medication regimens, cessation of smoking, and updating immunizations.

Stressing the importance of taking their medication regularly to decrease the possibility of the development of antiretroviral drug resistance may encourage women to comply with therapy. Cigarette smoking, concurrent use of drugs (cocaine, heroin), and unprotected intercourse have been associated with increased risk of perinatal transmission.

It is encouraging to note there has been a substantial reduction in substance use in the past 2 decades. [22] In a retrospective study over a 23-year period (1990-2012) that evaluated data from two prospective cohort studies (Women and Infants Transmission Study, Surveillance Monitoring for Antiretroviral Therapy Toxicities Study), investigators noted a dramatic decrease in substance use among 5451 HIV-infected pregnant women (1990: 82%; 2012: 23%). There was a significant decline in use of each substance between 1990 and 2006, when it reached a plateau, which the investigators suggested may have been caused by an epidemiologic transition of the HIV epidemic among US women. [22] Substance use was inversely associated with receiving antiretroviral therapy. Women with multiple pregnancies with substance use in their previous pregnancy were at higher risk of substance use in their next pregnancy. [22]

Unfortunately, 15% of women infected with HIV receive no or minimal prenatal care, and 20% do not initiate prenatal care until late in the third trimester. Women who are not treated during pregnancy should be treated with one of the appropriate intrapartum antiretroviral drug regimens.

Even in the absence of antepartum treatment, intrapartum and early neonatal prophylaxis can reduce the mother-to-child transmission risk. Women should be extensively counseled regarding the ability to decrease the risk of perinatal transmission with highly active antiretroviral therapy (HAART) prophylaxis or treatment. In women who are being treated with HAART and planning a pregnancy, the teratogenic potential of certain antiretroviral medications must be reviewed and effective contraception discussed. These medications should be stopped prior to planning a pregnancy.

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History and Physical Examination

History

In pregnancy, the initial history should assess the status of the patient’s HIV disease (eg, CD4+ T-cell count, viral load), the need for beginning or altering antiretroviral medication, and ways to reduce perinatal transmission. A careful review of the medical and surgical history, gynecologic history, high-risk habits, and previous obstetric history should be done at the first prenatal visit.

Physical examination

During pregnancy, a complete physical examination must be performed. Knowledge of the normal physiologic changes of pregnancy, such as an enlarged thyroid gland and a systolic murmur, is important to differentiate from disease process. HIV infection can affect essentially all body systems.

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Screening

The American Congress of Obstetrics and Gynecology (ACOG) recommends routine HIV screening for women aged 19-64 years and targeted screening for at-risk women outside of this age reference. All pregnant women should have their HIV serostatus evaluated when they first present for prenatal care.

Women should have the right to refuse testing after being informed that HIV testing will be drawn as part of their routine prenatal panel. This opt-out approach to prenatal screening, as advocated by the Institute of Medicine, is associated with higher testing rates among pregnant women. However, several states have laws that prohibit this approach and mandate that patients sign consent forms for testing, known as the opt-in approach. [23]

ELISA

The most common screening test is an enzyme-linked immunosorbent assay (ELISA), which looks for the presence of antibodies. If this test result is positive, the ELISA is repeated to eliminate laboratory error prior to proceeding to a confirmatory test by Western blot. The ELISA has 98% sensitivity. False-negative results may occur early in the disease, and false-positive results have been reported after certain vaccines. Repeat testing several months later usually confirms seronegativity in such cases. A positive test is sent for Western blot.

Western blot

For the Western blot, specific viral proteins are separated by electrophoresis, and reaction of antibody to 3 proteins must occur for the test to be considered positive. Indeterminate results occur when 1 or 2 of the proteins are present. In low-risk populations, indeterminate results usually revert to negative over several months. Western blot has a false-positive rate of 1 in 20,000.

Blood counts and viral load

For pregnant women infected with HIV, in addition to the standard prenatal assessment, continued assessment of HIV status is important. A complete blood count to assess anemia and white blood cell count as well as renal and liver function tests should be included. Initial evaluation includes CD4+ counts, which help determine the degree of immunodeficiency.

Viral load, determined by plasma HIV RNA copy number (copies/mL) assesses the risk of disease progression. The viral load is important in decisions regarding maternal treatment and delivery management; however, because perinatal HIV transmission can occur even at low or undetectable HIV RNA copy numbers, the viral load is not used in pregnancy to decide whether to start antiretroviral medications.

If a viral load is detected, antiretroviral drug resistance studies (HIV genotype) should be performed before starting therapy unless the diagnosis is made late in the pregnancy, in which case starting medications while awaiting results is recommended. In general, pregnancy has not been associated with a risk of rapid progression of HIV. [17]

With appropriate therapy, the viral load should drop by 1 log within the first month and become nondetectable within 6 months after initiating treatment. The higher the viral load, the longer the decrease may take; however, if the viral load persists or increases at 6 months, treatment failure must be considered.

Lipid profile and ultrasound

Other laboratory studies should include a lipid profile, which is not usually obtained in pregnancy. Although cholesterol normally increases in pregnancy, baseline values are required, as certain medications have been associated with increased triglyceride and cholesterol levels. Evaluation of other infectious disease states and possible opportunistic infections, such as syphilis, cytomegalovirus, and toxoplasmosis, also needs to be done.

Initial obstetric ultrasonography for viability and dating is important for determining treatment and planning delivery. Potential teratogenicity is highest during the first trimester, and some patients may consider delaying treatment until after the first 12 weeks of pregnancy. In women who are severely ill, the risks and benefits of this delay must be weighed. A targeted ultrasonography may be warranted depending on medication exposure.

Hepatitis testing

Hepatitis B surface antigen status is recommended for all pregnant women. In the case of acute hepatitis B infection (HBV), the risk of vertical transmission also varies with gestational age, with an 80-90% risk of transmission to the offspring if the infection occurs in the third trimester. [23] Women who are co-infected with HIV and chronic hepatitis B may require different management in pregnancy.

Co-infection with HIV and hepatitis C virus (HCV) is common and may range from 17-54%. [24] The diagnosis of hepatitis C is confirmed by identification of the hepatitis C antibody via an ELISA test. False-negative HCV test results may occur if the CD4 count is very low. More specific tests, (eg, hepatitis C viral RNA detection by polymerase chain reaction) are available. High maternal viral titers have been associated with an increased risk of vertical transmission.

All women who are chronic carriers of HBV or HCV should inform sexual partners, household contacts, and needle-sharing contacts and review precautions to decrease transmission.

Opportunistic infection assessment

Assessment of the need for prophylaxis against Pneumocystis jiroveci pneumonia (PCP) or Mycobacterium avium complex (MAC) infection is necessary. For women with low CD4 counts, prophylaxis for PCP is with trimethoprim-sulfamethoxazole (TMP-SMX). Due to potential teratogenicity, aerosolized pentamidine may be substituted in the first trimester, as it is not absorbed systemically. For prophylaxis of MAC, azithromycin is used in place of clarithromycin because of potential teratogenicity. [14]

Other sexually transmitted disease testing

Screening for other maternal sexually transmitted diseases is recommended in pregnancy. For example, screening for maternal syphilis is important not only for the prevention of congenital syphilis but also because maternal syphilis has been associated with an increased risk of mother-to-child transmission of HIV. [25]

Vaginal speculum examination should be performed to obtain cervical cytology smear and assays for gonorrhea and chlamydia. All sexually transmitted diseases should be treated promptly. Genital warts and vulvar intraepithelial neoplasia are more common among HIV-seropositive than HIV-seronegative women, but wart regression is as common in women with HIV as those without and cancer is infrequent. [26] Women infected with HIV have a higher incidence of cervical dysplasia.

Vaccination

Vaccinations should be kept updated. During pregnancy, live attenuated vaccines (eg, measles-mumps-rubella [MMR], varicella vaccines) should be avoided. Annual influenza vaccine and pneumococcal vaccine should be administered to all pregnant women who are HIV positive. The H1N1 influenza vaccine should be administered to all pregnant women and is safe in women with HIV.

Tuberculosis testing

Co-infection with HIV and tuberculosis is very common in developing nations. Immunosuppression from HIV infection contributes not only to a higher rate of tuberculosis reactivation but also to an increased disease severity.

Tuberculosis skin testing should be performed and a 5-mm purified protein derivative (PPD) result interpreted as positive. If positive, chest radiography can be performed during pregnancy because radiation risk is exceedingly low.

Presentation during labor

For women who present in labor and have not had prenatal testing, rapid testing should be offered. Unlike the ELISA, the rapid HIV test is a blood or saliva antibody test and results are usually available within an hour. The rapid test is reported to have a high negative predictive value (100%) and to be highly sensitive and specific (approaching 100%); however, the positive predictive value in pregnancy varies from 44-100%. [4] Patients who test positive in labor by ELISA should be treated as HIV positive until confirmatory results are available.

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Antiretroviral Therapy

Overview

Mother-to-child transmission is linked to viral load. As such, antiretroviral therapy should be offered to all pregnant women infected with HIV to reduce the risk of perinatal transmission to below 2%. [27] Combination antiretroviral therapy should be offered in all cases. As zidovudine (ZDV) is the only agent specifically shown to reduce perinatal transmission, it should be used whenever possible as part of the highly active antiretroviral therapy (HAART) regimen. [2]

If a pregnant woman has received antiretroviral medication in the past but is not currently on any medication, the choice of regimen may vary according to the history of prior use, the indication for stopping treatment in the past, gestational age, and resistance testing. In this setting, if there is no resistance to the drugs and the regimen suppressed viral load, antiretroviral medication can be used again, but avoid drugs with teratogenic potential or adverse maternal effects.

If a patient who is on a HAART regimen presents for prenatal care, continuing her treatment during the first trimester is reasonable, provided that care is taken to avoid medications that are contraindicated in early pregnancy. HIV antiretroviral drug resistance testing is recommended if a viral load is detectable. Considerations of drugs not usually used early in pregnancy may be necessary if drug resistance is confirmed and the patient receives extensive counseling regarding risk and benefits.

In an HIV-infected pregnant woman who has never been exposed to antiretroviral medication, HAART should be started as soon as possible, including during the first trimester. Again, recommendations are for drug-resistance testing and care to avoid medications that may potentially cause adverse maternal and fetal effects.

If prenatal HIV testing was not performed and a rapid HIV test returns preliminarily positive, the patient should be treated like any other woman infected with HIV. Certainly, the gestational age and obstetrical scenario may dictate the treatment options available, but as the exposure risk to antiretroviral medication is minimal to both mother and fetus, antiretroviral therapy should be initiated. [4]

The patient with a positive rapid test must be counseled regarding the possibility of a false-positive screen, and the results should be documented as preliminary in the medical chart. If this test was performed on arrival in labor, treatment with the ZDV protocol through labor is recommended, followed by administration to the neonate until confirmatory testing on the mother becomes available.

Antiretroviral regimens

Treatment of women infected with HIV should not be withheld because of pregnancy. Although the decision regarding starting or maintaining current antiretroviral therapy is based on the same criteria as in nonpregnant patients, several considerations must be taken into account because of potential effects on the fetus.

The use of the 3-part ZDV prophylaxis regimen, alone or in combination with other antiretroviral medications, should be discussed and offered to all pregnant women because ZDV was the first agent to show significant decrease in the mother-to-child transmission of HIV. [2] The regimen chosen should also take into account prior therapy and response to that regimen, as well as resistance testing. Gestational age and potential fetal and neonatal toxicity must also be taken into account when selecting a regimen.

The mechanism of action with which these drugs reduce perinatal transmission includes lowering maternal viral load; however, as these drugs cross the placenta, there appears to be prenatal prophylaxis as well. The third component, prophylaxis of the newborn, further decreases the risk of perinatal transmission.

The antiretroviral drugs used in pregnancy fall broadly into 3 categories: the nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). There are insufficient data to allow recommendations regarding the use of entry inhibitors or integrase inhibitors in pregnancy.

Guidelines for perinatal ART were revised in July 2012 regarding which agents are considered preferred, alternative, or to be used under special circumstances. Combination regimens, usually including 2 NRTIs with either an NNRTI or 1 or more protease inhibitors (PIs) are recommended. For further information, see Table 1.

Table 1. ART agents during pregnancy [18] (Open Table in a new window)

ART Class Preferred* Alternate Special Circumstances Insufficient Data to Recommend
NRTIs zidovudine (ZDV)



lamivudine (3TC)



abacavir



emtricitabine



tenofovir



didanosine



stavudine



-
NNRTIs nevirapine - efavirenz etravirine



rilpivirine



PIs atazanavir



lopinavir + ritonavir



ritonavir



darunavir



saquinavir



indinavir



nelfinavir



fosamprenavir



tipranavir



Fusion Inhibitors - - - enfuvirtide



maraviroc



Integrase Inhibitors - - raltegravir -
*ZDV plus 3TC is a recommended dual-NRTI backbone regimen plus an NNRTI and 1 or more PIs for pregnant women with HIV

Nucleotide analogue reverse transcriptase inhibitors

The NRTIs are generally well tolerated and cross the placenta. The FDA has classified these as pregnancy class B or C, depending on the agent. These drugs do bind to mitochondrial DNA gamma polymerase and may cause mitochondrial dysfunction manifesting as cardiomyopathy, neuropathy, lactic acidosis, and liver dysfunction. Genetic susceptibility to these drugs may play a role, and the effects usually resolve with cessation of the medication. [1]

The combination of didanosine and stavudine has been associated with lactic acidosis and hepatic failure leading to fatalities and should be used with caution or only in cases where other NRTIs cannot be used due to resistance or toxicity. Finally, ZDV and stavudine have overlapping toxicities and are antagonistic and should be avoided in combination. [27]

Non-nucleoside reverse transcriptase inhibitors

Five NNRTIs are FDA approved: delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), nevirapine (Viramune), and rilpivirine (Edurant). Although less information is available regarding NNRTI use in pregnancy, nevirapine and efavirenz both cross the placenta. The most common side effect is rash, which can occur in up to 17% of patients on nevirapine. [14]

Use of efavirenz is not recommended in the first trimester because of reported cases of fetal neural tube defects. The FDA has changed the pregnancy classification of this drug to category D. [28]

Severe nevirapine-associated skin rash and hepatic toxicity have been reported in pregnancy. The potentially fatal hepatotoxicity appears to be increased in women, during pregnancy, and in patients with a CD4+ T-cell count greater than 250 cells/mL. Because of these significant complications, nevirapine should not be used as first-line therapy unless no other option is available.

In women whose CD4+ T-cell counts were below 200 cells/mL and who were previously exposed to peripartum single-dose nevirapine, ritonavir-boosted lopinavir plus tenofovir-emtricitabine was superior to nevirapine plus tenofovir-emtricitabine for initial antiretroviral therapy. [29]

In children previously exposed to single-dose nevirapine for perinatal prevention of HIV transmission, zidovudine and lamivudine plus ritonavir-boosted lopinavir for antiretroviral treatment resulted in better outcomes than treatment with zidovudine and lamivudine plus nevirapine. [30]

Protease inhibitors

Protease inhibitors do not cross the placenta easily, and no teratogenic effects have been noted in animals. They are classified as class B or C by the FDA.

Also see the Medscape Drugs & Diseases topic Antiretroviral Therapy for HIV Infection.

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Peripartum Treatment

In any pregnant woman infected with HIV who presents in labor, whether her HIV-positive status was previously known or was determined by rapid test result, more than one treatment option is available during labor and delivery. All HIV-infected women with HIV RNA ≥400 copies/mL (or unknown HIV RNA) near delivery should be administered IV zidovudine (ZDV) during labor, regardless of antepartum regimen or mode of delivery. IV ZDV is no longer required for HIV-infected women receiving combination ART regimens who have HIV RNA < 400 copies/mL near delivery. [18]

ZDV is given intravenously during labor at a dose of 2 mg/kg infused over 1 hour, followed by a continuous infusion of 1 mg/kg throughout labor. This regimen, along with maternal antepartum and infant zidovudine, reduced perinatal transmission by 66% overall. [18] If the patient is having a planned cesarean delivery, the IV infusion should begin 3 hours before the procedure. [14, 27, 31] Another option is ZDV infusion followed by a single dose of 200 mg of nevirapine. This regimen should be followed by lamivudine (3TC) 150 mg every 12 hours. If the latter regimen is used in pregnancy, the patient must continue ZDV/lamivudine (Combivir) for at least 7 days post partum to avoid nevirapine resistance. [14]

Women with documented drug resistance to ZDV or whose antepartum regimen did not include ZDV should still be given the intravenous ZDV protocol during labor and delivery or before cesarean delivery. [14, 31] Furthermore, the other antiretroviral agents must be continued on schedule throughout the intrapartum or preoperative period. Stavudine is the only agent that can antagonize ZDV and should be stopped prior to the IV infusion of ZDV. [27]

In patients attempting a vaginal delivery, all invasive procedures such as amniotomy, internal fetal scalp electrode, or scalp sampling should be avoided, as these may increase the risk of transmission.

When HAART is given solely for prevention of perinatal HIV transmission, it may be stopped in the postpartum period. The risk of promoting the development of resistant viral strains by using short courses of HAART can be decreased by using a maximally suppressive regimen and discontinuing all agents at the same time. The exception remains if the regimen includes a nucleoside reverse transcriptase inhibitor (NRTI). The NRTI should be continued for an additional 7 days to decrease the risk of resistance. [14]

Infant ART prophylaxis  [18]

All HIV-exposed infants should receive zidovudine in the following doses:

  • < 30 weeks’ gestation: 2 mg/kg PO or 1.5 mg/kg IV BID; after age 4 weeks, advance to 3 mg/kg PO or 2.3 mg/kg IV q12hr
  • >30 to < 35 weeks’ gestation: 2 mg/kg PO BID; after age 15 days, advance to 3 mg/kg PO or 2.3 mg/kg IV q12hr
  • >35 weeks’ gestation: 4 mg/kg PO or 3 mg/kg IV BID x6 weeks

Initiate as soon after delivery as possible (preferably within 6-12 hours) and continue through age 6 weeks and administer birth through 6 weeks.

Additional prophylaxis with nevirapine is needed for HIV-exposed infants of women who did not receive antepartum ART at the following weights and dosages:

  • Birth weight 1.5-2 kg: 8 mg/dose PO
  • Birth weight >2 kg: 12 mg/dose PO

Administer 3 doses in the first week of life; 1st dose 48 hours after birth, give 2nd dose 48 hours after 1st dose, and 3rd dose 96 hours after 2nd dose.

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Hepatitis Co-infection

The current recommendation for treating women co-infected with HIV and HBV is to treat these women with tenofovir and lamivudine or emtricitabine. [32] All 3 have shown activity against HBV. A meta-analysis found that the use of lamivudine effectively prevents mother-to-child transmission, even in pregnant women who have a high degree of HBV infectiousness in late pregnancy. [33]

Although data are insufficient for the use of tenofovir in pregnancy, the benefits likely outweigh the risks in women with HBV/HIV co-infection. Women receiving treatment should be advised of the signs and symptoms of liver toxicity, and regular follow-up of transaminase levels is warranted. The infant should receive hepatitis B immunoglobulin and start the 3-dose series of hepatitis B vaccine within the first 12 hours of life. [18]

Pregnancy does not appear to alter the course of HCV infection; however, co-infection with HIV does appear to increase the risk of perinatal transmission of HCV. As such, a 3-drug antiviral combination is recommended regardless of the viral load. As with HBV co-infection, patients should be made aware of the signs and symptoms of liver toxicity, and transaminases should be followed every 2-4 weeks.

As with HIV, prolonged rupture of membranes may increase the risk of perinatal HCV transmission; however, the data remain inconclusive regarding the use of cesarean section delivery to decrease the risk of transmission. As such, delivery recommendations are based on the HIV status. Infants can be evaluated by testing HCV RNA at 2 and 6 months of age or HCV antibody after 15 months of age. [18]

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Cesarean Delivery

Cesarean delivery must be discussed and the patient counseled regarding the possibility of an unnecessary surgical procedure should the final HIV result be negative. [18] Care should be individualized according to clinical scenario.

Early studies regarding cesarean delivery and transmission risk showed conflicting results. Cesarean delivery before the onset of labor may prevent microtransfusion that occurs with uterine contractions, and avoiding vaginal delivery eliminates exposure to virus in the cervicovaginal secretions and blood at time of delivery.

In the late 1990s, prospective cohort studies noted a decrease in mother-to-child transmission in women on zidovudine (ZDV) who underwent elective cesarean delivery compared with women who did not take ZDV prophylaxis. [34, 35] In 1999, results from a large meta-analysis of individual patient data from 15 prospective cohort studies demonstrated a 50% reduction of vertical transmission with the use of elective cesarean delivery for women with HIV, after adjusting for antiretroviral therapy, maternal stage of disease, and infant birth weight.

Of note, vertical transmission risk did not change when the study group was limited to those women who had rupture of membranes shortly before surgery. The transmission risk was decreased by about 80% for women who had both an elective cesarean delivery and were taking antiretroviral medication. [36]

In the same year, ACOG issued an opinion that elective cesarean delivery should be discussed and offered to all pregnant women who were HIV positive at 38 weeks’ gestation to avoid the potential risk of spontaneous labor and rupture of membranes. [31]

These studies did not adjust for viral load and were performed before HAART came into use. In patients on HAART with an undetectable viral load (< 1000 copies), the risk of transmission is very low, and whether cesarean delivery offers any further benefit remains unknown.

This led to an updated ACOG statement in 2000, stating that women infected with HIV whose viral loads are greater than 1,000 copies/mL should be counseled regarding the potential benefit of scheduled cesarean delivery to further reduce the risk of vertical transmission of HIV beyond that achieved with antiretroviral therapy alone. [31] However, data are insufficient to demonstrate a benefit for neonates of women with viral loads less than 1,000 copies/mL.

Longer duration of ruptured membranes may be associated with a higher rate of mother-to-child transmission. The International Perinatal HIV group meta-analysis found that the risk of vertical transmission increased by 2% for every increase of 1 hour in the duration of ruptured membranes. If cesarean delivery is performed after the onset of labor or rupture of membranes, the benefit of surgery may be lost. In this scenario, a decision regarding the route of delivery should be individualized. [31, 36]

Operative risk may outweigh the potential benefit of further reducing HIV transmission. In a study by Louis et al that compared the outcome of cesarean section in 378 women infected with HIV and in more than 54,000 uninfected women, HIV-infected women had a higher rate of intraoperative need for blood transfusion as well as increased incidence of postpartum endometritis, sepsis, pneumonia, admission to the intensive care unit, and maternal death. [37]

In the HIV-infected group, morbidity and mortality were associated with infection and related to immune function, with the greatest risk being for women with a CD4 count less than 200 cells/mL. [37]

Because morbidity is increased in women infected with HIV who undergo cesarean delivery, prophylactic antibiotics should be administered. Scheduled cesarean delivery should be discussed and recommended for women with viral loads greater than 1000 copies/mL, whether or not they are taking antiretroviral therapy.

Discussion of the option of scheduled cesarean delivery should begin as early as possible in pregnancy with every pregnant woman infected with HIV, to give her an adequate opportunity to consider the choice and plan for the procedure. The risks, which appear to be greater for the mother, must be balanced with the benefits expected for the neonate. The patient's autonomy must be respected when making the decision to perform a cesarean delivery, because the potential for maternal morbidity is significant.

Consultation and follow-up with specialists in infectious disease and maternal-fetal medicine is recommended.

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Diet and Activity

During pregnancy, a healthy, well-balanced diet is recommended, and this recommendation is not altered by HIV. Certain foods need to be limited and avoided during all pregnancies. Alcohol should be avoided. Generally, eating fish low in mercury content is recommended. Caffeine must also be limited, as well as foods high in nitrites and soft cheeses. Current available evidence suggests that vitamin A supplementation during pregnancy (not to exceed 10,000 IU in the first trimester) improves birth weight. [38] Light exercise is recommended in pregnancy, and this recommendation is not altered by HIV infection. Walking and swimming are excellent programs during pregnancy. Women should discuss their exercise routine with their physician.

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Deterrence and Prevention

Currently, no vaccine is available for HIV; therefore, prevention is crucial to decreasing the risk of transmission. [39] Women must be counseled on methods to avoid transmission to others, including safe sex practice and avoiding donation of blood or organs.

Regular use of latex condoms and avoidance of unprotected intercourse is important. Treatment of genital tract infections and inflammation in both partners is important to avoid mucosal breaks. The frequent use of nonoxyynol-9 vaginal gel has been associated with increased risk of HIV acquisition in the high-risk population. Women should not share toothbrushes or razors, as small amounts of blood may be present.

In areas of the world where safe alternatives are available, breastfeeding is not recommended. This also applies to women on antiretroviral therapy. [5, 14] Passage of antiretrovirals into breast milk has been shown for several agents, including zidovudine and lamivudine. [18]

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