HIV in Pregnancy

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. That figure now stands at less than 200 infants per year since 2010 (there were 86 perinatal transmissions in the US in 2015).

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%. 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.  Unfortunately, it has been reported that 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.

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.

In couples planning a pregnancy where only the female is HIV-infected, assisted insemination at home or with a treatment provider with her partner’s semen is the safest conception option after ART (antiretroviral therapy) has been initiated and maximum viral suppression has been attained.

In couples planning a pregnancy where only the male partner is infected, natural conception carries a risk of sexual transmission to the uninfected female and alternatives to natural conception are the safest options. Safe alternative options include adoption or sperm donation with assisted reproduction techniques. If a couple cannot or declines alternatives to natural conception, counseling regarding pre-exposure prophylaxis(PreP), sperm analysis, sperm washing, and transmission risks should be reviewed. While antiretroviral therapy can reduce viral load in the blood to undetectable levels, semen analysis is recommended prior to attempting conception as HIV-infected men can still have a substantial viral concentration in semen in the presence of an undetectable plasma viral load. If HIV viral load cannot be suppressed, semen washing can be considered with appropriate counseling as it 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.  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. Furthermore, pregnancy does not seem to affect survival of women infected with HIV. 

For concordant couples (both partners are HIV-infected) who wish to conceive, both partners should attain maximum viral suppression and be screened and treated for genital tract infections before attempting conception. For serodiscordant couples who want to conceive, in addition to above, counseling should include the recommendation to only attempt conception once antiretroviral therapy (ART) is started and viral loads are undetectable. Additionally, NIH guidelines include educating patients regarding PrEP in serodiscordant couples. Recommendations regarding periconception administration of antiretroviral PrEP for HIV-uninfected partners are an additional tool to reduce the risk of sexual transmission and are continually evolving. The current 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. FDA labeling information and perinatal ART guidelines permit off-label using in pregnancy, however safety data regarding teratogenicity are limited. 

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.  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 sensitivity. Timed condomless sex has low cost but necessitates understanding how to precisely predict the fertile period in a menstrual cycle.

Clinical features

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. Women with HIV should be screened for current and past exposure to intimate partner violence and depression and referral made to supportive and mental health services if indicated.

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.

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 and the National Institute of Health, is associated with higher testing rates among pregnant women. However, some states have laws that prohibit this approach and mandate that patients sign consent forms for testing, known as the opt-in approach. 

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 to decide whether to start antiretroviral medications. Moreover, newer guidelines now recommend initiation of ART for all HIV-infected individuals, regardless of CD4 count, to reduce the morbidity and mortality associated with HIV infection and the risk for all modes of transmission.

If a viral load is detected, antiretroviral drug resistance studies (HIV genotype) should be sent but providers should not wait for results before initiation of ART. In general, pregnancy has not been associated with a risk of rapid progression of HIV. 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.

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 testing is recommended for all pregnant women. HIV-infected pregnant women who screen negative for HBV (i.e., HBsAg-negative, anti-HBc-negative, and anti-HBs-negative) should receive the HBV vaccine series. 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. Women who are co-infected with HIV and chronic hepatitis B may require different management in pregnancy.  Current guidelines recommend tenofovir disoproxil fumarate plus lamivudine or emtricitabine. 

Co-infection with HIV and hepatitis C virus (HCV) is common and may range from 17-54%.  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.

Chronic carriers of HBV or HCV should receive education on the importance of informing sexual partners, household contacts, and needle-sharing contacts and review precautions to decrease transmission.

Vaccination

Vaccinations should be kept updated. During pregnancy, live attenuated vaccines (eg, measles-mumps-rubella [MMR], varicella, Bacille Calmette-Guérin [BCG] vaccines) should be avoided. Inactivated annual influenza, H1N1, and tetanus vaccines should be administered to all pregnant women, including women who are HIV positive. Hepatitis A and B vaccines (if non-immune) and pneumococcal vaccines should be administered to HIV-positive pregnant women.

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 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).   Additionally, raltegravir is an integrase inhibitor with a growing body of data that is reassuring in pregnancy. There are insufficient data to allow recommendations regarding the use of entry inhibitors in pregnancy.

Guidelines for perinatal ART were revised in January 2017 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 and refer to updated guidelines (published annually).

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