Reducing the Risk of HIV Transmission from Mother-to-Child: An In-Depth Guide

The National Institutes of Health guidelines for prevention of HIV transmission from mother to child were updated on March 28, 2014.

On March 28, 2014, the National Institutes of Health released updated guidelines for the prevention of mother-to-child spread of HIV. The guidelines describe how, using antiretroviral therapies, it is possible to prevent transmission of HIV from a pregnant mother with HIV to an unborn child—also known as vertical transmission.

The guideline panel recommends that all pregnant women with HIV receive combination antiretroviral therapy (cART). Combination therapy helps reduce the risk of transmission, regardless of the number of copies of HIV present in the body or the level of T cell depletion. However, in women with levels of HIV RNA exceeding 500 copies/mL to 1,000 copies/mL, guidelines recommend a drug resistance study before initiating cART therapy.

Guideline authors make several recommendations covering which treatments are preferred for use in ART-naïve pregnant women among the 3 main classes of ART medications: nucleoside analogue reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitor (NNRTIs), and protease inhibitors (PIs).

The preferred agent may vary by patients based on patient-specific factors. However, for ART-naïve pregnant women, certain agents are preferred over others including the following medications:

• NRTIs: preferred combinations of 2 NNRTIs include abacavir plus lamivudine (Epzicom) or tenofovir plus emtricitabine (Truvada)
• PIs: preferred combinations include atazanavir (Reyataz) boosted with ritonavir or lopinavir (Kaletra) boosted with ritonavir
• NNRTIs: the preferred agent is efavirenz (Sustiva) (started during the first 8 weeks of pregnancy), and nevirapine (Viramune) was listed as the next-line agent

Safety

Although limited data are available regarding the safety of cART, metaanalyses indicate that birth defects do not occur at a higher rate in women who receive antiretrovirals (ARVs) compared with women who do not receive ARVs. It is worth noting, however, that the folate antagonist antibiotic trimethoprim-sulfamethoxazole may increase the risk of birth defects, but only if used during the first trimester of pregnancy. Trimethoprim-sulfamethoxazole is often used for prophylaxis of Pneumocystis jirovecii pneumonia in patients with HIV/AIDS.

Some patients may have concerns about use of ART due to reports of birth defects with efavirenz, hepatotoxicity with nevirapine, and errors of mitochondrial DNA transcription with NRTIs. Pharmacists should be aware of the evidence regarding these concerns, although it is important to emphasize that the benefits of treatment are far outweighed by concerns about these possible rare adverse events.

Efavirenz

A metaanalysis of 21 studies in 1437 pregnant women exposed to efavirenz found no increased risk of birth defects with use of efavirenz versus use of other ARV medication. Despite this result, 2 other small trials (the Pediatric AIDS Clinical Trials Protocols 219 and 219C studies) reported a higher than normal incidence of birth defects among fetuses exposed to efavirenz in the first trimester of pregnancy (hazard ratio: 4.31; 95% CI, 1.56 to 11.86).

Nevirapine

Pregnant women taking nevirapine may have an increased need for monitoring of hepatic enzymes and should be monitored for nevirapine-related rash, which can be dangerous.

Mitochondrial DNA

In vitro studies show that the potential for suppression of synthesis of mitochondrial DNA (mtDNA) with NRTIs are highest with zalcitabine, although didanosine, stavudine, zidovudine, lamivudine, abacavir, and tenofovir have also been shown to suppress mtDNA replication. Lactic acidosis and hepatic steatosis may be related to mitochondrial toxicity induced by NRTI drug exposure. Specifically, NRTIs may induce dysfunction of mitochondrial fatty acid oxidation, leading to buildup of fatty acids in the liver.

The incidence of mitochondrial toxicity in newborns exposed to HIV is low. In a French cohort study of 1754 pregnancies of HIV-infected women that resulted in uninfected newborn infants, 8 cases of mitochondrial toxicity occurred after cART with zidovudine/lamivudine or zidovudine alone.

During Delivery and After Delivery

The NRTI zidovudine is often administered during delivery to reduce the risk of transmission during birth. After birth, newborn children may receive postexposure prophylaxis with a 2-drug combination of 3 doses of nevirapine administered to the infant during the first week of life combined with 6 weeks of treatment with zidovudine. The Centers for Disease Control and Prevention and American Academy of Pediatrics recommend that women with HIV forego breastfeeding to reduce the risk of HIV transmission to infants through breast milk.

For Further Information

This guideline is not a comprehensive description of current recommendations for prevention of vertical transmission of HIV. Full guidelines are available at http://aidsinfo.nih.gov/. Pharmacists may direct pregnant women with HIV to call the National Perinatal HIV Hotline (1-888-448-8765) for more information.