HIV AIDS and pregnancy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editors-in-Chief: Ujjwal Rastogi, M.B.B.S. [2]
Overivew
About 120,000 to 160,000 women in the United States are infected with HIV. Nearly one out of four of these women are unaware of their disease, which puts them at high risk of passing the virus to their babies. Mother-to-child transmission is the most common way children become infected with HIV. Nearly all AIDS cases in U.S. children are because of mother-to-child transmission.
Epidemiology
According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), 19.2 million women are living with HIV/AIDS throughout the world. In many countries, the rate of HIV infection in women is rising faster than in any other group.
Mother to child transmission
- Not all women who have HIV will give it to their children. Without treatment or breastfeeding about 25% (1 in 4) of pregnant women with HIV will transmit the virus to their babies.
- HIV transmission is reduced from 25% to less than 2% in women taking ART before and during birth, and if their babies are given therapy after birth. Before the current ART era, each year in the United States alone, approximately 2000 babies were infected with HIV. Despite increasing HIV prevalence, the HIV infected infants are approximately 300 per year.[1]
Prevention Challenges
- The main challenge to preventing mother-to-child HIV transmission remains the fact that too many women don’t know they are HIV positive and they are not being routinely tested when pregnant.
- At the same time, many women aren’t aware that the right treatment can reduce the risk of passing the virus to their babies.
- Other important challenges include:
- Sexual Contact with HIV-infected Men : The risk factors for women have changed. Earlier in the epidemic, more women were exposed to HIV through injection drug use. During the 1990s, women were increasingly likely to become infected through sexual contact with HIV-infected men. This is why women should know their own -- and their partners’ -- HIV status and risk factors.
- Lack of Prenatal Care : Women at highest risk for HIV often don’t get prenatal care or don’t have access to ongoing care during their pregnancy. These women are more likely to enter the delivery room not knowing their HIV status, and have not taken the antiretroviral drugs that can treat their own disease and reduce the risk of transmitting to their infant.
- Problems with Treatment : Many HIV-infected women and their infants still do not receive the correct drugs and other treatment or do not take the drugs properly. They may not get treatment or medical care. They may not live close to an HIV specialist who can make sure they receive proper treatment and care. Or they simply don’t have the information and resources to make decisions about their future
HIV Testing
HIV testing is recommended for all pregnant women. HIV testing is provided to pregnant women in two ways:
- Opt-in : In areas with opt-in testing, women may be ofered HIV testing. Women who accept testing will need to sign an HIV testing consent form.
- Opt-out : In areas with opt-out testing, HIV testing is automatically included as part of routine prenatal care. With opt-out testing, women must specifically ask not to be tested and sign a form refusing HIV testing. The Centers for Disease Control and Prevention (CDC) recommends that opt-out testing be provided to all pregnant women.
CDC Recommendations
- In the 2006 Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Womenin Health-Care Settings, CDC recommended the opt-out approach to testing for all adult and adolescent patients in health-care settings, including pregnant women.
- These recommendations emphasize:
- Universal “opt-out” HIV testing for all pregnant women early in every pregnancy;
- A second test in the third trimester in certain geographic areas or for women who are known to be at high risk of becoming infected (e.g., injection-drug users and their sex partners, women who exchange sex for money or drugs, women who are sex partners of HIV-infected persons, and women who have had a new or more than one sex partner during this pregnancy);
- Rapid HIV testing at labor and delivery for women without a prenatal test result; and
- Exploration of reasons that women decline testing.
Treatment
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.[2]
Therapeutic goals of ART in pregnancy
- Reduction of perinatal transmission of infection.
- Treatment of maternal HIV disease.
ART Regimen
Preferred agents include the following:
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.[3]
- 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.[4]
- 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:[3]
- 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.
- Recommendations for Nevirapine:[3]
- 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.
Antepartum Care
NIH Recommendations
Monitoring of the Woman and Fetus during Pregnancy
- CD4 cell count should be monitored at the initial antenatal visit (AI) and at least every 3 months during pregnancy (BIII). Monitoring of CD4 count may be performed every 6 months in patients on antiretroviral treatment (ART) for more than 2–3 years who are adherent to therapy, clinically stable, and have sustained viral suppression (BIII).
- Plasma HIV RNA levels should be monitored at the initial visit (AI); 2–4 weeks after initiating (or changing) antiretroviral (ARV) drug regimens (BI); monthly until RNA levels are undetectable (BIII); and then at least every 3 months during pregnancy (BIII). HIV RNA levels also should be assessed at approximately 34–36 weeks’ gestation to inform decisions about mode of delivery.
- Genotypic ARV drug-resistance testing should be performed at baseline in all HIV-infected pregnant women with HIV RNA levels >500–1,000 copies/mL, whether they are ARV-naive or currently on therapy (AIII). Repeat testing is indicated following initiation of an ARV regimen in women who have suboptimal viral suppression or who have persistant viral rebound to detectable levels after prior viral suppression on an ARV regimen (AII).
- Monitoring for complications of ARV drugs during pregnancy should be based on what is known about the adverse effects of the drugs a woman is receiving (AIII).
- First-trimester ultrasound is recommended to confirm gestational age and, if scheduled cesarean delivery is necessary, to guide timing of the procedure.
- Given the limited data on the effect of combination ARV drugs on the fetus, most experts would recommend second-trimester ultrasound to assess fetal anatomy for women who have received combination ARV regimens during the first trimester, particularly if the regimen included efavirenz (BIII).
- In women on effective combination ARV regimens, no perinatal transmissions have been reported after amniocentesis, but a small risk of transmission cannot be ruled out. If amniocentesis is indicated in HIV-infected women, it should be done only after initiation of an effective combination ARV drug regimen and, if possible, when HIV RNA levels are undetectable (BIII). In women with detectable HIV RNA levels in whom amniocentesis is deemed necessary, consultation with an expert should be considered.
Intrapartum Care
NIH Recommendations
Intrapartum Antiretroviral Therapy/Prophylaxis
- Intrapartum intravenous zidovudine is recommended for all HIV-infected pregnant women, regardless of their antepartum regimen, to reduce perinatal transmission of HIV (AI).
- For women who are receiving a stavudine-containing antepartum regimen, stavudine should be discontinued during labor while intravenous zidovudine is being administered (AI).
- Women who are receiving an antepartum combination antiretroviral (ARV) drug regimen should continue this regimen on schedule as much as possible during labor and before scheduled cesarean delivery (AIII).
- Women receiving fixed-dose combination regimens that include zidovudine should receive intravenous zidovudine during labor while other oral ARV components are continued (AIII).
- For women who have received antepartum ARV drugs but have suboptimal viral suppression near delivery (i.e., HIV RNA >1,000 copies/mL), scheduled cesarean delivery is recommended (AI). The addition of single-dose intrapartum/newborn nevirapine is not recommended (AI).
- Women of unknown HIV status who present in labor should undergo rapid HIV antibody testing (AII). If the results are positive, a confirmatory HIV test should be done as soon as possible and maternal/infant ARV drugs should be initiated pending results of the confirmatory test (AII). If the confirmatory HIV test is positive, infant ARV drugs should be continued for 6 weeks (AI); if the test is negative, the infant ARV drugs should be stopped.
- Intravenous zidovudine is recommended for HIV-infected women in labor who have not received antepartum ARV drugs and infant combination ARV prophylaxis is recommended for 6 weeks (AII).
Related Chapters
Reference
- ↑ Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JA, Koopmans PP (1998). "Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway". AIDS. 12 (14): 1735–44. PMID 9792373. Retrieved 2012-06-11. Unknown parameter
|month=ignored (help) - ↑ Bulterys M, Weidle PJ, Abrams EJ, Fowler MG (2005). "Combination antiretroviral therapy in african nursing mothers and drug exposure in their infants: new pharmacokinetic and virologic findings". J. Infect. Dis. 192 (5): 709–12. doi:10.1086/432490. PMID 16088819. Retrieved 2012-02-22. Unknown parameter
|month=ignored (help) - ↑ Powis KM, Kitch D, Ogwu A, Hughes MD, Lockman S, Leidner J, van Widenfelt E, Moffat C, Moyo S, Makhema J, Essex M, Shapiro RL (2011). "Increased risk of preterm delivery among HIV-infected women randomized to protease versus nucleoside reverse transcriptase inhibitor-based HAART during pregnancy". J. Infect. Dis. 204 (4): 506–14. doi:10.1093/infdis/jir307. PMID 21791651. Retrieved 2012-03-23. Unknown parameter
|month=ignored (help) - ↑ Lockman S, Hughes MD, McIntyre J, Zheng Y, Chipato T, Conradie F, Sawe F, Asmelash A, Hosseinipour MC, Mohapi L, Stringer E, Mngqibisa R, Siika A, Atwine D, Hakim J, Shaffer D, Kanyama C, Wools-Kaloustian K, Salata RA, Hogg E, Alston-Smith B, Walawander A, Purcelle-Smith E, Eshleman S, Rooney J, Rahim S, Mellors JW, Schooley RT, Currier JS (2010). "Antiretroviral therapies in women after single-dose nevirapine exposure". N. Engl. J. Med. 363 (16): 1499–509. doi:10.1056/NEJMoa0906626. PMC 2994321. PMID 20942666. Retrieved 2012-03-23. Unknown parameter
|month=ignored (help)