If you don’t ask moms about HIV, they won’t be tested
Be proactive with pregnant women
Clinicians need to do a better job of asking women about their HIV status, sometimes even when the women are only thinking about becoming pregnant, experts say.
The national effort to eliminate vertical transmission of HIV breaks down at the individual level when physicians are reluctant to actively identify pregnant women who may be infected. And while some studies have shown that physicians do a much better job of identifying HIV-infected women among African-American and lower income populations, the same studies show that they often ignore the possibility among their white, middle-class patients.1
The stigma of HIV infection may make it uncomfortable for some physicians to broach the subject with their middle-class patients, which is why they need to look at this as just another prenatal test, experts suggest.
The HIV test should be as commonplace as syphilis testing, says Marc Bulterys, MD, PhD, medical epidemiologist for the Centers for Disease Control and Prevention in Atlanta.
Clinicians could make HIV testing and counseling routine by simply giving women a videotape and some brochures they can peruse while waiting in the office, suggests Lynne Mofenson, MD, associate branch chief for clinical research in the Pediatric, Adolescent and Maternal AIDS Branch of the National Institute of Child Health and Human Development at the National Institutes of Health (NIH) in Rockville, MD.
"Then, when women have their blood drawn, the physician can say, I do a number of tests routinely on pregnant women, and these are for syphilis, blood glucose, and HIV — is this okay?" Mofenson says. "Then if the woman doesn’t want to be tested for HIV, have her sign some documents."
Mofenson and other HIV experts offer some more suggestions for how clinicians can help stop vertical transmission of the virus:
1. Identify and counsel high-risk patients.
Because research indicates that the women who are most at risk for HIV infection are also the women who may not seek prenatal care, it’s important that clinicians identify these high-risk patients even before they become pregnant.
Clinicians treating high-risk women of childbearing age might routinely ask the women whether they are taking precautions to protect themselves from HIV infection. Clinicians could have educational material on HIV and pregnancy, including posters, available in their clinics.
The next step involves encouraging women who are at risk or who have HIV to use contraceptives. "The same women who are at risk for HIV are also at risk for an unplanned pregnancy," Mofenson says.
Also, communities that have needle-exchange programs can direct injection drug-using women of childbearing age to HIV and pregnancy counseling. Studies repeatedly show that women who abuse drugs are the least likely to seek prenatal care or HIV treatment. Any programs that target this population have the potential to greatly decrease vertical transmission.
Anti-drug efforts impede HIV care
Clinicians who work in states that forbid needle-exchange programs or that arrest women for exposing their fetuses to drugs may find it much more difficult to reach these patients. "Increasing efforts to criminalize illicit drug use as opposed to providing treatment for it might drive some of these women further from prenatal care rather than into prenatal care," Mofenson says.
"We need to make a special effort to bring pregnant infected women who are using drugs into prenatal care," she adds. "And then once she’s in prenatal care, she needs to learn her HIV status."
While Mofenson cites statistics showing that 99% of pregnant women in the United States receive prenatal care, she also acknowledges that those most at risk for HIV are the most likely to be among the 1% who do not seek medical help until they go into labor.
"Inadequate or no prenatal care is the most important reason for continuing infection in the United States today," she says.
2. Provide state-of-art antiretroviral treatment to pregnant HIV-positive women.
Two recent NIH studies strongly suggest that the amount of HIV in a pregnant woman’s blood is the prime risk factor for transmitting the virus to her baby. Plus, research on HIV-infected newborns suggests about one-third of newborns are infected in utero less than two months before delivery. In the remaining 65% of cases, infants are infected at birth.2 This means a physician’s first priority should be to lower the woman’s viral load through antiretroviral therapy administered during gestation.
Pregnant HIV-infected women should be evaluated for antiretroviral therapy the same as any other HIV-infected patients. If their viral load is over 10,000 copies of HIV RNA/ml of plasma and their CD4 cell count is less than 400 CD4 T cells/mm3, they should be started on combination therapy, Mofenson says.
Counsel women about dangers of meds
"But then you need to provide additional counseling, because we know very little about these drugs in pregnant women and the effect on their babies, and that includes AZT," she adds.
Mofenson suggests clinicians use two nucleoside analogs and a protease inhibitor. The Rockville, MD-based Food and Drug Admini stration has rated no antiretroviral in the "A" category, meaning that adequate and well-controlled studies of pregnant women have shown no risk to the fetus during the first trimester and later trimesters of pregnancy. The drugs that received a "B" rating, meaning that animal reproduction studies failed to demonstrate a risk to the fetus, include didanosine, saquinavir, ritonavir, and nelfinavir.3
Antiretrovirals, including zidovudine, zalcita bine, stavudine, lamivudine, indinavir, nevirapine, and delavirdine, were rated "C." This indicates that safety in human pregnancy has not been determined and that animal studies may have been conducted. If animal studies have been conducted, they are positive for fetal risk.3
Mofenson also recommends physicians steer clear of efavirenz, a non-nucleoside reverse transcriptase inhibitor, because the drug causes abnormalities in animals, including a central nervous system malformation in monkey fetuses.
Despite zidovudine’s "C" rating, there is considerable human data to suggest there is a very small risk to the fetus if it’s given to the woman after 14 weeks of gestation.2
Also, Mofenson says nevirapine is a good drug to include in combination therapy because it has been studied over the short term in pregnant women and it appears to be safe.
When HIV-infected women do not qualify for antiretroviral treatment, clinicians may prescribe a prophylactic perinatal transmission regimen of 100 mg zidovudine five times daily, beginning at 14-34 weeks of gestation and continuing through the pregnancy.4
During labor, clinicians can give the woman 2 mg/kg of zidovudine intravenously for more than one hour and follow this with a continuous infusion of one mg/kg intravenously until delivery. Then the baby should be given a prophylactic of 2 mg/kg oral zidovudine every six hours for the first six weeks of life, beginning as early as an hour after birth.4
3. Encourage women in labor to be tested and receive treatment.
But all of the above actions cannot be taken if the pregnant woman refuses to see a doctor until she’s in labor. And this is where clinicians in states in which HIV testing of pregnant women is not mandatory need to be aware of what is at risk.
CDC research indicates that 85% of the 15,000 HIV-infected children in the United States were infected by their mothers either before, during, or soon after birth, says Jeanne Bertolli, PhD, an epidemiologist in the mother-to-child pediatric and adolescent study section of the epidemiology branch of the CDC’s division of HIV/AIDS prevention.
HIV is particularly hard on children
HIV-infected children are vulnerable to a host of diseases, and many will develop AIDS and die before they reach their teen-age years. So the best strategy is for public health officials and clinicians to do everything they can to prevent transmission.
Some of the more exciting research published this year details how a short course of nevirapine can reduce HIV infection by nearly 50%. The treatment studied consisted of a single dose of the drug to the mother when she was in labor, followed by a single dose to the baby at three days of age, Mofenson says. This treatment was studied in Uganda and is touted by HIV experts as an excellent and inexpensive regimen that can be used in developing nations where high percentages of pregnant women are infected with HIV. (See story on nevirapine in AIDS Alert International, p. 2.)
"I would go for the nevirapine regimen only in the cases of women who can’t get AZT for at least two weeks during pregnancy, because this will prevent transmission during labor, but not transmission before labor," Mofenson says.
Also, because nevirapine has research data showing its success, Mofenson wouldn’t recommend adding unproven drugs to the short-course regimen. "Some physicians might mix nevirapine with AZT, and I think that would be a horrible thing to do," she says.
"My understanding is that some states are looking at this, and their recommendations may be different from what I just gave you, but to me, less is better than more until we can prove more is better," Mofenson explains.
The only change she advises is to give the baby a three-day dose of nevirapine instead of the single dose.
"Some hospitals are initiating rapid testing during labor so they can obtain the woman’s HIV status and offer her the nevirapine regimen," she adds.
Cesareans could provide prevention option
Other last-minute options discussed in recent months include offering HIV-infected women a cesarean section, which studies say will dramatically reduce the chance of passing the disease to the infant. The American College of Obstetricians and Gynecologists has recommended that clinicians suggest pregnant HIV-positive women have a cesarean delivery two weeks before the anticipated birth date.
The option of a cesarean should be part of a discussion between the pregnant woman and her provider, Bulterys advises.
"If the woman’s HIV infection is very well-controlled and her viral load is zero or undetectable, then we really don’t know if it would still provide an additional benefit to provide a C-section, because the transmission rate already would be very low," Bulterys says.
The stakes are high when it comes to stopping vertical HIV transmission. Without antiretroviral treatment and prophylaxis, the future of many infants born to HIV-infected women is bleak.
Based on a study of 190 perinatally HIV-1-infected children born between 1986 and 1997 in New York City, researchers found that nearly half developed AIDS by age three, and only one-third were AIDS-free at age 13.5
"Experts advise that antiretroviral therapy begin as soon as HIV diagnosis is confirmed," Bertolli says. "Adherence to medication regimens should be discussed routinely with caregivers, because a lack of adherence may lead to drug resistance."
Also, it’s critical that clinicians support caregivers in identifying problems with giving medications and developing solutions, she adds.
Maintain defenses against PCP
"You need to start treatment as early as possible, because there are several opportunistic infections that could affect really young children, and if they’re on early treatment, they’re more likely to maintain immune function," she explains.
In addition to antiretroviral drugs, HIV-infected infants need to be given a Pneumocystis carinii pneumonia (PCP) prophylaxis of trimethoprim-sulfamethoxazole at four to six weeks of age. "That’s really important, because PCP is a main killer of HIV-infected infants," Bertolli says.
4. Counsel HIV-positive women to not breast-feed their babies.
HIV-infected women in the United States should not breast-feed their babies, Bulterys states.
"The risk of transmission is about 14% through breast-feeding," he adds. "In developing countries there’s much more debate, but in the United States, it is never recommended for an HIV mother to breast-feed."
Unlike developing countries, the United States has safe and reliable drinking water sources, and formula is readily available. Therefore, babies who are fed formula are not at risk for developing diarrheal illnesses that could kill them.
Most HIV-infected women will agree with this policy, once it’s explained to them. But occasionally, the state has had to step in to prevent an HIV-infected woman from breast-feeding, such as in the case of the Oregon mother who lost custody of her four-month-old son because she insisted on being allowed to breast-feed her baby.
In the future, clinicians may be able to reduce HIV transmission from breast-feeding through the use of an antiretroviral implant. Investiga tors in Massachusetts have been studying an implant similar to Norplant that could deliver antiretroviral therapy for sustained periods in an effort to reduce vertical HIV transmission through breast-feeding.
References
1. Prenatal discussion of HIV testing and maternal HIV testing — 14 states, 1996-1997. MMWR 1999; 48:401-404.
2. Rouzioux C, Costagliola D, Burgard M, et al. Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission by use of a Markov model. The HIV Infection in Newborns French Collaborative Study. Am J Epidemiol 1995; 142:1,330-1,337.
3. Panel on Clinical Practices for Treatment of HIV Infection Convened by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation. Preclinical and Clinical Data Relevant to Use of Antiretrovirals in Pregnancy. Guidelines for the Use of Antiretroviral Agents in HIV-infected Adults and Adolescents. 1998:39.
4. Panel on Clinical Practices for Treatment of HIV Infection Convened by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation. Zidovudine Perinatal Transmission Prophylaxis Regimen. Guidelines for the Use of Antiretroviral Agents in HIV-infected Adults and Adolescents. 1998:40.
5. Pliner V, Weedon J, Thomas PA, et al. Perinatal HIV transmission collaborative study group. AIDS 1998; 12: 759-766.
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