Reproductive Options of HIV-Infected Patients
Advances in anti-HIV therapy and improved treatment of opportunistic infections have produced a significant increase in the life expectancy and quality of life of HIV-infected adults. Since the majority of HIV-infected men and women are of reproductive age, many are likely to consider becoming parents. To date, most of the attention in reproductive HIV medicine has focused on preventing mother-to-child (vertical) transmission of HIV. However, when only one partner is infected (serodiscordant couples), there is the added concern that the negative partner might become infected through unprotected intercourse (such as when attempting pregnancy). This article summarizes the reproductive options of HIV-infected individuals as well as the current treatment guidelines for pregnant women with HIV infection.
Pregnancy in HIV-Infected CouplesPrior to planning any pregnancy, couples should assess their readiness to have a child. This includes looking at their emotional, physical, and financial well-being. In the case of HIV-infected couples, health status is of utmost concern. Assessing their anticipated life expectancy is important particularly if one or both partners is not on treatment, not adhering to treatment, or failing treatment. In this case they should seek expert medical advice about potential medical complications due to HIV.
For couples in which both individuals are infected with HIV, conception can occur naturally, but with the additional risk of transmitting drug-resistant HIV to the other partner. This can be minimized if both partners have an undetectable viral load and carefully time the unprotected intercourse (not using a condom) at the midcycle, when the woman is most fertile.
Treatment with highly active antiretroviral therapy (HAART) should be initiated or optimized prior to conception in an HIV-infected woman with the goal of achieving an undetectable viral load. This will nearly eliminate any risk of vertical transmission, assuming an undetectable viral load is maintained during the pregnancy. Triple combination therapy -- including AZT (Retrovir) whenever possible -- is the standard of care for the treatment of pregnant women. In some cases treatment may need to be changed. The current perinatal guidelines recommend against the use of ddI (Videx) and d4T (Zerit) during pregnancy because of 3 reported maternal deaths due to lactic acidosis.
Another drug that may need to be avoided is efavirenz (Sustiva), which has been shown to cause a type of neural tube defect in animal studies. Since these types of defects occur in the first 4 weeks of pregnancy, a woman conceiving on this drug has the greatest risk of this birth defect occurring. Women who desire to conceive a child should reconsider whether they should be started on this drug. Those who are currently on efavirenz and want to plan a family could switch to another non-nucleoside drug such as nevirapine (Viramune). Some women choose to remain on efavirenz because their prior drug history makes it difficult to switch to other drugs. Currently there are no data in humans to assess the risk of having a birth defect from efavirenz. However, we know that the general risk of having a birth defect in humans is 1 in 40 based on data about other animal teratogens. If a woman chooses to remain on efavirenz, there may be some theoretical benefit to taking folate supplements preconceptually through the first few weeks of pregnancy. Folic acid has been shown to substantially reduce the occurrence of neural tube defects in women who are at high risk for such defects.
Women with HIV should also consider being screened for hepatitis B and C, which can be transmitted to the fetus. In the case of hepatitis C virus (HCV), there is no treatment available to decrease the risk of vertical transmission of HCV in HIV-positive women. For HIV-infected pregnant women who test positive for HCV, 23 out of every 100 infants will be infected with HCV. Newborn infants should be tested for HCV by a pediatrician between 6 and 12 months. If the infant has HCV, then mother and child should be referred to a specialist who can manage this disease.
Pregnancy in Serodiscordant CouplesIn the case where the woman is HIV positive and the male is negative, there is the risk of sexually transmitting the virus to the male during unprotected intercourse. Having an undetectable viral load in the blood does not eliminate the possibility of transmitting the virus because levels of HIV in the blood and semen or vaginal secretions are poorly correlated. The risk per act of unprotected intercourse is estimated to be between 1 in 500 and 1 in 1,000. Nevertheless, a single act of unprotected intercourse is sufficient to infect one's partner. Careful preconceptual counseling of the risks involved and advice on how to time intercourse accurately are necessary for couples prepared to risk unprotected intercourse to have a child. Couples may try to minimize the transmission by accurately timing intercourse using ovulation detection methods. The Centers for Disease Control and Prevention (CDC) does not recommend post-exposure prophylaxis (taking anti-HIV medications after a possible exposure to try to prevent infection) in cases of repeated sexual intercourse between serodiscordant couples.
Another option to consider is washed intra-uterine insemination (IUI), commonly referred to as artificial insemination. IUI eliminates the need for intercourse and subsequent risk of HIV transmission. In this case special techniques are used to separate the sperm from the seminal fluid. The sperm are then placed directly into the uterus after accurately assessing the time of ovulation. The pregnancy rate per cycle of IUI is 10% to 12% and it costs approximately $350.
There are several options available to couples in whom the male is HIV positive and the woman is negative. Conception through natural means (intercourse) creates a risk of HIV transmission to the female and is not generally recommended for the reasons discussed earlier. Insemination using donor sperm eliminates the risk of transmitting the virus to the woman and subsequently to her infant. However, removing the possibility of genetic parenthood from one partner, particularly the one whose life is threatened with disease, has tremendous moral and ethical implications and requires thorough counseling beforehand. Although a perfectly safe method, this is not the option of choice for most serodiscordant couples.
Researchers in Italy (Semprini and colleagues) pioneered inseminating HIV-negative women with sperm washed free of HIV. By eliminating the cell-associated and free virus from the semen, this process significantly reduces the risk of transmitting the virus. Using a special technique they developed in the lab, the Italian doctors have successfully performed nearly 2000 IUIs without any reported seroconversions. Although this technique is widely used in Europe, especially Italy and Spain, the CDC does not recommend IUI of women with washed sperm from men infected with HIV. This position followed a single case report of HIV transmission to a woman who underwent IUI from her HIV-positive husband in 1990. This led the American Society of Reproductive Medicine to advise against the provision of assisted reproductive technology services to HIV-infected individuals. To date, this is the only documented case of HIV seroconversion following insemination and is presumed to be a result of inadequate washing. In Europe, washed IUI is usually tested for HIV using PCR technology, but this is not routinely done in the United States. This further step essentially eliminates the possibility of HIV transmission to the woman.
Another option that is more commonly performed in the US is in vitro fertilization. This should be considered when IUI is not feasible or is unsuccessful. The specific technique used is called intracytoplasmic sperm injection (ICSI). The woman's oocytes (eggs) are harvested after undergoing ovulation induction and the male's sperm is isolated. The ICSI technique involves fertilizing each egg with one sperm instead of exposing the egg to millions of sperm as is done in IUI. Once several eggs have developed into embryos, they are then transferred back to the uterus and the woman is monitored using a blood pregnancy test to determine if implantation was successful. The success rate of ICSI in a woman under the age of 35 is 45% to 50% per cycle. Although this technique yields a higher rate of pregnancy, it is also considerably more expensive and costs approximately $12,000 per cycle.
Adoption is a final option for those couples who do not want to risk HIV transmission from unprotected intercourse or who fail or choose not to undergo assisted reproductive techniques. In practice, the presence of HIV infection in one or both partners may make adoption a challenge.
Management of HIV in Labor and Mode of DeliveryApproximately 50% of pregnant women with HIV are diagnosed for the first time during pregnancy. Also, of those women who know they are HIV positive, only half are on HAART prior to their pregnancy. This is unfortunate since almost all perinatal HIV transmission could be eliminated if women were diagnosed with HIV and treated so as to achieve an undetectable viral load before pregnancy.
The current standard of care is to treat pregnant women with HAART to try to obtain an undetectable viral load. Women who are newly diagnosed or who are currently not on treatment are offered triple combination drug therapy. Therapy is delayed until the woman is more than 10 weeks pregnant to avoid the risk of birth defects altogether. A viral load test is performed 4 to 6 weeks after starting therapy and every 3 months thereafter. The test should be performed at 35 to 37 weeks gestation in order to plan the mode of delivery. If the viral load is less than 1,000 then the woman can go into labor because the risk of vertical transmission is less than 1%. AZT is given intravenously to the mother during labor and in a syrup formulation to the infant for 6 weeks to further reduce the chance of HIV transmission. Based on expert opinion of the American College of Obstetricians and Gynecologists (ACOG), women whose viral loads exceed 1,000 (whether or not on HAART) are offered a Cesarean section. This opinion was formed solely on data that transmission of HIV is less than 1% for a viral load less than 1,000. There are no data yet that examine the risk of HIV in women with a viral load greater than 1,000 who are on HAART and undergo a Cesarean. If a Cesarean is done, it should be elective, before the onset of labor or rupture of the membranes. Studies show absolutely no benefit to a Cesarean if it is not done electively. ACOG also recommends that AZT be given for 3 hours prior to an elective Cesarean. Infants who are delivered by Cesarean are also given AZT syrup for 6 weeks.
ConclusionThe options available to couples with HIV infection are far greater today than even 5 years ago. Advances in treatment have significantly reduced the perinatal transmission rate and offer new hope to women with HIV infection who desire to have a pregnancy. Ideally, HIV-infected women should achieve an undetectable viral load prior to conception to virtually eliminate the risk of HIV transmission. However, even those who start HAART during pregnancy have less than 1% risk of transmission if they obtain and maintain an undetectable viral load.
This article was provided by The Center for AIDS. It is a part of the publication HIV Treatment ALERTS!. Visit CFA's website to find out more about their activities and publications.