Dr. Deborah Money, an obstetrician/gynaecologist at the Oak Tree Clinic recently gave an update on the issues around HIV and pregnancy. Her presentation at St. Paul’s Hospital is summarised for Living +.

Good news about HIV and pregnancy has been coming from the Oak Tree Clinic for some time now, but Dr. Money was able to sum up their obstetrical HIV accomplishments in one sentence: No HIV+ babies born to HIV+ mothers where the mothers were being treated for HIV in the past four years. Many significant advances have been made over the past few years for the expectant mother living with HIV but it is important to note that most of these advances are limited to the western world where drug therapy and good overall healthcare are readily available. The Oak Tree Clinic has 0% vertical transmission (mother to child) as their continuing goal for their patients.

Most new infections of women with HIV are in the reproductive age group. The two main routes for HIV transmission in Canada, unprotected sex and injection drug use, are most likely to affect people 15 to 50 with very few infections outside that range. The way to prevent HIV infection in children is to be able to find out a new mother’s HIV status before delivery. By reducing her viral load to "undetectable" levels the dual benefits of improving mother’s health as well as greatly reducing the risk of transmission can be achieved. The current incidence of HIV+ babies in Canada is about 5 per 10,000 born, which is comparable to the incidence of Down’s syndrome. For this reason, offering HIV screening to all pregnant women is cost effective. Only about half of women who test positive are aware of a known risk factor (such as injection drug use, sexual behaviour or the behaviour of their partner). The test should not be mandatory as that may deter some women from receiving prenatal care and if physicians simply order it as a routine test they may miss the opportunity for counselling and determining if the patient is at risk of HIV. Often people with HIV have other health problems such as hepatitis C. Most pregnant women in B.C. are willing to be tested when offered.

About 40% of all pregnancies are unplanned (but not necessarily unexpected). For this reason, HIV counselling often comes to HIV+ women after they find out they are pregnant. There are several key issues for HIV+ women who want to become pregnant or find out they are pregnant. There is no evidence that HIV itself causes teratogenicity (congenital birth defects). Although some other viral diseases such as rubella (German measles) can cause malformations, the rate of birth defects with HIV+ mothers is the same as HIV- mothers. In Canada, an HIV+ diagnosis does not increase the rate of maternal death, but this is not the case in developing nations. Pregnancy itself does not appear to have any effect on the progression of HIV nor does it appear to change the efficacy or metabolism of HIV medications. The HIV appears to have little if any effect on the placenta or the foetus, although there is an increase in post-birth complications. Women with low CD4+ counts may be less fertile and hence are less likely to get pregnant. Low CD4+s put anyone at greater risk of PCP (pnuemocistis carinii pneumonia).

Pregnancy does alter the recommendations for drug therapy for expectant mothers, although the primary goal remains of giving the mother the most suitable regimen. Dr. Money urged that reproductive counselling should be part of all HIV care of people of reproductive age so that prospective parents can make informed decisions before pregnancy. Because of the unknown risks to the foetus of the HIV medications, some doctors recommend stopping all HIV medications before attempted conception and during the first trimester when organogenesis (the formation of the baby’s organs) is occurring. For women who become pregnant while on medication, Dr. Money usually continues the drugs through the first trimester. While the standard recommendation of triple therapy applies to expectant mothers, in some cases the side effects of the medications preclude the use of all three. Sometimes two or even one drug may be used when triple therapy causes nausea and vomiting or other side effects that are intolerable or cause reductions in drug bioavailability. The primary obstetrical aim of therapy is to reduce viral load as much as possible for three months prior to delivery.

Issues around assisted reproductive technology remain unknown for the HIV+ woman who is having difficulties conceiving. The potential toxicities and stresses of the therapies must be weighed against the benefits. Some IVF (in vitro fertilization) labs have expressed concerns about handling body fluids (ova and semen) that could contain HIV. Where couples are serodiscordant (one HIV+, one HIV-), artificial insemination can safely be used if the mother is positive and the father negative. For the reverse situation, sperm washing has been tried in some countries. The ethics of such unproven (and ethically untestable) techniques have precluded their use in Canada. Semen analysis to determine viral load and infectiousness is neither available nor quantified. Insemination (artificial or natural) from an HIV- sperm donor is currently the only safe alternative for the HIV- woman and HIV+ man. The health issues around unprotected sex between two people who are HIV+, wanting to conceive, are not known.

The rate of transmission from mother to child in B. C. was 21% before 1994. Transmission rates in the developing world are somewhat higher. The rates in Canada for 1998 were 25% for HIV+ women not receiving any HIV care and 5% for women receiving some HIV therapy. From 1995 to 1999 at the Oak Tree Clinic in Vancouver 38 pregnant women took antiretroviral therapy and all had HIV- babies.

Maternal HIV transmission occurs in late pregnancy or at time of delivery. The rate of placental transmission is under 2%. Although the placenta becomes infected with HIV it is a barrier to its spread. Many factors affect vertical transmission. Premature birth or birth weight below 2.5 kg., mother’s immune response, HLA type (human leukocyte antigen type – markers of tissue compatibility), and membrane integrity during birth (skin and mucous membranes) increase HIV transmission. Plasma viral load (pVL) has a linear correlation to transmission; one study published in The New England Journal of Medicine showed no transmission out of 57 mothers with pVL below 1000, whereas 63% transmission occurred where the pVL was above 100,000. Primary infection where pVL may be very high may also be associated with vertical transmission. Low CD4+ counts may also be correlated to transmission. Injection drug use is also associated with transmission. Chorioamnionitis (inflammation of foetal membranes) may also increase transmission. Some obstetrical issues may also increase risk. Amniocentesis (a procedure to look at amniotic fluid to find birth defects) is usually avoided because of a theoretical risk. Abruptions (haemorrhage under the placenta), preterm delivery, ruptured membranes for more than four hours, and caesarean sections after many hours of labour may also increase risk.

Breast-feeding is another route of HIV transmission. It increases the transmission by 14%, mostly in the first six months, but probably up to two years. In Canada, the stigma associated with bottle feeding may cause people to challenge a bottle-feeding mother, not realizing that it is her right to choose and that she may have private medical reasons for formula feeding. One recent study showed higher HIV transmission for women who both breast and bottle fed, lower for those who exclusively bottle fed, and lowest for women who exclusively formula fed. A possible interpretation is that breast milk does offer some immune protection from HIV, but in B. C. where formula is available free of charge to all HIV+ mothers, bottle-feeding remains the safest alternative.

Combination therapy is the preferred treatment for pregnant women. With maximal suppression of pVL, there is a minimum of drug resistance selection. The drugs should be chosen for the maximum potential for adherence and the minimum risk of side effects. Dr. Money emphasized that patient counselling was of as much importance in determining outcome for both mother and child as the selection and administration of drugs. Just as with any HIV regimen, the right therapy must be individualized for the person so that her lifestyle and diet can be accommodated by the drugs with as little interference as possible. The maximum reduction in transmission probably is achieved by reducing pVL to undetectable levels for the three months prior to delivery. Where side effects or lifestyle issues preclude triple therapy or where the mother is unwilling to accept the unknown risks of triple therapy to her baby, dual or monotherapy may be offered. There may be an increased risk of viral drug resistance, which could be reduced by selecting drugs that do not have single point mutations for resistance. The long-term foetal toxicity of any of the drugs is unknown, but short-term retrospective data show that nevirapine appears to be safe in the first trimester. The non-nucloeside, efavirenz is not recommended in pregnancy because of potential teratogenicity. Protease inhibitors frequently cause lipid abnormalities, the significance of which has not been determined in pregnancy. The high level of gastrointestinal side effects, such as nausea, vomiting and diarrhoea, along with the liver toxicity of the proteases especially for those with hepatitis C may limit their usefulness in pregnancy. The best time to start therapy for an expectant mother would be when she is ready after her first trimester. Dr. Money recommends starting after the 18-week scan, so she can reassure the mother that everything is OK. Nausea is one of the most important side effects to deal with when starting medications. When nausea and vomiting occur, Diclectin +/- Gravol may be used.

For women who have been able to achieve a consistently undetectable pVL, a vaginal birth appears to be safe. The additional risk of a surgical procedure may be greater than the benefit, given that transmission is almost 0% for such women. For those for whom therapy had not been virologically successful, for those who had remained undiagnosed until delivery and for those who had not wished to take antiretrovirals, a caesarean section reduces transmission from 22% to 8% in one recent study in the New England Journal of Medicine 1999. Even for the woman who refuses drug therapy during pregnancy, single dose drugs at delivery can dramatically reduce transmission. Such drugs include zidovudine and/or nevirapine. It is possible that a single dose of nevirapine at childbirth while significantly reducing transmission could compromise future therapy for the mother by selecting resistance mutations. Once the baby is born, PCR diagnostic tests are done at 2, 4 and 8 weeks. If the baby is not on therapy other than a single post-birth dose, a negative viral load strongly suggests the baby does not have HIV. The baby’s HIV antibodies are also followed, with the baby typically becoming HIV- at 12 to 18 months with the loss of the maternal antibodies.