Prenatal Care

• Prenatal Care and HIV Treatment
• HIV Drugs During Pregnancy
• Resistance, Monitoring and Other Tests
• OI Prevention and Treatment During Pregnancy
• Vaccine Use While Pregnant
• Treating Recurrent Genital Herpes During Pregnancy
• HIV and Hepatitis Coinfection
• HIV and TB Coinfection
• HIV Drugs and the Baby's Health

Prenatal Care and HIV Treatment

Prenatal care is also called antenatal care. This covers all the extra care that you receive during your pregnancy in preparation for your baby's birth.

Prenatal care is not only about medicine and about tests. It includes counselling and providing information like this booklet. It also includes advice on your general health such as taking exercise and stopping smoking.

As with all aspects of HIV care, it is very important that members of your healthcare team have had specialist experience with HIV-positive women. This includes your obstetrician, midwife, paediatrician and other support staff.

It is also important that the people responsible for providing your care understand the most recent developments in preventing mother-to-child transmission and in HIV care.

Does every HIV-positive woman need to use treatment in pregnancy?

Every pregnant woman with HIV should strongly consider treatment during pregnancy, even if it is only used for a short time or just at the end of the pregnancy and stopped after the baby is born. This is regardless of the mother's CD4 or viral load counts.

"Treat as non-pregnant adult" This is a very commonly used phrase in HIV and pregnancy. This means that generally your HIV is treated as if you were not pregnant. There are some exceptions -- particularly when you do not need treatment for your own HIV and concerning some of the commonly used HIV drugs.

"Treat as non-pregnant adult" is advice generally given when caring for HIV-positive pregnant women who need treatment. However, treatment recommendations for pregnant women are slightly different than those for other HIV-positive adults.

Usually it is best once you start HIV treatment, you continue for the rest of your life. In pregnancy people often use treatment just for a period; then they stop.

What if I do not need treatment for my own HIV?

UK guidelines recommend starting treatment while your CD4 count is about 350 cells/mm³. Treatment is not usually recommended at much higher CD4 levels unless you have HIV related health problems.

However, studies show that HIV treatment can reduce the risk of transmission even with mothers who had low viral loads that are less than 1,000 copies/ml before they started treatment, (Transmission dropped from almost 10% in untreated women to less than 1% in women treated with anti-HIV drugs.)

As a result, treatment is offered to all HIV-positive pregnant women, even those with CD4 counts over 350 cells/mm³ who have never been on treatment before.

British HIV pregnancy guidelines recommend two options for women in this situation who have higher CD4 counts:

1. Use Short Term Triple Antiretroviral Therapy (START). With START, you begin treatment during the second trimester at 20 to 28 weeks, and then stop after delivery. You can choose to plan a C-section at 38-39 weeks or a vaginal birth.
2. Use AZT three-part monotherapy (as in the 076 study) and have a planned pre-labour C-section at 38 weeks.

You will need to recognise the benefits and risks of these two options. Discuss and consider the following very carefully until you are happy with the approach you are going to use:

Benefits of START:

• Using three drugs will reduce your viral load to undetectable
• You will have a choice over mode of delivery.

Risks of START:

• You and your baby will be exposed to a greater number of drugs, which may increase the risk of premature delivery.

Benefits of AZT/C-section:

• The risk of transmission is also low (less than 1%)
• You will use fewer drugs

Risks of AZT/C-section:

• Caesarean sections are major surgery and can carry additional risks for the mother.
• A very low risk of developing resistance to AZT

The second option is only suitable for women with a high CD4 count and a low viral load who would not need to use ARV treatment for several years.

Choosing START does not mean you will definitely not have a C-section. You may need to for other obstetric reasons.

What if I'm HIV-positive and need treatment for my own HIV?

You may only find out that you are HIV-positive when you are already pregnant. As mentioned earlier, this can be a very difficult time practically and emotionally. Ask for extra support if you need it.

Guidelines currently recommend that all HIV-positive people with CD4 counts under 350 cells/mm³ should be on treatment, including pregnant women. Treatment will also depend on when in your pregnancy you are diagnosed with HIV.

If you are diagnosed early on in your pregnancy, you may wish to delay starting treatment until the end of the first trimester. This is the first 12 to 14 weeks from your last missed period. You may also want to delay treatment over this period if you already know your HIV status but have not yet started treatment.

There are two main reasons for delaying treatment.

The first is that the baby's main organs develop in the first 12 weeks in the womb. This is called organogenesis. During this time the baby may therefore be vulnerable to negative effects from any medicines, including anti-HIV drugs.

Studies have not shown any increased risk to babies whose mothers have used HIV treatment during the first trimester, compared to those who did not use treatment in this period. But some women and their doctors may still prefer to delay treatment.

A second reason to delay treatment is that most women will experience nausea or "morning sickness" in the early stage of pregnancy. This is very normal. But symptoms of morning sickness are very similar to the nausea that can occur when starting HIV treatment. You do not want (or need) to have both at the same time.

This can also make adherence harder. If you feel rough because of morning sickness, you are unlikely to want to take any treatments that increase this nausea. And if you are unlucky and get bad morning sickness or are being sick, this could cause problems with missed doses which may lead to the treatment failing and the development of resistance to anti-HIV drugs.

If morning sickness continues after the first trimester, you and your doctor should take this seriously as it could signal other problems.

If you want to begin treatment immediately, or need to start urgently because you have a low CD4 count, your doctor will recommend it.

What if I discover I am HIV-positive late in pregnancy?

Even late in pregnancy, there is still a benefit to using treatment. Even after 36 weeks, it can reduce your viral load to very low levels. Treatment for one week with combination therapy can reduce your viral load very quickly by a large amount and some anti-HIV drugs reduce the risk of HIV transmission by crossing the placenta to the baby and blocking the infection, regardless of the amount of HIV in the mother's blood.

See also: "Which drugs should I use?"

What if I am already using HIV treatment when I become pregnant?

Many women decide to have a baby when they are already on therapy. This speaks volumes about the tremendous advances made with HIV drugs.

Women feel better. They are healthier. They are thinking about long-term relationships. They are thinking about a future and possibly a family.

It is now increasingly common for women who conceive while they are on treatment to continue on treatment throughout their pregnancy.

Studies have not shown any increased risk to the mother or baby from using continuous treatment throughout the pregnancy.

HIV Drugs During Pregnancy

Which drugs should I use?

Like all decisions relating to HIV treatment, there are no hard and fast rules. Your treatment should be individual. It should suit your own health and your own situation.

Using triple combinations

It is likely you will be recommended to use AZT as part of your combination.

This is because AZT is still the only HIV drug licensed for use in pregnancy. You should have a resistance test to confirm whether AZT is active against your own HIV. This test will help decide which other drugs you need to use.

If you do not need to use treatment for your own health, you may decide to use "START" (see START). You will probably be recommended to use AZT plus 3TC as two of the drugs as there is a lot of data on them regarding pregnancy (see the box Safety Data).

However, because 3TC resistance develops very easily it you should not just use these two drugs alone. You should use them with another HIV drug in a triple combination. This third drug will probably be a protease inhibitor. Again, the resistance test will help ensure that you choose drugs that will work.

The protease inhibitor is likely to be lopinavir boosted with ritonavir (called Kaletra and in one pill) or either atazanavir boosted with ritonavir or saquinavir boosted with ritonavir.

If you plan to stop treatment straight after your baby is born a protease inhibitor has another advantage. Your body processes protease inhibitors relatively quickly. If you are taking it with AZT and 3TC, you can stop all your treatments at the same time with a low risk of resistance.

Another drug that is often used is an NNRTI called nevirapine, which is a drug that has been widely used in pregnancy.

There is however a caution against the use of nevirapine for women with CD4 counts above 250 cells/mm³ because of a risk of liver (hepatic) toxicity.

Nevirapine appears to be safe for women with lower CD4 counts (below 250 cells/mm³). There is no concern with people who have used nevirapine successfully in their combination and now have a higher CD4 count on treatment.

You will probably receive nevirapine if you start your treatment with a CD4 count less than 250 cells/mm³.

If you are already using combination therapy, you are likely to remain on the same combination. If you are using efavirenz, ddI or ddI and d4T together, you may need to stop or switch those drugs. This will also depend on what other choices are available to you. See the section about which drugs are not recommended for pregnancy.

If you have side effects, or your viral load is detectable, your doctor will also look for a possible switch in therapy.

Although it is rare, some women have even delivered babies on combinations of five or more anti-HIV drugs (sometimes called mega-HAART).

Finally, if you only find out that you are HIV-positive very late into your pregnancy or in labour you will have specific treatment. You are likely to be offered nevirapine regardless of your CD4 count because a singledose appears to be safe, nevirapine is absorbed very rapidly and is the most effective drug for reducing mother-to-child transmission in this situation.

As resistance to nevirapine develops easily, you need to use it with two other drugs. These are often AZT and 3TC (called Combivir, when together in one pill).

It is best to continue with this triple combination until your viral load is below 50 copies/ml. This will reduce the risk of resistance. If your CD4 count is less than 250 cells/mm³ you will be given a boosted protease inhibitor, instead of continuing with nevirapine, for at least a week but ideally until your viral load is undetectable.

If your CD4 count is less than 250 cells/mm³ you will be advised to continue HIV treatment but should you choose to stop treatment, you will need to stop the nevirapine before the other two drugs.

You should only continue treatment if you are strictly taking every dose as prescribed.

In some circumstances, depending on the drugs you are using and your birth plan, you may also receive AZT directly into a vein (intravenously (IV)) during labour.

Are any drugs not recommended in pregnancy?

Efavirenz is not recommended in pregnancy. This drug caused brain damage in the developing foetus in a single animal study. So far there are no reports of a similar increased risk of in human babies. But, if other treatment options are available, there is a strong caution against its use. This is most important during the first 12 weeks of pregnancy when the neural tube is developing.

If you are already 12 or more weeks pregnant and have been taking efavirenz during this time you will need two tests. Firstly, it is important that you receive early ultrasound evaluation. You will also have another test called maternal alpha foetoprotein test. This is a screening test for neural tube defects. After the first trimester, there may be no point in stopping efavirenz if you are doing well on it. Sometimes it may even be a good option to use after a late diagnosis if you have a higher CD4 and nevirapine is not recommended.

The liquid formulation of amprenavir, a less commonly used protease inhibitor, is also not recommended in pregnancy (or for children under four). This is because pregnant women and young children are unable to break down one of its components called propylene glycol. The capsule form of amprenavir does not contain propylene glycol.

ddI is not recommended in pregnancy as there is a small increased risk of birth defects with this drug.

There is also a strong warning to avoid using the drugs ddI and d4T together in pregnancy. There have been several reports of fatal side effects in pregnant women using both these drugs together. d4T is no longer recommended for first-line therapy in the UK guidelines.

As we described earlier, nevirapine is not recommended for women with higher CD4 counts (above 250mm³).

Should I expect more side effects when I am pregnant?

Approximately 80% of all pregnant women using HAART will experience some sort of side effects with these drugs. This is similar to the percentage of people using HIV treatment who are not pregnant.

Most side effects are minor and include nausea, headache, feeling tired and diarrhoea. Sometimes, but more rarely, they can be very serious.

i-Base has produced a 36-page guide, Avoiding and Managing Side Effects, which can be very helpful for anyone using HIV treatment. The sections in this booklet about getting on with your doctor can also be helpful whether or not you are on treatment.

One big advantage of being pregnant is the thorough monitoring at regular clinic visits. This will make it easier to discuss any side effects with your doctor.

Some side effects of HIV medicines are very similar to the changes in your body during pregnancy, such as morning sickness. This can make it harder to tell whether treatment or pregnancy is the cause.

Preclinical testing. Before any drugs are tested on humans they will be tested in the laboratory and on animals. This will not always show what will happen when people use the drugs, but it can provide a guide to serious problems that could occur.

Safety data means that a drug has been used safely in a certain number of people. Generally the more information we have on use of a drug in a large number of people, the more confidant we can be that it is safe to use in that population.

Nucleoside analogues (NRTIs or nukes) are one type of HIV drug and include AZT, ddI, 3TC, abacavir and tenofovir (a nucleotide). Usually a first HIV combination will include two of these drugs and either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are both types (or classes or families) of antiretrovirals that control the virus in different ways, both to each other and to NRTIs. So in addition to two nukes, triple therapy will generally contain either an NNRTI or a PI.

Many HIV medicines can cause nausea and vomiting. This is more common when you first begin taking them. If you are pregnant, though, such side effects can present extra problems with morning sickness and adherence. Some tips to reduce nausea, and to help with adherence, are included at Tips to help with morning sickness or drug-associated nausea.

You may feel more tired than usual. Again, this is to be expected, especially if you are starting HIV treatment and pregnant at the same time. Anaemia (low red blood cells) can cause tiredness. It is a very common side effect of both AZT and pregnancy. A simple blood test checks for this. If you have anaemia you may need to take iron supplements.

All pregnant women are at risk of developing hyperglycemia and diabetes during pregnancy. Women taking protease inhibitors in pregnancy may have a higher risk of this common complication. So, you should be sure to have your glucose levels closely monitored and be screened for diabetes during pregnancy. This is routine for all pregnant women.

Outside of pregnancy, protease inhibitors have been associated with increased levels of bilirubin. This is a measure of the health of your liver.

This is a side effect of the protease inhibitor atazanavir. There is not yet very much experience of using this drug in pregnancy but so far it seems to be fairly safe. Your healthcare team will follow you and your baby's bilirubin levels very carefully. This is because extremely high levels of neonatal levels may damage a baby's developing brain.

A report from the UK of 33 pregnancies of mothers using atazanavir did not show seriously high bilirubin levels in mothers or in their babies.

Pregnancy may be an additional risk factor for raised levels of lactic acid. Your liver normally regulates this. Lactic acidosis is a rare but dangerous and potentially fatal side effect of nucleoside analogues. Using d4T and ddI together in pregnancy appears to be particularly risky for lactic acidosis. This combination is now not recommended in pregnancy.

Please check the i-Base side booklet Avoiding and Managing Side Effects for more details on symptoms and monitoring.

Resistance, Monitoring and Other Tests

What about resistance?

Drug resistance is an important issue during pregnancy. Some strategies to reduce mother-to-child transmission can also easily lead to resistance.

Using only one drug (monotherapy) or two drugs (dual therapy) are not good options as the minimum treatment for an HIV-positive person. Therefore, neither of these should be used for HIV-positive women who are pregnant and require treatment for their own HIV. Of strategies for pregnant women who do not require treatment, AZT used alone is less likely to induce resistance than AZT plus 3TC or nevirapine alone.

If you are already using combination therapy and your viral load is not undetectable, it is important that you look at why this is occurring with an expert. This is very important for your own and your baby's health.

Resistance can develop when your viral load is detectable. This will affect your long-term health. Viral load at time of delivery is also strongly linked with risk of transmission to your baby.

Taking a treatment break, if not managed properly, can lead to resistance. Not taking all your pills at the right time can also lead to resistance.

It is also possible to transmit resistant virus. A baby born with drug-resistant HIV virus is much harder to treat.

We explain drug resistance and how to avoid it, and include advice on adherence, in the i-Base booklet Introduction to Combination Therapy.

Should I have a resistance test?

Current British pregnancy guidelines recommend a resistance test if you are changing therapy. These guidelines are the same as for a "non-pregnant adult". They also recommend a resistance test if you have just been diagnosed and if you are just starting therapy for the first time.

Women stopping HAART should have a resistance test on their first viral load after they stop treatment, ideally within 6 weeks. Women taking AZT monotherapy should have a resistance test on the viral load sample taken at delivery.

A resistance test is important to determine whether all the drugs in your combination will be active and working (both during pregnancy and in the future). It should be able to tell whether you were infected with resistant virus.

You should check that your doctor has included this test.

Will I need extra tests and monitoring?

Both pregnancy and HIV care require good monitoring. For HIV you will have your viral load and CD4 carefully monitored. You may also need a resistance test. Some doctors may recommend TDM (therapeutic drug monitoring). TDM uses blood tests to check whether you are absorbing the correct amount of a drug. Drug levels, particularly of protease inhibitors vary greatly between individuals and tend to be lower during pregnancy.

In addition to your HIV care you will be screened for hepatitis, syphilis and other sexually transmitted diseases, anaemia and tuberculosis (TB). Sexually transmitted diseases and vaginal infections can increase HIV transmission.

You may also need to be screened for toxoplasmosis and cytomegalovirus (CMV). These are two common infections that can be transmitted to your baby. The tests should be performed as early as possible in your pregnancy. You should be treated for these if necessary.

Your clinic will provide a thorough gynaecological check up. This will include a cervical (Pap) smear, which is particularly important if your CD4 is below 200 cells/mm³. Otherwise, tests will be fairly routine, and may vary slightly from doctor to doctor. Routine tests include blood pressure, weight and blood and urine tests.

Unless you need extra care you will probably visit your clinic monthly for most of your pregnancy and every two weeks after the eighth month.

Are there any tests that I should not have?

Prophylaxis is when you take a drug to prevent an infection or reinfection before it occurs.

Mono and dual therapy. Monotherapy is using only one HIV drug and dual therapy uses two drugs. Neither strategy has been as effective as using three drugs for treating HIV. In some circumstances though, AZT monotherapy is still recommended for reducing mother-to-child transmission.

Some tests and procedures commonly used to evaluate mothers and developing babies carry a theoretical risk of increased HIV transmission. However, this risk has not been clearly demonstrated in a study of women taking combination therapy.

HIV-positive pregnant women are generally advised to avoid the following tests unless they are essential:

• foetal scalp sampling
• cordocentis
• percutaneous umbilical cord sampling
• internal foetal labour monitoring (external ultrasound and foetal monitoring are perfectly OK)

If amniocentesis or chorionicvillus sampling are essential then covering the procedure with anti-HIV drugs is recommended.

Your healthcare team can explain what these tests are and why it is not recommended to have them.

OI Prevention and Treatment During Pregnancy

Treatment and prophylaxis for most OIs during pregnancy is broadly similar to that for non-pregnant adults. Only a few drugs are not recommended.

Your healthcare provider should check for OIs as part of your ongoing HIV care, and as your immune system recovers using HAART. You may need to be treated for other infections, especially if you are diagnosed with HIV during pregnancy.

Prophylaxis and treatment of pneumocystis jiroveci pneumonia (PCP), mycobacterium avium complex (MAC) and tuberculosis (TB) infections are recommended if necessary during pregnancy.

Prophylaxis against cytomegalovirus (CMV), candida infections, and invasive fungal infections is not routinely recommended because of drug toxicity. Treatment of very serious infections should not be avoided because of pregnancy.

Vaccine Use While Pregnant

Hepatitis B, flu and pneumococcal vaccines may be used during pregnancy. They should only be used after your viral load has become undetectable with combination therapy, however, because there is a temporary increase in viral load after vaccination.

Live vaccines including measles, mumps and rubella should not be used during pregnancy.

Treating Recurrent Genital Herpes During Pregnancy

A large number (about 75%) of women with HIV also have genital herpes. HIV-positive mothers are far more likely to experience an outbreak of herpes during labour than negative mothers. To reduce this risk, prophylaxis treatment for herpes with acyclovir is often recommended.

Herpes is very easily transmitted from mother to child. Even if someone has a HIV viral load that is below detection on combination therapy, herpes sores contain high levels of HIV. The herpes virus can also be released from the sores during labour. This will put the baby at risk from neonatal herpes and at increased risk of HIV.

Prophylaxis and treatment with acyclovir is safe to use during pregnancy.

HIV and Hepatitis Coinfection

How easy is it to transmit hepatitis C from mother to baby?

If you are co-infected with hepatitis C virus (HCV) and HIV?you may discover this through routine screening in pregnancy?there is a risk of transmission of HCV of up to 15%. Treating your HIV will reduce this risk of transmitting HCV.

BHIVA guidelines recommend a planned C-section delivery for those who are co-infected.

What about hepatitis B?

It is very likely that mothers with active hepatitis B virus (HBV) will transmit to their babies (90%). However, transmission can be prevented by immunising the baby against HBV shortly after he or she is born. This is standard practice in the UK.

It may be appropriate for the mother's combination to include HIV drugs that also work against HBV, in particular 3TC and tenofovir.

HIV and TB Coinfection

It is important to treat TB in pregnancy. Additionally HIV/TB coinfection increases the risk of mother-to-child- transmission of both infections. TB can also increase the risk of the less common in utero (in the womb rather than during labour) mother-to-child transmission of HIV.

Like HIV, TB is a much greater risk to a pregnant woman and her infant than its treatment or prophylaxis.

Most TB first line TB drugs are safe to use in pregnancy. The TB drug streptomycin is not recommended in pregnancy as it can cause permanent deafness in the baby. This drug is now only rarely used in the treatment of TB in the UK.

HIV Drugs and the Baby's Health

Some mothers and doctors have been reluctant to use or to prescribe anti-HIV drugs during pregnancy. This is out of concern about unknown effects to the baby.

It is difficult to know if there are any long-term effects.

Today, even children who were first exposed to AZT monotherapy during their mothers' pregnancy are not older than teenagers.

Children first exposed to combination therapy are not likely to be much older than 10 now.

Careful follow-up of children exposed to AZT has not shown any differences compared with other children.

All children born to HIV-positive women in the UK (and many other countries) are also being monitored. This close monitoring will provide important safety information in the future.

Ultimately, it seems clear that the biggest risk to a baby born to a mother with HIV is HIV itself. HIV drugs can prevent this.

Will HIV drugs affect the baby?

These concerns are justifiable. Unfortunately there are no definite answers, although overall the drugs do seem reasonably safe.

Some reports have looked at the risk of prematurity, birth defects and mitochondrial toxicity in babies.

Prematurity

Several studies show a greater risk of prematurity (baby born at less than 37 weeks) and low birth weight for babies born to mothers taking anti-HIV treatment with three or more drugs.

A recent British study found an overall rate of 13% (normally the rate here is about 6-8%).

This should not be a reason for a mother to avoid treatment in pregnancy, particularly if she needs it for her own health. It is important to be aware of the risks though, discuss them with your healthcare team and make sure that you are receiving the best possible treatment, care and monitoring for yourself and your baby in your situation.

Can anti-HIV drugs cause birth defects?

There have been very few reports of birth defects in babies whose mothers have taken these drugs in pregnancy. The only caution at the moment is with the drug ddI, which is not usually recommended in pregnancy in the UK.

What about mitochondrial toxicity?

Mitochondria are the "energy producing factories" within our cells. There have been a small number of reports that the use of 3TC and AZT in pregnancy may be linked to mitochondrial damage in children.

In a large study from America, medical records of over 20,000 HIV-negative children born to HIVpositive mothers were searched for abnormalities associated with mitochondrial damage. The study was designed after reports from France of two deaths of infants exposed to AZT and 3TC and six other cases of mitochondrial toxicity.

This large study failed to show evidence of fatal mitochondrial damage in children exposed to these drugs during their mothers' pregnancy. This was very reassuring.

In a rare number of cases though, short-term mitochondrial toxicity can be a problem in newborn babies. A very small number of babies have been reported with severe lactic acidosis and anaemia believed to be linked to anti-HIV drugs. All have recovered with appropriate care.

What about anaemia?

Anaemia has been reported in babies born to mothers on HIV medications but this passes quickly and rarely requires a transfusion.

Will my baby be monitored for these symptoms?

Yes. Babies born to HIV-positive mothers on treatment will be monitored very carefully.