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2 HIV in pregnancy

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Contents

Objectives

When you have completed this unit you should be able to:

HIV infection in pregnancy

2-1 Is HIV infection common in pregnant women?

In Africa, where HIV infection is usually spread by sexual intercourse, HIV is more common in women than in men. In South Africa in the public health service during 1990 less than 1% of pregnant women were HIV positive. Then the prevalence increased rapidly, and has remained between 28 and 30% from 2004 onwards. The rates of infection vary widely from region to region. In some regions up to 40% of all pregnant women are HIV positive. Today about 260 000 HIV-positive women deliver infants in South Africa each year.

Almost a third of pregnant women within the public health service in South Africa are HIV positive.

2-2 Should pregnant women be screened for HIV?

Yes. All women should be tested for HIV when they first book for antenatal care, unless they are women living with HIV and already on antiretroviral (ARV) treatment. HIV infection in women is often diagnosed for the first time when they are screened during pregnancy. HIV screening is very important as it is the gateway to care. Therefore, women should book early for antenatal care and all should be offered screening for HIV infection. This should be done by 12 weeks of gestation or as soon as possible thereafter. In South Africa all pregnant women, except women living with HIV on ARV treatment, should be screened for HIV unless they ask not to be screened.

If the first HIV screen is negative in early pregnancy, it should be repeated after 12 weeks and again around 32 weeks gestation to detect any late infections.

All pregnant women should be offered HIV screening by 12 weeks gestation.

2-3 How may pregnant women be screened for HIV infection?

A blood test is used to screen for antibodies to HIV. The presence of HIV antibodies indicates the presence of HIV infection. A number of tests are available to screen for HIV antibodies. Usually the rapid test is used. Rapid tests are cheap, highly accurate and can be done on a drop of blood in the antenatal clinic. Two positive rapid tests, using kits from two different manufacturers on two separate blood samples, are needed before a definite diagnosis of HIV infection is made, in order to be sure that the diagnosis is correct.

2-4 Can HIV be transmitted from a pregnant woman to her fetus?

Yes. HIV can cross the placenta from mother to fetus at any time during pregnancy. Without antiretroviral (ARV) prophylaxis, the risk of transmission up until the last few weeks of pregnancy is about 5%. However, most fetal infections during pregnancy takes places in late pregnancy or during labour and delivery. The combined risk of HIV transmission to the fetus during pregnancy, labour and delivery is about 20% if ARV prophylaxis is not used (5% during pregnancy and 15% during labour and vaginal delivery). The spread of HIV from a mother to her fetus or infant is called mother-to-child transmission (MTCT) or vertical transmission. Avoiding vertical transmission is one of the most important methods of preventing the spread of HIV in a community. In women not on antiretroviral treatment (ART) who do not breastfeed, most vertical transmission takes place during labour and delivery.

Note
HIV has been found as early as 8 weeks of gestation in aborted fetuses. First trimester HIV infection may cause abortion and be more common than is presently believed. It is thought that the risk of HIV crossing the placenta in pregnancy increases in the last weeks of pregnancy as the lower segment is being formed.

2-5 Which HIV-positive women are at high risk of infecting their infants with HIV during pregnancy?

All HIV-positive women are at risk of infecting their fetus. However, the following women have the greatest risk of transmitting HIV to their fetus:

Women who become infected during pregnancy and women with advanced HIV infection have high viral loads that increase their risk of vertical transmission of HIV. It has been suggested that women not on ART who have an antepartum haemorrhage or an amniocentesis may also have a higher risk of transmitting HIV to their infants.

2-6 What are the benefits of antenatal HIV screening?

  1. The risk of HIV transmission to the fetus during pregnancy, labour and delivery can be reduced to a very low level.
  2. Women found to be HIV positive may decide to have a termination of pregnancy if before 13 weeks or with impaired health or extremely poor socio-economic circumstances if before 20 weeks gestation.
  3. Women who are HIV negative can be reassured and be advised to practise safer sex to lower the risk of becoming infected.
  4. Women who are living with HIV should be encouraged to practise safer sex to avoid infecting others.
  5. Clinical signs of HIV infection may be detected early and complications treated in both the mother and her infant.
  6. Lifelong ARV treatment with 3 drugs will be given to all women living with HIV.
  7. Infants born to women living with HIV can be correctly managed.
  8. Women living with HIV can be counselled about infant feeding options while HIV-negative women should be encouraged to breastfeed.
  9. Women living with HIV may decide not to have any more children.

All pregnant women should be counselled about the benefits of knowing their HIV status. This must be done at the first antenatal (booking) visit.

All pregnant women should be counselled about the benefits of knowing their HIV status.

Yes. Verbal consent must be obtained from all women before they are screened for HIV infection. Provider initiated counselling and testing will result in a high uptake of HIV testing. All antenatal women must be informed about investigations, specifically mentioning the HIV test that will routinely be done at the first antenatal visit. This information can be given in a group or individually. Thereafter each woman must be asked individually whether she wants a HIV test prior to taking blood. Women declining a HIV test must be referred to the counsellor for comprehensive counselling. This ‘opt out’ method increases the number of women who are screened for HIV. Screening of individuals without their consent is a violation of human rights.

The results of the HIV screen must be added to the antenatal card so that, with shared confidentiality, all health workers caring for her and her infant know her status.

2-8 How should women be told the results of the screening test?

The results should be given privately to each woman. The implications of the results should be explained and post-test counselling offered if needed. Nurses, doctors, social workers or trained lay counsellors usually provide counselling. It is very important that breaking the news of a positive HIV test be done correctly. The rapid test gives the great benefit of same-day results which avoids a long wait for the test outcome.

2-9 When should termination of pregnancy be considered in HIV-positive women?

The option of termination of pregnancy should be discussed with women living with HIV if the gestational age is less than 13 weeks and up to 20 weeks for women with impaired health or poor socio-economic circumstances. Most of these women will elect to continue with their pregnancy, especially with ARV treatment now available.

The following should be taken into consideration when termination of pregnancy is discussed with the mother:

  1. The stage of her HIV infection is important. Clinical signs of stage 3 or 4 infection indicate a much shorter life expectancy for the mother if adherence to ARV treatment is poor.
  2. Other children and family members may have HIV infection and need care.
  3. The family support structures. Who will look after this child if the mother becomes ill or dies?
  4. The risk of the fetus or newborn infant becoming infected with HIV must be explained to the mother.

Every effort should be taken to prevent unplanned or unwanted pregnancies in women living with HIV. The primary goal in preventing HIV infection is to prevent parents-to-be from becoming infected with HIV.

2-10 What precautions should HIV-negative women take to avoid becoming infected in pregnancy?

HIV-negative women should take precautions not to become infected with HIV both during pregnancy and breastfeeding. Becoming infected with HIV during pregnancy or while breastfeeding, or in the weeks before falling pregnant, places the fetus or infant at high risk of also becoming infected. As with non-pregnant women, the best precaution is either not having sexual intercourse or to have intercourse with a single HIV-negative partner only. If both such sexual partners are faithful to each other and are not abusers of intravenous drugs, there is no risk of HIV infection. High-risk sexual activity by either partner, such having multiple sexual partners, must be avoided at all costs during pregnancy and breastfeeding. If this is not possible then a condom must always be used.

2-11 Does HIV have an effect on the pregnancy?

Yes. Pregnancy complications are far commoner in women living with HIV. They occur most frequently in women with clinical signs of advanced HIV infection.

2-12 Which pregnancy complications are commoner in women who are living with HIV and not on antiretroviral treatment?

  1. Infections
    • Pulmonary and extra-pulmonary tuberculosis
    • Other sexually transmitted diseases
    • Urinary tract infection
    • Pneumonia
    • Opportunistic infections
    • Severe chicken pox or shingles (Varicella zoster infections)
    Note
    Any pregnant woman who presents with pneumonia must be suspected of having HIV infection.
  2. Early pregnancy complications
    • Abortion (miscarriage)
    • Ectopic pregnancy
  3. Late pregnancy complications
    • The risk of stillbirth is doubled
    • Chorioamnionitis
    • Intra-uterine growth restriction, especially if the mother is underweight
    • Abruptio placentae
    • Anaemia
    • Preterm labour and prelabour rupture of the membranes, especially if chorioamnionitis is present
Note
As a result of pregnancy complications, the neonatal mortality rate is increased fivefold if the mother has advanced HIV infection (AIDS).

2-13 Are there any procedures in pregnancy which may increase the risk of HIV transmission?

Amniocentesis and external cephalic version may possibly increase the risk of vertical transmission. Amniocentesis should only be done if there is a good indication and there is easy access to a pool of amniotic fluid, without having to pass through the placenta. ARV treatment with 3 drugs should be started 4 weeks, but preferably 6 weeks before the procedure if the woman is not already on ARV treatment. Viral loads should be determined prior to the procedures. Both procedures will be safe if women are on ARV treatment and known to have non-detectable viral loads.

HIV treatment in pregnancy

2-14 What is the benefit of antiretroviral drugs in pregnancy?

ARV drugs are used during pregnancy to both treat HIV infection in the mother and reduce the risk of HIV transmission to her infant. The mother will then stay on lifelong ARV treatment. Healthy pregnant women living with HIV and on ART with a non-detectable viral load can look forward to a normal pregnancy and avoid the complications as mentioned in section 2-12.

2-15 How effective are antiretroviral drugs in reducing HIV transmission?

Treatment with ARV drugs during pregnancy, labour and delivery reduces the risk of HIV transmission from mother to infant. If ARV drugs are given, the transmission rate during pregnancy, labour and delivery for non-breastfeeding women can be reduced from 20% to 0.5%. The risk of transmission is lowest if 3 ARV drugs are used. The risk of transmission through breastfeeding if on 3 ARV drugs is about 0.1% per month of breastfeeding.

HIV transmission during pregnancy, labour and delivery is 0.5% when on HIV treatment with 3 antiretroviral drugs.

2-16 Which antiretroviral drugs are used to treat pregnant women?

The most commonly used drug to reduce the risk of mother-to-infant transmission during pregnancy is TLD as a daily single pill fixed dose combination of TDF (tenofovir), 3TC (lamivudine) and DTG (dolutegravir).

TDF (tenofovir), FTC (emtricitabine) and EFV (efavirenz) as a single daily pill fixed dose combination (FDC) regimen was the previous first line regimen. Many women living with HIV will still be on FDC.

TDF, 3TC and DTG as a daily single dose combination (TLD) regimen are the ARV drugs of choice for HIV treatment during pregnancy.

Note
The global pharmaceutical company Mylan manufactures TLD and uses the same name for their trade name. Trade names of the fixed dose pill of TDF, FTC and EFV include Odimune, Tribuss, Atroiza and Atripla.

2-17 How can antiretroviral drugs be used to reduce the risk of vertical transmission of HIV?

ARV drugs can be used in a number of ways to reduce the risk of mother-to-child transmission of HIV:

  1. ARV treatment with 3 drugs will reduce the viral load in most women to non-detectable levels. As a result the risk for vertical transmission is reduced during pregnancy, labour and breastfeeding to very low levels.
  2. Treatment (therapy) with ARV drugs is given to both treat HIV infection in the woman and reduce the risk of HIV transmission to her infant. ARV treatment with 3 drugs as a single pill fixed dose (TLD) regimen is started when pregnant women are diagnosed to be HIV positive. This will reduce the viral load in the maternal blood.
  3. Treatment must be started in all women living with HIV irrespective of their CD4 count and the stage of the disease. The treatment is continued for life. This management is according to the WHO Option B+ programme.
  4. The prophylactic use of a single TLD tablet with a single dose of neviropine (NVP) during labour, is used when pregnant women decline taking 3 ARV drugs, defaulted their treatment or are only diagnosed to be HIV positive during labour. After delivery these women should be started on TLD treatment for life.
  5. Prophylactic daily NVP syrup is given to infants after delivery. This is particularly important in breastfed infants if their mothers are not taking ARVs or if on ART with a viral load of 1000 copies/ml or more.
Note
All countries have implemented WHO Option B+. In South Africa Option B+ was implemented in 2015.

It is best to start treatment with TLD as soon as the diagnosis of HIV is made.

2-18 What is the dose of TLD and FDC?

TLD is a single fixed dose regimen that consists of TDF 300 mg, 3TC 300 mg and DTG 50 mg. TLD is taken once a day early in the morning with breakfast.

FDC is a single pill fixed dose regimen that consist of TDF 300 mg, FTC 200 mg and EFV 600 mg. One FDC pill is taken once a day at bedtime (and not at suppertime).

2-19 When is AZT used for prophylaxis during pregnancy?

If AZT is used alone to reduce the risk of HIV transmission during pregnancy (WHO Option A) the dose is 300 mg (three 100 mg capsules twice a day). This option can be used if women living with HIV decline to use or cannot tolerate combination ARVs.

2-20 Can DTG cause fetal neural tube defects?

The neural tube closes 4 weeks after conception or 6 weeks after the date of the last normal menstrual period. If a portion of the neural tube remains open the baby will be born with spina bifida.

The background risk for neural tube defects is 1:1000. If women are taking a DTG containing ARV regimen during the first 4 weeks since conception the risk increases slightly to 3:1000.

Note
The result of a birth outcome surveillance of 119,477 women in Botswana as reported by Zash RM et al, NEJM, July 2019.

2-21 Can EFV cause congenital abnormalities or harm the fetus?

There was a concern about a possible association between use of EFV in the first trimester of pregnancy and congenital abnormalities. Sufficient information is now available that supports the safety of EFV in the first trimester. There is no need to postpone treatment with ARVs if women are in the first trimester.

2-22 What is the role of vitamins in reducing vertical transmission of HIV?

There is no evidence that giving vitamins, especially vitamin A, during pregnancy reduces the risk of vertical transmission of HIV from mother to fetus in most communities. A high dose of vitamin A during the first trimester may cause congenital abnormalities. Therefore, if women take vitamins during pregnancy, they should not take more than one multivitamin tablet a day.

HIV and AIDS during pregnancy

2-23 Is AIDS an important cause of maternal death?

As the HIV epidemic spread, the number of pregnant women dying of advanced HIV infection (AIDS) increased dramatically. In some countries, such as South Africa, AIDS is now the commonest cause of maternal death. However the number of maternal deaths caused by HIV has declined by about 50% since 2011 due to universal ART.

Note
The Seventh Triennial Report on Confidential Enquiries into Maternal Deaths in South Africa (2014 to 2016) showed that non-pregnancy related infections as a result of HIV infection remains the commonest cause of maternal death. Most women in this group die due to tuberculosis, bacterial and Pneumocystis carinii pneumonia.

Non-pregnancy related infections as a result of HIV infection is the commonest cause of maternal death in South Africa.

2-24 Does pregnancy increase the risk of progression from asymptomatic to symptomatic HIV infection and AIDS?

Pregnancy appears to have little or no effect on the progression from asymptomatic to symptomatic HIV infection. However, in women who already have symptomatic HIV infection and not on ARVs, pregnancy may lead to a more rapid progression from stage 3 to 4 disease.

Progression of HIV infection during pregnancy can be monitored by:

  1. Laboratory tests
  2. Clinical symptoms and signs

2-25 Which laboratory tests indicate the progression of HIV infection?

  1. A falling CD4 count is an important marker of progression in HIV. It is an indicator of the degree of damage to the immune system. The normal CD4 count is 700 to 1100 cells/µl. A CD4 count below 200 cells/µl indicates severe damage to the immune system.
  2. A high viral load indicates a large number of virus particles in the blood and gives an idea as to how fast the HIV infection is progressing to AIDS. This test is used to monitor the response to ART.

The CD4 count is an important marker of HIV progression during pregnancy.

2-26 How is the clinical severity of HIV infection classified?

The World Health Organisation (WHO) classification of clinical staging is used in both pregnant and non-pregnant individuals. Stage 1 is very mild while stage 4 is most severe. Life expectancy is best with stage 1 and worst with stage 4.

WHO staging is as follows:

Stage 1: Clinically well. Generalised lymphadenopathy may be present.

Stage 2: Mild weight loss or minor rashes or recurrent upper respiratory tract infections.

Stage 3: Moderate weight loss with oral thrush, pulmonary tuberculosis (TB), or severe bacterial infections.

Stage 4: Severe HIV-associated (opportunistic) infections (i.e. atypical pneumonia, esophageal thrush, extrapulmonary TB), cancer and wasting.

HIV infection is classified clinically into four stages.

Stage 4 HIV disease is also called AIDS. Therefore the complications seen in stage 4 are called ‘AIDS-defining conditions’. This is confusing to many as the word ‘AIDS’ is often used incorrectly to mean any stage of HIV infection where a women have symptoms and signs of illness.

Women with stage 4 HIV infection have AIDS.

2-27 Can an HIV-positive woman be cared for in a primary-care clinic?

Most women who are HIV positive are clinically well with a normal pregnancy. Others may only have minor problems (grade 1 or 2). These women can usually be cared for in a primary-care clinic throughout their pregnancy, labour and puerperium provided their pregnancy is normal and they are healthy irrespective of their CD4 counts. Women with pregnancy complications should be referred to hospital as would be done with HIV-negative women. Women with HIV-related problems who do not respond to treatment at a primary-care clinic may have to be referred to an HIV/ARV (antiretroviral) clinic where staff are trained to care for women with more severe HIV infection. Due to the large numbers of women, the HIV/ARV clinics cannot see all pregnant women who have minor problems related to HIV infection.

Most HIV-positive women who are clinically well during their pregnancy can be cared for at a primary-care clinic.

It is very important that the primary-care clinic and the HIV clinic work in close partnership. Maternal and HIV care must be integrated.

The primary-care clinic and the HIV clinic must work together in a close partnership.

2-28 How are pregnant women with HIV infection managed at a primary-care clinic?

In a country with limited healthcare resources the management of women with HIV infection or AIDS in pregnancy is restricted to affordable protocols. The management of pregnant women is the same as that of non-pregnant adults. All women living with HIV, irrespective of the CD4 count or stage of disease, should be started on treatment with 3 ARV drugs for life. The most important step is to identify pregnant women living with HIV.

The principles of management of pregnant women with HIV infection at a primary-care clinic are:

  1. Make the diagnosis of HIV infection by offering routine HIV screening to all pregnant women at the start of their antenatal care.
  2. Assess the CD4 count in all women living with HIV.
  3. Screen for tuberculosis and stage women according to the WHO classification of HIV infection. At each subsequent visit check whether the stage of HIV infection has not deteriorated.
  4. A cervical cytology (PAP) smear should be done if the woman has not had a smear reported to be normal within the last year. If the woman is already 32 weeks or more pregnant the smear needs to be postponed to the 6 weeks postnatal visit.
  5. Good diet. Nutritional support may be needed.
  6. Emotional support and counselling.
  7. Prevention of mother-to-child transmission (PMTCT) of HIV.
  8. Start all women on 3 ARV drugs using TLD.
  9. Treating HIV with 3 ARV drugs is also called Highly Active Antiretroviral Treatment or HAART.
  10. During pregnancy the viral load count is done 12 weeks after starting ART and again at delivery. During breastfeeding the viral load is done every 6 months.

All HIV-positive women should have their CD4 count measured.

2-29 Which health workers should care for women with HIV infection?

Most women with HIV infection can be cared for by nurses at a primary-care clinic. Even in hospital, much of the care can be done by nurses. Nurse-initiated ARV treatment is essential if the large numbers of pregnant women needing treatment are to be adequately managed. Doctors should support the nurses and help with complicated problems.

Clinical staging of HIV infection

2-30 What clinical signs suggest stage 1 and 2 HIV infection?

  1. Women with stage 1 disease are generally well but may have persistent generalised lymphadenopathy.
  2. Women with stage 2 disease may have:
    • Repeated or chronic mouth or genital ulcers
    • Extensive skin rashes
    • Repeated upper respiratory tract infections such as otitis media or sinusitis
    • Herpes zoster (shingles)

Most of these women can be managed at a primary-care clinic. These clinical problems are usually treated symptomatically with simple drugs which are not expensive.

2-31 What are the important features suggesting stage 3 HIV infection?

Features of stage 3 HIV infection include:

  1. Unexplained weight loss. Pregnant women normally gain rather than lose weight.
  2. Oral candidiasis (thrush)
  3. Cough, fever and night sweats suggesting pulmonary tuberculosis
  4. Cough, fever and shortness of breath suggesting bacterial pneumonia
  5. Chronic diarrhoea or unexplained fever for more than one month
  6. Severe or repeated bacterial infections, especially pneumonia

It is important to think of these HIV-associated conditions at every clinic visit. These women may need to be referred to an HIV clinic for further investigation and management. Pulmonary tuberculosis is common in women with HIV infection. Women with pulmonary tuberculosis have stage 3 disease irrespective of their clinical condition or CD4 count.

Pulmonary tuberculosis is common in women with symptomatic HIV infection.

2-32 What are the important features suggesting stage 4 HIV infection?

Features of stage 4 HIV infection include:

  1. Severe weight loss
  2. AIDS-defining illnesses such as:
    • Severe HIV-associated (opportunistic) infections
    • Malignancies such as Kaposi’s sarcoma

Common, severe opportunistic infections include:

It is important to recognise the signs of stage 3 and 4 HIV infection.

2-33 What are the principles of managing pregnant women with AIDS?

In addition to the steps in the management of all women living with HIV, the following should be done at the HIV/ARV clinic:

Prophylactic co-trimoxazole 2 tablets daily are given when the CD4 count is less than 200 cells/ml to prevent pneumocystis pneumonia. Women with any of these signs of stage 4 HIV infection must be urgently referred to hospital.

  1. Stage the disease according the WHO classification.
  2. Treatment of opportunistic and other bacterial infections, such as pneumonia and urinary tract infections
  3. Multivitamin supplements
  4. If active tuberculosis is diagnosed, treatment must be started
  5. Urgently prepare the woman for ARV treatment
  6. Start ARV treatment according to the correct protocol
  7. Monitor the progress on ARV treatment with viral load 12 weeks after starting treatment.
Note
TB prophylaxis with INH should be provided but be deferred for healthy pregnant women to 12 weeks postpartum.

Use of antiretroviral (ARV) treatment in pregnancy

2-34 What is antiretroviral treatment?

Lifelong ARV treatment is the use of three or more ARV drugs in combination to treat all women with HIV infection. The aim of ARV treatment is to lower the viral load and allow the immune system to recover. Women will be kept healthy to take care of their children and be employed to provide an income for their families. ARV treatment is rolled out to all South Africans living with HIV. This require extensive strengthening of the primary-care system in South Africa.

2-35 What are the indications for antiretroviral treatment in pregnancy?

All pregnant women who are HIV positive need to start on a single pill fixed dose (TLD) regimen. According the Option B+ programme, women will remain on ARV treatment for life.

All pregnant women are started on lifelong ARVs for life.

2-36 What preparation is needed for antiretroviral treatment?

Preparing a woman to start ARV treatment is very important. This requires education, counselling and social assessment before ARV treatment can be started. These women need to learn about their illness and the importance of excellent adherence (taking their ARV drugs at the correct time every day) and regular clinic attendance. They also need to know the side effects of ARV drugs and how to recognise them. Careful general examination and some blood tests are done when starting ARV treatment. If there is doubt about readiness of women to start ARV treatment, they could be asked to come back after a day or two for further counseling and to then start treatment.

2-37 What drugs are used for antiretroviral treatment during pregnancy?

Usually ARV treatment is provided to pregnant women in South Africa with a single pill fixed dose (TLD) regimen consisting of 3 drugs:

This is the national first-line standard drug combination used during pregnancy.

Women already on a different ARV regimen should switch to TLD if:

Women planning to fall pregnant should remain on FDC until at least 6 weeks pregnant. Women that defaulted ART, should be started on TLD if they are known to have a non-detectable viral load while on treatment. If the viral load was not suppressed or unknown they should be started on AZT, 3TC and DTG.

Women who do not respond to first-line treatment, or have severe side effects to the drugs used in first-line treatment, may have to be considered for second-line treatment with either AZT, 3TC and lopinavir/ritonavir (LPV/r) or Truvada and lopinavir/ritonavir (LPV/r). Truvada is a combination of TDF 300 mg and FTC 200 mg as a single tablet taken once daily. LPV/r is taken as 2 tablets 12 hourly.

Note
LPV/r is a combination of 200 mg LPV and 50 mg ritonavir in a single tablet.

2-38 Is it dangerous for a woman to fall pregnant if she is already receiving antiretroviral treatment?

No. Most women who are clinically well on ARV treatment when they fall pregnant remain well with few treatment problems during their pregnancy.

If a woman is already on ARV treatment when she falls pregnant the following is useful to note:

2-39 When can pregnant women be started on antiretroviral treatment?

DTG may increase the risk of neural tube defects (NTDs). However the absolute risk is very low and translates into a risk difference of 2 additional NTDs per 1000 periconception exposures to DTG (0.3% risk), compared to ART using EFT at conception (0.1% risk). Therefore DTG should not be started around the time of conception and in the first 6 weeks of pregnancy. The neural tube closes by the end of the sixth week of pregnancy (fourth week post-conception). Thereafter DTG is safe and will not cause a neural tube defect.

Usually ARV treatment should be started on the day of diagnosis. However if HIV is diagnosed early in pregnancy, the recommendation is to commence ART only at 12 weeks if the mother is healthy and does not require ARV drugs for her own health. However, it is best to start treatment as soon as possible, in women who are seriously ill or with a CD4 count less than 50 cells/µl.

Women living with HIV who are on ARV with TLD and desiring a pregnancy and are concerned about the risk of NTDs, can be offered a switch from TLD to FDC, provided they have a suppressed VL in the last 6 months.

Note
Women who fall pregnant on DTG should be entered into the antiretroviral pregnancy register.

2-40 Can antiretroviral treatment be started close to term?

Yes, the TLD regimen could be started close to term. This would be especially important for women seriously ill or with a CD4 count is less than 50 cells/µl.

Women only diagnosed with HIV infection in labour and women who have defaulted treatment must be given a single dose of TLD and single dose NVP 200 mg during labour. The mother will then be started on TLD following the delivery.

Note
The viral load starts reducing following 2 weeks of ART and will mostly be low following 4 weeks of treatment.

2-41 What are the benefits of antiretroviral treatment during pregnancy?

  1. ARV treatment improves the health of the mother and prevents her dying from HIV infection during or soon after pregnancy.
  2. ARV treatment also reduces the risk of vertical transmission.
  3. Women on ARV treatment can be kept alive and well for many years, enabling them to care for their children and be economically active. Therefore the number of AIDS orphans will be significantly reduced.

2-42 What are the side effects of antiretroviral treatment?

Pregnant women on ARV treatment may have side effects to the drugs. These are usually mild and occur during the first six weeks of treatment. However, side effects may occur at any time that women are on ARV treatment. It is important that the staff at primary-care clinics are aware of these side effects and that they ask for symptoms and look for signs at each clinic visit.

Common early side effects during the first few weeks of starting ARV prophylaxis or treatment include:

  1. Lethargy, tiredness and headaches
  2. Nausea, vomiting and diarrhoea
  3. Muscle pains and weakness

More severe side effects of some ARV drugs, which can be fatal, include renal impairment, lactic acidosis, hepatitis, anaemia and pancreatitis.

Drugs specific side effects are:

Staff at primary-care clinics must be aware and look out for these very important side effects. Like most drugs, TLD have side effects. These are a combination of the side effects of each of the 3 drugs. TLD should be taken at breakfast in the morning with a glass of water. In this way the possible insomnia caused by DTG will be avoided.

Note
Stavudine (d4T) and NVP were part of first line ARV treatment in the past and commonly caused side effect, including lactic acidosis, severe blistering skin rashes and hepatitis.

Antiretroviral treatment can have severe side effects.

2-43 What drug interactions must be considered when taking DTG?

Calcium supplements decrease DTG serum concentration if taken together on an empty stomach. To prevent this, DTG and calcium supplements can be taken at the same time if taken with food. Iron supplements decrease DTG concentrations if taken together on an empty stomach. To prevent this, DTG and iron supplements can also be taken at the same time if taken with food. However, calcium and iron supplements must be taken at least 4 hours apart.

Magnesium/aluminium containing antacids decrease DTG concentrations regardless of food intake and should be taken a minimum of 2 hours before or 6 hours after DTG.

2-44 What are contra-indications to the use of antiretroviral drugs?

TDF is contraindicated in chronic renal disease as it can cause renal failure if renal impairment is already present. TDF is also contraindicated if there is a history of chronic hypertension, previous hospitalisation for kidney disease or if one plus or more proteinuria is present on urine dipstix. TDF can be commenced if the serum creatinine is reviewed 1 week later and found to be less than 85 mmol/l.

Note
With a history of possible chronic renal disease, a serum creatinine concentration should be requested and the woman started on AZT, 3TC and DTG regimen. If the serum creatinine is less than 85 µmol/l a TDF containing regimen could be used, with careful follow-up of the serum creatinine.

EFV is contra-indicated in any women with active psychiatric illness. Mild depression is not a contra-indication for the use of EFV.

Note
With active psychiatric illness commence on TLD.

As AZT can cause anaemia, a laboratory hemoglobin concentration should be done at the start of treatment. Women with a haemoglobin concentration below 8 g/dl should not be given AZT.

TDF should not be used if there is renal disease, EFV with psychiatric illness or AZT with severe anaemia.

2-45 What blood tests should be done to monitor antiretroviral treatment during pregnancy?

  1. The serum creatinine value must be measured before starting an ARV regimen containing TDF. This drug should not be used if the serum creatinine is 85 µmol/l or more or a creatinine clearance of 50 ml/l or less. The serum creatinine is repeated at 3 months, 6 and 12 months following initiation of treatment.
  2. As AZT can cause anaemia, these women should have a full blood count at the start of treatment and then a laboratory haemoglobin measurement done every month for 3 months and then 3 monthly during the rest of pregnancy. Women with a haemoglobin concentration below 8 g/dl should not be given AZT.
  3. An ARV regimen containing NVP requires a serum ALT (alanine aminotransferase liver function test) to be done at the start of treatment (baseline) and again at 2 and 4 weeks. Thereafter ALT should be measured monthly until delivery.

2-46 Who should follow up on women on antiretroviral treatment during pregnancy?

Whenever possible, a pregnant woman on ARV treatment should be followed up at the clinic or hospital where she is receiving antenatal care. Only women with serious problems related to their HIV infection or ARV treatment need be referred to a special HIV clinic.

At every visit these women must be encouraged and supported to continue with excellent drug adherence. They should also be monitored for clinical signs of HIV infection and side effects of ARV treatment, as well as having their serum creatinine (if in TDF) and haemoglobin (if on AZT) monitored.

TB and HIV co-infection

2-47 How is TB and HIV co-infection diagnosed?

All pregnant women, especially if they have HIV infection, should be asked about the symptoms of tuberculosis at every antenatal visit. These are:

2-48 How is the diagnosis of pulmonary TB confirmed?

Three sputum specimens should be sent for TB GeneXpert testing. A single posterior anterior chest x-ray is requested with the fetus screened off with a lead apron. If enlarged lymph nodes are palpable a fine needle aspiration should be requested for microscopy and a culture.

Note
GeneXpert testing for tuberculosis has replaced conventional cultures and results are available within one day.

2-49 When should anti-TB treatment be started?

Pulmonary tuberculosis is a feature of stage 3 disease in women with HIV infection. Therefore they need both anti-TB treatment and be started on lifelong ARV treatment:

EFV has no significant interaction with rifampicin. First start anti-TB treatment together with FDC for 2 weeks. If already on FDC continue with FDC and add anti-TB treatment. In both instances after 2 weeks switch FDC to TLD.

Rifampicin result in more rapid metabolism of DTG. Therefore DTG boosting of the TLD is required if used together with TB treatment. A single dose DTG (50 mg) is added and taken 12 hours apart from the time TLD is taken, usually in the evening.

If women develop tuberculosis while on lifelong ARV treatment, anti-TB treatment can be started without delay.

2-50 How is a woman with tuberculosis treated in pregnancy?

If possible, antenatal care, HIV management and anti-TB treatment should be integrated at a primary-care clinic. Treatment is usually started with rifampicin, INH, pyrazinamide and ethambutol. These 4 drugs are combined in Rifafour and taken as 4 tablets per day.

The dose of LPV/r should be doubled if receiving both anti-TB treatment and an ARV regimen containing LPV/r as rifampicin lowers the blood levels of LPV/r.

Case study 1

A woman with an unplanned pregnancy books for antenatal care at 8 weeks of gestation. During screening she is found to be HIV positive. She is clinically well. After counseling, blood for a CD4 count is taken. She is then started immediately on TLD and asked to come back for a follow-up visit in 4 weeks time.

1. What should have been discussed with her in addition to post-test counselling following a positive HIV test?

The possibility of termination of her pregnancy should been discussed. She is less than 13 weeks pregnant and the pregnancy is unplanned.

2. Should TLD have been started at the first visit?

No, she is healthy and early in the first trimester of her pregnancy. Starting FDC could have been delayed until 12 weeks.

3. Which additional special investigations should have been requested at the first antenatal visit because she is to start on ARV treatment with TLD?

In addition to the routine blood tests done at the first antenatal visit a serum creatinine concentration should have been requested. TLD contains TDF that could cause renal impairment and is contraindicated with women that have chronic renal disease.

4. At what level would the serum creatinine concentration will be a contraindication to the use of TDF?

A serum creatinine concentration of 85 µmol/l or more.

5. Was a follow-up date in 4 weeks’ time, the correct management?

No, HIV positive women are always asked to come again in 1 week’s time for follow-up of the CD4 count and serum creatinine. Healthy women may have an unexpected low CD4 count that would require cotrimoxazole to be started.

Case study 2

A woman who is clinically well is found to be HIV positive when screened during her first antenatal visit at 20 weeks gestation. She has one plus protein on dipstick screening of her urine. She is started on TLD. A serum creatinine test is requested and she is asked to come back in 1 week’s time. When she is seen 1 week later her serum creatinine is 95 mmol/l. She is reassured that she has stage 1 disease and should continue with TLD.

1. Is she correctly managed according the new WHO guidelines at the first visit?

Yes, she was started on TLD, a single pill fixed dose regimen containing 3 ARV drugs (TDF, 3TC and DTG) according the WHO Option B+ regimen. A serum creatinine test was requested and she was asked to come back in 1 week.

2. What contraindications are there to continue treatment with TLD?

TDF is contraindicated in chronic renal disease as it can cause renal failure if renal impairment is already present. TDF is also contraindicated if there is a history of chronic hypertension, previous hospitalisation for kidney disease or if there is one plus or more proteinuria on urine dipstix. TDF can be started if the serum creatinine is reviewed 1 week later and found to be less than 85 mmol/l.

3. What ARV regimen should be used if renal function appears to be impaired?

The TLD must be replaced with a combination of AZT and 3TC (Combivir) twice daily with DTG 50mg taken with the morning dose.

4. What contraindications are there to the use of AZT?

AZT can cause anaemia. Therefore women with a haemoglobin concentration below 8 g/dl should not be given AZT.

5. Which special investigates are required if a women is placed on an ARV regimen containing AZT?

A laboratory hemoglobin concentration should be done at the start of treatment and every month during pregnancy for 3 months and then 3 monthly.

6. What additional medical management is required?

A referral to a medicine department is required to investigate the reason for her renal impairment and provide appropriate treatment and follow-up.

Case study 3

When booking for antenatal care at 24 weeks gestation, a woman who is clinically well is found to be HIV positive on routine screening. She is started on ARV treatment with TLD and asked to come back in 1 week’s time. When she is seen 1 week later she complains of nausea and has had diarrhoea a few times daily. She also feels lethargic. Her CD4 count is 300 cells/µl. She is advised to stop her FDC temporarily until the side effects of the drugs have stopped.

1. Are these side effects to be expected when starting on FDC?

Yes, common early side effects during the first few weeks of starting ARV treatment include: lethargy, tiredness and headaches, nausea, vomiting and diarrhea, muscle pains and weakness.

2. Should ARV treatment be stopped if these side effects occur?

These are mild side effects and usually disappear on their own. They can be treated symptomatically. It is important that ARV treatment is continued even if there are mild side effects.

3. During counselling regarding infant feeding options later during the pregnancy, the woman indicates that she would like to breastfeed her infant. She is told that she needs to continue with the FDC until 1 week following weaning. As she is clinically well should she then stop the FDC?

The woman should not stop the FDC. According to the Option B+ programme, she must remain on TLD for life.

4. Why is it important that she continues with TLD for life?

Without ARV treatment she is at risk of progressing to stage 3 or 4 disease in the future. Keeping the mother healthy is of great importance as the health of the infant also depends on a healthy mother.

Case study 4

A woman is found to be HIV positive when screened during her first antenatal visit at 22 weeks gestation. She complains of a cough, feeling feverish at times and that she has heavy night sweats. These symptoms have been present for a few weeks. As she is clearly not healthy, she is started on TLD without delay.

1. What co-infection should be considered with this woman?

She has a cough, fever and night sweats. The presence of any one of these symptoms requires tuberculosis to be excluded.

2. Which measures should have been taken to exclude tuberculosis?

Three sputum specimens should be sent for TB GeneXpert tests. A single posterior anterior chest x-ray is requested with the fetus screened off with a lead apron. If enlarged lymph nodes are palpable a fine needle aspiration should be requested for microscopy and a culture.

3. If she is diagnosed with tuberculosis, could she be started on anti-TB treatment and TLD at the same time?

Anti-TB treatment must be given for 2 weeks together with FDC. If the clinical condition did not deteriorate and no drug side effects are experienced, commence on TLD after 2 weeks.

4. Could anti-TB drugs and TLD be taken together?

Yes, but rifampicin does lower the blood levels of DTG. Therefore DTG must be boosted by adding an additional single 50 mg tablet of DTG 12 hours apart from taking the TLD. Anti-TB drugs do lower the blood levels of LPV/r.

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