Abstract
The acquired immunodeficiency syndrome (AIDS) was first recognised among homosexual men in the United States in 1981. It has since then spread like wildfire, becoming one of the worst epidemics of the twentieth century, affecting all populations.
Global HIV burden is estimated at 37 million individuals, and women account for more than half of them. In the most affected countries in the world, such as in sub-Saharan Africa, 20–40 per cent of pregnant women are HIV-infected and one-third of their babies become infected.
These children are vulnerable to HIV transmission in utero, at birth, or through breastmilk.
Mother-to-child transmission (MTCT) accounts for 90 per cent of HIV infections among children worldwide.
The management of HIV in pregnancy has evolved over the last few decades due to an improved understanding of prevention of perinatal transmission of HIV and development of better drugs to control the infection. The successful prevention efforts can be attributed to universal testing and screening of pregnant women for HIV infection, the use of caesarean delivery (when appropriate), new and effective antiretroviral medications and avoidance of breastfeeding, when feasible. This chapter focuses on understanding the effects of HIV in pregnancy, MTCT and the intervention control strategies.
In developed countries, the introduction of antiretroviral drugs has resulted in a significant reduction in AIDS-related mortality and improved survival.
Introduction
The acquired immunodeficiency syndrome (AIDS) was first recognised among homosexual men in the United States in 1981. It has since then spread like wildfire, becoming one of the worst epidemics of the twentieth century, affecting all populations.
Global HIV burden is estimated at 37 million individuals, and women account for more than half of them. In the most affected countries in the world, such as in sub-Saharan Africa, 20–40 per cent of pregnant women are HIV-infected and one-third of their babies become infected.
These children are vulnerable to HIV transmission in utero, at birth, or through breastmilk.
Mother-to-child transmission (MTCT) accounts for 90 per cent of HIV infections among children worldwide.
The management of HIV in pregnancy has evolved over the last few decades due to an improved understanding of prevention of perinatal transmission of HIV and development of better drugs to control the infection. The successful prevention efforts can be attributed to universal testing and screening of pregnant women for HIV infection, the use of caesarean delivery (when appropriate), new and effective antiretroviral medications and avoidance of breastfeeding, when feasible. This chapter focuses on understanding the effects of HIV in pregnancy, MTCT and the intervention control strategies.
In developed countries, the introduction of antiretroviral drugs has resulted in a significant reduction in AIDS-related mortality and improved survival.
Virology
HIV is a genetic member of the Lentivirus genus of the Retroviridae family. The retrovirus genome is composed of two identical copies of single-stranded RNA molecules. The virus isolates into two types, HIV-type 1 (HIV-1) and HIV-type 2 (HIV-2).
HIV-1 is the worldwide agent for HIV and the AIDS infections
HIV-2 is restricted to some regions of Western and South Africa
In the majority of cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of pre-ejaculate, semen and vaginal fluids. Non-sexual transmission can also occur from contaminated blood and other body fluids.
The virus cannot survive outside the bloodstream or lymphatic tissue, but transfer of non-sexual infection requires direct exposure to infected blood or secretions in the presence of skin damage, i.e. by needles (as in drug abusers) or sharp tools.1
A CD4 (cluster of differentiation 4) count less than 200 cells/mm3 indicates that a person has AIDS. In general, the time from infection with HIV to the development of AIDS is approximately 10–12 years.
Seroconversion – after the initial infection, HIV continues to multiply in the lymph nodes. Lymph nodes are packed with CD4 cells, which HIV uses to reproduce. Then the nodes burst, sending the virus into the blood from three to five weeks, with an average of 22 days.
HIV levels of viral load become detectable in blood and reach very high levels (often millions of copies/mL) in three to five weeks.
A viral load test is a measurement of the amount of HIV virus in a sample of blood. This is usually reported as the number of copies per millilitre (copies/mL).
HIV and CD4
CD4 is a glycoprotein found on the surface of immune cells such as T-helper cells, monocytes, macrophages and dendritic cells. CD4 and T-helper cells are an essential part of the human immune system to fight infections and other conditions. Depletion of CD4 leaves the body vulnerable to a wide range of infections.
Normal values for CD4 cells are 500–1200 cells/mm3.
HIV infection leads to a progressive reduction in the number of T cells expressing CD4.
CD4 tests can be used to determine efficacy of treatment.
However, viral load testing is more informative about the efficacy for therapy than CD4 counts.2
Clinical Presentation
The clinical picture of HIV in pregnancy is the same as that in non-pregnant women.
The World Health Organization (WHO) case definition of HIV infection includes:
1) A positive result on an HIV antibody test confirmed by a positive result on a second, different HIV antibody test and/or
2) A positive virologic test confirmed by a second virologic test.3
Stages of HIV Infection4
1. Acute Primary HIV infection (also called acute seroconversion syndrome). This generally lasts for 2–4 weeks. The infected person is usually asymptomatic but may experience flu-like symptoms. In the acute stage HIV multiples rapidly and spreads throughout the body destroying the CD4 cells. Increased level of HIV increases the risk of transmission.
2. Chronic HIV infection. People with chronic infection may not have any symptoms but can spread to others. Without treatment this usually advances to AIDS in approximately 10 years.
3. AIDS, when the immune system has been so extensively damaged that it can no longer fight off serious infections and diseases.
Symptoms of reduced immunity start to appear including: weight loss, chronic diarrhoea, night sweats, fever, persistent cough, mouth and skin problems, regular infections, serious illnesses or diseases.
Kaposi’s Sarcoma and Pneumocystis Pneumonia (PCP)5
1. Asymptomatic – persistent generalised lymphadenopathy
2. Early symptomatic HIV infection (previously known as AIDS-related complex (ARC) or Class B)
3. AIDS characterised by a CD4 cell count <200 cells/μl or the presence of any AIDS-defining condition
4. Advanced HIV infection characterised by a CD4 cell count <50 cells/μL
5. Before the introduction of antiretroviral therapy to treat HIV, about three-quarters of HIV-positive people who developed AIDS got PCP
6. Antiretroviral therapy (ART) has prevented HIV-infected people from developing AIDS, and among persons who have developed AIDS, additional preventive therapy has brought this number way down. However, PCP is still the most common opportunistic infection in persons who contract AIDS.
Effects of Pregnancy on HIV
Studies have not shown an association between pregnancy and disease progression.
Lieve et al. investigated the effect of pregnancy on HIV disease progression and survival among HIV-infected women in rural Uganda, prior to the introduction of ART.
HIV women who subsequently became pregnant had higher CD4 counts at enrolment and had a slower CD4 decline than those who did not become pregnant. In women who became pregnant, CD4 decline was faster after pregnancy than before (p < 0.0001). The survival analyses showed no significant differences between women who became pregnant and those who did not with respect to median time to CD4 count <200, AIDS or death.
The initial comparative immunological advantage possessed by fertile women before they become pregnant is subsequently lost as a result of their pregnancy.
Women should be informed about the potential negative effect of pregnancy on their immunological status and should be offered contraception.
In resource-limited settings, women determined to become pregnant should be given priority for ART if eligible.6
Effects of HIV on Pregnancy
Stillbirth
Low birthweight
Prematurity
Intrauterine growth retardation7 [EL 1]
Ectopic pregnancy. HIV-1 and HIV-2 infection in Africa have both been linked to a higher rate of ectopic pregnancy, which may be related to the effects of other concurrent sexually transmitted diseases
Glucose intolerance and gestational diabetes. The development of glucose intolerance may be more common in pregnant women with HIV8
Postpartum haemorrhage. HIV-positive women were more likely to have a postpartum haemorrhage
Maternal Mortality
1. There were an estimated 19 000–56 000 maternal deaths attributed to HIV-related causes in 2011, contributing to some 6–20 per cent of all maternal deaths worldwide.9 [EL 1]
2. In a study by Zaba et al., HIV-infected pregnant or postpartum women had around eight times higher mortality than did their HIV-uninfected counterparts.10
3. In Africa, it seems there is a higher mortality rate among HIV pregnant women which may be accounted for by the coexisting tuberculosis infection.
4. It is important to note that many HIV-related deaths can be prevented by the implementation of high-quality obstetric care, prevention and treatment of common co-infections, and treatment of HIV with ART.
Mother-To-Child Transmission of HIV
Every mother-to-child perinatal HIV transmission indicates either a missed opportunity for prevention or, more rarely, a failure of interventions to prevent HIV infection.
Without antiretroviral preventive interventions, the risk of perinatal HIV transmission has varied between 15 and 45 per cent, depending on maternal risk factors and whether breastfeeding is practised.11
The most important risk factors for MTCT:
1. Maternal plasma viral load
2. Breastmilk viral load12
3. Maternal immunologic status
4. Clinical stage
5. Low CD4 cell counts
6. Anaemia
7. Maternal mastitis
8. Duration of membrane rupture greater than four hours
Rates of Transmission
A) In non-breastfeeding settings prior to the availability of antiretroviral interventions,
• 30 per cent during pregnancy
• 70 per cent during labour and delivery
B) In breastfeeding settings prior to the availability of antiretroviral interventions,
• 25 to 40 per cent of infant infections were estimated to occur in utero
• 50 per cent around the time of labour/delivery or through very early breastfeeding
• 10 per cent during the reminder of breastfeeding periods
HIV RNA can be detected in colostrum and breastmilk.
Risk of transmission through breastfeeding is highest in the early months of the infant’s life.
Fetal Congenital Malformations
The absence of an HIV-related dysmorphic syndrome and the lack of congenital abnormalities is a consistent finding in developed and developing countries. These findings are compatible with the view that a substantial proportion of vertical transmission occurs late in pregnancy or at the time of the delivery.
In an African study, there was no influence of HIV on congenital malformations.13
Diagnosis and Investigations
Early diagnosis of HIV infection in pregnancy and initiation of ART not only improves the obstetric outcomes and reduces perinatal transmission but also helps in improving the health of the mother in the long run.
1 Rapid Tests, Duo Test14
In low-income group countries, syphilis and HIV are the major public health problem affecting the mother and their newborn baby.
Therefore, a rapid diagnostic test for HIV and syphilis, a ‘duo test’ (an HIV test that looks for antibodies for HIV-1 and HIV-2 and also looks for evidence of the p24 protein which is on the surface of the HIV particle) has been developed which can be performed with venous, arterial or capillary whole blood, or oral secretions.
The test was 100 per cent accurate if the result is negative and 94 per cent accurate if the result is positive.14
These tests are used in clinical and non-clinical settings, usually with blood from a finger prick or with oral fluid.
The oral fluid antibody self-test provides faster results. Results are available in 20 minutes.
For the blood test, the home collection kit involves pricking the finger to collect a blood sample, sending the sample by mail to a licensed laboratory, and then calling in for results as early as the next business day.
These tests are available for purchase in stores and online.
This antibody test is anonymous.
As with other types of HIV tests, a positive result needs to be confirmed with a different test.
2 Antigen/Antibody
3 Nucleic Acid Amplification Test (NAAT)
NAAT looks for the actual virus in the blood.
The test can give either a positive/negative result or the amount of virus present in the blood (known as an HIV viral load test).
This test is very expensive and not routinely used for screening individuals unless they recently had a high-risk exposure and they have early symptoms of HIV infection.
Nucleic acid testing is usually considered accurate during the early stages of infection.
However, it is best to get an antibody or antigen/antibody test at the same time to help the health care provider understand what a negative NAAT means.
Screening
HIV infection does not usually cause symptoms at the early stage. Consequently people need to be screened to learn whether they are infected even if they are feeling well. They can then start treatment early and avoid giving the disease to other people.
There is strong evidence that screening for HIV in pregnant women has many benefits. If infected pregnant women start treatment, they have a better chance for themselves and their children of staying healthy. Treatment can also reduce their chances of passing the infection to other people.
Potential harms of screening are small. False-positive results are rare.
All pregnant women should be screened for HIV infection as soon as possible in each pregnancy. [CDC, RCOG & WHO recommendations]
Repeat testing in the third trimester is recommended for women in areas of high HIV prevalence or women known to have high risk for acquiring HIV infection. [Grade A recommendation]
Pregnant women not previously tested or whose HIV status is undocumented at the time of delivery should be offered rapid screening. If the rapid HIV test in labour is reactive then ART should be started immediately while waiting for the supplemental test results.15 [Grade A recommendation]
Antenatal Investigations
A thorough history and physical examination must be performed to rule out any other health concern in the mother that would affect the fetus, such as sexually transmitted infections, tuberculosis and drug abuse.
Newly diagnosed HIV-positive pregnant women do not require any additional baseline investigations compared with non-pregnant HIV-positive women other than those routinely performed in the general antenatal clinic. [Grade B recommendation]
Accurate estimation of the gestational age should be done because early delivery may be necessary to reduce risk of perinatal transmission.
Pregnant HIV-infected women should be screened for both hepatitis B and hepatitis C virus infections since co-infection is common in HIV-infected patients due to shared routes of transmission (e.g. injection drug use).
HIV-infected women without evidence of hepatitis B infection should be given HBV immunisation, since the recombinant vaccine is safe during pregnancy.16
Women should also be screened for antibodies to the hepatitis C and should receive immunisation if they are hepatitis C negative.17
Women should also be screened for antibodies to the hepatitis A virus (HAV). Those testing negative should receive the HAV vaccine.18
Latent tuberculosis testing should be done as there is a higher risk for developing active disease.
Screening should also be performed to rule out other sexually transmitted infections, especially maternal syphilis, to avoid another major contributing factor in adverse obstetric and neonatal outcomes.
Monitoring Disease Progression and Treatment
1 HIV Resistance Testing (HIVDR)
HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem.
HIV resistance testing should be performed prior to initiation of treatment except for late-presenting women.19 [Grade C recommendation]
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