Antiretroviral Therapy And Pregnancy

What to consider when taking antiretroviral therapy (ART) in pregnancy with human immunodeficiency virus (HIV) infection?

Antiretroviral therapy (ART) is a recommended treatment for all individuals with human immunodeficiency virus (HIV) infection. HIV attacks the body’s immune system, particularly the CD4 cells.¹ Antiretroviral medications disrupt crucial viral replication processes and are categorised based on the specific stage they hinder in the viral life cycle.² As the viruses replicate themselves, the host’s immune system weakens and generates acquired immunodeficiency syndrome (AIDS), showing various kinds of symptoms. There has not been a cure to eradicate the viruses. Once infected, HIV will stay in a host’s body throughout life. However, ART can reduce the replication of HIV, marked by reduced viral load in the body, allowing for an improved state of health, and, in turn, preventing transmission to others.¹ Every year, there are around 1.4 million women with HIV who become pregnant globally.³ In that population, HIV infection puts both the mothers and the babies at risk.⁴ Thus, all pregnant women with HIV are suggested to receive ART.^5,6 This article will elaborate on the importance of ART in pregnancy, focusing on its benefits and concerns. 

Benefits of antiretroviral therapy in pregnancy

The main benefits of ART in pregnancy are as follows:

Prevention of mother-to-child transmission (MTCT)

As mothers and fetuses are connected to a network of blood vessels, the use of ART during pregnancy reduces the MTCT by suppressing the number of viruses circulating in the mothers thus reducing the risk of transferring the viruses to the babies. In addition, it can minimise the risk of transmission during labour. The risk of transmission is <2% if ART is used from early in pregnancy with HIV levels are suppressed.⁴ Earlier use of ART was argued to have a better outcome as evidenced by a study in France of pregnant women with HIV who took ART before conception and had a low HIV viral load near delivery, perinatal transmissions were absent.⁷ Antenatal ART administration also provides the infant with prophylaxis as the drugs will cross the placenta and generate a proper level to inhibit replication of the viruses in the fetus.⁶

Prevention of sexual transmission

HIV can be transmitted through the exchange of body fluids, including blood, breast milk, semen, and vaginal secretions. Thus, systematically reducing the viral load in the body by the actions of ART would subsequently minimise the possibility of transmitting viruses to others, primarily through sexual contact.¹

Maintenance of maternal health

Reducing the replication of HIV will prevent pregnant women with HIV from acquiring AIDS. In addition, the immunodeficiency state enables them to be at risk of or have presented with opportunistic infections. Some of the most common infections are tuberculosis,⁸ pneumocystis pneumonia,⁹ and candidiasis.¹⁰ Therefore, initiation of ART should not be delayed because of pregnancy, to protect both maternal and fetal health.⁵

Improved pregnancy outcomes

Other than preventing complications for mothers with HIV, ART can lower the risk of perinatal adverse events, including miscarriage, small-for-gestational-age fetuses, preterm birth, and stillbirth.^4,6,7

Concerns and considerations

Despite the benefits, several risks of taking ART drugs during pregnancy should be considered.

Effectiveness of ART during pregnancy

Common changes and body adaptations during pregnancy may affect the distribution and effectiveness of ART drugs to deter viral replication. It is more notable in later gestations. Several studies have reported that vertical transmission is significantly associated with treatment initiated later in pregnancy.⁷ 

Potential risks

Birth outcomes are generally better in pregnant women with HIV taking ART compared to those not taking ART. However, certain adverse outcomes of ART in pregnancy, such as congenital anomalies, may arise, varying depending on the regimen. One of the conditions is neural tube defects.¹¹Givenn that, it is recommended for all women to receive folic acid supplementation before pregnancy until 12 weeks gestation, and they may need a higher dose if receiving certain ART regimens.⁵ Women planning a pregnancy and/or conceiving with HIV on ART should have a thorough discussion around the subject with their physicians.

Initiation of therapy

ART should be started the first time a diagnosis of HIV is confirmed.¹¹ Pregnant women with HIV are suggested to initiate ART at the earliest time of pregnancy, even before conception, regardless of their viral load or CD4 count, to optimise their health and prevent MTCT and sexual transmission.⁶ The likelihood of MTCT decreased significantly with each consecutive week of treatment in the early initiation period, followed by a slower fall up to roughly 15 weeks of ART, with significant variances depending on baseline viral load.¹²

Side effects

Some of the reported side effects of ART are as follows:¹³

• Headache
• Diarrhea
• Anorexia
• Nausea
• Vomiting
• Flatulence
• Fatigue
• Rash
• Kidney stones
• Abdominal pain
• Rash¹³

In a study of 793 pregnant women, maternal side effects of ART, ranked from highest to lowest percentage, were: 

• Dyslipidemia
• Anaemia
• Liver function test abnormalities (including hyperbilirubinemia) 
• Changes in fasting glycemia level
• Thrombocytopenia, and
• Allergic reaction 

Most of these effects were reported to be mild. Maternal anaemia risk factors included co-existing infections and initiating ART during pregnancy, while a CD4 count higher than 200 cells/mm³ provided a protective effect.¹⁴

Types of antiretroviral drugs used in pregnancy

​​The selection of an ART regimen should be individualised based on ART history, drug resistance testing results, comorbidities, and available data on safety in pregnancy. The therapy decision should always be discussed between patients and physicians. This ensures the therapy can be individualised for the patient, considering their concerns and preferences while aligning with established treatment guidelines. ART regimens currently recommended during pregnancy include combinations of different drug classes to enhance effectiveness.⁶ Guidelines available regarding the drugs of choice or their alternatives may vary but commonly involve the combination of several drugs below:

• Tenofovir 
• Abacavir
• Lamivudine
• Emtricitabine
• Dolutegravir
• Efavirenz
• Atazanavir
• Darunavir
• Lopinavir
• Ritonavir^5,15

Monitoring and management

It is essential to have monthly assessments of viral loads to monitor the progress and efficacy of management. Continuation of ART is advised after delivery. With clinician evaluation and recommendation, if a woman decides to breastfeed, she and her infant should be reviewed regularly for viral load testing during and for two months after stopping breastfeeding. ART may be adjusted by the clinician for certain contraceptive choices after pregnancy.⁵

FAQ’s

Should I have ART during pregnancy?

Yes. ART is recommended in pregnancy with HIV infection primarily to prevent mother-to-child and sexual transmission. However, as risks may occur alongside the benefits, the decision should be discussed with your healthcare provider.

Are antiretroviral drugs safe to use in pregnancy?

Antiretroviral drugs are generally safe to use in pregnancy, but certain types of regimens may have a higher risk of adverse pregnancy outcomes. Some results from research are uncertain, thus requiring a comprehensive evaluation by your clinician to decide the proper drugs, considering your personalised safety risk profiles, particularly in early pregnancy.

How long should I take ART?

ART is advised to be taken before, during, and after pregnancy to enhance its effectiveness in sustaining viral suppression, reducing the risk of transmission, and preventing disease progression, both for mothers and infants.

Summary

ART is recommended for use in pregnancy with HIV infection to prevent and reduce adverse outcomes for mothers and infants. However, the decision regarding starting or selecting the regimens should be discussed with the healthcare provider, considering their risks and benefits. It is encouraged to always seek professional medical advice to ensure the best possible care.