Integrase inhibitor-based treatment with either raltegravir (Isentress) or dolutegravir (Tivicay, also in Triumeq) reduces viral load more rapidly than efavirenz if started in pregnancy, findings from two randomised studies presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle show.
Investigators on the raltegravir study say that their findings support the use of raltegravir-based antiretroviral treatment during pregnancy, especially for women who start treatment late in pregnancy.
Professor Saye Khoo of Liverpool University said that the findings of the DOLPHIN-2 study of dolutegravir initiated in late pregnancy suggest that dolutegravir is a drug that could be used in this high-risk situation for mother-to-infant transmission.
Many women with HIV learn of their HIV status when they are tested during pregnancy, often after the first trimester. Reducing viral load rapidly during pregnancy is essential to achieve an undetectable viral load at the time of delivery. Undetectable viral load at delivery maximises the chance that HIV will not be transmitted during delivery.
But achieving undetectable viral load at delivery requires diagnosis of HIV and treatment initiation in time to suppress viral load. In South Africa, one-fifth of pregnant women start treatment in the third trimester of pregnancy (week 24 onwards).
Integrase inhibitors reduce viral load more quickly than other antiretroviral drugs, so a combination that includes an integrase inhibitor might be expected to increase the likelihood of viral suppression by the time of delivery in women who start antiretroviral treatment during pregnancy.
However, the safety and efficacy of integrase inhibitor treatment in pregnancy has not previously been tested in a randomised trial.
As integrase inhibitor-based treatment becomes the standard of care in many countries, it is important to know whether an integrase inhibitor is more effective than efavirenz (the currently recommended standard of care for pregnant women) in suppressing viral load during pregnancy.
Safety is also a major concern. Although integrase inhibitors have been used to treat tens of thousands of people, there are few data on their use in pregnant women, especially from randomised studies.
Preliminary data from an observational study in Botswana showed an increased risk of neural tube defects in infants exposed to dolutegravir in the first 12 weeks of pregnancy. The foetus is vulnerable to birth defects due to drug exposure during the first 12 weeks of pregnancy as organs and tissues form. In later pregnancy (after week 12) drug exposure may affect infant growth or lead to premature delivery or may cause side-effects for the mother.