As 2019 draws to a close, TheBodyPro takes stock of the year's most noteworthy developments in HIV. And not just any developments: We're looking specifically at those with the largest impact for people who provide HIV care and services in the U.S. In this series, veteran clinician-researcher David Alain Wohl, M.D., guides us through the new research and other important moments of 2019 that have the greatest potential to alter the HIV clinical landscape in the months and years to come.
A lot of pregnancies in Botswana were anxiously followed after results from the Tsepamo study were revealed in late 2018. At that time, the researchers leading Tsepamo, a large observational study of pregnant Botswanan women, reported a higher rate of neural tube defects (NTD) in women living with HIV who were being treated with dolutegravir (Tivicay) at the time of conception relative to women treated with other HIV meds. The number of babies with NTD in the dolutegravir-exposed women was low: 4 out of 426 births. But the NTD rate -- 0.94% -- was high compared to that for infants born of women treated with dolutegravir later in pregnancy (0 of 2,812), as well as compared to any non-DTG regimen during conception (14 out of 11,300, or 0.12%).
In acknowledgement that the high rate of defects seen in the dolutegravir-during-conception group could have been a fluke, the investigators worked to expand the cohort by adding 10 additional hospitals to the original eight, effectively covering almost three quarters of all live births in the nation. As a result, 1,275 additional women with DTG during conception were added, for a total of 1,683.
The results of this expanded study were presented at this year's IAS Conference on HIV Science: One additional neural tube defect case was identified in these women, dropping the rate from 0.94% to 0.3%. This was still higher than the rates seen in other categories of antiretroviral exposures during conception and pregnancy, albeit to a lesser degree. Interestingly, among these other two groups of women with HIV infection, there were only two additional NTD seen among the 6,692 women added; nine additional NTD were seen among the 23,315 HIV-uninfected women added.
The Bottom Line on Dolutegravir Use in Pregnancy
The updated Tsepamo results provided a medium-sized sigh of relief. This was generally welcome news, given the many advantages of this integrase inhibitor over previously recommended first-line agents (the weight-gain issue notwithstanding). Indeed, it is almost as good a result as could be hoped for, with only a single new NTD among the babies born in the dolutegravir-during-conception group. Just one or two more than that would have made the results much more equivocal -- and damning.
The World Health Organization agreed: Based on these data, it issued a recommendation that dolutegravir be preferred for first- and second-line HIV treatment.
Advocates have made it clear that the use of dolutegravir by women living with HIV should be guided by the preferences of the women themselves. The Tsepamo study team has done a tremendous amount of work to answer the question of whether a relationship exists between dolutegravir and NTD. Their update is mostly reassuring, and should help women and their clinicians make decisions that are both well-informed and mutually shared.