Questions remain on safety of ART pill, DTG-Tsepamo Study

There have been no new cases of neural tube defects (NTD) reported among infants born to women taking dolutegravir (DTG) at conception, as ongoing surveillance on NTD link to dolutegravir,continues according to scientists. In 2014, researchers in Botswana began a 4-year surveillance study, called Tsepamo, of all babies born to both HIV-infected and uninfected mothers at eight clinics to evaluate the safety of ART in pregnancy and the frequency of neural defects. This rare condition can cause large holes in the spine or can prevent the top of the skull from forming. Neural tube formation occurs during the first 28 days of pregnancy. The Tsepamo study was initially designed to look at whether efavirenz, the first-line antiretroviral used in Botswana at the time, was associated with neural tube defects. But when dolutegravir became the first-line treatment in Botswana in 2016, it was added to the study. An unplanned interim analysis of data from a cohort of pregnant women living with HIV in Botswana was then conducted at WHO’s request to help inform the guidelines review process in 2016. The interim analysis identified four cases of Neural Tube Defects (NTD) among 426 infants born to women who were taking DTG at the time they became pregnant. Immediately after, safety alerts were issued, governments and health organisations including the World Health Organisation changed their guidelines to recommend against the use of dolutegravir by women who might become pregnant. However, at the seventh Botswana International HIV Conference themed; ‘Time to End It: Find Treat and Prevent-The Last Mile’, Principal Medical Officer at the Health and Wellness Ministry, Dr Max Kapanda reported since that cut off date of May, 180 babies have been born to women taking the drug during conception and none have such defects, Dr Kapanda reported. Between May and July, there have only been two more neural tube defects among this cohort: one in an infant exposed to DTG started during pregnancy at eight weeks’ gestation and one birth to an HIV negative woman. He however stressed that the new findings don’t clear the air. “This is still a preliminary signal and we need more data to confirm or refute it,” he said. The Tsepamo study continues, with an additional 10 sites planned including Bamalete Lutheran Hospital, Palapye Primary Hospital, Kanye SDA Hospital and Letlhakane Primary Hospital amongst others. Researchers expect to capture nearly 72% of all births in the country and to have information on another 1200 conceptions in women taking the drug by March 2019. The final analysis in March 2019 will include NTDs, all major malformations as well as other adverse birth outcomes. “A lot still hangs on Tsepamo and its important for the public to know the what the risks and benefits are,Dr Kapanda said. He however also said that“if it is shown that DTG is the cause of defects, it will be stopped altogether on women of child bearing age. But beyond the current issue of DTG, the aim for this study is for Botswana to build a robust birth defect system”. Meanwhile the ministry has urged women taking DTG not to stop therapy, but seek help from their health providers. Those who are pregnant and have conceived while on DTG should alert their healthcare providers so they can be counselled and advised appropriately. For those women who are currently on DTG and do not desire pregnancy at this time, should consult their healthcare providers for effective contraception in addition to the use of condoms. DTG has been the drug of choice for people living with HIV as it has very few side effects, is easier to take (one small tablet taken daily), and patients are less likely to develop resistance. In 2015, the World Health Organisation (WHO) recommended DTG as an alternative first-line regimen for adults and adolescents.