We, the thirty-nine women living with HIV representing 18 countries, met in Kigali on July 13 and 14 to discuss the potential neural tube defect (NTD) safety signal in women taking dolutegravir (DTG) at conception and develop a joint position on behalf of women for access to optimal HIV treatment and prevention.
We deliberated on the potential safety signal data from the Botswana Tsepamo study and determined unanimously based on the data currently available that DTG’s benefits – reduced side effects, improved efficacy, and a high barrier to resistance –outweigh its potential risks.
Although this decision was reached unanimously, DTG, like all ARVs, has associated risks of side effects, including adverse birth outcomes. For example, the rate of any adverse birth outcomes with use of efavirenz (EFVs) is 36 percent.1 Furthermore, the risks associated with EFV use in settings with high rates of background EFV resistance must be recognized and factored into this evaluation of risks and benefits, just as the potential risk of adverse birth outcomes for women on DTG must be weighed against the benefits of DTG for the mother and unborn baby. However, the short and long-term side effects of EFV, and the associated impact on individuals and families, cannot be ignored simply because it has been in use longer than DTG. Meeting participants repeatedly expressed the severity of everyday challenges that they encounter using EFV, including fatigue, forgetfulness, depression, and even suicidality. These side effects discouraged them from continuing to use the drug, or negatively affect their ability to work and care for themselves and their families. As one meeting participant expressed:
1 Zash R. 9th IAS Conference Abstract MOAX0202LB
“On TLE, I felt dizzy, tired, couldn’t work, and couldn’t take care of my small kids properly. It’s been one month since I started using it [DTG]. It’s a big change. I’m active, my kids are happy because they have an active mother, and I can do my work without depending on anybody.”
As a result of these struggles, and the lack of conclusive evidence linking DTG to increased risk of NTDs, we, the women living with HIV at this meeting, concluded that blanket exclusions that deny women equitable access to this optimal HIV treatment are not warranted or justified.
The following are key takeaways and recommendations for policymakers:
- We reviewed the existing data and believe the potential risk to be an exposure similar to the other ARV treatments that are currently available to women.
- We strongly believe in our diversity – not all women seek to have children.
- We believe in our ability to make decisions about our reproductive health, including when to have children and what medications are best for us.
- We are disappointed at our lack of involvement in decision making in regards to our treatment access.
- We believe that with correct information and contraceptive access and support we are able to make informed choices in using DTG and planning our pregnancy. When ARVs first became available years ago, some people said that Africans should not be allowed to access them because they did not have watches and could not tell time to know when to take their medicine. Those people were wrong then, and they are wrong today when they say that African women are incapable of making an informed choice.
- We strongly believe that this is an opportunity for integrating the much-needed access to contraceptives within HIV treatment and care in order to achieve universal reproductive health care for all.
- Policy makers and stakeholders must not deny us, women living with HIV, access to DTG regardless of our childbearing potential.
- Global stakeholders and national programmes should strengthen HIV and SRH services to ensure access to DTG together with acceptable, available, affordable and accessible contraception to women and girls.
- Global stakeholders and national programmes should better integrate HIV, sexual and reproductive health (SRH), and other treatment support services, such as viral load monitoring and resistance testing.
- We, the women living with HIV, should not be forced or coerced to take a particular medication and should be provided adequate information to make informed choices.
- Health care workers and ministries of health should clearly communicate the short and long-term side effects of ARVs to enable us to make informed decisions.
- Key stakeholders and national programmes must involve us, the women living with HIV, in local, national, and global discussions and decisions regarding HIV treatment options.
- Research studies must make deliberate effort to include women in clinical trials and studies.
- National programmes must strengthen surveillance systems in order to detect any and all potential risk and harm due to use of ARVs.
We strongly urge key stakeholders – especially national programmes and global partners – to respect the voices of those affected by HIV. The actual women living with HIV must be consulted in the guidance offered by global and national bodies, especially now in light of the potential early NTD signal with DTG. We are calling for TLD to be made available urgently across Africa, with everyone having access, regardless of gender or reproductive capability, and with integration of sexual and reproductive health services.
It is critical to not just view a pregnant mother, or any woman of childbearing potential, as a vessel for a baby, but as an individual in her own right, who deserves access to the very best, evidence-based treatment available and the right to be adequately informed to make a choice that she feels is best for her. As a result, women must not be forced to accept any one ARV regimen. All women should be able to make an informed choice for their own treatment and we call on key stakeholders to join us and help us make access to TLD, and improved health services, a reality for everyone.
NOTHING FOR US WITHOUT US.
For further information please feel free to contact:
Statement by the African Community Advisory Board (AfroCAB) on Dolutegravir and neural tube defects in women living with HIV of child bearing age
Since information has been shared from a cohort of women living with HIV in Botswana indicating a potential link between neural tube defects (NTD) and dolutegravir (DTG) use at the time of conception, many statements have been released by various stakeholders. Some of the statements have been helpful, others alarmist and misleading. But they all have one thread in common: no community consultation.
What we know
In preparation for the review of WHO guidelines, an unplanned interim analysis of data from a cohort of pregnant women living with HIV in Botswana was conducted at WHO’s request to help inform the guidelines review process. This interim analysis identified 4 cases of neural tube defects among 426 infants born to women who were taking DTG at the time they became pregnant. This is in comparison to 14 infants out of a total of more than 11,000 deliveries to women receiving antiretroviral therapy that did not contain DTG. This difference of 0.9% compared to 0.1% was considered statistically significant. lt should also be noted that the overall adverse pregnancy outcomes among women who started taking DTG after they became pregnant were identical to the outcomes among women taking efavirenz (EFV), and lower than those among women taking a protease inhibitor.
NTD are a severe birth defect that can have many different causes, including dietary folate deficiency, genetics, and drug exposures. Since the neural tube develops very early in a pregnancy, exposures resulting in NTD occur within the first few weeks following conception.
Previously, several human cases as well as laboratory animal data suggested that EFV could also be associated with NTD, although years of routine use in pregnant women have shown that this fear was unfounded. Studies of DTG in laboratory animals have shown no evidence for NTD, despite being administered in extremely high doses (27x higher than the adult human dose).
Furthermore, contrary to EFV, DTG has been shown to have no drug-drug interaction with hormonal birth control methods.
What we don’t know
Because this information from Botswana came to light as a result of an unplanned interim analysis, a more thorough analysis of other potential causes for NTD in these 4 cases is lacking. The absolute number of cases is small, and if another plausible explanation for these cases could be identified the association with DTG could be coincidental. As yet this analysis has not been conducted, although further investigation of the cases is understood to be underway.
Other countries have also been providing DTG to both pregnant and non-pregnant women, with other women giving birth after conceiving on DTG, but no other reports of NTD have been made from other countries or cohorts. More detailed analysis from other areas is being conducted but as yet these results are not publicly available. There are an additional 600 women in Botswana who were taking DTG at the time of conception that have yet to deliver. The outcomes of these additional cases are not yet known.
No plausible causative mechanism has been identified to explain why DTG might be associated with NTD.
While we appreciate the concern created by the recent description of the possible teratogenic effects of DTG, we are concerned that the statements were released without allowing PLHIV especially affected women being consulted or included in any appropriate course of action. We strongly urge WHO and various stakeholders — especially our governments — to respect the voices of those actually affected. At no point have we, or any actual women living with HIV, been consulted in the guidance offered by Ministries of Health especially now in light of the potential early NTD signal with DTG. We know women fall pregnant frequently and unexpectedly on ARVs, but we feel it is patronising to not give women the choice in this. We were shocked to learn of the potential harm to babies, but we do think it is critical to not just see the pregnant mother, and indeed all women of childbearing potential, as vessels of babies, but as individuals in their own right, who deserve access to the very best, evidence-based treatment available and the right to choose what they feel is best for them. We therefore think that to deny all women (and we believe, possibly men, as well) this new drug and fixed-dose formulation, should not be an option especially in the absence of any consultation with the community. We do not think that women are getting enough credit to be able to make conception decisions, and we hear this rhetoric as the same rhetoric that denied Africans treatment in the past.
Women living with HIV must be applauded for achieving and maintaining high levels of viral suppression, surpassing many developed countries. We see it as imperative that an education and information dissemination process is put in place so that women fully understand the risks, and a training programme is made available for healthcare workers to be able to appropriately counsel women on these risks and enable them to make an informed decision on their choice of treatment and conception decisions. Ministries of Health and other stakeholders should improve access to hormonal family planning methods rather than deny better treatment options to women who do not wish to conceive, especially that DTG can be used with many effective contraceptives currently in use, with less drug interactions than alternative regimens.
We want to know when is TLD coming?
Why we have not been consulted?
We understand that moving to TLD, while maintaining tenofovir-lamivudine-
We are calling for TLD to be made available urgently across the continent with everyone having access, and with appropriate education and support with regard to pregnancy (and the option of using TLE), and TB, for all stakeholders.
What we need is honest and open communication and consultation with all stakeholders, including Civil Society.
AfroCAB is a regional access to treatment network focusing primarily on Sub-Sahara Africa. The network prioritises optimised treatment – drugs and diagnostics, to ensure innovative high quality and effective health products and commodities are quickly accessible to all Africans at affordable prices.