New HIV pregnancy study uses latest ART: IMPAACT 2010 study (VESTED) includes dolutegravir and tenofovir alafenamide (TAF)

9 February 2018. Related: Pregnancy.

Polly Clayden, HIV i-Base

The US National Institutes of Health recently launched VESTED: a large international study comparing the safety and efficacy of three ART regimens for HIV positive pregnant women and their infants. [1]

VESTED or IMPAACT 2010 is a phase 3 study that aims to enrol 639 ART naive HIV positive women at 14–28 weeks gestation. [2]

The women will be randomised to one of three treatment arms.

• Efavirenz (EFV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF).
• Dolutegravir (DTG)/FTC/ tenofovir alafenamide (TAF).
• DTG/FTC/TDF.

Their infants will also be enrolled and will receive local standard of care for HIV prophylaxis and infant feeding options, which might be breast or formula feeding.

Primary endpoints include the proportion of mothers with viral load less than 200 copies/mL at delivery. The study will also compare rates of adverse pregnancy outcomes, plus maternal and infant adverse events, between arms.

Both mothers and infants will be monitored for 50 weeks after delivery. The study is expected to last for approximately three years.

The first mothers have begun receiving treatment at clinical trial sites in Zimbabwe. Sites in the US, Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, Uganda, are open for enrolment or expected to open in the next few months.

comment

VESTED is a key ART optimisation study, so it is excellent news that it has started. It is also one of very few studies looking at TAF in pregnancy.

The randomised DolPHIN-2 study, comparing DTG-based to EFV-based ART in late-presenting women, with sites in South Africa and Uganda, has also recently begun. [3]

Almost 60 low- and middle-income countries have adopted or have plans to transition to DTG-based ART and PEPFAR is supporting rapid uptake in the countries where it operates. [4, 5]  

Early adoption of DTG has led to reassuring pregnancy data from Botswana, which, combined with those from high-income countries will make countries more comfortable with adopting DTG for pregnant women. [6] But clinical trial data on DTG are still needed and any data on TAF in pregnancy are woefully lacking.

It is also notable that two arms of the NIH funded VESTED study include TDF/FTC, despite the much-rejected recent recommendation from the British Medical Journal (BMJ) against using these drugs in pregnancy. [7]

The ADVANCE study, ongoing in South Africa, is evaluating the same three ART regimens as VESTED in non-pregnant adults but any women that become pregnant during the study can remain on their randomised treatment. [8]

The i-Base Fit for Purpose report tracks and reviews ongoing or planned ART optimisation initiatives for adults and children. [9] Our next edition will be published in March 2018 to coincide with CROI.

References

1. US National Institutes of Health press release. NIH begins large HIV treatment study in pregnant women. 24 January 2018.
   https://www.nih.gov/news-events/news-releases/nih-begins-large-hiv-treatment-study-pregnant-women
2. US National Institutes of Health. Evaluating the efficacy and safety of dolutegravir-containing versus efavirenz-containing antiretroviral therapy regimens in HIV-1-infected pregnant women and their infants (VESTED). ClinicalTrials.gov Identifier: NCT03048422.
   https://clinicaltrials.gov/ct2/show/NCT03048422
3. US National Institutes of Health. Dolutegravir in pregnant HIV mothers and their neonates (DolPHIN-2). ClinicalTrials.gov Identifier: NCT03249181.
   https://clinicaltrials.gov/ct2/show/NCT03249181
4. World Health Organisation. Transition to new antiretrovirals in HIV programmes. July 2017.
   http://apps.who.int/iris/bitstream/10665/255888/1/WHO-HIV-2017.20-eng.pdf (PDF)
5. Siberry G. PEPFAR support for transition to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD). ICASA Conference, Abidjan, Cote d’Ivoire. 4–9 December 2017.
6. Clayden P. Preliminary results on dolutegravir use in pregnancy are reassuring. HTB. 10 August 2017.
   https://i-base.info/htb/32182
7. Clayden P. Experts disagree with controversial BMJ support for older HIV drugs in pregnancy. HTB. 1 October 2017.
   https://i-base.info/htb/32705
8. US National Institutes of Health. ADVANCE Study of DTG + TAF + FTC vs DTG + TDF + FTC and EFV + TDF+FTC in First-line Antiretroviral Therapy (ADVANCE). ClinicalTrials.gov Identifier: NCT03122262.
   https://clinicaltrials.gov/ct2/show/NCT03122262
9. Clayden P. Antiretroviral treatment optimisation for adults and children. 20 July 2017.
   https://i-base.info/htb/32022