eHIV Review

The Greek philosopher Heraclitus is often quoted as stating, “The only thing that is constant is change.”  As noted in the eHIV Review newsletter “Understanding AE in the New ART Regimens” (Volume 4, Issue 7) and the podcast “Clinical Perspective: New AEs from Newer ART” (Volume 4, Issue 8), data regarding adverse effects of newer antiretroviral therapy (ART) is constantly evolving. Since the release of this newsletter and podcast, important data from the Conference on Retroviruses and Opportunistic Infections 2019 have become available and add further depth and context to these publications.

The interim analysis of a birth defect surveillance study in Botswana previously reported a possible increase in the rate of neural tube defects among newborns exposed to dolutegravir at the time of conception.¹ Multiple reports presented at CROI 2019 have not found consistent associations between neural tube defects and integrase strand transfer inhibitor (INSTI) use during pregnancy.^2-4 These reports included studies from Uganda, HIV cohorts, and pregnancy registries. Ongoing monitoring will be essential to identify the potential impact of dolutegravir as well as other ART on pregnancy outcomes.

The nonvirologic impacts related to INSTI regimens were a popular topic of ongoing study at CROI 2019. In the recent eHIV Review, the NEAT 022 study revealed that cardiovascular risk was lowered by switching from a boosted protease inhibitor (PI)-based regimen to an INSTI-based regimen.⁵ At CROI 2019, lower cardiovascular disease risk was again noted with INSTI-based ART as compared to non-INSTI-based ART.⁶ On the other hand, the association between INSTI medications and weight gain were strengthened based on multiple reports among treatment-naïve, treatment-experienced, and other subpopulations (ie, women, blacks, and older adults).^7-12 The potential impacts of this weight gain on cardiovascular health and other metabolic outcomes will undoubtedly be the subject of ongoing study.

Finally, neuropsychiatric adverse effects related to dolutegravir highlighted in the recent eHIV review were rigorously studied in one cohort presented at CROI 2019; it again highlighted the increase in somatic effects (including insomnia) when switching to a dolutegravir-based regimen, though it did not find significant contributions to severe depression symptoms.^12-13

Heraclitus has also been credited with the following quote: “No man ever steps in the same river twice, for it's not the same river and he's not the same man.” As providers, we must be ready to assimilate new information and adapt practice accordingly. With new treatments come new opportunities and threats, and we must remain vigilant to best care for people living with HIV.

References

1. Zash R, Makhema J, Shapiro RL. Neural-tube defects with dolutegravir treatment from the time of conception. N Engl J Med. 2018 Sep 6;379(10):979-981. 
2. Barlow-Mosha L, Mumpe DM, Williamson D, et al. Neural tube defects, HIV, and antiretrovirals: birth-defect surveillance in Uganda. CROI 2019, Abstract 743, Seattle, Washington, March 4-7, 2019.
3. Sibiude J, Le Chenadec J, Madelbrot L, et al. No increase in birth defects in infants exposed to integrase inhibitors at conception. CROI 2019, Abstract 744, Seattle, Washington, March 4-7, 2019.
4. Albano JD, Vannappagari V, Scheuerle, et al. InSTI exposure and neural tube defects: data from Antiretroviral Pregnancy Registry. CROI 2019, Abstract 747, Seattle, Washington, March 4-7, 2019.
5. Gatell JM, Assoumou L, Moyle G, et al; European Network for AIDS Treatment 022 (NEAT 022) Study Group. Immediate versus deferred switching from a boosted protease inhibitor-based regimen to a dolutegravir-based regimen in virologically suppressed patients with high cardiovascular risk for age >= 50 years: final 96-week results of the NEAT 022 Study. Clin Infect Dis. 2018 Jun 14.
6. O’Halloran JA, Sahrman J, Butler AM, et al. Lower cardiovascaulr disease risk associated with integrase inhibitors. CROI 2019, Abstract 680, Seattle, Washington, March 4-7, 2019.
7. Bourgi K, Jenkins C, Rebeiro P, et al. Greater weight gain among treatment-naïve persons starting integrase inhibitors. CROI 2019, Abstract 670, Seattle, Washington, March 4-7, 2019.
8. McComsey GA, Eron JJ, Santiago S, et al. Weight gain during treatment among 3,468 treatment-experienced adults with HIV. CROI 2019, Abstract 671, Seattle, Washington, March 4-7, 2019.
9. Palella FJ, Rayeed N, Li J, et al. Weight gain among virally suppressed persons who switch to InSTI-based ART. CROI 2019, Abstract 674, Seattle, Washington, March 4-7, 2019.
10. Kerchberger AM, Sheth AN, Angert CD, et al. Integrase strand transfer inhibitors are associated with weight gain in women. CROI 2019, Abstract 672, Seattle, Washington, March 4-7, 2019.
11. Lake JE, Wu K, Erlandson KM, et al. Risk factors for excess weight gain following switch to integrase inhibitor-based ART. CROI 2019, Abstract 669, Seattle, Washington, March 4-7, 2019.
12. Hoffman C, Welz T, Sabranski M, et al. Higher rates of neuropsychiatric adverse effects leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017 Jan;18(1):56-63. 
13. Chan P, Goh O, Kroon E, et al. Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy. CROI 2019, Abstract 440, Seattle, Washington, March 4-7, 2019.