Clinical, pharmacological, and qualitative characterization of drug–drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa

Kiiza, Daniel, Rostami-Hochaghan, Danial, Alhassan, Yussif ORCID: https://orcid.org/0000-0003-4155-546X, Seden, Kay, Reynolds, Helen, Kaboggoza, Julian P, Taegtmeyer, Miriam ORCID: https://orcid.org/0000-0002-5377-2536, Chen, Tao ORCID: https://orcid.org/0000-0002-5489-6450, Challenger, Elizabeth, Malaba, Thokozile, Wang, Duolao ORCID: https://orcid.org/0000-0003-2788-2464, Else, Laura, Hern, Faye, Sharp, Jo, Neary, Megan, Dilly Penchala, Sujan, Waitt, Catriona, Orrell, Catherine, Colbers, Angela, Myer, Landon, Owen, Andrew, Rannard, Steve, Khoo, Saye and Lamorde, Mohammed (2024) 'Clinical, pharmacological, and qualitative characterization of drug–drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa'. Journal of Antimicrobial Chemotherapy, Vol 79, Issue 9, pp. 2334-2342.

Text DolPHIN-2 DDI TM Paper_accepted Manuscript.pdf - Accepted Version Restricted to Repository staff only until 13 July 2025. Download (607kB)

Abstract

Background
We investigated the impact of Drug–Drug Interactions (DDIs) on virologic control among HIV-positive pregnant women initiating antiretroviral therapy while identifying drivers for Traditional Medicine (TM) use and exploring the nature and extent of TM-related DDIs.

Methods
Employing a three-pronged approach, we examined DDIs arising from comedication, including TM, in ART. The DolPHIN-2 trial (NCT03249181) randomized 268 HIV-positive pregnant women in Uganda and South Africa to dolutegravir (DTG)-based (135) or efavirenz-based (133) regimens while systematically recording comedications and screening for DDIs. We used Cox regression models to compare time-to-virologic control between participants with and without DDIs. We conducted in-depth interviews and focus group discussions among 37 and 67 women with and without HIV, respectively, to explore reasons for TM use during pregnancy. Additionally, in-vitro and in-vivo studies evaluated the composition and impact of clay-based TM, mumbwa, on DTG plasma exposure.

Results
The baseline prevalence of DDIs was 67.2%, with TM use prevalent in 34% of participants, with mumbwa being the most frequent (76%, 69/91). There was no difference in virologic response between participants with and without DDIs. Fetal health and cultural norms were among the reasons cited for TM use. Analysis of mumbwa rods confirmed significant amounts of aluminium (8.4%–13.9%) and iron (4%–6%). In Balb-C mice, coadministration of mumbwa led to a reduction in DTG exposure observed in the AUC0-24 (−21%; P = 0.0271) and C24 (−53%; P = 0.0028).

Conclusions
The widespread use of clay-based TM may compromise HIV treatment, necessitating medication screening and counselling to manage DDIs in pregnant women.

Item Type:	Article
Subjects:	QV Pharmacology > QV 38 Drug action. WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WQ Obstetrics > Pregnancy Complications > WQ 256 Infectious diseases
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/jac/dkae232
Depositing User:	Rachel Dominguez
Date Deposited:	31 Jul 2024 13:46
Last Modified:	10 Oct 2024 13:08
URI:	https://archive.lstmed.ac.uk/id/eprint/24983

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