Assessment of minority frequency pretreatment HIV drug-resistant variants in pregnant women and associations with virologic non-suppression at term

• Published in: PloS one Vol. 17; no. 9; p. e0275254
• Main Authors: Boyce, Ceejay L, Beck, Ingrid A, Styrchak, Sheila M, Hardy, Samantha R, Wallner, Jackson J, Milne, Ross S, Morrison, R Leavitt, Shapiro, David E, João, Esaú C, Mirochnick, Mark H, Frenkel, Lisa M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-09-2022; Public Library of Science (PLoS)
• Subjects: Alkynes; Analysis; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiviral agents; Benzoxazines; Biology and Life Sciences; Case-Control Studies; Cyclopropanes; DNA sequencing; Dosage and administration; Drug resistance; Drug Resistance, Viral - genetics; Efavirenz; Enrollments; Female; Genotypes; Health aspects; Health risks; HIV; HIV infection; HIV Infections - drug therapy; HIV Integrase Inhibitors - therapeutic use; HIV-1 - genetics; Human immunodeficiency virus; Humans; Integrase; Load; Medicine and Health Sciences; Mutation; Nucleotide sequencing; Pharmaceutical Preparations; Plasma; Pregnancy; Pregnant Women; Pretreatment; Prevention; Raltegravir Potassium - therapeutic use; Randomization; Research and Analysis Methods; Ribonucleic acid; Risk factors; RNA; Social aspects; Viral Load; Women; United States; United States > US; Germany; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0275254

To assess in ART-naïve pregnant women randomized to efavirenz- versus raltegravir-based ART (IMPAACT P1081) whether pretreatment drug resistance (PDR) with minority frequency variants (<20% of individual's viral quasispecies) affects antiretroviral treatment (ART)-suppression at term.
A case-control study design compared PDR minority variants in cases with virologic non-suppression (plasma HIV RNA >200 copies/mL) at delivery to randomly selected ART-suppressed controls.
HIV pol genotypes were derived from pretreatment plasma specimens by Illumina sequencing. Resistance mutations were assessed using the HIV Stanford Database, and the proportion of cases versus controls with PDR to their ART regimens was compared.
PDR was observed in 7 participants (11.3%; 95% CI 4.7, 21.9) and did not differ between 21 cases and 41 controls (4.8% vs 14.6%, p = 0.4061). PDR detected only as minority variants was less common (3.2%; 95% CI 0.2, 11.7) and also did not differ between groups (0% vs. 4.9%; p = 0.5447). Cases' median plasma HIV RNA at delivery was 347c/mL, with most (n = 19/22) showing progressive diminution of viral load but not ≤200c/mL. Among cases with viral rebound (n = 3/22), none had PDR detected. Virologic non-suppression at term was associated with higher plasma HIV RNA at study entry (p<0.0001), a shorter duration of ART prior to delivery (p<0.0001), and randomization to efavirenz- (versus raltegravir-) based ART (p = 0.0085).
We observed a moderate frequency of PDR that did not significantly contribute to virologic non-suppression at term. Rather, higher pretreatment plasma HIV RNA, randomization to efavirenz-based ART, and shorter duration of ART were associated with non-suppression. These findings support early prenatal care engagement of pregnant women and initiation of integrase inhibitor-based ART due to its association with more rapid suppression of plasma RNA levels. Furthermore, because minority variants appeared infrequent in ART-naïve pregnant women and inconsequential to ART-suppression, testing for minority variants may be unwarranted.