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Clinical Trial
. 2023 Jul 5;78(7):1711-1722.
doi: 10.1093/jac/dkad161.

Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study

Laurent Mandelbrot  1   2   3 , Roland Tubiana  4   5 , Pierre Frange  2   6 , Gilles Peytavin  3   7 , Jerome Le Chenadec  8 , Ana Canestri  9 , Philippe Morlat  10   11 , Cécile Brunet-Cartier  12 , Jeanne Sibiude  1   2   3 , Delphine Peretti  13 , Véronique Chambrin  14 , Amélie Chabrol  15 , Eida Bui  16 , Caroline Simon-Toulza  17 , Lucie Marchand  18 , Christelle Paul  18 , Sandrine Delmas  8   19 , Véronique Avettand-Fenoel  2   6   20 , Josiane Warszawski  8   21 ; Monogest study group
Collaborators, Affiliations
Clinical Trial

Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study

Laurent Mandelbrot et al. J Antimicrob Chemother. .

Abstract

Objectives: Because NRTIs can have fetal toxicities, we evaluated a perinatal NRTI-sparing strategy to prevent perinatal HIV transmission. Our primary objective was to determine the proportion maintaining a viral load (VL) of <50 copies/mL up to delivery on darunavir/ritonavir monotherapy, without requiring treatment intensification.

Methods: In a one-arm, multicentre Phase 2 clinical trial, eligible patients in the first trimester of pregnancy on ART with plasma VL < 50 copies/mL received maintenance monotherapy with darunavir/ritonavir, 600/100 mg twice daily. VL was monitored monthly. ART was intensified in the case of VL > 50 copies/mL. Neonates received nevirapine prophylaxis for 14 days.

Results: Of 89 patients switching to darunavir/ritonavir monotherapy, 4 miscarried before 22 weeks' gestation, 2 changed treatment for elevated liver enzymes without virological failure, and 83 were evaluable for the main outcome. Six had virological failure confirmed on a repeat sample (median VL = 193 copies/mL; range 78-644), including two before switching to monotherapy. In these six cases, ART was intensified with tenofovir disoproxil fumarate/emtricitabine. The success rate was 75/83, 90.4% (95% CI, 81.9%-95.7%) considering two patients with VL missing at delivery as failures, and 77/83, 92.8% (95% CI, 84.9%-97.3%) when considering them as successes since both had undetectable VL on darunavir/ritonavir throughout pregnancy. In ITT, the last available VL before delivery was <50 copies/mL in all of the patients. There was no case of perinatal HIV transmission.

Conclusions: Darunavir/ritonavir maintenance monotherapy required intensification in nearly 10% of cases. This limits its widespread use, thus other regimens should be evaluated in order to limit exposure to antiretrovirals, particularly NRTIs, during pregnancy.

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Figures

Figure 1.
Figure 1.
Flow chart for Monogest ANRS 168 study.
See this image and copyright information in PMC

References

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