Concentration of PrEP drug lower in pregnant girls and young women
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Levels of tenofovir-diphosphate, or TFV-DP, in dried blood spots were 31% to 37% lower among African pregnant adolescent girls and young women taking pre-exposure prophylaxis, or PrEP, compared with those who were postpartum, according to study findings from the IMPAACT 2009 trial presented during CROI.
The lower drug concentrations were consistent with findings from past studies that included pregnant women, said Peter Anderson, PharmD, director of the pharmaceutical graduate program at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.
During the trial, Anderson and colleagues watched participants take their daily doses of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) — either in person or via live video streaming — ensuring their adherence.
“PrEP with daily TDF/FTC is an effective intervention and should be offered to pregnant and postpartum women as part of comprehensive HIV prevention services,” Anderson told Healio. “Strict adherence should be encouraged.”
From March to June 2019, the researchers enrolled 20 pregnant and 20 postpartum women (median age of 20 years) from Malawi, South Africa, Uganda and Zimbabwe and directly observed them taking daily oral doses of PrEP (FTC 200 mg/TDF 300 mg) for 12 weeks. They measured weekly TFV-DP using a hole punch taken from each dried blood spot.
According to the study, TFV-DP accumulated with a half-life of 15.3 days in pregnancy (95% CI, 12.8-17.8) and 18 days postpartum (95% CI, 15.3-20.7), with a steady state achieved by both parties in 8 to 10 weeks.
Median TFV-DP was 965 fmol/punch in pregnancy (interquartile range [IQR], 691-1,166) vs. 1,406 fmol/punch postpartum (IQR, 1,053-1,859), a difference of 31%. Using a model, they predicted the median TFV-DP to be 890 fmol/punch in pregnancy (IQR, 704-1,143) vs. 1,418 fmol/punch postpartum (IQR, 1,179-2,139), a difference of 37%.
No HIV transmissions occurred during follow-up.
Anderson noted that 99.6% of PrEP doses were taken under direct observation.
“No other study to our knowledge has documented this level of adherence over 12 weeks in pregnant and postpartum adolescents and young women from sub-Saharan Africa,” he said. “These newly established drug concentrations in dried blood spots allow us to interpret and understand PrEP adherence in these populations in future studies.”
Because the goal of the study was to establish drug concentrations in dried blood spots, Anderson said they did not conduct any “intensive pharmacokinetic” studies. He said future studies will collect drug concentrations in additional biomatrices, including peripheral blood mononuclear cells.
“It is unknown whether the lower drug concentrations in dried blood spots will reduce the effectiveness of PrEP in pregnant women, but the experience with PrEP in clinical trials and demonstration projects suggests that — in the setting of strict adherence — PrEP will still provide substantial protection from HIV,” Anderson said. – by Ken Downey Jr.
Reference:
Anderson PL, et al. Abstract 980LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
Disclosures: Anderson reports receiving grants, contracts and personal fees from Gilead Sciences. Please see the study for all other authors’ relevant financial disclosures.