Antiretroviral Pharmacokinetics in Pregnant Women

Abstract

For women infected with the human immunodeficiency virus (HIV) who become pregnant, the use of combination antiretroviral therapy (ART) significantly reduces transmission of HIV from mother to child. Selection of an appropriate ART regimen for use among pregnant women requires consideration of numerous factors including maternal and fetal safety, antiretroviral pharmacokinetics, and regimen efficacy. Optimization of antiretroviral pharmacokinetics during pregnancy requires special consideration because pregnancy-associated changes in drug absorption, distribution, metabolism, and excretion are known to occur throughout pregnancy and postpartum. Understanding antiretroviral placental transfer may offer additional insight into each drug's potential role in preventing HIV transmission in utero and may also have implications regarding viral resistance in cases where transmission does occur. In this review, we summarize key published data describing antiretroviral pharmacokinetics in pregnant women, providing suggestions for clinical application of these data where appropriate.

Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells

“…HIV-1 positive non-pregnant (PnP) and pregnant (PP) women were recruited from Chelsea and Westminster Hospital and St. Mary's Hospital, with any participant who delivered preterm excluded from analysis. Where possible blood was sampled at each trimester and delivery; two first trimester (<13 weeks gestation), 15 second trimester (13-27 weeks), 31 third trimester (>28 weeks) and 9 delivery samples were collected (median and range gestation were 8 (8), 22 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), 30 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), and 40 (37-40) respectively). Samples were processed within 6 h of collection, with peripheral blood mononuclear cells (PBMC) isolated in a containment level 3 laboratory.…”

“…Through anti-CD3 stimulation of peripheral leukocytes pregnant HIV-1 positive women have been shown to have higher IL-10 and lower TNFα and IFNγ responses than non-pregnant HIV-1 positive women (32). Physiological changes occurring during pregnancy are also known to affect ART pharmacokinetics (33). However, pregnancy's effect on HIV-1-specific responses is unknown, with work demonstrating higher acquisition of HIV-1 and other pathogens during pregnancy signifying such responses may be suppressed, suggesting control of HIV-1 and risk of transmission could be affected by gestation (34,35).…”

Toward a universal antiretroviral regimen

“…Even with substantial pregnancy-induced changes to drug metabolism, ARV exposure adequate to achieve viral suppression is most often reached, with the exception of boosted-protease inhibitors (PI) (Table 1) [21, 22**]. …”

“…Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), including FTC, 3TC and TDF, undergo increased renal elimination during pregnancy due to elevated renal blood flow and glomerular filtration particularly during the third trimester [22**]. Despite demonstrated increased clearance, pregnant women still met drug exposure targets for FTC, 3TC and TDF comparable to that during the post-partum period or in non-pregnant adults [23–29*].…”

“…With standard dosing of EFV (600mg/day), pregnancy trough concentrations are reduced due to increased metabolism by hepatic cytochrome P450 (CYP450) enzymes that are induced by elevated progesterone during pregnancy [21, 22**, 30, 31]. Despite this, 88% of pregnant women remained within the therapeutic range for EFV in the third trimester [30].…”