Genital tract pharmacokinetics of ten antiretroviral drugs in HIV-positive women

A poster authored by Julie Dumond and coworkers from the University of North Carolina evaluated first dose and steady state pharmacokinetics of 10 antiretrovirals (ARVs) in the female genital tract. The authors explained: ARVs rapidly achieving high genital tract concentrations may be targets for optimal PREP and PEP.

The study was open label and performed in 23 HIV-positive women initiating treatment including combinations of the following ARVs: 3TC, AZT abacavir, FTC, ddI, d4T, efavirenz, lopinavir/ritonavir, and atazanavir

Six paired blood plasma and genital tract samples were obtained over a dosing interval around observed doses on Day 1 and after Day 21 (steady state). Genital tract: blood plasma AUC ratios were calculated and are presented as median (IQR). Table 1.

Drug	AUC ratio day 1	AUC SS	Drug	AUC ratio day 1	AUC SS
AZT	3.7 (0.9, 10.1)	2.3 (1.2, 21.2)	ABC	0.4 (0.1, 2.0)	<0.1 (<0.1, 0.1)
3TC	2.7 (1.1, 19.0)	4.4 (2.3, 6.4)	EFV	<0.1 (<0.1, <0.1)	<0.1 (<0.1, <0.1)
FTC	6.1 (1.3, 11.0)	6.7 (6.7, 6.7)	LPV	0.3 (<0.1, 1.0)	<0.1 (<0.1, 2.4)
ddI	1.3 (<0.1, 2.4)	0.4 (0.4, 0.4)	RTV	0.2 (0, 0.4)	1.2 (0.2, 3.1)
d4T	<0.1 (<0.1, 0.5)	<0.1 (0.1, 0.1)	ATV	<0.3 (<0.1, 1.2)	0.7 (0.1, 1.9)

Drug

AUC ratio day 1

AUC SS

Drug

AUC ratio day 1

AUC SS

AZT

3.7 (0.9, 10.1)

2.3 (1.2, 21.2)

ABC

0.4 (0.1, 2.0)

<0.1 (<0.1, 0.1)

3TC

2.7 (1.1, 19.0)

4.4 (2.3, 6.4)

EFV

<0.1 (<0.1, <0.1)

FTC

6.1 (1.3, 11.0)

6.7 (6.7, 6.7)

LPV

0.3 (<0.1, 1.0)

<0.1 (<0.1, 2.4)

ddI

1.3 (<0.1, 2.4)

0.4 (0.4, 0.4)

RTV

0.2 (0, 0.4)

1.2 (0.2, 3.1)

d4T

<0.1 (<0.1, 0.5)

<0.1 (0.1, 0.1)

ATV

<0.3 (<0.1, 1.2)

0.7 (0.1, 1.9)

The authors reported that at day 1 and steady state, AZT, 3TC, and FTC genital tract exposures were higher than blood plasma (p<0.02); d4T, ritonavir, efavirenz, lopinavir, and atazanavir genital tract exposures were less than blood plasma (p<0.03). They also noted a trend towards higher genital tract exposures on day 1 compared to steady state was noted for AZT, abacavir, and ddI, but this was not significant

The authors concluded that as AZT, 3TC, and FTC achieved genital tract exposures greater than that of blood plasma, it would be expected that the higher genital tract concentrations would make these excellent candidates for PREP/PEP regimens. They added: Understanding exposure profiles for ARVs in the genital tract is particularly important for PREP, PEP, and possibly the prevention of mother to child transmission.

Dumond J, Yeh R, Patterson K et al. First dose and steady-state genital tract pharmacokinetics of ten antiretroviral Drugs in HIV-infected women: implications for pre- and post- exposure prophylaxis. 13th CROI, Denver, 2006. Abstract 129.