[O18] PENETRATION OF EFAVIRENZ INTO THE MALE GENITAL TRACT: DRUG CONCENTRATIONS AND ANTIVIRAL ACTIVITY IN SEMEN AND BLOOD PLASMA OF HIV-1 INFECTED MEN (THE TRIPLE S STUDY)

7th Annual Conference Of The British HIV Association [BHIVA]

27 – 29 April 2001, The Hove Centre, Brighton

[TITLE:] PENETRATION OF EFAVIRENZ INTO THE MALE GENITAL TRACT: DRUG CONCENTRATIONS AND ANTIVIRAL ACTIVITY IN SEMEN AND BLOOD PLASMA OF HIV-1 INFECTED MEN (THE TRIPLE S STUDY)

[AUTHOR(S):] S Taylor^1,2, H Reynolds³, CA Sabin⁴, S Drake², DJ White², D Back³ and D Pillay¹
¹ PHLS Antiviral Susceptibility Reference Unit, Birmingham, ² Birmingham Heartlands Hospital, ³ University of Liverpool and ⁴ Royal Free Medical School, London, UK

BHIVA Conf 2001 Apr 27-29;7:O18

OBJECTIVE: A prospective study to determine efavirenz (EFV) concentrations and antiviral activity in blood plasma (BP) and seminal plasma (SP) in HIV-1 positive men over the 24 hour dosing period.

METHODS: Nineteen HIV-1 positive men on EFV-containing regimens were enrolled to donate matched semen and blood samples at baseline (week 0) and at 24 weeks of EFV therapy for viral load determination. BP and SP samples were assayed for EFV drug concentrations at 12 and 24 hours after EFV administration. When SP and BP samples were collected within 1 hour of each other, a time-specific SP:BP ratio was calculated. SPVL was measured using NABSA. EFV drug concentrations were measured using a sensitive HPLC.

RESULTS: A total of 70 BP and 69 SP samples were analysed. The median EFV concentrations in BP and SP 12 hours post-dose were 2,184 ng/ml (843–14,356) and 215 ng/ml (62–622), respectively. At 24 hours postdose, median values were 1,785 ng/ml (694–8,096) and 238 ng/ml (49– 1,256), respectively. The median SP:BP ratio was 0.08 (0.04–0.16) at 12 hours and 0.09 (0.03–0.43) at 24 hours. Absolute median trough SP EFV concentrations exceeded an estimated BP protein-corrected 90% effective concentration (EC₉₀) of 92.8 ng/ml for wild-type HIV-1 by over twofold. Viral load at 24 weeks was reduced below the limit of detection in 18/18 patients in SP and 16 /18 patients in BP.

CONCLUSIONS: Standard EFV doses give greater than expected SP concentrations according to protein-binding considerations alone. These data suggest that EFV has antiviral activity in the male genital tract.

PRESENTING AUTHOR: S Taylor

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