Antiretroviral drug concentrations and HIV RNA in the genital tract of HIV-infected women receiving long-term highly active antiretroviral therapy.
OBJECTIVE
Our objective was to determine antiretroviral drug concentrations and human immunodeficiency virus (HIV) RNA rebound in cervicovaginal fluid (CVF) in relation to blood plasma (BP) in women receiving suppressive highly active antiretroviral therapy (HAART).


METHODS
Thirty-four HIV-infected women who had plasma HIV RNA levels < or =80 copies/mL for at least 6 months were enrolled. Sixty-eight paired CVF and BP drug concentrations and HIV RNA levels were determined before and 3-4 h after drug administration. For each woman and antiretroviral drug, the CVF:BP drug concentration ratios before and after drug administration were calculated. The nonparametric Wilcoxon rank sum test was used to determine if these ratios were different from 1.0.


RESULTS
Lamivudine (administered to 20 patients) and tenofovir (administered to 16) had significantly higher concentrations in CVF than in BP before drug administration, with mean CVF:BP concentration ratios of 3.19 (95% confidence interval, 1.2-8.5) and 5.2 (95% confidence interval, 1.2-22.6), respectively. Efavirenz (administered to 13 patients) and lopinavir (administered to 6) had significantly lower concentrations in CVF, with mean CVF:BP concentration ratios of 0.01 (95% confidence interval, 0.00-0.03) and 0.03 (0.01-0.11), respectively. During the study visit (median time after enrollment, 6 months), BP and CVF detectable HIV RNA levels were observed 7 patients (20.6%) and 1 patient (2.9%), respectively.


CONCLUSIONS
Despite lower CVF concentrations of key HAART components, such as efavirenz and lopinavir, virologic rebound was rare. The high concentrations of tenofovir and lamivudine in CVF may have implications for the prevention of sexual transmission during HAART and for pre-exposure or postexposure prophylaxis.
Kwara
Awewura
A
Miriam Hospital, Providence, Rhode Island 02906, USA. akwara@lifespan.org
Delong
Allison
A
Rezk
Naser
N
Hogan
Joseph
J
Burtwell
Heather
H
Chapman
Stacy
S
Moreira
Carla C
CC
Kurpewski
Jaclyn
J
Ingersoll
Jessica
J
Caliendo
Angela M
AM
Kashuba
Angela
A
Cu-Uvin
Susan
S
D000328:Adult; D019380:Anti-HIV Agents / Q000032:analysis* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001826:Body Fluids / Q000737:chemistry / Q000821:virology; D005260:Female; D005836:Genitalia, Female / Q000737:chemistry* / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry / Q000821:virology; D012367:RNA, Viral / Q000032:analysis*
D019380:Anti-HIV Agents; D012367:RNA, Viral