Antiretroviral Drug Concentrations and HIV RNA in the Genital Tract of HIV-Infected Women Receiving Long-Term Highly Active Antiretroviral Therapy

Abstract

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.

Lopinavir Up-Regulates Expression of the Antiviral Protein Ribonuclease L in Human Papillomavirus-Positive Cervical Carcinoma Cells

“…On this point, it is noteworthy that the concentration of lopinavir found in the vaginal fluid of HIV patients taking oral Kaletra is <2 µM [28], which has been discussed in our previous study [13].…”

Persistence of Genital Tract T Cell Responses in HIV-Infected Women on Highly Active Antiretroviral Therapy

“…Pharmacokinetics studies have shown that NRTIs penetrate the female genital tract more efficiently than either PIs or NNRTIs (17, 34), achieving higher drug concentrations at the female genital tract than in blood (16,11,34). In this study, all of the HAART ϩ women were receiving NRTIs as part of either a first-line treatment regimen (24/27 women), together with NNRTIs, or a second-line regimen (3/27 women), together with PIs.…”

“…Suboptimal bioavailability of antiretroviral drugs at mucosal surfaces has been associated with incomplete immune reconstitution in individuals receiving HAART (17,34). Several studies speculate that this is a result of low levels of HIV replication within persistently infected cells, in the inflammatory environment associated with mucosal tissue (20,24,45,54,58).…”

“…This is perhaps not surprising, since in the absence of HAART, CD4 T cell restoration and preservation during HIV infection are generally less efficient at mucosal sites than in blood (23,38). Ongoing low levels of HIV replication, the persistence of proviral DNA within infected cells of the mucosa (19, 43,52,56), and the poor penetration of drugs through to the mucosa have been implicated in the incomplete reconstitution of mucosal CD4 counts seen in individuals receiving HAART (17,34).…”

Use of Animal Models for Anti-HIV Drug Development

“…Tenofovir prevents HIV-1 replication, it is already approved for use in humans in the oral formulation, and high drug concentrations can be achieved in the male and female genital tracts (Kwara et al, 2008;Vourvahis et al, 2008). The use of a gel may not provide complete coverage of the mucosal surface, possibly leading to breakthrough infections.…”