Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract

Antivir Ther. 2011;16(8):1149-67. doi: 10.3851/IMP1919.


HIV resides within anatomical 'sanctuary sites', where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Suboptimal antiretroviral concentrations in the genital tract may result in compartmentalized viral replication, selection of resistant mutations and possible re-entry of wild-type/resistant virus into the systemic circulation. Therefore, achieving adequate antiretroviral exposure in the genital tract has implications for the prevention of sexual and vertical transmission of HIV. Penetration of antiretrovirals in the genital tract is expressed by accumulation ratios derived from the measurement of drug concentrations in time-matched seminal plasma/cervicovaginal fluid and plasma samples. Penetration varies by gender and may be drug (as opposed to class) specific with high interindividual variability. Concentrations in seminal plasma are highest for nucleoside analogues and lowest for protease inhibitors and efavirenz. Seminal accumulation of newer agents, raltegravir and maraviroc, is moderate (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitors [lamivudine/zidovudine/tenofovir/didanosine > stavudine/abacavir] > raltegravir > indinavir/maraviroc/nevirapine >> efavirenz/protease inhibitors [amprenavir/atazanavir/darunavir > lopinavir/ritonavir > saquinavir] > enfuvirtide). In the female genital tract, the nucleoside analogues exhibit high accumulation ratios, whereas protease inhibitors have limited penetration; however, substantial variability exists between individuals and study centres. Second generation non-nucleoside reverse transcriptase inhibitor etravirine, and maraviroc and raltegravir, demonstrate effective accumulation in cervicovaginal secretions (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitor [zidovudine/lamivudine/didanosine > emtricitabine/tenofovir] > indinavir > maraviroc/raltegravir/darunavir/etravirine > nevirapine/abacavir > protease inhibitors [amprenavir/atazanavir/ritonavir] > lopinavir/stavudine/efavirenz > saquinavir).

Publication types

  • Review

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Body Fluids / drug effects
  • Body Fluids / virology
  • Capillary Permeability / physiology*
  • Female
  • Genitalia, Female / anatomy & histology
  • Genitalia, Female / drug effects*
  • Genitalia, Female / physiology
  • Genitalia, Male / anatomy & histology
  • Genitalia, Male / drug effects*
  • Genitalia, Male / physiology
  • HIV Fusion Inhibitors / pharmacokinetics
  • HIV Fusion Inhibitors / therapeutic use
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / transmission
  • HIV Infections / virology
  • HIV Integrase Inhibitors / pharmacokinetics
  • HIV Integrase Inhibitors / therapeutic use
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Organ Specificity
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Semen / drug effects
  • Semen / virology
  • Sex Factors
  • Viral Load / drug effects
  • Virus Replication / drug effects*


  • Anti-HIV Agents
  • HIV Fusion Inhibitors
  • HIV Integrase Inhibitors
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors