icon- folder.gif   Conference Reports for NATAP  
 
  XVII International AIDS Conference
Mexico City
3-8 August 2008
Back grey_arrow_rt.gif
 
 
 
Nevirapine Is Best Semen Penetrator in Study of Six PIs and Nonnucleosides
 
 
  XVII International AIDS Conference
August 3-8, 2008
Mexico City
 
Mark Mascolini
 
Nevirapine penetrated semen better than efavirenz or any protease inhibitor (PI) analyzed in a cross-sectional study of 119 Australian patients [1]. Despite this difference, the investigators could detect no HIV RNA in semen of any patient, all of whom had an undetectable RNA in blood plasma. Understanding the impact of antiretrovirals in semen is critical in estimating the effect of therapy on sexual transmission of HIV, especially with a heightened focus on wider antiretroviral therapy as a way to limit HIV transmission [2].
 
Researchers at the Prince of Wales Hospital and St. Vincent's Hospital in Sydney measured seminal and plasma concentrations of nevirapine in 17 people, efavirenz in 15, ritonavir-boosted lopinavir in 16, boosted atazanavir in 10, unboosted atazanavir in 2, boosted saquinavir in 5, boosted indinavir in 2, boosted fosamprenavir in 1, and nelfinavir in 1.
 
Age averaged 41 years in the men studied, median CD4 count stood at 595, and average treatment duration measured 33 months with nonnucleosides and 31 months with PIs. Everyone had a blood plasma load below 50 copies/mL, and concurrent seminal load was uniformly undetectable below a cutoff of 250 copies/mL. Among 4 men taking a nonnucleoside and 6 taking a PI who had repeat seminal plasma measures after a median of 16 months, HIV RNA remained undetectable in semen.
 
Of the four antiretrovirals taken by most study participants, the researchers set therapeutic concentrations at 150 micrograms/L for boosted atazanavir, more than 1000 micrograms/L for boosted lopinavir, at least 3450 micrograms/L for nevirapine, and at least 1000 micrograms/L for efavirenz. For boosted atazanavir and lopinavir, seminal concentrations ranged from 0 to 277 micrograms/L (median 87.5) and from below 124 to 502 micrograms/L (median 465). The investigators concluded that drug concentrations "were largely subtherapeutic for both of these protease inhibitors."
 
All 6 men taking efavirenz had therapeutic levels of this nonnucleoside in blood, but no efavirenz could be detected in semen. Nine of 11 men taking nevirapine had blood concentrations above the target of 3450 micrograms/L. For the 2 men with no nevirapine detected in blood, seminal levels were 1862 and 3570 micrograms/L. For all 11 nevirapine takers, seminal concentrations ranged from 1656 to 10,868 micrograms/L (average 3462 micrograms/L). Blood nevirapine levels correlated with seminal levels in these 11 men (rho = 0.683, P = 0.019). For 1 man who had a repeat nevirapine level assay, concentrations in blood and semen were 4911 and 3082 micrograms/L on the first assay and 6228 and 3833 micrograms/L on the second.
 
Suppressed seminal HIV RNA loads in all men despite variable nonnucleoside and PI concentrations probably reflects seminal penetration by nucleosides in the regimens, which included lamivudine, abacavir, and/or tenofovir in most people.
 
The investigators suggested another explanation of undetectable HIV RNA in semen despite often subtherapeutic drug concentrations: They proposed it is possible that "in the absence of therapeutic seminal antiretroviral concentrations, seminal plasma viral load is not produced locally," but may rather reflect "spill-over of virus from blood plasma."
 
References
1. Chan DJ, Ray JF. Differential penetration of antiretroviral agents in semen and effect on seminal plasma HIV-1 RNA load. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract TUPE0077.
 
2. Lima VD, Johnston K, Hogg RS, et al. Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic. J Infect Dis. 2008;198:59-67.