Adding maraviroc and raltegravir to standard HIV treatment regimens achieves rapid suppression of viral load in semen, Canadian investigators report in the online edition of the Journal of Infectious Diseases. Intermittent, low level shedding of HIV in semen was also less likely to occur in people taking intensified therapy than in people treated with a standard three-drug regimen.
“We found that the incidence of IHS [isolated semen HIV shedding] was significantly reduced in participants taking iART [intensified antiretroviral therapy],” write the authors. “However, one participant demonstrated high level (often > 10,000 HIV RNA copies/ml) IHS that persisted for 14 months after starting treatment. This indicates that occasional HIV sexual transmission might still be possible despite ART with an undetectable blood viral load.”
HIV treatment that suppresses viral load to undetectable levels has been shown to reduce the risk of transmission by up to 96%. There is a growing consensus that antiretroviral therapy has an important role in prevention. However, virus has occasionally been detected in the genital fluids of people who have an undetectable blood viral load, and there have been isolated case reports of transmissions in such cases.
Investigators in Toronto had previously found that the antiretroviral drugs maraviroc (Celsentri) and raltegravir (Isentress) had good penetration into semen. They therefore wanted to see if intensifying standard antiretroviral treatment with the addition of these drugs reduced the frequency of intermittent shedding of virus in semen.
Their study population comprised 13 gay men who started HIV treatment with the intensified regimen and 25 controls who received standard triple-drug therapy. None had a sexually transmitted infection, a known factor associated with shedding of virus in semen.
Paired blood and semen samples were obtained over two years.
People treated with the intensified regimen had a higher nadir (lowest ever) CD4 cell count and lower baseline viral load in blood than the men who were treated with the standard combination (340 vs 213 cells/mm3; p = 0.001; 7000 vs 50,000 copies/ml, p = 0.05). However, baseline viral load in semen was similar (5136 vs 2979 copies/ml).
Viral load in semen fell more rapidly among the men taking intensified therapy, who were significantly more likely than those treated with a standard regimen to have undetectable viral load in semen after two weeks of therapy (12/13 vs 20/26, p = 0.036).
“Individuals initiating an intensified ART regimen were more likely to achieve virologic suppression in semen by two weeks,” comment the investigators.
Isolated shedding of virus in semen was detected in 48% of participants taking standard treatment compared to 15% of men taking the intensified regimen, a significant difference (p = 0.048).
Restricting analysis to men with an undetectable viral load in their blood showed that intensified therapy was associated with a reduced frequency of shedding of virus in semen (7 vs 15%).
High level shedding in semen (viral load above 5000 copies/ml) was observed in 16% of men treated with a three-drug regimen and one participant (8%) whose therapy also included maraviroc and raltegravir.
One man with an undetectable viral load in his blood continued to have detectable viral load in his semen for 14 months after commencing intensified treatment.
This prompted the investigators to see if virus continued to be shed in the semen of men taking long-term HIV therapy.
They examined paired blood and semen samples obtained from 26 additional men who had been taking long-term standard antiretroviral treatment, in some cases for over five years. All had an undetectable viral load in blood and no sexually transmitted infections.
Approximately half the men who had been taking treatment for under six months had virus intermittently detectable in semen; this fell to 20% of men who had been taking therapy for between one and three years; but no man treated for over three years had virus detectable in semen.
“It is encouraging that IHS was not observed after prolonged ART,” write the authors.
The authors believe their results support research showing that effective HIV therapy has a significant impact on the risk of transmission.
Nevertheless, they conclude “it remains clear that IHS, potentially at very high levels, can occur despite effective antiretroviral therapy, even with the addition of agent with enhanced semen penetration…whether the phenomenon of IHS relates to actual transmission is not known.”
Osborne BJW et al. The impact of antiretroviral therapy duration and intensification on isolated HIV-1 RNA shedding. J Infect Dis, online edition, 2013.