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
“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
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
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