The human immunodeficiency
virus (HIV) infects millions of people across the globe. Sexual transmission is the main channel of
Researchers from the Infections of the Respiratory Tract and
in Immunocompromised Patients group of the Bellvitge Biomedical Research
Institute (IDIBELL), led by Dr. Daniel Podzamczer, have evaluated the
speed at which a new antiretroviral drug, Dolutegravir, is able to
reduce the viral load in semen, an area of the body considered to be a
reservoir of the virus and where access for drugs is more difficult.
‘A triple regimen based on an integrase inhibitor decreases human immunodeficiency virus (HIV) load in semen very quickly, reducing sexual transmission risk.’
results, published in Journal of Infectious Diseases
, show the potential of these new treatments to reduce the chances of sexual transmission of the virus.
Current antiretroviral treatments are able to decrease blood viral
load and make it undetectable in most patients within six to nine months
of starting treatment, although it is estimated that about 5-25% of
patients maintain detectable levels of virus in their semen after this
time due to several factors, which are not always known.
the case of serodiscordant couples, in which only one of the members is
carrying the virus, in addition to condoms it is recommended that the
seronegative person also takes antiretroviral drugs as prophylaxis while
the viral load of their partner decreases in both blood and
reservoirs", says Dr. Podzamczer.
However, there are new drugs, known as integrase inhibitors, which
can act much faster. "In this study we have focused on evaluating the
rate of viral load drop in patients receiving these new treatments,
namely Dolutegravir", explains Dr. Arkaitz Imaz, first author of the
"We have measured the viral load in blood and semen before
starting treatment, at three days, at seven, at 14, at one month, at three
months, and at six months. We know that viral load drop goes quick
during the first few days/weeks, then slower and it finally stabilizes.
Adapting a complex mathematical-statistical model to our data and to the
characteristics of our patients, we have been able to obtain a kinetic
model of the specific viral load drop for each compartment, blood and
semen, with this treatment regimen".
The researchers observed that while the rate at which viral load
falls during the first few days is significantly higher in blood than in
semen, it is equal during the second phase of fall. However, despite
the speed difference, viral load becomes undetectable faster in semen
than in blood because the base values are much higher in blood, i.e. there
are many more viruses to eliminate. "These results suggest the
possibility of reducing the time of previous antiretroviral prophylaxis
when using these new treatments," the researchers note.
On the other hand, the fall pattern is much more homogeneous in
blood than in semen. This heterogeneity demonstrates the differential
and more unpredictable nature of semen as a reservoir of the virus. In
this sense, it is interesting to note that there is no clear correlation
between the concentration of drug in semen and the decrease in viral
load: "the concentration of dolutegravir in semen is more than enough to
ensure viral load drop in this reservoir", explains Dr. Podzamczer,
"because even though only 7-8% of the drug in the blood reaches the
semen, the proportion of active drug is much higher than what the
observed in blood. This was something that we did not know until now."
Integrase inhibitors are currently recommended by all clinical
guidelines as the first line of treatment. "Our study reinforces this
decision, especially in light of the current HIV transmission landscape.
If we reduce the time of viral load drop we clearly reduce the
possibility of transmission, especially in groups at risk", argues Dr.
In the editorial that Journal of Infectious Diseases
the article, it is pointed out the need to replicate this study with
other new drugs currently under development, namely long-term
antiretrovirals, to evaluate the potential of these new therapies and
their activity in this viral reservoir.