Viral load
rebounds rapidly in semen to potentially infectious levels following
interruption of combination antiretroviral therapy (cART), according to French
research published in AIDS.
Increases
in viral load in both blood and semen were observed within two weeks of
treatment interruption. Four weeks after stopping therapy, all participants had
detectable virus in their semen. Viral load in semen peaked at approximately
16,000 copies/ml, high enough for transmission to sexual partners.
“Early HIV-RNA
rebound was observed in all participants in both compartments,” comment the
authors. “This finding supports evidence of a very high risk of sexual
transmission during self-driven cART breaks or during ATI [antiretroviral
treatment interruption] stemming from clinical trials. Thus, prevention
strategies for HIV-negative partners of HIV-infected participants undergoing
ATI need reinforcement (counselling, condoms, PrEP).”
There is now
overwhelming evidence that people with an undetectable viral load when taking
cART cannot transmit HIV to their sexual partners. Undetectable
= Untransmittable has been widely endorsed and is now an important
component of HIV prevention strategies.
Continuous HIV
therapy with high levels of adherence is needed to maintain sustained viral
suppression. However, it is unclear how quickly and to what level viral load in
the genital tract rebounds when cART is interrupted. This is an important
question for people using HIV treatment as prevention. It also has implications
for therapeutic and vaccine trials which typically involve interruption of
cART.
The ten HIV-positive men were taking part in a randomised, placebo-controlled vaccine study
(VR102/ANRS149-LIGHT). They were randomised to receive an active vaccine or
placebo between baseline and week 24 of the study, then interrupted antiretroviral treatment at week 36. Participants were able to resume cART at week 48 (or before) if viral load rebound occurred. The original study's primary outcome was
viral load in blood plasma at week 48, following the 12-week interruption.
Paired blood and semen
samples were provided at week 36 (the time of the treatment interruption) and
again at weeks 38, 40, 42, 44 and 48. These samples provided investigators with an opportunity to assess the timing and extent of viral rebound in both blood and semen after discontinuation of HIV therapy.
Participants' median
was 42 years. They had been taking cART with viral suppression for a median duration of 44 months and had a median CD4 cell count of 768
cells/mm3. Four men received the experimental vaccine, the
other six were randomised to take a placebo.
All participants had a
blood plasma viral load below 20 copies/ml when cART was interrupted at week 36.
Rebound occurred within two weeks of interruption in eight of the participants,
and all men had detectable viral load in blood within eight weeks. Maximum viral
load was over 125,000 copies/ml, comparable to peak levels before initiation of
HIV therapy.
Similarly, viral
load in semen was undetectable (below 60 copies/ml) in all ten people at the point when cART was interrupted. In four participants, viral load was detectable within two weeks. In four other participants, viral load in semen was detectable within four weeks. Samples were missing for the other two individuals. Viral load in semen
peaked at over 15,000 copies/ml.
HIV-DNA levels in
peripheral blood mononuclear and non-sperm cells also increased after the
treatment interruption. Phylogenetic analyses showed intermingling of HIV-RNA
between blood and semen during the treatment interruption. This suggested that
virus in semen was being replenished from blood cells, arguing against separate
HIV replication in blood and semen.
The findings have
clear implications for the use of HIV treatment as prevention, showing that
viral load can increase rapidly in semen to potentially infectious levels after
interruption of cART. The investigators note that a transmission occurred from
a study participant to his partner during the treatment interruption phase of
the trial.
“The rapid and
intense HIV-RNA rebound observed very early in both blood and semen after ATI
emphasizes the need for targeted prevention strategies to reduce the risk of
sexual transmission during all the trials involving treatment interruptions,”
conclude the authors.