Studies
in Uganda3
and the United States4 established that viral load
during untreated primary HIV infection is much higher – and therefore
individuals are more infectious – than during untreated chronic infection.
A prospective study in heterosexual couples in Rakai,
Uganda,where one partner was HIV-positive at the start of the
study, and one partner HIV-negative, showed that the likelihood of heterosexual HIV transmission is
highest in the first two and a half months following initial infection with HIV,
and that this correlated with higher viral load levels in early HIV infection.5
The investigators estimated that 43% of transmissions in the
study occurred within ten weeks of the index partner’s infection. They also
estimated that primary HIV infection increased the risk of HIV transmission per
sexual act more than seven-fold compared to the risk of HIV transmission per
sexual act during the chronic (and longest) period of untreated HIV infection. A
second analysis of these data6
estimated that relative to chronic infection, infectiousness during primary
infection was actually enhanced 26-fold (and 3.6-fold during late/end-stage
infection).
However, taking into account primary infection’s relatively
short duration, they concluded that 14% of onward transmission occurred during
primary infection, compared with 46% during the chronic stage and 40% during
end/late-stage HIV disease.
Similarly, a 2007 US mathematical modelling studyestimated that fewer than 9% of all new sexually transmitted HIV
infections originated in people with untreated primary HIV infection, compared
with 48% of new infections resulting from sexual contact with people with untreated
chronic HIV infection.2
Although it agreed with previous studies that individuals
with primary HIV infection have exceptionally high viral loads, and estimated
that they were 16 times more infectious than during chronic infection, because
the period for which they are highly infectious is relatively short, typically
no more than 49 days, individuals with acute HIV infection only represented
0.5% of all HIV-infected individuals in the United States.
Studies in populations that include a higher proportion of
gay men and other men who have sex with men (with potentially much more
frequent partner change than heterosexual couples in Africa – even those with
concurrent relationships), have come to different conclusions regarding the role
of primary infection on new HIV infections.
A 2007 study from Quebec, Canada,used phylogenetic analysis of
blood samples in Quebec’s
genotypic-resistance database. It estimated that almost half of all sexually
transmitted HIV infections were attributed to primary or early infection.7
However, in this study, although some onward transmission
took place within a month of infection, the average time between infection and
onward transmission was 15 months. The investigators found that whilst
primary/early HIV infection represented just 10% of the total sequenced samples
in the genotypic-resistance database, it accounted for 49% of all onward
transmission events. In contrast, they found that treatment-naive and
treatment-experienced chronically infected individuals accounted for 15 and 12%
of onward transmission, respectively, with the other 25% uncertain.
A 2012 phylogenetic analysis study from Denmark
provided further evidence that men who have only recently been infected with
HIV are largely sustaining new infections amongst gay men and other men who
have sex with men.8
The investigators looked at networks and clusters of HIV
transmissions in the country. Approximately a fifth of people were found to
have primary HIV infection, and half of all people with primary HIV infection
could be placed within a transmission cluster, compared to only 22% of people
whose HIV was diagnosed late. Some 40 clusters involved gay men, and the two
largest transmission networks involved half of all people with primary infection.
If people are diagnosed quickly, identified as having a
recent infection and begin antiretroviral therapy immediately, this can have a
significant impact on viral loads and onward transmission. Clinicians in Bangkok, Thailand,
developed such a programme, with most participants being diagnosed an estimated
10 to 23 days after infection. Viral loads dropped dramatically, with 55% of
participants achieving an undetectable blood plasma viral load at week 8, 80%
at week 16, 91% at week 24, and 97% at week 48.
Of note, seminal plasma viral load dropped to undetectable levels more
rapidly – 59% were undetectable by week 2, 73% by week 4, 95% by week 12 and
100% by week 24.
It is commonly reported that risk behaviours reduce
following an HIV diagnosis. Moreover, in this Thai cohort, risk reduction
counselling was credited with achieving substantial behaviour change. Whereas
at baseline 84% of men reported having had unprotected anal intercourse in the
previous four months (including 57% with a casual partner), by week 24, the
figures had dropped to 25 and 8%, respectively, with the changes sustained to
week 48.
The researchers’ preliminary modelling work suggested that
when an individual with acute infection receives this package of interventions,
it may avert 78% of onward transmissions in the first six months after
infection.9
Perhaps the most intriguing study on the relative impact of
primary versus chronic infection used mathematical modelling to estimate the
impact of untreated HIV infection on transmission.10
The investigators examined the link between viral load and
transmission from a Zambian study of serodiscordant heterosexual couples and
found that the periods of highest viral load (during primary infection and
again during late-stage HIV disease) did not actually have the highest
transmission potential, because these lasted relatively short periods of time.
Instead, they found that the viral load with the highest transmission potential
(of a hypothetical average of 1.5 infections per person per lifespan) was found
to be during chronic infection.
The study concluded that the 'ideal' viral load for HIV in
its 'quest' for continued survival was 33,113 (4.52 log10)
copies/ml. At this viral load, someone could live for around ten years without becoming
ill and still feel well enough to have sex, providing HIV with the longest
transmission potential. The investigators hypothesise that HIV may have
actually evolved so that average viral loads during chronic infection are
finely balanced between being the optimal for HIV transmission and the optimal
for human survival.