taking HIV therapy, a persistent detectable viral load at any level is
associated with an increased risk of virologic failure, Canadian research
published in the online edition of Clinical
Infectious Diseases shows. Comparison with people who maintained an
undetectable viral load showed that ongoing, low-level HIV replication between
50 and 199 copies/ml doubled the risk of a subsequent increase in viral load to above
1000 copies/ml – a recognised benchmark for virologic failure.
increased risk of VF [virologic failure] shown here suggests that, for all
persistent LLV [low level viraemia] > 50 copies/ml, even when <200
copies/ml, it might be beneficial to act aggressively (adherence, plasmatic ART
dosage if available, interactions, genotyping, closer monitoring, etc.),” say
The goal for
almost all people taking modern HIV therapy is an undetectable viral load,
typically defined as suppression of virus to below 50 copies/ml. An
undetectable viral load allows the immune system to recover and is associated
with a very low risk of virologic failure and the development of drug
Not all people on treatment
achieve and maintain an undetectable viral load and the consequences of a
persistent low viral load are uncertain. This lack of clarity is reflected in
US antiretroviral guidelines, which state “there is no definitive evidence that
patients with VL [viral load] quantified as <200 copies/ml…are at increased
risk of VF”.
investigators therefore analysed the impact of three categories of persistent
low-level viral load (50 to 199 copies/ml, 200 to 499 copies/ml, 499 to 999 copies/ml)
on the subsequent risk of virologic failure.
The study involved
1357 people with HIV receiving routine HIV care in Montreal. They were required to have taken
combination antiretroviral therapy for at least twelve months. Follow-up
started in 1999 (the year that use of viral load assays with a lower limit of
detection of 50 copies/ml became standard) and lasted for up to twelve years.
The majority of
participants were white, gay men, their median age was 41 years and the median
duration of follow-up was seven years.
The cumulative twelve-month
incidence of virologic failure among participants who maintained an undetectable
viral load was 7%.
rates were significantly higher for people whose viral load was detectable at
low levels for up to six months. Almost a quarter (23%) of participants with a
persistent viral load between 50 and 199 copies/ml had an increase in viral load
above 1000 copies/ml, as did 24% of participants with a viral load between 200 and 499
copies/ml and 59% of those with a viral load between 500 and 999 copies/ml (p =
similar when the investigators looked at the persistence of low-level viraemia
for nine and twelve months.
for potential confounders, the investigators calculated that a persistent viral
load of between 50 and 199 copies/ml or 200 and 499 copies/ml for at least six months
doubled the risk of virologic failure (HR = 2.22; 95% CI, 1.60-3.09 and HR =
2.15; 95% CI, 1.46-3.17, respectively). A persistent viral load between 500 and 999
copies/ml increased the risk almost five times (HR=4.85; 95% CI, 3.16-7.45).
believe strengths of their study include the large number of participants and the
extended period of follow-up. However, they were unable to show if the risk of
virologic failure for people with low-level viral replication differed
according to type of antiretroviral therapy. Despite this
limitation, they believe their results are of clinical significance.
copies/ml is known to have clinical consequences, and our analyses showed than
any persistent LLV >50 copies/ml increased the risk of such failures,” write
the investigators. “For patients with LLV (especially 50-199 copies/ml), the
decision to either change ART rapidly or observe further is a difficult one to
take; the clinician has limited data to support either decision…we hope that
our data may contribute to the knowledge required to guide clinical conduct in