Higher baseline viral load, longer time to viral
suppression and low-level viraemia below the level of detection of standard
tests raise the risk of viral rebound amongst people with HIV on antiretroviral
therapy (ART), according to a pair of studies presented at the 14th European AIDS Conference this
month in Brussels.
Only about 20 to 25% of people with HIV
in Europe, the US and sub-Saharan African are on ART with full viral suppression,
whilst the remainder fall out at various stages of the 'treatment cascade'.
Lack of access and poor adherence are known problem areas, but reasons for loss
of virological control amongst people who achieve viral suppression are not
Laura Waters of the Mortimer Market
Centre in London reported findings from a study of the effects of baseline
viral load and time to viral suppression on risk of viral rebound amongst
participants receiving first-line combination ART in the UK Collaborative HIV
Cohort. UK CHIC regularly collects data from HIV-positive adults attending 13
centres for HIV care, including demographic information, ART treatment history,
clinical events and laboratory test results.
Several clinical trials have shown
lower rates of viral suppression amongst people with high baseline viral load,
but the impact of high pre-treatment viral load on longer-term virological
outcomes in patients who achieve viral suppression is unknown, the researchers
noted as background.
Eligible participants were selected
from amongst 14,477 treatment-naive UK CHIC participants who started treatment with
combination ART including a protease inhibitor or non-nucleoside reverse
transcriptase inhibitor (NNRTI) after the year 2000. People who started ART
within three months of HIV diagnosis, experienced AIDS-related events within three
months after starting ART or lacked follow-up data were excluded, leaving 8184
Of this group, 7475 people (91%)
achieved viral suppression on their initial ART regimen and were included in
the main analysis. Rates of suppression were 92% for people with viral load <10,000
or 10,000 to 100,000 copies/ml at baseline, 91% for those with 100,000 to 500,000
copies/ml and 87% for those with >500,000 copies/ml prior to treatment.
The participants in the main
analysis were mostly men (80%), two thirds were white, one quarter were black
and the median age was 38 years; 65% were men who have sex with men and 29%
were heterosexual. The median baseline CD4 cell count was 245 cells/mm3.
All started three-drug combination ART, with 76% starting on a NNRTI-based
regimen and 24% starting on a protease inhibitor.
Looking at baseline viral load, 23%
had <10,000 copies/ml, 42% had 10,000 to 100,000 copies/ml, 30% had
100,000 to 500,000 copies/ml and only 5% had >500,000 copies/ml.
Most participants achieved viral
suppression to <50 copies/ml either within three months (42%) or three to six months
(40%) after starting first-line ART. However, 15% did so between six and twelve
months after starting therapy and 5% took longer than a year to reach
undetectable viral load.
A total of 1289 participants (17%)
experienced viral rebound -- defined as two consecutive measures >50
copies/ml – during a median follow-up period of 3.5 years. Adjusting for other
factors, the probability of viral rebound was significantly higher for people
who started treatment with 100,000 to 500,000 copies/ml (hazard ratio [HR] 1.34,
or 34% higher than those with 10,000 to 100,000 copies/ml) and highest for those
with >500,000 copies/ml (HR 1.67).
In addition, viral rebound rates also
rose significantly for people who took six to twelve months to achieve suppression (HR
1.47 compared to those who took three to six months) and even more so for those who took
longer than a year (HR 2.49, or nearly 2.5-fold higher risk).
Patterns for both baseline viral
load and time to viral suppression were similar when looking separately at people
who started NNRTIs and those who started protease inhibitors. Again, people
with the two highest baseline viral load levels and those who took either six to twelve months or more than a year to achieve viral suppression were at significantly
greater risk for viral rebound.
The overall median CD4 cell rise
between baseline and time of viral suppression was 115 cells/mm3,
but gains rose with baseline viral load: 69 cells/mm3 for those with
<10,000 copies/ml, 110 cells/mm3 for those with 10,000 to 100,000
copies/ml, 153 cells/mm3 for those with 100,000 to 500,000 copies/ml
and 187 cells/mm3 for those with >500,000 copies/ml.
CD4 cell gains were likewise larger
for those who took longer to achieve viral suppression: 75 cells/mm3 for
those who took less than three months, 135 cells/mm3 for those
taking three to six months, 180 cells/mm3 for those taking six to twelve months and
190 cells/mm3 for those taking more than a year.
"Baseline viral load correlated
significantly with achievement of viral suppression on initial combination
ART," the researchers concluded. "Amongst individuals who have achieved
viral suppression on first-line combination ART, higher baseline viral load and
slower time to suppression were also associated with a higher chance of
subsequent virological rebound."
Although this study was limited by
lack of adherence data, Waters noted that all participants included in the main
analysis managed at least good enough adherence to achieve undetectable viral
"[T]his study adds to the trial data that suggests we may need to investigate
new strategies, with modern drugs, for individuals with high pre-treatment
viral load," the investigators added. "We recommend that
patients with high baseline viral load should continue to be monitored closely,
even after virological suppression, as they remain at higher risk of rebound."
Anecdotally, Waters said, her group has been trying
plus raltegravir (Isentress) for people
starting treatment with very high viral load.