Remaining on the
same regimen is a “reasonable” strategy for people taking first-line
antiretroviral therapy (ART) based on a ritonavir-boosted protease inhibitor
who experience virologic failure, according to a study in the online
edition of Clinical Infectious Diseases.
Investigators from the United States retrospectively examined outcomes 24 weeks
after virologic failure according to treatment strategy. Rates of HIV
suppression did not differ significantly between people who remained on their
first-line combination and those who switched therapy.
provides important information that adds to current knowledge about management
of ART after VF [virologic failure] on first-line PI/r [protease inhibitor/ritonavir] plus two
NRTIs [nucleoside reverse transcriptase inhibitors],” comment the authors. “Our
study suggests that a large proportion of patients failing these regimens can
subsequently achieve virologic suppression without changing their ART regimen.”
comprising a ritonavir-boosted protease inhibitor plus two NRTIs is one of the
strategies recommended for first-line ART. An advantage of this strategy is
that virologic failure rarely results in the emergence of virus with resistance
to protease inhibitors.
However, the best approach
for people who experience virologic failure while taking
first-line ART based on a ritonavir-boosted protease inhibitor is unclear.
A team of
investigators therefore examined outcomes among 209 people who had at least
24 weeks of follow-up after the virologic failure of their treatment.
Subsequent HIV treatment strategy and virologic suppression were assessed. "Virological failure" was defined differently by the three studies but meant broadly that HIV was either still incompletely suppressed 8-16 weeks after starting therapy, or that the viral load 'rebounded' to above 200-400 copies/ml after 24-32 weeks.
The 209 patients who had virological failure were among 1429 (i.e. 15% of the total) who participated in three ACTG (AIDS Clinical Trials Group) studies examining the safety and efficacy of first-line
HIV therapy consisting of a ritonavir-boosted
protease inhibitor (lopinavir/ritonavir [Kaletra],
or atazanavir/ritonavir [Reyataz])
plus two NRTIs. Most of the 209 patients
(83%) were enrolled in the United States, the other 17% in South Africa.
Overall, 43% of participants were female, and median viral load before the
initiation of ART was 63,000 copies/ml, with median CD4 count being 118
The median time
between the initiation of ART and virologic failure was 39 weeks. Over
three-quarters (78%) of patients achieved a viral load below 400 copies/ml at
sometime before treatment failure.
Median viral load
and CD4 count at the time of virologic failure were 8000 copies/ml and 246
cells/mm3, respectively. Only one person had a new protease
inhibitor-associated major resistance mutation detected at the time of
virologic failure. However, four other people had such resistance at
baseline. New NRTI resistance was detected in 15 people (9%) at the time
of virologic failure, with 23 people having such resistance before they
patients remained on their first-line regimen after virologic failure, 13%
changed to an NNRTI-based regimen, 12% switched NRTIs and 5% changed to a
non-standard second-line combination of drugs.
Follow-up, 24 weeks
after virologic failure, showed that 67% of patients remaining on their
first-line combination now had a viral load below 400 copies/ml compared to 72%
of participants who changed therapy. The difference was non-significant.
Restricting analysis to patients with no resistance (protease inhibitors, NRTIs
and NNRTIs) showed that rates of virologic suppression were identical between people who remained on first-line treatment and people who switched
therapy (62 vs 61%).
For people who
remained on their initial treatment regimen, the factors associated with
subsequent achievement of a viral load below 400 copies/ml were a viral load
below 10,000 copies/ml at the time of treatment failure (p = 0.007) and a viral
load below 400 copies/ml at any time before virologic failure emerged (p =
The chances of achieving virologic suppression were also increased by
high levels of adherence (p = 0.016). Twenty-four weeks after virological failure, two-thirds of patients who did not switch reported 100% adherence. Three-quarters (75%) of patients with self-reported adherence of 100% were virally suppressed, 54% who reported their adherence was less than 100%, and 14% of the small minority (7 individuals or 5.5%) who said they had decided to stop taking therapy.
Analysis of the
patients who switched therapy showed a new regimen was started a median of ten
weeks after virologic failure was detected. A viral load below 400 copies/ml 24
weeks after changing treatment was achieved by 71% of individuals who switched
to an NNRTI-based regimen, by 44% of patients changing to another
ritonavir-boosted protease inhibitor and by 72% of those who only changed their
NRTIs. Achieving a viral load below 400 copies/ml at any time before the
initial treatment failure was the only factor associated with virologic
suppression after the treatment change (p= 0.003).
suggest that if no or limited drug resistance is detected at VF on a first-line
PI/r containing regimen, remaining on the same regimen after VF coupled with
strategies to improve adherence could be a reasonable and effective approach to
achieving virologic suppression,” conclude the authors. “Further evaluation of
approaches to treatment management following VF on a first-line PI/r containing
regimen are warranted.”