A dual combination of lopinavir/ritonavir (Kaletra or Aluvia) plus
3TC (lamivudine, Epivir) as
first-line therapy produced good virological suppression regardless of baseline
viral load and was well tolerated in the multinational GARDEL study, according
to a late-breaking report at the 14th European AIDS Conference this week in Brussels.
regimens that contain two nucleoside/nucleotide reverse transcriptase
inhibitors (NRTIs) are the standard of care for antiretroviral therapy, but many
NRTIs can cause side-effects and simplifying treatment may improve adherence
and reduce cost. Lopinavir/ritonavir as monotherapy has been shown to be
inferior to standard therapy, but adding one NRTI may be adequate.
from Fundacion Huesped in
Buenos Aires and fellow investigators with the GARDEL Study Group compared the
safety and effectiveness of a dual combination versus triple therapy for
randomised open-label phase 3 study included 426 previously untreated people
in Argentina, Chile, Mexico,
Peru, Spain and the US. Nearly
85% were men (about 60% men who have sex with men and 35% heterosexual) with a
median age of about 35 years.
median baseline CD4 cell count was approximately 325 cells/mm3,
43% had high viral load (HIV RNA >100,000 copies/ml) and only 3% had a
history of AIDS. People with NRTI or protease inhibitor resistance mutations at
baseline were excluded.
were randomly assigned to receive 400/100mg lopinavir/ritonavir plus 150mg 3TC,
both taken twice daily, or a standard regimen of lopinavir/ritonavir plus two
NRTIs in a fixed-dose combination. About 9% used abacavir/3TC
(Kivexa), 37% used
tenofovir/emtricitabine (Truvada) and
the rest (54%) used AZT/3TC (Combivir).
explained that NRTI choice was based on national treatment guidelines in the
various countries. Whilst Combivir is
no longer considered a preferred option in Europe and the US, it is still used
in middle- and lower-income countries.
participants withdrew before receiving any therapy. Among those who started
treatment, about half as many discontinued prematurely in the double-therapy
arm compared with the triple therapy arm (8 vs 14%).
At 48 weeks, 88% of people taking dual therapy and
84% taking triple therapy had undetectable viral load (<50 copies/ml) in the
primary intention-to-treat 'snapshot' analysis, indicating that the simplified
single-NRTI regimen was non-inferior to standard therapy. In an observed or
as-treated analysis, response rates were 96 and 97%, respectively. CD4 cell
gains were also similar in both arms at 227 and 217 cells/mm3.
Dual therapy also performed at least equally well amongst
people with high baseline viral load, with response rates of 87 and 78% in the
two arms, allaying one of the concerns about a potentially less potent regimen.
Virological failure rates were similar in the dual-
and triple-therapy groups at 5 and 6%, respectively. However, fewer people in
the dual arm discontinued early due to adverse events or death (1 vs 5%). Two
people in the dual arm and eight in the triple arm never achieved viral
suppression, whilst eight and four, respectively, experienced viral rebound.
Amongst the small number of viral samples that were
amplified and sequenced (in most cases, virus levels were too low), two patients
in the dual-therapy arm, but none in the triple-therapy arm, had emergent NRTI
resistance mutations (M184V); no one in either group had primary protease
Both regimens were generally safe and well tolerated
with most side-effects being mild to moderate. There were significantly fewer grade
2 or 3 adverse events in the dual compared with the triple-therapy arm (65 and 88
events, respectively). One person taking dual therapy and ten taking triple
therapy discontinued due to adverse events.
The most common side-effects were elevated lipid
levels (11 and 8%) and diarrhoea (7% in both arms). Nausea and dyspepsia were
more common in the triple-therapy arm (<1 vs 3 to 4%). Laboratory
abnormalities were uncommon and similar in both arms. There was one serious
adverse event considered probably drug-related, a case of gastritis in the dual-therapy arm.
results demonstrate that dual therapy with lopinavir/ritonavir + 3TC was
non-inferior to triple therapy after 48 weeks of treatment, regardless of
baseline viral load," the researchers concluded. "The dual therapy
regimen showed fewer discontinuations due to safety and tolerability."
failure, occurring at similarly low levels in both treatment arms, did not
result in protease inhibitor resistance development, preserving a
wide range of drugs for second-line antiretroviral therapy," they
Amongst NRTIs, 3TC is very well tolerated. Cahn
noted that the dual regimen does not require monitoring for kidney,
liver or blood cell toxicities, making it a useful option in settings with limited