Second-line antiretroviral therapy in South
Africa achieves durable viral suppression in three-quarters of patients and is
associated with an increase in CD4 cell count, investigators report in the
online edition of the Journal of Acquired
Immune Deficiency Syndromes. Therapy was based on a boosted protease
inhibitor (lopinavir/ritonavir, Kaletra).
Unsurprisingly, adherence was associated
with virological outcomes, with each 10% improvement in the rate of adherence
more than doubling the chances of achieving an undetectable viral load.
An increasing proportion of people who
have started HIV therapy in resource-limited settings have experienced
first-line treatment failure. Second-line options are limited, and are usually
based on a ritonavir-boosted protease inhibitor, which is taken in combination with two
drugs in the NRTI class.
There is currently little information on
the virological efficacy and durability of second-line treatment in poorer
countries. However, it is important that this is established, and that an understanding
is achieved of the factors associated with the effectiveness of such treatment.
“An improved understanding of second-line
ART [antiretroviral therapy] in resource-limited settings will be critical in
maximizing the durability of second-line regimens, preventing disease
progression and reducing long-term AIDS-related mortality in high
HIV-prevalence countries without access to third-line ART regimens,” explain
They therefore designed a study monitoring
the outcomes of 136 patients who initiated second-line therapy in Durban, South
Africa. This treatment consisted of lopinavir/ritonavir, which was taken in
combination with two NRTIs (usually AZT and enteric-coated ddI). The
investigators also conducted analyses to see which factors were associated with
the efficacy of this treatment.
All the patients had experience of
first-line therapy (usually efavirenz [Sustiva, Stocrin] with d4T and 3TC).
The median duration of first-line treatment
was 13 months. At the time therapy was changed, the patients had a median CD4
cell count of 153 cells/mm3 and a median viral load of approximately
Adherence in the six months before this
therapy was discontinued had been poor. The median rate (calculated by pharmacy
refill) was just 67%. The investigators believe that this low rate may have
been partly due to the toxic effects of d4T, a drug which is no longer used in
routine HIV therapy.
Switching to second-line treatment was
associated with a significant improvement in adherence. In the first six months
after the treatment change, the median rate of adherence was 100%. Adherence
remained high throughout follow-up; the median rate at month 12 being 92%,
which increased to 96% at month 24.
Almost three-quarters of patients (74%) had
an undetectable viral load (below 50 copies/ml) six months after switching
treatment. This rate of suppression changed little during the two years of
Factors associated with viral suppression
after twelve months of therapy were evaluated by the investigators. A higher
rate of adherence was independently associated with an increased chance of an
undetectable viral load at this time point. Each 10% increase in adherence more
then doubled the chances of virological suppression (OR = 2.5; 95% CI, 1.3-4.8,
p = 0.01).
Time to virological suppression was most
rapid in patients who took 90% or more of their doses (p = 0.01).
Adherence of this level was associated with
rates of virological suppression at months 6, 12, 18 and 24 of 73, 87,
93 and 97% respectively. In contrast, the rates of suppression at these time
points for patients who took fewer than 80% of their doses were just 20, 44,
67 and 83% respectively.
Changing to second-line therapy also
had immunological benefits. Median CD4 cell count increased to 228 cells/mm3
six months after switching therapy and continued to increase during follow-up,
reaching a median of 330 cells/mm3 at month 24.
“The switch to second-line ART in South
Africa was associated with an improvement in adherence and a rapid
immunological recovery,” comment the authors.
However, they express concern that
approximately one quarter of patients continued to have a detectable viral load.
“Median adherence was not uniformly > 90% after initiation of second-line
ART and differences in second-line adherence help explain why some
patients… achieved virologic suppression after switch and other patients did
They therefore conclude: “Novel adherence
interventions may usefully target patients with second-line ART failure who –
given a low likelihood of failure with major protease inhibitor resistance
mutations – have a high likelihood of achieving viral suppression.”