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Most patients taking second-line ART in sub-Saharan Africa achieve viral suppression but there's a need for third-line treatment options
Michael Carter, 2016-08-12 09:30:00
of patients switched to protease inhibitor-based second-line antiretroviral
(ART) in sub-Saharan Africa achieve and maintain an undetectable viral load
with their new regimen, according to research in the online edition of Clinical Infectious Diseases.
Non-standard first-line treatment, poor adherence and previous resistance to
protease inhibitors were also associated with the virological failure of
second-line treatment. Genotypic resistance testing on patients with a viral
load above 1000 copies/ml showed that a fifth had major resistance to drugs in
the protease inhibitor class and that resistance to nucleoside reverse
transcriptase inhibitors (NRTIs) was widespread.
“This study found
high VL suppression rates with second-line PI-based ART in sub-Saharan Africa.
However, 1 in 4 participants had a detectable VL (> 400 copies/ml at
any point during 2-3 years of follow-up, and 1 in 5 had a VL > 1000
copies/ml,” write the authors. “These
findings indicate that future treatment of individuals with failure of
second-line ART requires third-line drug options…which are currently
unavailable and/or unaffordable in the public sector in sub-Saharan Africa.”
Expanded access to
ART in sub-Saharan Africa means that an increasing number of patients will
experience virological failure and require second-line treatment based on the
protease inhibitors lopinavir/ritonavir or atazanavir/ritonavir.
However, there are
limited data on longer-term outcomes of patients taking second-line therapy in
southern Africa and the extent to which third-line regimens – which are for the
most part unavailable in poorer settings – will be required.
the Pan-African Study to Evaluate Resistance Monitoring (PASER-M) cohort
therefore designed a study to establish rate of virological failure among
patients taking second-line ART; the risk factors for viral breakthrough; and
the rate and pattern on major protease inhibitor resistance mutations.
population comprised 227 adult patients who experienced the virological failure
of their first-line ART and switched to a second-line combination based on a
protease inhibitor. All received second-line treatment for at least 180 days.
Most of the patients were women (51%) and the median age at switch to
second-line therapy was 39 years. Patients had received first-line therapy for
a median of 26 months, the majority (84%) treated with a standard
non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination. Six
patients (3%), however, had prior use of a protease inhibitor.
At the time of the
switch, 81% of patients had a viral load above 1000 copies/ml and genotypic
resistance testing showed that 88% had at least one drug-resistant mutation
present, with five patients having some resistance to a protease inhibitor.
Overall, 73% of patients were predicted to be sensitive to their new regimen.
Viral load results
after changing therapy were available for 205 patients.
months 12, 24 and 36 showed that 85%, 85% and 89%, respectively, had a viral
load below 400 copies/ml.
Overall, a quarter
of patients had a detectable viral load at some point during follow-up, but 76%
of these individuals subsequently re-established virological control.
with second-line treatment failure were treatment with non-standard NNRTI-based
first-line ART (p < 0.001), non-standard protease inhibitor-based ART (p =
0.001), resistance to a protease inhibitor at the time of treatment change (p
< 0.001) and adherence below 95% to second-line treatment (p = 0.025).
Of the 43 patients
with a viral load above 1000 copies/ml, 32 (74%) had genotypic resistance data.
Major drug resistance was detected in 69% of these patients and 22% had
mutations conferring resistance to protease inhibitors. However, the majority
of these mutations were associated with resistance to older protease
After up to three
years of follow-up, five of the seven patients with resistance to protease
inhibitors were still alive and receiving second-line ART; one patient had died
of an AIDS-related illness; the remaining patient had switched to a third-line
“Our data show
that the majority of patients receiving PI-based second-line ART in HIV
treatment programs in sub-Saharan Africa achieve virological suppression,”
conclude the authors. “As more persons start ART and VL monitoring is expanded,
the number in need of second- and third-line regimens is expected to increase.
There is a real and growing need for expanded access to third-line drug
options, ideally guided by genotypic resistance testing.”