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A quarter of people with second-line ART treatment failure in Kenya have exhausted current treatment options
Michael Carter, 2017-04-25 07:40:00
antiretrovirals are urgently needed in resource-limited settings, according to
research conducted in Kenya and published in the online edition of AIDS. The study showed that a quarter of
patients taking a failing second-line antiretroviral treatment regimen had exhausted current treatment options and only 18% had virus that was
fully susceptible to the three main classes of anti-HIV drugs.
“This study in the
Kenyan national ART [antiretroviral therapy] program suggests that about 27% of patients with
second-line failure are in need of a switch to third-line therapy, with 25%
demonstrating complete exhaustion of alternative first and second-line
regimens,” comment the authors. “These data indicate an urgent need for
increasing access to third-line drugs.”
500,000 people in sub-Saharan Africa are taking second-line ART, which is
typically based on a ritonavir-boosted protease inhibitor. Increaded access to
routine viral load monitoring means this number is expected to increase to up
to 6 million by 2030, approximately a fifth of all people taking ART.
failure of second-line therapy has been reported in over a third of patients in
sub-Saharan Africa. However, there are few data on the prevalence of
drug resistance among these patients.
therefore designed a cross-sectional study involving individuals who accessed
second-line treatment through the Kenyan national ART programme between 2010
and 2015 and who subsequently experienced the failure of this treatment.
was defined according to various criteria, including low CD4 cell count,
emergence of HIV-related symptoms, and viral load rebound.
Blood samples from
people with treatment failure were sent for resistance testing. The
susceptibility of virus to first-, second- and third-line therapy was
Samples from 123
people were included in the analysis. These individuals had a median age of
24 years, median CD4 cell count was dangerously low at just 115 cells/mm3
and median viral load was 63,000 copies/ml. Patients had been taking ART for a
median of six years and half this time was on second-line therapy. Almost all
the patients (97%) were taking lopinavir-ritonavir and the most commonly used
nucleoside reverse transciptase inhibitor (NRTI) backbones were
tenofovir/lamivudine (35%) and abacavir/lamivudine (23%).
There was a very
high prevalence of drug-resistant virus. Just under two-thirds (63%) of
patients had at least one NRTI resistance mutation, mainly (51%) M184I/V, though
resistance to older NRTIs such as zidovudine was also common (37%).
A third of
patients had at least one protease inhibitor-associated resistance mutation.
The median number of mutations was three.
A quarter of
patients had resistance to the three main classes of antiretrovirals (NRTIs,
NNRTIs and protease inhibitors). Only 34% of patients had virus with no resistance to NRTIs or
protease inhibitors and just 18% had
virus that was fully susceptible to all anti-HIV drugs.
high resistance to boosted protease inhibitors was common (lopinavir/ritonavir,
27%; atazanavir/ritonavir, 24%; darunavir/ritonavir, 7%).
second generation NNRTIs was also highly prevalent (rilpivirine, 46%;
A quarter of
patients had completely exhausted all first- and second-line treatment options.
If anything, the
investigators believe their study may have under-estimated the prevalence of
second-line treatment failure, with many treatment centres lacking the tools to
identify these patients.
third-line drugs are expensive, typically costing between 6 and 14 times more
than first- and second-line therapies. Affording these drugs is a challenge for
treatment programmes in low- and middle-income countries (LMICs), with Brazil
currently spending at least 40% of its ART budget on the 5% of patients in need
of third-line treatment.
indicates that nearly one in four patients in Kenya failing second-line
treatment has complete exhaustion of available antiretrovirals, emphasizing the
need for increased access to third-line treatment in LMICs,” conclude the