Switching to
second-line antiretroviral therapy (ART) after a single viral load measurement
above 1000 copies/ml has the potential to save lives, avert a significant
burden of AIDS-related illnesses and help achieve the 90-90-90 target,
according to the results of a modelling study published in AIDS.
Current World
Health Organization (WHO) ART guidelines recommend that people taking first-line
efavirenz-based ART with a viral load above 1000 copies/ml should only switch
to second-line protease inhibitor-based therapy if their viral load remains
above 1000 copies/ml three months later and after receiving enhanced adherence
support.
But research by Dr Amir Shroufi and colleagues from Médecins Sans Frontières and University College London showed that switching immediately after a viral
load measurement above 1000 copies/ml would not only increase the proportion of
people starting second-line treatment but also substantially reduce the
burden of AIDS-related illness and death, as well as the prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI)
resistance. It would help meet the virological suppression component of the 90-90-90
target (90% of people with HIV diagnosed; 90% of diagnosed people on ART; 90%
of ART-treated people virally suppressed) to end the AIDS epidemic.
“As a step towards
reducing unnecessary mortality associated with delayed second-line ART switch,
defining failure of first-line efavirenz-based regimens as a single viral load of
more than 1000 copies/ml should be considered,” write the authors.
WHO now recommends
routine viral load monitoring to identify individuals who are experiencing
first-line ART treatment failure. But patients only switch to more expensive
protease inhibitor-based second-line ART if their viral load remains elevated
in a confirmatory test three months later and after receiving enhanced
adherence support.
However, there are
several potential problems with this approach. Only a minority of people experiencing an elevation in viral load to over 1000 copies/ml subsequently
re-suppress while remaining on first-line ART, in part because up to 90% have NNRTI resistance. Many programmes fail to
switch failing patients promptly with
delays of a year or more widely reported. Such delays lead to avoidable HIV
transmissions, AIDS-related illness and
death.
Investigators
therefore wanted to see if switching treatment immediately after a single viral
load test above 1000 copies/ml would overcome these problems.
They therefore
used the HIV Synthesis Model (a well-established individual-based simulation
model of HIV transmission, disease progression, effect of ART and
resistance-risk), to compare the merits of the existing WHO guidance and
simplified switching.
The model was
based on the demographics and HIV epidemic in Malawi, but it was repeated 500
times to take account of the full range and extent of the HIV epidemic in
sub-Saharan Africa.
The results
clearly showed the benefits of simplified switching (using a single elevation in viral load above 1000 copies to define NNRTI-based first-line treatment failure).
Over a three-year
period, it would lead to an 18% decrease in AIDS-related
mortality among people with a viral load above 1000 copies while on ART (fall
in incidence from 3.1 to 2.5 per 100 person-years).
The simplified
strategy reduced by almost a third the six-month incidence of AIDS-defining
illnesses among people on ART and a viral load above 1000 copies/ml.
In a country with
10 million adults and 8.8% HIV prevalence, use of the simplified switch
strategy would avert 1322 AIDS-related deaths over three years. This would mean
that 10,125 AIDS deaths would be prevented in South Africa annually.
There would also
be a significant increase in the number of people switching to second-line
therapy before developing drug resistance. Modelling for a country of 10
million showed that there would be 301 switches annually without resistance
when using the existing WHO guidelines. This increased to 7285 switches with
the simplified strategy.
The proportion of
people with resistance who switched to second-line treatment would increase
from 48% using the baseline scenario to 65% using a single viral load
measurement.
There would also
be a small but significant (3%) increase in the overall proportion of ART-treated people who were virally suppressed, therefore
surpassing the third of the 90-90-90 targets needed to end AIDS.
“The likelihood of
an increase in switching is not implausible given that the single switch
strategy reduces the number of steps necessary to switch and the observed
delays at every step of the current strategy,” comment the investigators.
Reductions in the
cost of protease inhibitors and the adoption of more tolerable
dolutegravir-based regimens as second-line therapy would also make simplified switching more
affordable and acceptable for patients.
“As the cost of
second-line regimes decline, a change of strategy to define failure of efavirenz-based first-line ART after a single viral load value more than 1000
copies/ml should be considered, allowing faster switch to second-line boosting
effort to achieve the 3rd 90 and reducing AIDS-related deaths,”
conclude the researchers.