A dual antiretroviral regimen containing dolutegravir
(Tivicay) and boosted darunavir (Prezista) maintains viral suppression in
most people who switch from a suppressive three-drug regimen, according to an
observational study presented at the recent IDWeek in San Francisco. However, two drugs may not be
enough for those who wish to switch while
their viral load is detectable.

More than 90% of people who switched to
dolutegravir plus darunavir from a suppressive regimen containing nucleoside/nucleotide
reverse transcriptase inhibitors (NRTIs) kept their virus under control. But
this fell to 80% among those who had detectable
viral load when they changed treatment, Kellie Hawkins of Denver Public Health
reported.

Standard therapy for HIV involves three drugs,
usually two NRTIs plus a non-nucleoside reverse transcriptase inhibitor
(NNRTI), a protease inhibitor or an integrase inhibitor.

However, some people find it difficult to tolerate
NRTIs. One of the most widely used agents in this class, tenofovir disiproxil
fumarate (Viread, also a component of
Truvada, Atripla and Stribild), can cause kidney toxicity and
bone loss in susceptible individuals. Another, abacavir (Ziagen, also in Kivexa
and Triumeq), can cause
hypersensitivity reactions in people with genetic susceptibility and has been
associated with an increased risk of cardiovascular problems.

Hawkins presented findings from a retrospective cohort study that included all 65
treatment-experienced individuals who received dolutegravir plus boosted
darunavir at the two largest HIV clinics in Denver between January 2013 and
December 2017. Most were men, the median age was 55 years and the median
baseline CD4 cell count was 527 cells/mm3. Study participants were
analysed in two subgroups:

  • 49 people with viral suppression ( 200
    copies/ml) at baseline
  • 16 people with HIV RNA above 200 copies/ml at baseline.

Participants had been
on antiretroviral therapy for a median of 19 years. All of them had used NRTIs
and a majority had been exposed to all three of the other major drug classes. More
than 90% were currently on a once-daily regimen. They were roughly evenly divided
between those who used cobicistat and those who used ritonavir as a booster.

Almost half (46%) switched
to dual therapy because of proven or suspected tenofovir resistance. A third had
experienced tenofovir-related toxicities or intolerance and 20% had chronic kidney disease (a
contraindication for tenofovir DF), but they needed to avoid abacavir due to resistance,
intolerance or presence of the HLA-B*5701 genetic mutation that predicts
hypersensitivity risk.

After a median
follow-up period of 14 months, 95% overall had HIV RNA below 200 copies/ml and
94% had undetectable viral load using a stricter 50 copies/ml cut-off.

Among people with
viral suppression at baseline, 100% and 98% maintained viral load below these
respective cut-offs. But among those with unsuppressed virus at study entry,
the response rate fell to 81% using either cut-off.

Response rates did
not differ according to once- versus twice-daily dosing, use of cobicistat versus
ritonavir as a booster or pre-existing resistance mutations.

The three individuals
with viral suppression at baseline who developed detectable viral load after
switching to dual therapy went on to achieve re-suppression with the new dual regimen.
But three people who started with unsuppressed virus were never able to achieve
undetectable viral load with the dual regimen.

Adherence was very
good, approaching 100% in both the virally suppressed and non-suppressed
groups. However, one of the three people with detectable viral load at baseline
who did not achieve viral suppression with dual therapy managed only 16%
adherence, according to Hawkins.

Treatment was
generally safe and well tolerated. Ten people (15%) stopped taking the dual
regimen during the study period. Five did so to avoid drug interactions with
the boosting agent, two had cardiovascular risk factors and wanted to avoid
darunavir (which can raise blood lipids), one had persistent low-level viral
load, one was lost follow-up and one entered hospice care for reasons unrelated
to HIV.

“Boosted
darunavir with dolutegravir dual therapy demonstrated sustained rates of viral
suppression, even in those failing therapy prior to initiation of the study
regimen,” the researchers concluded.

However,
session moderator Monica Gandhi of the University of California at San
Francisco expressed concern that this combination may not be potent enough for
some people.

“This
data is concerning to me because, even though the number was super small, for
some people who weren’t virologically suppressed to begin with, it wasn’t
enough to put them on two drugs.”

Gandhi
said that switching to dual therapy for simplification after a three-drug
regimen has brought down viral load – known as induction-maintenance – is
fine, but she was cautious about starting a dual regimen in someone without
viral suppression.

“It’s
the difference between induction-maintenance versus starting someone who really
isn’t doing well on two drugs. I think we’re going to need three drugs for
people who aren’t doing well,” she said.

She noted
that the ongoing DUALIS trial is evaluating whether switching to ritonavir-boosted darunavir plus
dolutegravir is non-inferior to staying on boosted darunavir plus either tenofovir
DF/emtricitabine or abacavir/lamivudine in a larger randomised population.