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Sub-type C infection does not increase the risk of virologic failure when patients are taking tenofovir-containing first-line ART
Michael Carter, 2016-06-08 07:50:00
There is no
evidence that HIV-positive patients with sub-type C infection have an increased
risk of treatment failure when receiving tenofovir-containing regimens,
investigators from the UK report in the online edition of the Journal of Infectious Diseases.
Investigators monitored over 8000 patients initiating standard first-line
tenofovir-containing regimens and found that after adjustment for demographic
and clinical factors, patients with sub-type C infection were no more likely to
experience virologic failure than patients with sub-type B infection.
observations may imply there is no intrinsic effect of viral subtype on the
efficacy of tenofovir-containing regimens, and specially alleviate concerns
that efficacy would be compromised for subtype C infections,” write the
authors. “This is a reassuring finding in light of the rapid worldwide
expansion in the prescribing of tenofovir and supports WHO recommendations that
this is an appropriate first-line drug, even in geographical regions where
subtype C HIV-1 infection is endemic.”
Some research has
shown that tenofovir-containing regimens have reduced efficacy in patients with
sub-type C infection. It has been suggested that this is because sub-type C is
especially likely to develop the K65R resistance mutation, which is selected by
tenofovir. If this is the case, it could have serious public health
implications. Approximately 50% of HIV-positive patients worldwide have sub-type
C infection and since 2013 WHO guidelines have recommended tenofovir for
first-line antiretroviral therapy.
concerns in mind, a team of investigators analysed evaluated whether HIV-1
sub-type influenced virologic outcomes in patients starting standard first-line
HIV therapy containing tenofovir. The study population comprised 8746 patients
enrolled in the UK Collaborative HIV Cohort Study (www.ukchic.org.uk).
eligible for inclusion if they initiated a first-line regimen that contained
tenofovir, plus emtricitabine or lamivudine, with either a non-nucleoside
reverse transcriptase inhibitor (NNRTI – efavirenz or nevirapine) or a
ritonavir-boosted protease inhibitor (lopinavir, atazanavir or darunavir).
was defined as two consecutive viral load measurements above 200 copies/ml in a
six-month period after suppression of viral load. The investigators took into
account other factors associated with treatment outcomes – type of therapy, HIV
risk group, baseline CD4 and viral load – to see if sub-type really did
influence the risk of virologic failure.
determined in 6149 patients. Approximately two-thirds (n = 4123) of patients
were infected with sub-type B, 823 patients with sub-type C and 1203 were
infected with non-B/C sub-types.
significant demographic differences according to sub-type. Patients infected
with sub-type B were predominantly white (83%) and gay men (85%), whereas
individuals with sub-type C infection were mainly black (70%) and heterosexual
Patients were followed
for a median of 3.3 years. During this time, virologic failure was observed in 6% of patients with sub-type B infection, 10% of patients with sub-type C
infection and 9.5% of patients with non-B/C sub-types.
This meant, that
in unadjusted analysis, the rate of treatment failure was approximately
two-fold higher in patients with sub-type C compared to those with sub-type B
(B vs. C, HR = 0.54; 95% CI, 0.43-0.67; p < 0.001). Outcomes were comparable
for patients with sub-type C and non-B/C sub-types.
adjustment for demographic and clinical characteristics, the difference in
outcomes between patients with sub-type B and sub-type C infections ceased to
be significant (HR = 0.87; 95% CI, 0.63-1.21; p=0.41). Comparison between C and non-B/C
sub-types was unchanged.
Examination of the
reasons for the change between the unadjusted and adjusted models showed that
the most important factors were HIV risk group (lower rate of virologic failure
in gay men) and ethnicity (lower rate of virologic failure among white and
Asian patients). Regimens based on NNRTIs were more durable than protease
inhibitor-containing combinations. Virologic failure was more common in
patients with a baseline CD4 count below 100 cells/mm3 and also in
individuals with a baseline viral load above 100,000 copies/ml.
Genotypic resistance test results were available for 41% of those who experienced virological failure. Tenofovir-associated resistance mutations (mainly K65R) were more common in people with sub-type C virus than in those with sub-type B or nonB/C viruses (22.7% vs 6.1% and 8.1%; p=0.003).
“In the present study
patients with HIV-1 subtype C infection on a first-line tenofovir-containing
regimen experienced a higher rate of virological failure than patients with
subtype B virus,” comment the investigators. “However, this effect was almost
entirely explained by differences between groups in demographic and clinical
They suggest that
adherence is a likely explanation for the differences in outcomes between risk
The authors of an
accompanying editorial were reassured by the findings of the study as they show
that WHO treatment guidelines for the treatment of sub-type C infection do not
need to change. However, they conclude, “it is of utmost importance to globally
improve treatment conditions so that adherence problems and treatment failures
can be identified early.”