FM DECEMBER 2018 ISSUE - digital edition

It is well known that 1% of viruses have
K103N mutation and patients carrying
these mutant viruses respond to firstline
Efavirenz (EFV)-based therapy if
they have 100,000 copies/mL versus
1,000 copies/mL. A review (Barth et
al 2010) analyzing 89 studies with
12,288 patients suggested that the most
common mutations are M184V (65%)
and K103N (52%). Thymidine-analog
mutations (TAMs: M41L, D67N, K70R,
L210W, T215Y/F, and K219Q/E) were
less common, ranging from 5%–20%
of patients, whereas K65R was found
in 5% patients. A larger cohort study,
PharmAccess African Studies to Evaluate
Resistance (PASER), where 37% of the
cohort received ZDV, 27% received
d4T and 33.5% received TDF. Majority
of patients (96%) acquired resistance
during the therapy was also carried
out. The most common mutations were
M184V (53.5%) and K103N (28.9%).
TAMs occurred in 12.7% of subjects
receiving ZDV, 5% in d4T and 4.3% in
TDF.
Viral tropism
Viral tropism is another factor
AN NGS BASED
PRETREATMENT AND
CLINICAL MANAGEMENT OF
HIV USING THE KNOWLEDGE
OF KNOWN MUTATIONS CAN
LEAD TO IMPROVEMENTS IN
CLINICAL CARE
to be considered, as it has been
demonstrated (Raymond et al., 2011;
Archer et al., 2010, 2009; Tsibris et al.,
2009; Westby et al., 2006) that in case
of maraviroc prescription, which is a
selective CCR5 co-receptor antagonist,
approximately 10-15% of treatmentnaïve
subjects and 50% of experienced
subjects have viruses that can also use
a CXCR4 co-receptor. It was also shown
that V3-loop 454 sequencing was a
better predictor than the first version of
Monogram’s phenotypic Trofile Assay in
a retrospective analysis of two clinical
trials of maraviroc (Swenson et al.,
2011a). Deep sequencing by NGS was
shown to also have better results from
MERIT trial reanalysis and to be cost
effective too.
In India, it was feared that the lack
of resources, coupled with tuberculosis,
would lead to very high HIV
transmission. However, with ART rollout,
transmission has been reduced by 54%.
With increased levels of first-line ART
comes the challenge of drug resistance.
It has been reported that (Hosseinipour
et al. 2013) there are predictable
mutation patterns at 12 month ART in
resource-limited settings. Till date, the
majority of Indian national programmes
have relied on clinic-immunological
monitoring for the diagnosis of
treatment failure, especially CD4 cell
count every 6 months. An NGS based
pretreatment and clinical management
of HIV using the knowledge of known
mutations can lead to improvements in
clinical care. Meanwhile, more studies
can help in better understanding
acquired disease mutations for better
outcomes in the future.
The author is medical scientist and former
director of SGRF, Bangalore
32 / FUTURE MEDICINE / DECEMBER 2018