backbone in combination with LPV/r and demonstrated equal efficacy with respect to viral load
suppression.48 The ACTG 5202 compared each of
these NRTI backbones head-to-head in combination with both EFV and ATV/r (each separately).
The ABC/3TC arm demonstrated higher cholesterol levels, more adverse effects (most likely from
ABC hypersensitivity in the setting of HLA-B5701
positivity), and, most importantly, significantly higher virologic failure in patients with high initial viral
loads (>100,000 copies/mL) compared to the TDF/
FTC arm.49 The rate of virologic failure was so significant that this group of patients was unblinded
and offered TDF/FTC as alternative therapy. This
increased rate of virologic failure was not observed
in a second randomized trial.48
As mentioned, ABC-based backbones have
been associated with concerning adverse reactions. A severe, life-threatening hypersensitivity
reaction is possible in patients positive for the HLA-
B5701 allele. Also, a large cohort review trial did
show increased risk of myocardial infarction in patients using ABC over the prior 6 months, although
follow-up studies have not clearly supported this
finding.50 Caution is therefore generally recommended in patients at risk for vascular disease,
and ABC/3TC is only considered a viable NRTI
combination in the setting of an HIV viral load of
<100,000 copies/mL and a negative HLA-B5701
allele test.
Selection of NNRTI
NNRTI-based regimens are frequently employed
in treatment-naïve patients. EFV is generally considered the first-line medication in this class, with
RPV and NVP being alternatives. 16 As mentioned
above, EFV is a Pregnancy Category D agent and
should not be initiated in pregnant patients. EFV
has generally demonstrated better efficacy and less
toxicity compared to NVP. EFV is available in a
single-pill, once-daily fixed-dose combination as
EFV/TDF/FTC (Atripla). RPV is also a popular
choice since it has been made available in the
single-pill combination RPV/FTC/TDF (Complera;
see Table 4 for complete formulation). However, it
is considered less effective than EFV in patients
with high viral loads and is contraindicated in patients requiring proton-pump inhibitors for stomach
acid suppression. ETR is not approved for treatment-naïve patients.
Selection of PI
PI-based regimens all generally make use of
RTV boosting, as discussed above. ATV and
DRV are considered first-line agents of this class
because of their toxicity profiles, although LPV,
fosamprenavir (FPV), and saquinavir (SQV) have
all demonstrated noninferiority with respect to efficacy. DRV is the most robust agent in the face of
multiple viral mutations. ATV has the least effect
on lipids, although DRV is almost equivalent. As
mentioned, COB may replace RTV as the boosting
agent of choice in these regimens, although hopes
it would have less adverse reactions compared to
RTV have not necessarily been seen to date.
If virologic failure occurs on an initial first-line
regimen, a switch to a boosted PI-based regimen
is often recommended. Again, the boosted PI is
usually combined with 2 NRTIs. If PI mutations
occur in addition to resistance to other classes, a
boosted DRV- or TPV-based regimen is especially
recommended. 16
Selection of INSTI
RAL is currently the preferred medication of
this class. The new COB-boosted EVG (as part
of Stribild) is an alternative regimen for treatment-naïve patients.
