On October 14th the US Department of Health
and Human Services (DHHS) issued updated guidelines for the use of
antiretroviral therapy (ART) in adults and adolescents, coinciding with the
release of revised European AIDS Clinical Society (EACS) guidelines at the 13th
European AIDS Conference last week in Belgrade.
The key changes in this version of the US
guidelines focus on which drugs to start in a first-line regimen for
In the non-nucleoside reverse transcriptase inhibitors
(NNRTI) class, efavirenz (Sustiva, Stocrin) plus tenofovir/emtricitabine
(the drugs in the Truvada
coformulation) continues to be the "preferred" first-line regimen,
except for pregnant women.
Regimens containing nevirapine (Viramune) are now classified as "acceptable" for
appropriate patients - that is, women with pre-treatment CD4 cell counts
below 250 cells/mm3 and men below 400 cells/mm3 (people
with higher counts are at greater risk for hypersensitivity reactions).
The recently approved NNRTI rilpivirine (Edurant) was included as an
"alternative" component of initial therapy thanks to accumulated data
supporting its safety and efficacy. The new EACS guidelines rate efavirenz and
nevirapine equally as recommended options, but do not include rilpivirine,
which still awaits final marketing approval in the European Union.
Turning to protease inhibitors, once-daily
ritonavir-boosted atazanavir (Reyataz)
or boosted darunavir (Prezista) plus
tenofovir/emtricitabine are the "preferred" options. Darunavir plus
abacavir/lamivudine (the drugs in the Kivexa
and Epzicom coformulations) was
reclassified as an "alternative" due to additional data. But
unboosted fosamprenavir (Telzir, Lexiva) was removed due to inferior
potency and risk of drug resistance.
Similarly, raltegravir (Isentress) - the sole approved integrase inhibitor - plus
tenofovir/emtricitabine remains the "preferred" regimen, whilst
raltegravir plus abacavir/lamivudine was upgraded to "alternative"
with accumulation of favourable data.
With regard to nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbones, the
DHHS guidelines keep tenofovir/emtricitabine as the sole
"preferred" option (except for pregnant women) and
abacavir/lamivudine as an "alternative".
The DHHS panel demoted abacavir/lamivudine from "preferred" to "alternative" status in 2008 due to
concerns that abacavir may increase the risk of heart attacks and may not be as
effective for people with high pre-treatment viral load.
By now, numerous studies have
produced conflicting data about the comparative risks and benefits of abacavir/lamivudine and tenofovir/emtricitabine. The
new DHHS guidelines include more extensive discussion of this issue, concluding
that abacavir/lamivudine "remains
a good alternative dual-NRTI option for some ART-naive patients". The EACS guidelines recommend the two backbones
dual NRTI backbones were demoted or removed entirely due to toxicities. The
first-ever NRTI combinations - zidovudine/lamivudine (the drugs in
the Combivir coformulation) - was reclassified from "alternative" to
"acceptable" overall, but remains the preferred NRTI combination for
pregnant women receiving antiretroviral drugs to prevent mother-to-child HIV
As for when to
initiate HIV treatment - a subject of ongoing controversy - the US
guidelines continue to advise starting when a person's CD4 cell count falls
below 500 cells/mm3. Above that level the panel was split on whether
to start or wait.
guidelines are more conservative, recommending treatment initiation at a
threshold of 350 cells/mm3, although ART is advised below 500
cells/mm3 - or even sooner - for several patient groups including pregnant women
and people with co-existing conditions such as HIV-associated kidney disease,
neurocognitive impairment and hepatitis B or C.
revised DHHS guidelines are available online at http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7&ClassID=1.
Changes are summarised in an introductory section, "What's New in the