One consideration
that applies both to PEP and to PrEP is that when antiretroviral drugs are
given to people who are HIV-negative, the level of toxicity that is acceptable
is lower than when drugs are used to treat a life-threatening illness.
Many
countries do not recommend three-drug regimens, due to their side-effects and
cost. Many countries use two NRTIs except in very high-risk exposures or when
there is evidence that the transmitted virus could be drug-resistant.
A poster
at the 13th Conference on Retroviruses and Opportunistic Infections (CROI) in
2006
1
discussed the tolerability of PEP regimens given at nine hospitals in France.
The regimens compared were:
- AZT/3TC (Combivir)
plus nelfinavir (Viracept)
- Combivir plus lopinavir/ritonavir (Kaletra)
- Combivir plus tenofovir
- Tenofovir/3TC plus
atazanavir (Reyataz)/ritonavir (Norvir).
The
regimen containing nelfinavir was significantly less well tolerated, with 34.5%
of patients discontinuing a 28-day course of PEP due to side-effects, compared
with an average of 20% on the other regimens.
Commentators
at the poster session said they had found AZT-free regimens were better
tolerated; questioned the usefulness of
Kaletra
due to its poor genital penetration; and aired the ever-controversial topic (in
PEP terms) of whether to provide two or three drugs.
When in
2005 an HIV clinic in Boston
2
switched the PEP combination it prescribed from
Combivir to
Truvada
they found lower rates of side-effects.
A survey
of occupational antiretroviral PEP among health workers in Canada
3
uncovered a major hidden cost. Time off work due to side-effects of the drugs
cost the health service as much as providing the drugs for the treatment. This
time off work appears to have doubled, from an average of 7.0 days to 15.8 days
in the year 2000, when the protease inhibitor nelfinavir was added to the
regimen (previously d4T plus 3TC).
Since
guidelines have changed the recommended PEP regimens, however, side-effects
have become much less burdensome. One study presented at the 2010 BHIVA/BASHH conference
4 showed that following
a change in the recommended PEP regimen to tenofovir/FTC/boosted lopinavir (
Truvada/Kaletra), drug side-effects and
interactions have become rare. In this study 140 patients took
Truvada/
Kaletra and there was only
one patient, a heavy drinker, whose PEP had to be changed (by stopping his
Kaletra
in the fourth week) because he had a significant rise in enzymes indicating
liver damage. Nine other patients had mild disturbances in liver and kidney
function but these resolved themselves. No patient who had abnormal liver or
kidney function tests at baseline developed PEP-specific toxicity.
The researchers suggested that it may therefore be
unnecessary to bring in most patients for monitoring of drug levels and liver
and kidney function during their four weeks on PEP unless they have
significantly abnormal baseline tests or the potential for drug interactions.
Another French study
5
was based on 249 participants who took PEP between November 2006 and June 2008 in 10
French hospitals, mostly (82%) after sexual exposure. Tolerability could be
evaluated in 188 cases. In 22 cases, PEP was discontinued for adverse effects
before day 28, including two cases of skin rash related to tenofovir and one
case of kidney stones ascribed to lopinavir. Two-thirds (166) of participants
completed the 28 days of PEP with tolerability judged as good in 96 (58%)
individuals. Among everyone who experienced at least one side-effect, 78%
reported diarrhoea, 78% weakness, and 59% nausea and/or vomiting.
Compared
to previous studies, the drop-out rate due to side-effects appeared to be
significantly lower in people taking
Truvada/Kaletra
tablets than in people taking either AZT/3TC/nelfinavir, AZT/3TC/
Kaletra soft-gel capsules, or
tenofovir/3TC/atazanavir/ritonavir.
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