Nevirapine
(Viramune) versus Abacavir (Ziagen) in Combination with AZT/3TC (Combivir) as
First-line Antiretroviral Therapy | Ziagen
Tablet |  | Viramune
Tablet |  | Combivir
Tablet |
The
primary objective of the current study, reported in the January 2008 issue of
Tropical Medicine & International Health, was to compare the safety
and tolerability of abacavir (Ziagen)
versus nevirapine (Viramune)
in HIV positive adults starting antiretroviral therapy in Uganda.
This
was a 24-week, double-blind trial conducted with 600 symptomatic antiretroviral-naive
adults with a CD4 cell count < 200 cells/mm3. Most (72%) were women with a
median age of 37 years (range 18-66). The median baseline CD4 count was 99 cells/mm3
(range 1-199) and 19% had WHO stage 4 HIV/AIDS. Participants
were randomly allocated to receive AZT/3TC (Combivir)
plus either:
•
300 mg abacavir and nevirapine placebo twice daily
(n = 300)
•
200 mg nevirapine and abacavir placebo twice daily
(n = 300).
The
primary endpoint was occurrence of any serious adverse event (SAE) definitely,
probably, or uncertainly related to nevirapine or abacavir. Secondary endpoints
were adverse events leading to permanent discontinuation of study therapy and
Grade 4 (severe) events.  Results
•
95% of participants completed 24 weeks of study therapy.
•
4% died and 1% were lost to follow-up.
•
37 SAEs occurred in 36 participants while on a blinded
drug.
•
20 events -- 6 (2.0%) in the abacavir arm and 14
(4.7%) in the nevirapine arm -- were considered serious adverse reactions definitely,
probably, or uncertainly related to abacavir or nevirapine.
•
Only 2.0% of abacavir recipients (6 patients) experienced
a suspected hypersensitivity reaction (HSR).
•
14 abacavir recipients (4.7%) and 30 nevirapine recipients
(10.0%) discontinued blinded therapy due to:
•
Toxicity (6 and 15, respectively; P = 0.07), all
rash, possible HSR, and/or hepatotoxicity;
•
Starting anti-tuberculosis therapy (6 and 13, respectively);
•
Other reasons (2 in each arm).
Conclusion In
conclusion, the study authors wrote, "There was a trend towards a lower rate
of serious adverse reactions in Ugandan adults with low CD4 starting antiretroviral
regimens with abacavir than with nevirapine. This suggests that abacavir could
be used more widely in resource-limited settings without major safety concerns." This
recommendation would be even stronger if the recently developed HLA-B*5701
genetic test for susceptibility to abacavir hypersensitivity were to become
widely available in resource-limited countries. However,
several studies have shown that triple-NRTI regimens are less effective than those
that include a NNRTI or a protease inhibitor (PI). The current DHHS
treatment guidelines list abacavir + AZT/3TC as a regimen that is not recommended
as initial therapy due to inferior virological efficacy. While this combination
might be considered in resource-limited settings where other options are not available,
a regimen that includes a NNRTI or a protease inhibitor is preferred whenever
possible. 3/21/08
Reference
P
Munderi, C Kityo, AS Walker, and others.Twenty-four-week safety and tolerability
of nevirapine vs. abacavir in combination with zidovudine/lamivudine as first-line
antiretroviral therapy: a randomized double-blind trial (NORA). Tropical Medicine
& International Health 13 (1): 6-16. January 2008. | 
