AN INTRODUCTION TO NEVIRAPINE

1
PIs in perspective

• Results of PIs as reported in clinical trials
  have not
• been seen in practice. Poor compliance??
• Inconvenient to take. 9-18 pills per day
• Food restrictions, timing of doses
• Long term toxicity i.e. lipodystrophy and
  alterations of
• glucose and lipid metabolism are of concern
• Limits future options
• NNRTIs have therefore emerged as a viable option
  for initial treatment of HIV infection
• Antiviral Therapy 1998 3 49-53.

2
Nevirapine is effective in patients with high
viral loads and advanced disease

• Duration 1 year, No. of patients 171
• Population Antiretroviral-naïve patients
  baseline viral load 138, 986 copies/ml mean CD4
  count 101 cells/mm3
• Regimen zidovudine lamivudine nevirapine or
  placebo
• Results 45 of patients taking triple therapy
  had undetectable HIV RNA (lt 50 copies/ml) at 1
  year using ITT. Mean increase in CD4 counts 137
  cells/mm3
• Simple to use regimen
• 7th CROI, San Francisco, USA, Feb 2000

3
Results of the ATLANTIC Study at week 48
of patients with HIV RNA lt 50 copies/ml
39th ICAAC, September 19997th ECCAT, October 1999
4
Nevirapine produced greater reduction in viral
load than nelfinavir

• No. of patients 142, Duration 24 weeks
• Regimen Zidovudine lamivudine nevirapine or
  nelfinavir
• Results Intent-to-treat analysis at 24 weeks

HIV RNA less than 20 copies/ml
Ref 7th Conference on Retroviruses and
Opportunistic Infections, Jan 30-Feb 2, 2000
Abstract 510.
5
Comparison of Combination Antiretroviral Therapy
in Patients with Low Initial CD4 Counts
115
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NNRTI-based
PI-based
NNRTI-based
PI-based
regimens
regimens
regimens
regimens
Ref. 6th Annual Conference, BHIVA, March 2000,
P18.
6
Response to NNRTIs in patients with high viral
load
At  3 months
At 9 months Parameter Efavirenz Nevirapine Efavir
enz Nevirapine Patients with viral 96 91 92 87
load lt 500 copies/ml Viral load lt 500
copies/ml 93 92 92 85in patients with
baseline viral loads gt 100,000 copies/ml Viral
load lt 500 copies/ml 100 91 91 89in patients
with baseline viral loads lt 100,000
copies/ml On-treatment analysis Ref. 6th
Annual Conference, BHIVA, March 2000, P17.
7
Nevirapine prevents vertical transmissionSingle
dose to mother and infant, HIVnet study
N626, breast fed
Estimated risks of HIV-1 transmission Age Zidovudi
ne group Nevirapine group At Birth 10.4 8.2 6-8
weeks 21.3 11.9 14-16 weeks 25.1 13.1 Ref
Lancet 1999 354 795-802
8
Safety Tolerability

Adverse event
Clin Ther 1998 20 1071-92
9
Dosing with Nevirapine
Lead in for
Long term
14 days
Adults
200 mg
o.d.
200 mg
b.d.
or
400 mg.
o.d.
Children
(2 months-8 years)
4 mg/kg
o.d.
7 mg/kg
o.d.
gt 8 years
4 mg/kg
o.d.
4 mg/kg
b.d.