THE REAL VALUE OF NEVIRAPINE
Over the past six months, a simple drug has become the centrepiece of a major political debacle in South Africa with all the intrigues and more twists than a Jeffrey Archer novel. Health professionals, AIDS activist, scientists, religious leaders, trade unionists and senior politicians have all entered into the fray arguing the merits of the drug, its benefits, and toxicities. It has been condemned as "the drug from hell' by AIDS dissidents while heralded as a "godsend" by many health professionals. Amidst all the rhetoric, there have been few attempts to decipher the real value of the drug except through public slanging matches played out in the courts and in the media.
How does nevirapine work?
The human immunodeficiency virus (HIV) uses the enzyme reverse transcriptase
to incorporate its own genetic material into host cells, which then allows it
reproduce freely. Nevirapine, one of a class of drugs known as non-nucleoside
reverse transcriptase inhibitors, prevents this enzyme from functioning. This
results in a reduced amount of virus in the body and an increase in the CD4
cell (T cell) count, improving the host's immune function, and thereby reducing
the risk of new and opportunistic infections, and death.
When is nevirapine used?
Nevirapine has been widely used in adults as one of a combination of drugs to
treat established HIV infection. It has a special role in the prevention of
mother to child transmission (MTCT) of HIV, as it is effective when given alone
as a single dose to the mother at the beginning of labour and one dose administered
to the baby within 72 hours of birth. Nevirapine given to HIV-positive pregnant
women rapidly crosses the placenta into the fetus with its effects lasting through
the first week of life. The timing of its delivery to the mother during labour
is important as up to two-thirds of infants born with HIV are infected in the
birth canal.
Is nevirapine effective?
Clinical trials have confirmed the efficacy of nevirapine in preventing mother-to-child
transmission (MTCT) of HIV. No trials are available comparing nevirapine with
placebo. The Ugandan HIVNET 012 study involving 626 women showed that nevirapine
was able to reduce MTCT by 47%, with only 8.1% of infants exposed to nevirapine
acquiring HIV at birth.1 Almost all the babies were breast fed, resulting in
ongoing exposure to HIV. Despite this, the benefits of nevirapine were maintained
with a 42% reduction in transmission at the age of 12 months. 2
In the South African Intrapartum Nevirapine Trial (SAINT), 1306 mother/infant pairs were randomised to either nevirapine during labour and post-delivery, or multiple doses of AZT/3TC during labour and for one week after delivery to mother and baby. In both treatment arms, about 40% of infants were breast-fed. Eight weeks after birth, there was no significant difference observed between the rate of HIV infection or death across the two treatment arms, with a rate of 14.3% in the simpler nevirapine arm and 12.5% in the more involved and expensive dual therapy arm.3 For pregnant women already receiving highly active antiretroviral therapy, there appears to be no additional advantage of adding nevirapine to an existing regimen.4
What about drug resistance?
Drug resistant mutations of HIV are usually naturally occurring variants that
are present at low frequency before the use of nevirapine and which are then
selected and expanded when the drug is introduced. However, resistance does
not impact on the efficacy of the treatment to prevent MTCT, and resistant mutations
wane over 12-24 months. Resistance to antimicrobials is not unique to HIV and
a recent study,5 reaffirmed the WHO's view that concerns over drug resistance
should not delay the widespread use of nevirapine for preventing MTCT.
Is the drug toxic?
Opponents of nevirapine cite toxicity as an important limitation for its use
in MTCT prevention. Long-term use of nevirapine in adults has resulted in significant
side effects including life-threatening liver toxicity and skin reactions. Similar
adverse events have been reported in health care workers taking nevirapine in
combination with other antiretroviral drugs for post-exposure prophylaxis after
occupational exposure to HIV. However, in the SAINT study where single doses
were given to mother and infant, none of these adverse events were noted, with
the commonest, but infrequent, side effect being a mild, self-limiting skin
rash.
Is nevirapine affordable and cost effective?
The low cost of nevirapine (< R10) and simplicity of administration offers
great advantage over more expensive MCTC prevention treatments, particularly
for low-income countries where women generally attend antenatal clinics irregularly
or late during pregnancy, and where many deliveries occur in home settings.
Further, the manufacturer has offered the drug to some governments at no cost.
The cost effectiveness of nevirapine and of MTCT strategies has been well described
in the South African setting, with all studies on the subject consistently showing
overwhelming cost benefit for prevention measures. Nevirapine is a minor component
of the costs of a total MCTC package. Annually, it would cost the South African
government (if it decided not to accept the free offer) about R 6 million to
provide the
drug to all eligible mothers and infants. A total MTCT package would cost about
R 150 million annually (less than 1% of the health budget), with testing (R15
million), counselling (R60 million) and replacement
infant feeding (R70 million) costs being the major contributors.6 It is estimated
that by providing the nevirapine package, the health ministry would save about
R360 million annually, by preventing about 31 000 children getting HIV and thus
saving on the medical cost of treating the disease (excluding the provision
of long-term antiretroviral treatment).7
Current research confirms the benefits of nevirapine for preventing MTCT of
HIV. Nevirapine is cost-effective, safe, and has no significant side effects
when used for short periods. Drug resistance is a transient phenomenon. The
benefits of nevirapine appear to be maintained even in the presence of continued
breast-feeding. The challenge now is to translate these research findings into
policy and practice in South African and other resource-poor settings.
Dr Haroon Saloojee, Principal Paediatrician,
Chris Hani Baragwanath Hospital, Johannesburg
tel: (011) 4815201; email: 092sal@chiron.wits.ac.za
The full version of this article can be accessed at Science in Africa:
Nevirapine - godsend or drug from hell? http://www.scienceinafrica.co.za/
References:
29-05-2002