Switching to NNRTIs reduces risk of further treatment switches

Research published in the 29 March edition of the journal AIDS suggests that

people who have had to switch antiretroviral therapy because of toxicity

substantially reduce their chances of having to make a subsequent change by

switching to nevirapine rather than another protease inhibitor (PI).

Dutch researchers found that between June 1996 and December 1999 some 776

members of the Dutch ATHENA treatment cohort, with a viral load below 500

copies m/L, had to change their antiretroviral therapy because of

side-effects. The study sample had an average CD4 count of 365, with 85 per

cent (659) being men and 15 per cent (116) women.

The most commonly reported

side-effects necessitating a change in treatment were gastrointestinal (37

per cent of the sample) and peripheral neuropathy (13 per cent).

Over a 12 month period the Dutch research team found that 53 per cent of the

study group had to change their therapy again because of toxicity. Once

again, gastrointestinal side effects (37 per cent) and peripheral neuropathy

(12 per cent) were the main reasons for making yet another treatment change..

Women appeared to be at a greater risk of having to make a second toxicity

drive change, the authors speculating that this may be due to "sex dependent

pharmacokinetics or adherence leading to higher plasma concentrations of the

PI."

However, switching from a PI to the non-nucleoside reverse transcriptase

inhibitor (NNRTI), nevirapine, "appeared to be protective against a

subsequent switch for toxicity reasons" with a fivefold lower risk of

subsequent side-effect related treatment changes. Of particular note was the

low incidence of further treatment changes because of gastrointestinal

problems in people switching to nevirapine: 22 people out of 100 were given

nevirapine after complaining of gastric problems on their first PI based

regimen and of these only one had to make a subsequent treatment change

because of the recurrence or continuation of toxicity. There was no data on

the the benefits of switching to efavirenz as it was not licensed in the

Netherlands during the study period.

However, it appeared that switching NRTIs as well as changing to nevirapine

did not lessen the chances of experiencing side effects severe enough to

warrant another treatment change. The researchers speculate that this may be

due to the additional toxicity of the newly introduced NRTIs. Changing NRTIs

at the same time as PIs did not reduce the risk of people having to make

subsequent toxicity driven switches.

The incidence of second toxicity-driven switches also dropped over the

period of the study, suggesting that physicians were becoming more

experienced in managing side effects and structuring appropriate regimens.

A recent report from the Swiss HIV Cohort reached similar conclusions regarding the effects of switching from a protease inhibitor to efavirenz.

A total of 184 switchers and 368 nonswitchers were compared. The groups

were matched for sex, age, CD4+ cell count, duration of follow-up, HIV-1

RNA level at the time of switch, the proportion who were switching from

a first HAART regimen, the duration of HAART treatment, and the viral

load before commencing therapy. The only significant difference lay in

the proportion of injection-drug users (16.9% in the switch group vs

30.4% in the protease inhibitor group).

Nonswitchers were more likely to have experienced virologic failure

after 1 year (27.2% vs 9.4%). Switchers had an odds ratio of 0.33 for

viral failure, which increased to an OR of 0.19 when injection-drug

users were excluded from the analysis. The reduced risk persisted (OR

0.47) even when subsequent (post-switch) treatment changes were not

censored, Switchers were less likely to change treatment again than

nonswitchers (40% vs 60%, OR 0.54, P

did not become apparent until more than 2 months after the treatment

switch, reflecting the early CNS toxicity of efavirenz.

Injection-drug users were more likely to discontinue efavirenz,

especially during the first month of treatment (P

injection-drug users who stopped efavirenz, 73% cited side effects as

the reason.