BHIVA guidelines on NNRTI use questioned

This article is more than 24 years old.

Recommendations concerning the use of NNRTIs in the recently

updated BHIVA guidelines have been questioned in two recent letters to The

Lancet.

Glossary

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

treatment-naive

A person who has never taken treatment for a condition.

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Dr Philip Hay of St George’s Hospital, London, and Dr Julio Montaner, INCAS

Principal Investigator, have both questioned the suggestion that the use of

non-nucleosides nevirapine and delavirdine should be confined to people with

baseline viral load below 50,000.

Dr Hay cites two studies: a poster presented in Geneva by Dr Julio Montaner

and colleagues on the INCAS study, and a retrospective audit of people in the UK

who received nevirapine through the expanded access programme.

"The meta analysis cited does not provide evidence to support the threshold

for an NNRTI and two nucleoside combination…there is evidence to indicate that

NNRTIs are effective in patients with pretreatment viral loads in excess [of

50,000 copies].", writes Dr Hay (The Lancet 352, October 10 1998, p1226)

Although Montaner’s group demonstrated a trend towards poorer viral

suppression as baseline viral load increased, the only significant threshold for

poorer viral load suppression was above 250,000 copies. People with baseline

viral load above 250,000 copies were 2.33 times more likely than those with

viral load below 50,000 copies to experience a rebound in viral load above 5,000

copies by week 48 of the study.

The audit of participants in the UK nevirapine expanded access programme by

Dr Martin Fisher and colleagues showed no relation between reaching undetectable

viral load and baseline viral load for treatment naïve patients.

Montaner and colleagues point out that although they found a significant

relationship between baseline viral load and subsequent viral suppression,

"there was no clear cut off point beyond which nevirapine was no longer

effective to reduce or maintain pVL at a low level…these results do not allow us

to propose an upper limit of baseline pVL for the effective initiation of

nevirapine or PI containing regimens".

Montaner also notes that there are no comparative data on the relative merits

of the currently available NNRTIs, and that it may be premature to suggest that

efavirenz is more potent than other NNRTIs on the basis of Staszewski’s open

label comparison of efavirenz with indinavir in DMP-266-006.

The full text of the British HIV Association 1998 guidelines can be

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