Standard tests underestimate resistance in mothers who received nevirapine when giving birth

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Highly sensitive resistance tests that can detect very small populations of drug-resistant virus have shown that in women exposed to single-dose nevirapine (Viramune) at the time of delivery, nevirapine resistance is more common than thought, and may persist for up to two years, according to findings from two studies published in the July 1st edition of the Journal of Infectious Diseases.

Standard resistance tests cannot detect drug-resistant strains of HIV if they make up less than 20% of the virus population in a sample. Using more sensitive tests, two different research groups investigated nevirapine resistance in women exposed to nevirapine for prevention of mother-to-child HIV transmission.

In the first study, conducted on samples from 50 South African women, no resistance mutations were found using a standard method in 40 women, but when single genome sequencing was used, the K103N mutation was detected in 16 samples. Forty-six samples showed no evidence of the Y181C mutation by standard testing, but more sensitive testing found the mutation in five samples.

Glossary

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

strain

A variant characterised by a specific genotype.

 

assay

A test used to measure something.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

The authors argue that their findings indicate that previous estimates of maternal nevirapine resistance have been far too low, and that the true rate may lie in the region of 65% in women with HIV-1 subtype C infection.

The second study compared standard resistance testing (ViroSeq) with two sensitive experimental assays (LigAmp and TyHRT) in detection of resistance mutations one year after delivery in nine mothers and five infants from the HIVNET 012 study. The group had previously reported that ViroSeq detected the K103N mutation in eight of nine mothers and in two of five infants, whilst LigAmp detected the K103N mutation at low levels in eight of nine women and in four of five infants six to eight weeks after delivery.

When resistance was assessed twelve to 24 months after delivery, the K103N mutation was not detected by ViroSeq in any samples. However K103N was detected by LigAmp in three of nine women and in one of five infants. K103N was also detected in those samples by use of the TyHRT assay.

Both research groups recommend that further research is required to assess the impact of low frequency drug resistance mutations on treatment outcomes of mothers exposed to nevirapine during pregnancy and delivery.

References

Flys T et al. Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis 192: 24–29, 2005.

Johnson JA et al. Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. J Infect Dis 192: 16-23, 2005.