Drug resistance: if transmitted, may persist more than 1 year

Keith Alcorn
Estimated reading time 2 minutes
This article is more than 23 years old.

US researchers have established that resistance to non-nucleoside reverse transcriptase inhibitors acquired at the time of HIV infection can persist for more than one year. Their findings were presented on Wednesday at the Ninth Annual Retroviruses Conference in Seattle.

Thirty seven patients were identified by Dr Susan Little and colleagues from the University of California out of a cohort of 301 seroconverters identified by multicentre surveillence in the US. Patients were identified within an average of 52 to 68 days of infection, and a sub-group of six patients with NNRTI resistance were tracked over one year to deteremine whether NNRTI resistance disappeared.

After 400 days, virus with reduced sensitivity to NNRTIs still made up 20-30% of the virus population, and resistance mutations associated with NNRTIs were still detectable. In at least one case, the K103N mutation associated with nevirapine resistance was detected after 500 days of infection.

Glossary

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

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).

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. 

These findings suggest that a sample taken during the first year after seroconversion can be used to determine the risk of NNRTI resistance when individuals start treatment in later years, since the NNRTI-resistant virus may no longer be detectable but will still be archived, ready to re-emerge under the selective pressure of drug therapy, particularly in the context of sub-optimal adherence or drug levels.

Dr Little noted that the persistence of NNRTI resistance may have implications for secondary transmission of resistance; if resistant virus persists for more than a year, it is possible that a large proportion of drug-resistant new infections could be generated by highly infectious individuals who have already acquired drug resistant virus, and who are experiencing acute HIV infection.

Dr Joep Lange, President of the International Society, suggested that the findings should give pause to proponents of short course nevirapine treatment for prevention of mother to child transmission.

"If we are seeing this degree of persistence, we should think carefully about what this means for adult treatment in resource limited countries" he said.

References

Little S et al. Persistence of transmitted drug resistance among subjects with primary HIV infection not receiving antiretroviral therapy. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 95, 2002.

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