Transmission of unusual HIV variants may increase risk of treatment failure

Anna Poppa
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This article is more than 24 years old.

Scottsdale, Arizona: The case for resistance testing prior to starting anti-HIV therapy in primary infection was strengthened by new data presented at the Fifth Resistance Worksop in Arizona today.

Genotypic analysis of 603 recently infected people, diagnosed between 1997 and 1999 in ten US cities found a high prevalence (3.3%) of HIV variants with unusual mutations at position 215 in HIV’s reverse transcriptase gene. Whilst the T215Y mutation is well established as conferring a high level of resistance to AZT, other mutations, at this position, including 215C, S and D do not cause resistance to AZT, but have been shown previously to increase HIV’s replicative capacity. In the presence of AZT, these mutants revert to T215Y in preference to wild-type. Infection with these unusual 215 variants therefore has important implications for choice of therapy.

In seven individuals infected with either 215C or D, who subsequently began anti-HIV treatment with an AZT-containing regimen, reversion to the AZT mutant T215Y occurred in an average of 25 or 31 days respectively. For comparison, three people infected with wild-type who later developed T215Y did so in an average of 63 days (Garcia-Lerma).

Glossary

capacity

In discussions of consent for medical treatment, the ability of a person to make a decision for themselves and understand its implications. Young children, people who are unconscious and some people with mental health problems may lack capacity. In the context of health services, the staff and resources that are available for patient care.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

primary infection

In HIV, usually defined as the first six months of infection.

gene

A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.

antiviral

A drug that acts against a virus or viruses.

A second presentation demonstrated that this problem stretches beyond the US. Deenan Pillay, of the PHLS Antiviral Susceptibility Reference Unit at the University of Birmingham, presented two case reports from UK seroconverters who were infected with unusual 215 variants, and who both subsequently transmitted these viruses to a sexual partner (Pillay).

References

Garcia-Lerma JG et al. Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naïve persons. Antiviral Therapy 2001; 6(Supplement 1):19.

Pillay D et al. Evidence of secondary transmission of HIV-1 with position 215 variants within reverse transcriptase. Antiviral Therapy 2001; 6(Supplement 1):114.

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