Drug resistance in half of US patients overstated

Over fifty per cent of Americans with HIV have drug-resistant virus, according to research presented at this week Interscience Conference on Antimicrobial and Antiviral .

Highly educated white, middle class gay men with access to first-rate health care were at the greatest risk of developing drug-resistant HIV in the population studied, according to researchers from the RAND Corporation of Santa Monica and the University of California San Diego (UCSD).

In the RAND/UCSD study, a cohort of 1600 people with HIV representative of the groups affected by the disease were monitored. The research team found that 63 per cent of these had detectable viral load, and of these 78 per cent had drug resistance (defined as reduced susceptibility to at least one antiretroviral).

Seventy per cent of patients with detectable viremia had resistance to at least one nucleoside analogue, and 31% had resistance to NNRTIs. Forty two per cent had resistance to at least one protease inhibitor.

Study author, Dr Doug Richman of UCSD said: "half of the people under care in the United States right now have resistant virus. It's quite frightening."

The study also found that 20 per cent of people newly infected with HIV, had acquired a strain of the virus resistant to at least one drug, suggesting that the sexual transmission of drug resistant HIV was already a serious public health concern which was likely to contribute to the increased prevalence of HAART resistant HIV.

White gay men were the group with the highest incidence of drug resistant virus. Commenting on this Dr Richman said: "It is not politically correct to say in public that both providers and patients are using these drugs suboptimally", highlighting frequent changes to HAART combinations made because of side effects, inadequate viral suppression or problems with adherence.

Comment: Selection bias ignored in media reports

Widespread US media reports highlighted the study's headline news, but failed to note that the results were biased by the selection of subjects for study.

Two possible selection biases should be noted for this study. Patients were recruited to the study if they were receiving treatment in 1996 and still receiving HIV care in 1998 or 1999 (which would tend to bias the sample towards people with a longer treatment history and a greater likelihood of resistance). Indeed, the likelihood of resistance was significantly associated with more advanced HIV disease (84% in individuals with a previous AIDS diagnosis) and lowest reported CD4 cell count (90% prevalence in individuals with lowest CD4 cell count below 50) but not current CD4 cell count. This sample is thus likely to typify the group of patients who received sequential suboptimal regimens, starting with sequential NRTI monotherapy, then adding protease inhibitors and attempting salvage with subsequent PI and NNRTI-containing regimens. This selection bias, rather than frequent changes in therapy in themselves, is a more plausible explanation for the high prevalence of drug resistance.

Also, the sample could only analyse drug resistance in patients with detectable viremia, thus excluding those receiving successful treatment who might or might not have resistance to some antiretroviral drugs. At the time of study, 37% of those sampled had undetetectable viral load. If experience at US clinical centres is similar to the experience in the UK, the proportion of patients with undetectable viral load is likely to have risen since 1998, when pessimistic assessments of the efficacy of HAART in everyday clinical practice were commonplace. A recent review of all patients receiving antiretroviral treatment at the Royal Free Hospital in London showed that close to 80% had undetetectable viral load in late 2000, compared to less than 50% in late 1997/early 1998.

The US study’s findings are in stark contrast to data presented at the recent UK Public Health Laboratory Service conference. A smaller study of patients attending South London hospitals, which recruited people from all the main communities affected by HIV, established that 13 per cent had a nucleoside analogue resistant strain of HIV. Furthermore, South London researchers found that the transmission of resistant virus was at a level significantly lower than the 20 per cent suggested in the RAND/UCSD study. A recent but poorly publicised report by researchers at St Mary’s Hospital, London, has also questioned the assumption that rates of transmitted drug resistance are on the rise. Fifteen individuals recruited to a study of treatment in primary infection were tested for drug resistance; none showed any evidence of drug resistance, in contrast to well publicised findings from the

References

Richman RD et al. The Prevalence of Antiretroviral Drug Resistance in the US. 41st ICAAC, Chicago, abstract LB-17, 2001.

D. D. Richman,