Transmission of drug resistant HIV will not become a major public health problem, according to a US study published in this month's Nature Medicine, but could affect one in seven newly infected individuals by 2005. However, the study also found that the prevalence of drug resistant HIV is already substantial and likely to increase further in the near future.
A research team at UCLA and University College San Francisco blamed the complexities of HIV dosing requirements and poor clinical support rather than sexual transmission for the rise in drug resistance.
Using a mathematical model, the Californian research team looked at the evolution of drug-resistant strains of HIV amongst a cohort of gay men in San Francisco from 1996 -2001, and predicted the epidemic's growth from 2001 - 2005. They estimated that only three percent of HIV cases were drug resistant in San Franciso in 1997. However, by 2005, they predict that 42 percent of all HIV-positive people in the city will be drug resistant.
The definition of drug resistance used in the study was loss of virological suppression with least one three drug regimen, not resistance to all available classes of antiretrovirals. The definition of drug resistant new infection, by implication, is loss of sensitivity to at least one antiretroviral drug.
The variables in their model which in turn determined the confidence intervals of their estimates of transmitted drug resistance included:
- the rate at which drug resistance would emerge in the treated population
- the level of unprotected sex and onward HIV transmission
- the proportion of men taking antiretroviral therapy
- the current prevalence of drug resistance
- the amount of time that patients spent on ineffective treatment (allowing the development of further resistance mutations)
Their model suggests that sexual transmission did not and will not play a major role in the rise of resistant cases. The researchers found that eight percent of resistance cases were due to sexual transmission in 2000. Lead researcher Dr Sally Blower said: "In the future the vast number of new HIV infections will still be drug-sensitive. We predict that in 2005 only 16 percent of new infections will be drug resistant." The team also found that drug resistance will not contribute to the overall number of new HIV cases.
Based on their findings about the likely low rates of resistant virus transmitted, the Californian team strongly advocated the use of antiretroviral treatments in the developing world, provided that the drugs were carefully administered and coupled with efforts to reduce HIV prevalence.
In a discussion accompanying the Californian study, Dr Andrew Phillips of London's Royal Free and University College School of Medicine looked at the likely extent of transmission of resistant HIV and pointed to optimistic data from his own patients.
He revealed that of the 1,500 HIV patients treated with HAART at his clinic, 70 percent had achieved a viral load below 50 copies/mL, and that in many of the others without full suppression there had been a reduction rather than an increase in viral load. He also examined data which suggested that most people starting antiretroviral therapy and maintaining adherence, experienced profound viral suppression, indicating that there was no substantial risk of transmitted drug resistance.
Phillips pointed out that the key unknown in the San Francisco study, and for public health in general, is the transmissibility of viruses with resistance to multiple classes of drugs. If these viruses can be transmitted as easily as wild type virus, and they reach high levels in blood and semen, this increases the long-term risk of acquired drug resistance becoming frequent in the population
The California study highlights steps which doctors and HIV policy makers can take to reduce drug resistance. These include:
- Delaying drug treatment as long as possible in order to maximise the medical benefits and reduce side effects;
- The creation of clinical centres of excellence for HIV treatment in order to most effectively limit the rate of acquired drug resistance;
- The development of more effective therapies for treating patients with drug resistance; and
- A reduction in the time a patient is taking ineffective treatment.
Endorsing these recommendations Dr Phillips also suggested that novel treatment approaches, which did not rely on antiretroviral drugs which HIV could become resistant to, should also be developed saying: "I would emphasise the evaluation of new treatment strategies that are less susceptible to resistance development, such as interleukin-2."
Speaking about their recommendations a member of the American research team said: "Antiretroviral treatment will do most good when a patient is ready to follow them. But the optimum timing is unknown...We need scientifically proven guidelines to help HIV specialists work with their patients in making this complicated decision."