The number of drug-resistant HIV cases has already reachedepidemic proportions in San Francisco, but transmission of drug-resistantstrains is not to blame, reports a new UCLA/UCSF study in the September issueof Nature Medicine.
"The good news is that transmission of drug-resistant HIVwill not become a major public health problem," said Dr. Sally Blower, leadauthor and UCLA professor of biomathematics and AIDS Institute member. "The badnews is that the prevalence of drug-resistant HIV is already high and willcontinue to substantially increase."
Antiretroviral drugs currently offer the best means forcontrolling the progression and symptoms of HIV disease. But combination drugtherapy, or the triple-drug "cocktail," demands a complicated dosage regimenthat is difficult to maintain and often provokes severe side effects.
According to the authors, physicians treating people withHIV may unwittingly contribute to the drug-resistant epidemic if they don'trecognize the risks associated with incorrect use of the antiretroviralmedications.
"These drugs are as dangerous as chemotherapy," warned Dr.James Kahn, UCSF associate professor of medicine and last author of the study."General practitioners should not be using them. You really need a skilled HIVspecialist to prescribe the medications and closely monitor the patient'sadherence and response to treatment."
Blower's team used a mathematical model to understand theevolution of drug-resistant HIV strains in the San Francisco gay community from1996 to 2001, and to predict the epidemic's growth from 2001 to 2005.
Their theoretical model included such variables as the number ofinfected drug-sensitive cases, the treatment rate, increases in risky sexualbehavior and the rate at which drug-resistant strains of HIV emerge duringtreatment. Blower's team modeled the evolution of 1,000 different strains ofdrug-resistant HIV.
Blower's team estimated that only 3 percent of cases in SanFrancisco were drug-resistant in 1997. However, by 2005, they predict that 42percent of all HIV cases will be drug-resistant.
Using their mathematical model, the research team determined thatthe rise in the number of drug-resistant cases was mainly due to the conversionof drug-sensitive cases to drug-resistant cases during antiretroviral therapy.Sexual transmission of drug-resistant virus did not — and will not — play amajor role in fueling the epidemic of drug resistance. Blower's team estimatedthat in 2000, only 8 percent of the new HIV drug-resistant infections were dueto transmission of resistant strains.
"In the future, the vast majority of new HIV infections will stillbe drug-sensitive," Blower said. "We predict that even in 2005, only 16 percentof new infections will be drug-resistant." The team also determined that thetransmission of drug-resistant strains has not increased, and will notincrease, the overall number of new HIV infections.
Blower and her co-authors point out that physicians andpolicymakers can take steps to minimize the prevalence and the transmission ofdrug-resistant HIV. Based upon their findings, they recommend fourepidemic-control strategies:
1. Delay drug treatment as long aspossible in order to maximize the medical benefit and reduce side effects.
2. Create clinical centers of excellencefor HIV/AIDS treatment to most effectively limit the rate of acquired drugresistance.
3. Develop therapies more effective fortreating patients with drug-resistant viral strains.
4. Reduce the amount of time adrug-resistant patient is on ineffective therapy.
Despite the predicted high prevalence of drug resistance,the authors emphasize that people shouldn't consider their findings an argumentagainst antiretroviral drug treatment in San Francisco or in developingcountries.
"We have shown that the surging number of drug-sensitive HIV cases— which are due to increases in high-risk sex — pose a substantially greaterpublic health problem than the transmission of drug-resistant virus," Blowersaid.
Based on their findings in San Francisco, the researchersstrongly advocate the expanded use of antiretroviral drugs in developingcountries. However, they caution that these therapies must be administeredcarefully and coupled with effective efforts to reduce the risk of infection.
"Antiretroviral treatment will do the most goodwhen the patient is ready to follow it. But the optimal timing is a realunknown," Kahn said. "We need scientifically proven guidelines to help HIVspecialists work with their patients in making this complicated decision."
The UCLA/UCSF study is discussed in anaccompanying News & Views in the same issue of Nature Medicine entitled,"Will the drugs still work? Transmission of resistant HIV," by Andrew Philipsof the Royal Free and University College Medical School, London.
The National Institute of Allergy and Infectious Diseases, a branchof the National Institutes of Health, and the University of California AIDSResearch Program funded the study. Nick Aschenbach and Hayley Gershengorn,research assistants in Blower's lab, are co-authors of the study.