VANCOUVER, BC--The goals of cost-effective therapy for HIV infection are to suppress viral replication to a level that halts disease progression, maximizes immune recovery, and limits the emergence of drug resistance, Margaret Fischl, MD, said at the 11th International Conference on AIDS.
VANCOUVER, BC--The goals of cost-effective therapy for HIV infectionare to suppress viral replication to a level that halts diseaseprogression, maximizes immune recovery, and limits the emergenceof drug resistance, Margaret Fischl, MD, said at the 11th InternationalConference on AIDS.
New data presented at the meeting (see last month's issue, pp1, 19, 28) offer the hope that these goals are achievable. Furthermore,new regimens that produce durable responses could be cost effective.But Dr. Fischl, who conducted the clinical trial that led to theapproval of the first anti-HIV drug, AZT (Retrovir), worries thatmany patients will not be able to benefit from these treatmentadvances due to lack of funding not only for drugs but also fortests to monitor the disease.
Like other experts at this meeting, Dr. Fischl recommends usingplasma viral RNA measurements to guide initiation of therapy andto monitor response to therapy. "Early treatment is likelyto achieve a greater magnitude of viral suppression and more durableresponses," she said.
Dr. Fischl also pointed out that early therapy is likely to resultin greater immunological recovery. "Even the data from thetriple-drug therapy trials suggest that there is a limit to immunesystem recovery," she said. There is extensive trapping ofHIV in lymph nodes, progressive destruction of the lymph nodes,and subsequent spillover of virus into the plasma, she said. "Thereal reservoir of virus is in the lymph nodes."
The immunological damage caused by HIV infection is progressiveand not necessarily reversible, Dr. Fischl said. "It is certainlypossible to suppress virus to such low levels that one cannoteven culture virus," she noted, "but one does not necessarilysee immunologic recovery in the majority of patients treated."
This is a reason for starting HIV treatment early, while the immunesystem is relatively intact. Dr. Fischl recommends that combinationantiretroviral therapy be initiated if the patient's plasma viralRNA load is 5,000 to 10,000 copies/mL regardless of symptoms orCD4 lymphocyte counts.
She explained that with triple-drug therapy, most patients' viralloads can be reduced below detectable levels and maintained overtime, and that this appears to delay development of drug-resistantstrains of the virus.
"It is very difficult to culture virus from these patients,and if patients do stop therapy, the virus that returns is wild-type,not a drug-resistant mutant," she said. "What we gainfrom more intensive suppressive therapy is durability. This isthe most critical factor for cost effectiveness."
Changing HIV therapy is generally advisable if there is evidenceof treatment failure or problems with toxicity, tolerance, orcompliance, she said. The main signs of failure are an increasein viral load to within 0.3 to 0.5 logs of pretreatment levels,a decrease in CD4 lymphocyte counts or percentage, or clinicalprogression of the disease.
Dr. Fischl had a strong warning about how to change therapy. "Sequentialtherapy results in the emergence of drug resistance, potentiallymultiple drug resistance," she said. Thus, it is better totreat patients with intensive drug combinations up front.
Changing a single drug or adding a single new drug to a failingregimen is likely to select for drug resistance and is the wrongapproach. "When we switch therapy, we must consider usingtwo new drugs or stepping up to a more potent regimen," sheadvised.
However, treatment costs escalate rapidly with the move to morepotent drug combinations. Dr. Fischl calculated the cost of drugtreatment and monitoring for 2,500 patients at the Universityof Miami, where she is professor of medicine (see table).That cost escalates from $6.2 million per year to $21 millionper year as more complex anti-HIV therapy is used.
"This means that for 60% or more of my patients, I do nothave viral RNA levels, because the patients are indigent and neitherMedicaid nor Ryan White funding will pay for viral RNA measurement,"she said. "Unless we see government assistance and a decreasein price, I cannot imagine how we will move ahead in applyingthis approach."