Can HIV Be Cured?
One of the most provocative and controversial questions to come out of the XI International Conference on AIDS in Vancouver is, "Can HIV Infection Be Eradicated?" Numerous presentations and much discussion outside the meeting rooms at the conference dealt with this issue. That such a radical notion could be seriously entertained at an international AIDS conference is the remarkable outgrowth of three important developments over the past two years. These advances are:
Work done by David Ho, George Shaw and others in the past two years has
greatly elucidated the dynamics of HIV replication and pathogenesis. Studies by
these investigators have demonstrated that HIV is not a "slow virus,"
as previously thought, but instead replicates at an extraordinary pace, with
billions of virions produced daily in patients with advanced disease. By
carefully evaluating patients receiving potent protease inhibitors and measuring
plasma HIV viral RNA levels, it has become clear that the half life of HIV is
extremely short (6 hours) and that as many as 10 billion new virions may be
produced daily. Moreover, with such rapid replication, mutations in viral DNA
can be expected that will confer a selective advantage to viral phenotypes that
are drug-resistant in patients on antiretroviral regimens that do not completely
halt viral replication.
The implications of these findings for clinical practice are profound. The figure shows the idealized response of plasma HIV RNA levels to several antiretroviral therapies. With AZT alone, viral load is reduced by about 0.5 log for up to six months and then returns to baseline levels. AZT therapy prolongs life for one to two years, despite a more transient effect on viral load. Combination nucleoside analogue therapy with AZT and 3TC or ddI reduces plasma HIV RNA levels by 1.5 logs, and this effect is more sustained than with AZT monotherapy. The survival advantage conferred by this treatment is superior to that of AZT. With triple combination therapy that includes a protease inhibitor, viral load can be reduced below the limits of detection. This therapy is obviously superior to treatment with one or two nucleoside analogues, but the long term implications remain unclear. Patients with sustained responses may be considered to be in remission as long as their therapy is continued, but what would happen if therapy is stopped? It is still not known if patients will experience immediate or delayed rebounds in viremia after prolonged suppression of HIV replication.
Triple combination therapy is extremely demanding for patients, requiring up to 20 pills per day. Additionally, such therapy is very costly and may be out of the reach of many patients. But in making treatment decisions with our patients, we are now faced with a troubling question: should we prescribe combination nucleoside analogue therapy that will partially suppress viral replication and prolong life, but which is ultimately doomed to fail because the virus will continue to replicate and develop resistance? Or, should we only prescribe "remission-inducing" triple combination therapy, despite its expense and complexity, in the hopes of completely shutting down HIV replication and preventing resistance from developing? There is no clear answer to this dilemma. A compromise position is to give triple combination therapy to those patients who are truly committed to taking it, and to stage treatment for other patients, using drug combinations that will not preclude more effective therapy in the future if drug resistance occurs and HIV disease progresses.
This article was provided by Johns Hopkins AIDS Service. It is a part of the publication Hopkins HIV Report.