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Can HIV Be Eradicated From an Infected Patient? |
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This was the provocative title of the opening plenary session at the Fourth National Retroviral Conference in Washington in January 1997. The
plenary was delivered by Dr. David Ho, researcher at the Aaron Diamond Center in New York. He and his clinical associate, Dr. Martin Markowitz, are conducting clinical studies to address this
question. At the presentation, Dr. Ho's answer to the above question is, "We don't know". In answer to the question, "Has HIV ever been eradicated from an HIV-infected
patient," his answer was, "No". Although the CD4 lymphocyte (a type of white blood cells) is a major reservoir for the HIV virus, there are two other populations of
infected cells: 1) cells of lymphoid tissue - these are present in the tonsils, lymph nodes, gut-associated lymphoid tissue and rectum; 2) peripheral blood and tissue macrophages.
If HIV were to be eradicated, it would have to be eliminated from all three of these reservoirs. Based on the known turnover rates of these cells (half-life or t1/2), mathematical models have
been developed to estimate the time that would be required to eliminate HIV from each pool. These models suggest that using highly active anti-retroviral therapy (HAART), which causes complete
suppression of viral replication, HIV could be eradicated from: 1) the CD4 pool in 10-13 days; 2) the lymphoid tissue pool in one month; and
3) the long lived macrophage pool in approximately three years. |
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To test this hypothesis, Ho and Markowitz are studying groups of HIV-infected patients shortly after their seroconversion to HIV. All patients
are receiving treatment with AZT and 3TC and a protease inhibitor (either Indinavir, Ritonavir, Nelfinavir, or Saquinavir and Ritonavir). The status of HIV replication is being determined by
culture of the virus and PCR assays of the virus in plasma, semen, lymphoid tissue and rectal biopsies. If after three years there is no evidence of virus in any of these sites, patients will be
offered the opportunity to discontinue their anti-retroviral therapy. They will be monitored at the above sites to determine whether or not viral replication resumes.
 At this time, this approach should be considered as experimental only. Even if a
patient's plasma viral load becomes undetectable on HAART, there is no evidence that any or all of the anti-retroviral therapies can be discontinued. Nor is there any
evidence that the person is not infectious and should not continue safe sex practices. "Undetectable" means the amount of circulating virus is below the limits of the test to
detect it, usually below 500 copies of virus per mL or one fifth of a teaspoon of blood. This
is still a significant number of virus particles. This approach could fail if virus were to be sequestered
in other sites, such as in the central nervous system or other long lived cell populations that have not yet been identified.
Nonetheless, these experiments and mathematical models are intriguing and all of us await the results of these fascinating clinical trials. SW |
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