When a patient is treated with highly active anti-retroviral therapy (HAART), such as a combination of a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors, the amount of HIV detectable in their blood plasma usually drops sharply. However, this rapid rate of decline is not sustained indefinitely, but slows over time. As a result, even the most potent therapies in use do not quickly eliminate all HIV from the blood and from the body. Although HIV viral load in the blood can be driven beneath the threshold of detection, it is not known whether current therapies can ever fully eliminate the virus.

Typical Decline of Viral Levels in Plasma due to HAART.
linked from Report of the NIH Panel to Define Principles of Therapy of HIV Infection.
MMWR April 24, 1998 / 47(RR-5);1-41.

Experiments using HAART have shown that viral clearance from the blood and turnover of HIV-infected cells both occur rapidly (Wei et al., 1995; Ho et al., 1995; Perelson et al., 1996). Thus, even during the asymptomatic period of HIV infection, infection of new cells by HIV occurs at a high rate (Coffin 1995; Ho et al., 1995; Wei et al., 1995; Markowitz et al., 1995). One result of such a situation is that the use of HAART causes an initial rapid decline of viral levels in a patient's blood as HIV replication is inhibited. This decline, however, slows into a second exponential decay with a longer half-time of 1 to 4 weeks (Perelson et al., 1997). This second phase is thought to be due to the persistence of HIV in longer-lived cells such as macrophages or dendritic cells, which are not killed as quickly by HIV as are replicating CD4+ T lymphocytes.

Although HIV concentrations in blood plasma drop below the threshold of detection during the second phase of decay, replication-competent virus has been recovered from both monocytes and resting (especially memory) CD4+ T cells after long periods of treatment with HAART (Finzi et al., 1997; Wong et al., 1997; reviewed in Finzi et al., 1998). Virus thus recovered does not show resistance to the anti-viral drugs being used, suggesting that it has instead remained in latency. HIV could persist in a latent state in such cells for years even with the most potent anti-retroviral therapy. The slow activation of the virus in such cells could give rise to a third and much more long-lived phase of decay. Alternatively, an outside event such as an infection could cause reactivation and rapid replication of infected memory T lymphocytes, resulting in a more rapid rise in plasma HIV levels. Since HIV proviral DNA integrated into the chromosomes of memory T cells can persist almost indefinitely without replication, current anti-retroviral therapy alone is unlikely to completely eliminate HIV from an infected patient's body.

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