Course of HIV Infection
Among people enrolled in large epidemiologic studies in Western countries, the median time from infection with HIV to the development of AIDS-related symptoms has been approximately 10 to 12 years in the absence of antiretroviral therapy. Researchers, however, have observed a wide variation in disease progression. Approximately 10 percent of HIV-infected people in these studies have progressed to AIDS within the first 2 to 3 years following infection, while up to 5 percent of people in the studies have stable CD4+ T cell counts and no symptoms even after 12 or more years.
Factors such as age or genetic differences among individuals, the level of virulence of an individual strain of virus, and co-infection with other microbes may influence the rate and severity of disease progression. Drugs that fight the infections associated with AIDS have improved and prolonged the lives of HIV-infected people by preventing or treating conditions such as Pneumocystis carinii pneumonia, cytomegalovirus disease, and diseases caused by a number of fungi.
HIV co-receptors and disease progression
Recent research has shown that most infecting strains of HIV use a co-receptor molecule called CCR5, in addition to the CD4 molecule, to enter certain of its target cells. HIV-infected people with a specific mutation in one of their two copies of the gene for this receptor may have a slower disease course than people with two normal copies of the gene. Rare individuals with two mutant copies of the CCR5 gene appear, in most cases, to be completely protected from HIV infection. Mutations in the gene for other HIV co-receptors also may influence the rate of disease progression.
Viral burden and disease progression
Numerous studies show that people with high levels of HIV in their bloodstreams are more likely to develop new AIDS-related symptoms or die than those with lower levels of virus. For instance, in the Multicenter AIDS Cohort Study (MACS), investigators showed that the level of HIV in an untreated person's plasma 6 months to a year after infection--the so-called viral "set point"--is highly predictive of the rate of disease progression; that is, patients with high levels of virus are much more likely to get sicker faster than those with low levels of virus. The MACS and other studies have provided the rationale for providing aggressive antiretroviral therapy to HIV-infected people, as well as for routinely using newly available blood tests to measure viral load when initiating, monitoring, and modifying anti-HIV therapy.
Potent combinations of three or more anti-HIV drugs known as highly active antiretroviral therapy, or HAART, can reduce a person's "viral burden" (amount of virus in the circulating blood) to very low levels and in many cases delay the progression of HIV disease for prolonged periods. Before the introduction of HAART therapy, 85 percent of patients survived an average of 3 years following AIDS diagnosis. Today, 95 percent of patients who start therapy before they get AIDS survive on average 3 years following their first AIDS diagnosis. For those who start HAART after their first AIDS event, survival is still very high at 85 percent, averaging 3 years after AIDS diagnosis.
Antiretroviral regimens, however, have yet to completely and permanently suppress the virus in HIV-infected people. Recent studies have shown that, in addition to the latent HIV reservoir discussed above, HIV persists in a replication-competent form in resting CD4+ T cells even in people receiving aggressive antiretroviral therapy who have no readily detectable HIV in their blood. Investigators around the world are working to develop the next generation of anti-HIV drugs that can stop HIV, even in these biologic scenarios.
A treatment goal, along with reduction of viral burden, is the reconstitution of the person's immune system, which may have become sufficiently damaged that it cannot replenish itself. Various strategies for assisting the immune system in this regard are being tested in clinical trials in tandem with HAART, such as the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) trial exploring the effects of the T cell growth factor, IL-2.
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