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 predicts disease progression
Numerous studies show that people with high levels of HIV in their bloodstream are more likely to develop new AIDS-related symptoms or die than individuals with lower levels of virus. For instance, in the Multicenter AIDS Cohort Study (MACS), investigators demonstrated that the level of HIV in an untreated individual'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" to very low levels and in many cases delay the progression of HIV disease for prolonged periods. However, antiretroviral regimens have yet to completely and permanently suppress the virus in HIV-infected people. Recent studies have shown that HIV persists in a replication-competent form in resting CD4+ T cells even in patients 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.

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