Page 39 - AIDSBK23C

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initial viral load difference between men and women, the rates of progression to AIDS are
similar.[200]
Persons with HIV infection can be categorized as typical progressors, rapid progressors,
nonprogressors, and elite controllers. The typical progressors average 8 to 10 years of “latent”
HIV infection before the appearance of clinical AIDS. These persons typically have a fall in
HIV viremia following acute infection. They maintain nonsyncytium-inducing HIV variants that
replicate slowly over time, until more rapidly replicating variants develop during progression to
AIDS. About 10% of HIV-infected persons rapidly progress to AIDS in only 2 to 3 years
following initial infection. These persons have a high viral load during acute HIV infection that
does not fall to the levels seen with typical progressors. They may have become infected with
more virulent strains of HIV.[192]
Genetic factors play a role in progression of HIV infection. Persons with HLA alleles
B*5701, B*5703, B*5801, B27, and B51 have better viral control and slower progression of
disease. Persons with the 801le variant of the Bw4 motif, a ligand for the killer
immunoglobulin-like receptors KIR3DS1 and KIR3DL1, which control NK cell function, also
have delayed progression to AIDS.[62] The course of HIV infection in children is often faster
than that for adults. Genetic factors known to accelerate HIV disease progression in children
include CCR5 59029A, CXCL12 3’A, CX3CR1 2491, MBL-2, and APOBEC3G.[213]
Though most HIV infections follow a standard progression, the course can be variable,
and previously asymptomatic persons may suddenly die from an overwhelming opportunistic
infection, while persons with clinically defined AIDS may survive for years. Progression to
AIDS in persons with HIV infection does not appear to be modified by gender, by race, or by
pregnancy, and the course of HIV infection is not modified by risk factor for infection.
Progression to AIDS does appear to be accelerated in persons who are older or who
smoke.[214,215,216,217] Persons who manifest symptomatic acute HIV infection have a faster
progression to clinical AIDS.[193]
Older age at seroconversion is associated with faster progression to AIDS. Elderly
persons may be at greater risk of HIV disease progression and poorer response to treatment
because: (1) they have greater thymic involution and fewer T cells, which may impair recovery
of CD4+ cell numbers with treatment; (2) they have increased T cell chemokine co-receptor
expression, which may facilitate viral entry into certain immune cells; and (3) older adults have
reduced production of IL-2 and IL-2 receptors that affects T cell function and promotes a shift
from naïve to more terminally differentiated T cells, leading to immunosenescence. Hence,
CD4+ cell reconstitution with antiretroviral therapy is significantly slower than in younger
patients, even despite a better virologic response. Side effects and toxicities of antiretroviral
drugs occur more frequently in older patients, who also have more co-morbidities and a higher
chance of pharmacological interactions with other medications they may be taking. [218]
Co-infection with the flavivirus GB virus C (GBV-C), also known as hepatitis G virus, is
associated with a slower rate of progression of HIV infection with a reduced mortality rate.
Hepatitis G virus itself is not known to be associated with any specific disease process.
However, the presence of GBV-C may inhibit HIV replication, as shown in vitro with inhibition
of HIV with coinfection of peripheral blood mononuclear cells by GBV-C. The prevalence of
GBV-C is 1.8% in blood donors, though its presence does not preclude blood donation. The
prevalence of GBV-C in HIV infected persons is about 40%.[219]
Dietary supplementation with the trace element selenium has been suggested to partially
suppress induction of HIV-1 replication in chronically infected mononuclear cells exposed to