Page 41 - AIDSBK23C

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associated with rapid progression, while the alleles B57, B27, B14, and C8 are significantly
associated with non progression of AIDS.[229,230,231]
HLABw480I alleles imparting reduced risk for HIV infection have the potential to bind
NK cell inhibitory KIR (KIR3DL1). The combined expression of specific KIRs in conjunction
with their HLA class I ligands is protective in HIV-1 disease. The HIV-1 Nef protein provides
immune evasion. Nef protein triggers the accelerated endocytosis or retention of HLA class I
molecules. Nef downregulates HLA class I molecules differentially to protect infected cells
from NK cell mediated lysis. Nef mostly downregulates HLA-A to reduce recognition by
specific cytotoxic CD8 cells. Nef partially downregulates HLA-B, but spares HLA-C, both of
which are the primary ligands for inhibitory NK cell receptors.[232]
For perinatally acquired HIV infection prior to availability of antiretroviral therapy, the
time period from birth or neonatal life to the development of clinical AIDS was variable and
possibly shorter than in adults. Clinical signs associated with HIV infection appeared in over
80% of seropositive infants by the age of 5 months. Infants in whom such signs appeared at 3
months or less tended to have decreased overall survival. In the era of antiretroviral therapy,
with over 90% receiving such therapy by age 5, at least three fourths survive to age 10 and
almost half to age 16, with only one fifth developing AIDS by adolescence.[233,234]
The level of HIV-1 RNA rises rapidly in the first one to two months of life but remains
high, and declines only slowly during the first two years of life. This suggests that the neonatal
and infant immune system is not able to effectively contain HIV replication. Those babies
whose HIV-1 RNA levels are very high, not only in the first few months of life, but also in the
first two years, tend to progress to AIDS more rapidly than those with lower levels.[235]
Progression of disease appears to be faster in children whose strains of HIV-1 show
tropism for monocyte-derived macrophages and whose viral strains are rapidly replicating.[236]
Skin test anergy as demonstrated by the loss of delayed-type hypersensitivity to standard
antigens such as Candida and Trichophyton also correlates with HIV disease progression.[237]
Adolescents with HIV infection may have variable courses. Adolescents acquiring HIV
infection via sexual intercourse or injection drug use tend to have progression of their infection
similar to adults. Those with congenital AIDS or who acquired their infection from blood
products as young children will have a course different from long-term surviving adults.[210]
In summary, multiple factors influence the time course for progression to AIDS. In
general the prognosis is worse from probable accelerated progression when:

* Less favorable chemokine receptor variants are present
* Syncytia-forming (SI) variants of HIV are present
* Acute HIV infection is symptomatic
* HIV infection occurs with a drug-resistant strain
* A higher “set point” of HIV-1 RNA follows initial viremia after infection
* There is an older age at seroconversion
* The infected person is a smoker
* An opportunistic infection or neoplasm is present
* In congenital cases there are signs of infection at <3 months of age