[procaare] HCC:Post Conference discussion -49

[Insight Initiative Team <insight@hdnet.org>]

HCC: Post Conference discussion - 49
- HDN Key Correspondents/Rapporteur Team,Thailand
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Long-term non-progression of HIV infection and factors affecting disease progression

The natural history of HIV progression was reviewed by Richard Marlink after which he went
on to describe the characteristics of long-term non-progressors (LTNP).

Observational cohorts in the United States show that, in the absence of ARV
(Antiretrovital) therapy, the interval between infection and the onset of AIDS is 9-10
years. High viral load and low CD4 cell count are associated with progression. This time
scale is not dissimilar in other countries, including resource-poor settings. Factors that
affect progression include age, gender, concurrent illness, nutrition and HIV-1 subtype.

Older people progress faster, probable because of a declining natural immunity. Gender
effects are not well understood but women possibly progress more rapidly at lower viral
loads compared to men.

The impact of TB (Tuberculosis) is not entirely clear but it may increase viral
replication by immune stimulation. There are also drug interactions between TB therapy and
ARV therapy. STIs (sexually transmitted illnesses) increase viral replication, both
locally, in the genital tract, and systemically, although treatment doesn't interfere with
ARV efficacy. Hepatitis G (Hep G) is a newly characterised infection of HIV positive
people in high-income countries. It is not associated with disease or liver damage but is
associated with non-progression. PLHA who are HepG negative have a 3.7 times greater
chance of HIV progression than HepG positive PLHA.

Macro- and micronutrients play an important role, as loss of body mass has an independent
adverse effect on survival. There is an association between vitamin status and disease
progression as well as mother to child transmission. Micronutrients reduce risk of death.
In the San Francisco Men's Health Survey, multivitamins were associated with a 30% reduced
risk of AIDS and a 40% reduction in CD4 decline.

Different HIV subtypes result in different rates of disease progression. Subtype B
infections cause a slower rate of disease progression than other subtypes. HIV-2 causes
slower progression and in West Africa it tends to be endemic rather than epidemic.

LTNPs are characterised by documented evidence of HIV-1 infection for longer than 10
years, during which they remain asymptomatic. They show a normal and stable immune profile
with CD4 counts greater than 500 and do not require ARV therapy. HIV replication continues
but the viral load remains low. The lymph tissue and immune function remains intact.

The mechanisms of LTNP are three-fold. There may be defects in the viral genome caused by
replication error. Such strains may have evolved into benign forms which can infect but
which do not ultimately kill their host. In the Sydney blood bank cohort where a number of
people were infected with the same contaminated blood, after16 years three showed a stable
CD4 cell count and undetectable viral load. Another three showed a slow decline in CD4
cells and a viral load between 1000 and 10,000. The infecting virus in these cases had
deletions in the nef gene.

The host immune response is likely to play an important role. HLA alleles differ between
individuals. These act as a filter to foreign proteins, binding HIV as the first step in
the host-specific immune response. Certain HLA alleles are better than others, determining
whether progression is fast of slow.

The host genotype is also important, particularly the secondary receptors which HIV uses
during infection. One such receptor is CCR5, a chemokine receptor. A 32 base pair deletion
of this gene occurs in 10-20% of Caucasians, while about one per cent is homozygous for
the mutation. Homozygous individuals are highly resistant to HIV infection, while
heterozygotes are partially resistant, showing slower progression and reduced plasma
viraemia. However, this mutation is virtually absent in Africa and Asia. On the other
hand, CCR2b is common in most ethnic groups. It is a point mutation causing resistance to
HIV.

In an observational study of 424 female sex workers in Kenya, 239 seroconverted yet 43
remained uninfected. Among the slow progressors the CCR2b mutation was three times more
frequent than normal.

Long-term non-progression is the result of individual variability both in the virus and in
the host. Thus there is the need for both virologic and immunologic monitoring to guide
prognosis and treatment decisions. Studies of LTNPs may well have important implications
for vaccine development.

HDN Key Correspondent Team
Rapporteur Team
E-mail: correspondents@hdnet.org

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The Insight Initiative Project is managed by Health & Development Networks (HDN) in
collaboration with the Thailand Red Cross Society, the World Health Organization and the
Royal Thailand Government, with financial support from AusAid and UNAIDS.

For more information about this project (the 'Insight Initiative'), visit the HDN website
at: http://www.hdnet.org

Fifth International Conference on Home and Community Care for Persons Living with HIV/AIDS
Chiang Mai, Thailand - 17-20 December 2001
Website: http://www.hiv2001.com


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