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Further
evidence of super-infection found in African sex
workers and Swiss drug injectors
Edwin
J. Bernard
15
July 2003
http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2178
Super-infection - that is, infection with a
genetically diverse strain of HIV once chronic
infection is established - was the topic of three
presentations on the first full day of the Second
International AIDS Society Conference on HIV
Pathogenesis and Treatment in Paris.
Although none of the studies provided any
major new insights in addition to the five
published studies that provided the ‘proof of
principle’ that chronic infection with one
strain may not provide protection against
challenge from another, they did add something
further to the knowledge-base that might begin to
answer the burning question of how often
super-infection occurs and what the clinical
relevance of super-infection might be in people on
HAART.
The first study looked at the emergence of
new recombinant viruses - one that combines
genetic material from two HIV subtypes or
recombinants to become a new type of HIV - in sex
workers in Africa. Long after her death in 1998, a
long-term survivor from the Nairobi Pumwani Sex
Workers Cohort was found to have been
super-infected with subtype C virus at least ten
years after being infected with subtype A. This
subsequently became a new recombinant virus that
dominated the other strains of HIV in her body.
This woman had been a commercial sex worker for
four years prior to entering the cohort in 1985,
aged 22, saw two or three clients a day, and used
condoms only 5% of the time, despite ongoing
counselling. In 1992, she suffered from what
appeared to be seroconversion illness and her CD4
cell count plummeted from around 800 to around 200
cells/mm3.
A US lab painstakingly performed serial,
complete RNA sequence analysis on three samples of
her blood: from 1986, 1995 and 1997, and provided
strong scientific proof that indeed
super-infection had led to recombination.
Another study also in African sex workers
appeared to find a super-infection rate of 1.3%
over four years, although the methodology was not
as rigourous as the previous report.
This study, from Burkina Faso, screened 152
high risk sex workers (i.e. those that continued
to practice unprotected sex with their clients)
out of a cohort of 447 that were enrolled in a
prospective study between 1998 and 2002. Using a
procedure based on the Heteroduplex Mobility Assay
they found that four of the 147 DNA samples
analysed had dual or co-infection. Retrospective
analysis of stored blood samples found that two of
the four had been co-infected with two strains of
the virus during initial infection. Two, however,
appeared to have acquired a second strain during
the four year study.
One of the women presented with two separate
recombinant strains - CRF02-AG and CRF06-cpx - and
the other with CRF02-AG and a divergent clade A
virus. The first woman had a rise in viral load
when she was apparently super-infected, from
55,287 to 187,927 copies/ml. The second woman,
however, only had a very slight rise in viral load
when she was apparently super-infected - from
134,173 to 155,421 copies/ml. Although
super-infection was the most likely cause of these
dual infections, RNA sequence analysis was only
done on the env gene, and could have missed
co-infection at the start of the study. In the
absence of virus from the infecting partner, it is
impossible to know whether super-infection
occurred here at all.
The most intriguing piece of data came from a
Swiss study of intravenous drug users (IDUs) using
both injected cocaine and heroin, that looked at
both new and chronic infections. No
super-infection was found during follow-up of 52
newly infected IDUs over a year or longer, but
amongst the chronically infected IDUs who had an
unexpected rise (> 1 log) in viral load, three
were found to have been super-infected. Two were
long-term non-progressors with subtype B not on
HAART who subsequently experienced acute
retroviral syndrome followed by subtype CRF11
becoming the predominant virus.
A third, however, was found to have been
super-infected transiently - that is, only one of
the eight blood samples examined contained both
CRF11 and B subtypes, where previously there had
only been subtype B. Unfortunately this intriguing
data was found during a systematic search of all
stored blood samples in the cohort, and no RNA
tests could be done on stored cells. This means
that sample contamination or some other factor may
be at play. Since this person had no change in
viral load or CD4 count at the time of the
apparent transient infection, it is difficult to
gauge what factors, if any, might have helped this
person fight off super-infection. If transient
super-infection is found again, this might provide
the ‘proof of principle’ that super-infection
may not always lead to chronic infection with the
new clade of virus: an intriguing idea.
Both injecting drugs and being a sex worker
put the people reported on in this article into
the highest possible risk category of being
exposed to new HIV subtypes, which may or may not
be equivalent to gay men barebacking with multiple
partners on a weekly basis. Therefore, no
conclusions should be drawn from these studies
about the relevance to the barebacking debate
currently raging amongst gay men in the West.
References
Fang G et al.Recombination following
super-infection by HIV-1. Antiviral Therapy 8
(Suppl 1): S392 (abstract 71), 2003.
Manigart O et al.HIV-1 Superinfection in a
cohort of commercial sex workers in Burkina Faso
as assessed by a novel autologous heteroduplex
mobility procedure, ANRS 1245 Study. Antiviral
Therapy 8 (Suppl 1): S392 (abstract 72), 2003.
Yerly S et al.Prevalence of co- and
super-infection in IVDUs. Antiviral Therapy 8
(Suppl 1): S392 (abstract 73), 2003.
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