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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. |
