A large clinical trial in
a Ugandan population heavily infected with the human immunodeficiency virus
(HIV) has shown that despite
reductions in sexually transmitted diseases (STDs), HIV incidence was
not reduced by STD control
measures.
The findings, by scientists
from Makerere University in Uganda, the Johns Hopkins School of Public
Health and the Columbia University
School of Public Health, contradicted those of an earlier study in
Mwanza, Tanzania, which found
that the rate of HIV infection was 38 percent lower after symptomatic
STDs were treated in clinics.
The report appears in the February 13 issue of The Lancet.
Although scientists have long
suspected an association between HIV and STDs, the connection
remains elusive. Senior author
Ronald H. Gray, professor, Population and Family Health Sciences,
Johns Hopkins School of Public
Health, said, "Given the significant impact that our mass treatment
campaign in Uganda had on
STDs, it's disappointing to find no differences in HIV incidence between
the treated and untreated
populations."
The study, which enrolled
a total of 15,127 HIV-negative subjects, was conducted in Rakai District,
a
rural region in southwestern
Uganda with a high prevalence of HIV infection (15.9 percent).
In the intervention arm of
the trial, the scientists brought an intensive STD control strategy into
participants' homes and provided
entire communities with broad-spectrum antibiotic treatment for
STDs ("mass treatment").
Control-arm subjects received mass treatment with vitamin and iron
supplements and worm medication.
Control-arm subjects whose blood tests revealed syphilis, or who
reported current STD symptoms
during the interviews, were referred during the 10-monthly visits for
free treatment provided by
the project itself.
At follow-up after mass STD
treatment, the prevalences of syphilis and trichomonas were lower in the
intervention arm compared
to the control arm. In pregnant women, trichomonas, bacterial vaginosis,
chlamydia, and gonorrhea
were all significantly reduced in those receiving the STD treatment.
Despite these significant
differences in STD rates realized between study arms, STD control had no
effect on HIV incidence,
and HIV incidence was especially high in pregnant women. This is in contrast
to the trial in Mwanza, Tanzania.
The scientists think it unlikely
that problems in study design or follow-up account for the failure to lower
HIV incidence in the Rakai
district. Treatment coverage was high. Over 80 percent of all eligible
adults
in the communities (and over
90 percent of those enrolled) accepted treatment. The researchers felt
that the fact that STD services
were offered to symptomatic control subjects at ten-month intervals
could not explain the absence
of any effect on HIV, since relatively few symptomatic persons used
these services.
Dr. Gray said, "Our data show
that STDs increase the risk of HIV infections at an individual level, but
with the high background
prevalence of HIV, most HIV transmission occurs independently of STD
transmission."
The earlier Mwanza trial involved
a population with a low-grade HIV epidemic (infection rate of 4.1
percent), whereas the epidemic
in Rakai was "mature" and generalized, with 15.9 percent of the
population HIV-positive.
First author Maria Wawer,
MD, MSH, Columbia University, and adjunct associate professor, Johns
Hopkins University, said,
"This trial raises important questions with regard to future policies on
STD
control and HIV prevention
and, thus, it is imperative to determine whether the divergent findings
between our trial and the
one in Mwanza reflect differences in the stage of the two HIV epidemics."
Wawer described ongoing collaborative
reassessment by the two research teams, and advocated new
trials in regions where HIV
incidence is high and where it is low. Nelson Sewankambo, MBChB, dean
of medicine, Makerere University,
and the Ugandan principal investigator, noted that "irrespective of the
impact on HIV, this trial
demonstrated important reductions in STDs and health benefits, particularly
for women and their children."
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