ISIS Report 05/04/07
Concentrating Exclusively on Sexual Transmission of HIV
Current medical interventions concentrate
exclusively on addressing sexual transmission of HIV while much higher rates
of non-sexual transmission are being ignored. Dr. Mae-Wan Ho
referenced version of this article is posted on ISIS members’ website. Details
An electronic version of this report,
or any other ISIS report, with full references, can be sent to you via
e-mail for a donation of £3.50. Please e-mail the title of the report to:
Alternatively, order you copy of ISIS Report Unraveling
AIDS and get a free CD of all new articles and others on AIDS from SiS archives to bring you right up to date
Anti-HIV Gels Fail
Clinical trial of a cellulose sulphate vaginal gel as a protective measure
against HIV infection has failed. The international trial organised by CONRAD,
a reproductive-health research group based in Virgina, USA>, ended
when the gel was found not only to be ineffective, but also to increase the risk of HIV infection . This
is the third large-scale clinical trial of a microbicidal
gel aimed at protecting against HIV infection and AIDS to fail so far.
in the United States,
have been heavily promoting the concept of microbicide
gels that might allow women to protect themselves from HIV infection through
Dozens of candidate micobicides are being tested in labs around the world. But
things have to change, according to the mainstream HIV research community.
Hard choices have to be made on which candidate gels should go on to phase
III trials because these trials are expensive and time-consuming . They
are also risky for trial subjects, as often turns out.
tested in phase II trials all belong to first generation products that aim
to make the vagina less hospitable to HIV, but don’t target the virus directly.
None of these has worked so far. One, Saffy gel,
simply failed to protect against infection; the other two, cellulose sulphate
and the spermicide nonoxynol-9, led to higher HIV
infection rates than controls. Meanwhile three other products are undergoing
phase III trials.
Most researchers see more
promise in new microbicides under development that
contain gel formulations of antiretroviral drugs, and many are in the pipelines.
The question now is whether all the products should automatically be pushed
into phase III trials.
It is difficult to choose the best candidates without doing
large human studies because different research groups use different preclinical
testing methods, and there is no agreement on which of these tests best predicts
how a microbicide will act in patients.
These problems beset all medical interventions aimed at prevention or therapy,
as there is no agreement over the mechanisms whereby HIV is supposed to cause
AIDS [3, 4] (On Quitting
HIV and Beyond
the HIV-Causes-AIDS Model, this series).
Each research group is investing in its own product and so
will be reluctant to step aside for others. The field may need a guiding hand
from an impartial body, which does not exist now. It has been suggested that
a working group on microbicides currently being
set up by the US National Institutes of Health’s Office of AIDS Research may
serve this role .
It is between the devil and the deep blue sea for the drug
developers. They may end up jettisoning useful products in avoiding redundancy,
or else waste a lot of financial resources and endangering trial subjects
in large clinical trials.
The question no one in the microbicide
development community is asking is why so much effort is dedicated to preventing
sexual transmission, which is disproportionate to the low probability of that
happening. The male to female HIV transmission probability varies from 0.0001
– 0.004, increasing with viral load in semen, and further increases when the
male partners are acutely infected .
The research community is
cheered by two pieces of good news despite the failure of microbicide
gels. First, drug treatment against the herpes simplex 2 virus (HSV-2) cuts
the levels of HIV RNA in the blood and genitals of women infected with both
viruses , raising hopes that it may contribute to controlling the disease.
Epidemiological evidence has suggested that infection with HSV-2 is associated
with increased genital shedding of HIV-1 RNA and HIV-transmission. Second,
the US National Institutes of Health has put a premature stop to two large
controlled trials on male circumcision in Uganda and Kenya that it funded
, because the effects of the procedure were already clear. As in a previous
study in South Africa, also terminated early, the results showed that circumcision
reduced a man’s risk of HIV infection by 50 to 60 percent. Further studies
are in progress to see if circumcision could reduce transmission of HIV to
women sexual partners.
Circumcision and non-sexual transmission
However, there is considerable doubt over whether sexual transmission of HIV
alone could account for the rapid spread of AIDS, given the acknowledged low
rate of heterosexual HIV transmission in Africa as elsewhere  (On
Quitting HIV, this series). Thus, concentrating efforts exclusively on reducing
sexual transmission at the expense of non-sexual transmission can seriously
backfire, even if we ignore the inherent racism involved in stigmatising black
Africans as sexually promiscuous and irresponsible [3, 8] (“Let
Us Live and Let Them Die”, this series).
In fact, remarkable proportions
of self-reported virgins and adolescents in eastern and southern Africa are
infected with HIV, but non-sexual routes of transmission have yet to be properly
investigated in these populations .
For example, a survey by
blood tests carried out in rural northeast Tanzania in 1995 found 4.5 percent
of self-reported virgins ages 15 to 24 were HIV positive. Similar studies
over the past 10 years found HIV prevalence in virgins between 0.1 – 6.5 percent
in Ethiopia, 6.4 percent in Kenya, 2.2 percent in Malawi, 0.7 –5.5 percent
in South Africa, 6.5 percent in Zambia and 0.5 percent in Uganda. In recent
prospective cohort studies in Malawi and Zimbabwe, the annual incidence of
HIV infection in persons reporting no sexual exposure during study intervals
was 1.2 to 2.4 percent. For decades, researchers, journalists and community
members (including children) in sub-Saharan Africa have recognized the potential
for HIV transmission through circumcision. Most circumcisions are done by
traditional practitioners outside formal healthcare settings, and typically
in large numbers in rapid succession. If someone circumcised is HIV infected,
then transmission may occur to those subsequently circumcised. Transmission
can also happen in formal healthcare settings through unhygienic practices
and blood-contaminated surgical instruments, or contaminated needles for injection.
The research team led by
Interdisciplinary Scientific Research in Seattle, Washington, in the United
States decided to conduct a study assessing the relationship between male
and female circumcision and prevalence of HIV infection among virgins and
adolescents in Kenya, Lesotho and Tanzania . The results confirmed what
they had surmised.
Circumcised male and female
virgins were substantially more likely to be HIV-infected than uncircumcised
virgins in every sample. Circumcision was common among Kenyan (75 percent)
and Tanzanian (63 percent) male virgins, but comparatively uncommon among
Kenyan females (18 percent) and Lesothoan male virgins
(21 percent). For Kenyan females, the prevalence was 3.2 percent among the
circumcised versus 1.4 percent among the uncircumcised, an odds ratio (OR)
of 2.38; for Kenyan males, 1.8 percent versus 0 percent; For Lesothoan males, 6.1 percent versus 1.9 percent, OR 3.36;
Tanzanian males: 2.9 percent versus 1.0 percent, OR 2.99.
Among adolescents, regardless
of sexual experience, circumcision was just as strongly associated with prevalent
HIV infection. However, this association changes direction dramatically with
age: from a moderate to strong positive association in adolescents (age <
18 years) to the lack of circumcision associated with HIV infection in early
adulthood, and remains so for older age groups; uncircumcised adults were
more likely to be HIV positive than circumcised adults.
Self-reported sexual experience
was independently related to HIV infection only among adolescent females in
Kenya, but not among all adolescent males in Kenya, Lesotho and Tanzania.
Circumcision does not exhaust
the non-sexual modes of HIV transmission, as some uncircumcised virgins and
adolescents were infected.
The authors warn  that
before promoting male circumcision as an
HIV preventive intervention, large and sustained investments and improvements
in the safety of care in all settings must be made. Otherwise, “such initiatives
may well facilitate transmission of HIV and other blood-borne pathogens.”
Other ISIS articles about HIV and AIDS