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24, 2011)
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AFP
Saturday, 23 July 2011
Scientists on Wednesday
wrapped up their biggest forum in the 30-year history of AIDS, unveiling
stunning weapons to prevent the spread of HIV.
But getting these
impressive prototypes to the battlefield will take time. Not all may be
suitable. And deploying them will need massive funding at a time of AIDS
fatigue.
"Now it's up to the
donors and the policymakers, with WHO (World Health Organisation) backup, to
grab this epidemic by the horns and finally turn it around," said Eric
Goemaere of Medecins Sans Frontieres (Doctors Without Borders).
The four-day conference in
- TREATMENT AS PREVENTION:
Experts have long suspected that giving antiretroviral drugs to an HIV-infected
person not only saves them from the death sentence of AIDS.
It also ratchets down the
virus to such low levels that the patient becomes a far smaller risk for
infecting others with the human immunodeficiency virus (HIV).
This hunch has been
dazzlingly proved, at least for heterosexual intercourse, in a trial among 1,763
couples where one partner was infected with HIV while the other was HIV-free.
When the infected partner
was given an early start on HIV drugs, this slashed the risk of infecting the
other by 96 percent.
"The message going
out from scientists to politicians is that treatment as prevention works. The
problem now is financial," said
- PRE-EXPOSURE
PROPHYLAXIS: Known by its acronym as PrEP, this means giving antiretrovirals
protectively to the non-infected partner, as opposed to the infected partner.
The risk of HIV
transmission falls by up to 73 percent, according to new trials reported in
But PrEP is likely to
remain a niche rather than mainstream strategy, at least for now.
It will be more
cost-effective to treat someone who is infected - and there are ethical
questions about giving powerful drugs to people who do not have a disease.
Around 6.6 million people
in poorer countries have now grasped the daily drugs lifeline but another nine
million badly-infected people are still in need.
- CIRCUMCISION: Efforts in
New cases of HIV among men
plunged by 76 percent after a circumcision programme was launched in a South
African township. Had no circumcisions been carried out, new infections among
the overall population would have been 58 percent greater.
"This study is a
fantastic result for a simple intervention which costs 40 euros (56 dollars),
takes 20 minutes and has to be done only once in a lifetime," said David
Lewis of the University of the Witwatersrand.
- QUEST FOR CURE: This
once-unimaginable goal is now firmly on the scientific agenda.
The idea is to attack the
virus in "reservoirs", where it retreats after being suppressed by
drugs.
But identifying these
lairs, flushing out the virus and devising drugs to kill it is the big task.
Even those who believe it attainable say it would be a "functional
cure", in the same way that cancer goes into remission and its rebound
cannot be ruled out.
The boost for prevention,
said campaigners, would halt and eventually reverse the tragic rise in new
infections. In 2009, more than 33 million people were living with HIV and 2.6
million people became newly infected.
But financial help is
flagging.
In 2010, resources drifted
downwards to $15.9 billion as Western countries tightened their belts.
Just to get 15 million
badly-infected people on AIDS drugs by 2015, in line with the newly stated goal
by UN members, will require between $22 billion and $24 billion annually.
Even more will be needed
if the WHO's guidelines are revised to recommend immediate treatment rather than
wait for infection levels to reach specific thresholds.
Emerging giant economies,
led by
Peter Piot, director of
the London School of Hygiene and Tropical Medicine and former director of UNAIDS,
said the results at
But he urged pragmatism.
"Science is running
much faster now than we can implement and what we can pay for," he said.
"When you look at
longer-term perspectives, even under the best-case scenarios there will still be
one million new infections (annually) 10, 20 years from now, and also about one
million deaths, and that's a very sobering thought."
The
The IAS stages this
science conference every two years; the next will take place in
The antiviral was
manufactured in GM tobacco with a view to using the same technique to slash the
cost of other life-saving drugs in the developing world
Sarah Boseley
guardian.co.uk, Tuesday 19
July 2011
The anti-HIV drug was
produced in GM tobacco plants. Photograph: Glenn Allison/Getty
An antiviral drug
synthesised by genetically modified plants is being tested on a small number of
women in the
The drug's developers hope
it can be used to prevent HIV infection, but the real breakthrough is that the
research demonstrates it is possible for similar molecules – known as
monoclonal antibodies – to be produced relatively cheaply in plants to the
high standards needed for their use in humans.
The human trial has been
approved by the
Pharma-Planta is a project
launched seven years ago with the objective of using GM plants to slash the cost
of drugs that are hard to produce. The scientists' aim is to increase the
availability of these modern medicines – which are often highly effective –
in the poorest countries of the world.
Access to medicines in the
developing world is extremely limited. The World Health Organization estimates
that 23 million infants worldwide do not get adequate basic immunisation and 1.7
million children under five die from vaccine-preventable diseases.
"The driver was to
produce these medicines economically and at a level that would satisfy global
demand," said Professor Julian Ma from
Many medicines are
synthesised at great expense in fermentation vats containing bacteria or
mammalian cells. By contrast Pharma-Planta produced the anti-HIV monoclonal
antibody in GM tobacco plants grown in soil in greenhouses in
The researchers say there
is little risk of such GM plants spreading or contaminating other crops because
they are contained and would not be grown on anything like an agricultural
scale.
Ma said it was "a red
letter day" when they received the go-ahead from the drugs regulator.
"The approval from the MHRA for us to proceed with human trials is an
acknowledgement that monoclonal antibodies can be made in plants to the same
quality as those made using existing conventional production systems. That is
something many people did not believe could be achieved," he said.
Eleven healthy women have
volunteered to take part in the trial and two of them have been given the
antibody so far, with a third woman having been given a placebo. The trial is
designed only to demonstrate the safety of the antibody, called P2G12, at
different dosages. Much bigger trials in women at risk of contracting HIV would
be necessary to test whether it could prevent infection.
If it does prove
effective, the drug would probably have to be used in combination with other
monoclonal antibodies to minimise the chance that the virus developed
resistance, as it easily does to antivirals.
The process is between 10
and 100 times cheaper than conventional production systems, said Professor
Rainer Fischer of the Fraunhofer Institute for Molecular Biology and Applied
Ecology in
The most useful monoclonal
antibodies, such as the anti-cancer drug Herceptin, are still covered by patents
owned by major pharmaceutical companies, but once these expire the new technique
could offer a way to make cheap versions available in poor countries.
guardian.co.uk © Guardian News and Media Limited 2011
By Richard Ingham (AFP)
– 20 July, 2011
New cases of HIV among men
fell by an astonishing 76 percent after a circumcision programme was launched in
a South African township, researchers reported.
Had no circumcisions been
carried out, the tally of new infections among the overall population, men and
women combined, would have been 58 percent higher.
"This study is a
fantastic result for a simple intervention which costs 40 euros (56 dollars),
takes 20 minutes and has to be done only once in a lifetime," said David
Lewis, of the Society for Family Health in Johannesburg and the University of
the Witwatersrand, South Africa.
In 2006, trials in
Longer-term analysis found
the benefit to be even greater than thought, with a risk reduction of around 60
percent.
After pondering risks and
benefits, health watchdogs set in motion circumcision campaigns in 13
sub-Saharan countries that have been badly hit by the AIDS virus.
Advocates call it
"surgical vaccine", describing it as a cheap yet effective form of
prevention.
Sub-Saharan
The new study was
conducted between 2007 and 2010 in Orange Farm, a township of 110,000 adults,
where more than 20,000 circumcisons had been performed, especially in the 15-24
age group which is most sexually active.
Two other studies released
in
-- Circumcised men say
they experience greater sexual pleasure after surgery, a finding that should
help overcome unease about the operation.
Investigators at the
A year after the
operation, 220 of the volunteers said they were sexually active, of whom a
quarter said they used condoms.
A total of 87.7 percent
said they found it easier to reach an orgasm after being circumcised, and 92.3
percent said they experienced more sexual pleasure.
-- Newly-circumcised men
are just as likely as uncircumcised men to practice safe sex, according to
interviews conducted among 2,207 men in western
This helps ease concerns
that circumcised men are tempted to abandon condom use in the belief they are
completely shielded from HIV.
"Nothing provides
100-percent protection, not even a vaccine," she told AFP. "Let's stop
thinking that one preventative tool is enough. Circumcision has to be part of a
combined approach."
The theory behind the
benefits of circumcision is that the inner foreskin is an easy entry point for
HIV. It is rich in so-called Langerhans cells, tissue that the AIDS virus easily
latches on to and penetrates.
On the downside, male
circumcision does not reduce the risk for women who have intercourse with an
HIV-infected man, and the protective benefit does not seem to apply to
homosexual intercourse.
There is an indirect
advantage, though. The fewer men who are infected with HIV, the smaller the risk
of infection for others.
"Science is proving
that we are at the tipping point of the epidemic," said Michel Sidibe,
executive director of UNAIDS.
Scaling up voluntary
circumcision to young men in places with HIV prevalence will help reach the UN's
2015 goal of halving sexual transmission of the disease, he said.
Copyright © 2011 AFP.
Keith Alcorn
Published: 20 July 2011
A 48-week course of
antiretroviral treatment started within six months of becoming infected modestly
delays the need for lifelong treatment, reported Dr Sarah Fidler of
Patients diagnosed with
HIV infection fewer than 12 weeks after exposure showed greater benefit from the
48-week course of treatment.
During the early days of
highly active antiretroviral therapy (HAART), Dr David Ho argued that treatment
in primary infection might offer an opportunity for eradicating HIV from the
body, or at least drastically limiting the damage caused to the immune system by
HIV.
Subsequent clinical
studies showed that early treatment did not eradicate HIV, and that when
treatment was withdrawn, HIV levels swiftly rebounded to very high levels.
However, there has been
continued interest in determining whether a period of treatment soon after
infection might limit damage to the immune system and so delay the need for
later lifelong treatment.
The SPARTAC study, led by
Dr Sarah Fidler of
Begin treatment within six
months of infection and stay on treatment for 48 weeks (ART-48 arm).
Begin treatment within six
months of infection and stay on treatment for 12 weeks (ART-12 arm).
Do nothing except monitor
the CD4 count and health of the patient (standard of care, SOC arm).
The study sought to
determine whether any of the strategies reduced the risk of a CD4 decline to the
level at which a person would normally need to start treatment (< 350
cells/mm3). It also sought to examine the effectiveness and tolerability of
early treatment, the risk of drug resistance, and the rate of CD4 cell decline
in each group.
SPARTAC recruited 371
patients in the
All participants had
verified infection with HIV-1 less than six months before randomisation, defined
as less than three Western Blot bands and/or antibody-negative, PCR-positive
infection. Five patients were subsequently excluded from randomisation due
either to incorrect diagnosis or to randomisation error.
Sixty per cent of
participants were male, with a median age of 32; 56% were gay or bisexual men.
However, all South African participants were women, so in effect, 96% of
participants outside
Participants had been
infected for a median of 12 weeks at the time of randomisation (range 9 to 15
weeks), and had a median CD4 count of 556 cells/mm3 and viral load of 4.53 log
10 copies (around 30,000 copies/ml).
Participants were
randomised equally to the three study arms and followed for a median of 4.2
years. Ninety-one per cent of participants received a regimen of AZT/3TC (Combivir)
and lopinavir/ritonavir (Kaletra). Approximately 6% of participants already had
at least one drug resistance mutation at baseline, suggesting that they had been
infected with drug-resistant virus. Nucleoside analogue and non-nucleoside
reverse transcriptase inhibitor mutations were equally common (13 and 11
patients respectively).
After 4.5 years of planned
follow-up, participants in the 48-week treatment arm had a significantly reduced
risk of reaching a CD4 count below 350 or needing to start long-term treatment
(hazard ration 0.63, 95% confidence interval 0.45 – 0.90, p=0.01) when
compared to the standard-of-care arm.
Participants in the
12-week treatment arm did not show a significant reduction in their risk of CD4
decline or in their need to start long-term treatment.
However, when the time
taken to reach the primary endpoint was compared, the average delay in the
48-week treatment arm when compared to the standard of care was 65 weeks.
In other words, 48 weeks
of treatment soon after infection only delayed disease progression to the extent
that a person treated soon after infection would need four months less treatment
during their life than someone who didn’t take treatment immediately after
infection.
But a secondary post hoc
analysis showed that among people who started treatment in the 48-week arm less
than 12 weeks after becoming infected, there was a somewhat greater reduction in
the risk of disease progression (hazard ratio 0.48, 95% CI 0.30 – 0.78,
p=0.003). Calculation of the subsequent delay in starting treatment among
this group of patients was not presented.
Among those who started
treatment more than 12 weeks after infection, there appeared to be no
significant difference in the risk of disease progression between the
standard-of-care group and the 48-week treatment group.
This finding suggests that
identifying very recent infection will be critical if any benefit of an early
course of treatment is to be realised.
Short courses of treatment
may carry risks however. While early treatment could limit the size of the viral
reservoir, removal of treatment would allow the viral reservoir to swiftly
expand. Stopping treatment might also cause inflammatory changes that would
increase the risk of other serious, non-AIDS defining illnesses.
However, patients in the
48-week treatment arm of the SPARTAC study continued to have lower levels of
viral load than untreated patients in the control arm for at least 60 weeks
after stopping treatment, and their average CD4 cell count remained 135
cells/mm3 higher than the control arm after 4.5 years follow-up. But the rate of
decline of CD4 count did not differ between the treatment arms and the
standard-of-care arm.
Levels of the inflammatory
markers IL-6 and d-dimer did not go up after treatment interruption, unlike in
the SMART study of treatment interruption.
There was no difference in
the rate of serious adverse events between patients in the treatment arms and
patients in the standard of care arm.
CDC: Hepatitis C From
High-Risk Sex Is 'Widespread' in
By Daniel J. DeNoon
WebMD Health News
Reviewed by Laura J.
Martin, MD
It's spread mainly by anal
sex, often enhanced by methamphetamine, according to a report in the July 21
issue of the CDC's Morbidity and Mortality Weekly Report.
"We are having an
explosion of sexually transmitted hepatitis C," study researcher Daniel S.
Fierer, MD, of
It's no surprise to
experts who treat hepatitis C. Liver cancer and cirrhosis caused by hepatitis C
virus (HCV) already is the leading cause of death among people with HIV
infection who have access to HIV drugs. Some 30% of Americans with HIV are
co-infected with HCV.
Sexual transmission of HCV
among people without HIV is rare, notes Eugene R. Schiff, MD, director of the
Center for Liver Diseases at the
The same may be true for
men who have sex with men -- if they practice safe sex.
"Our data do not
support sexual HCV transmission between HIV-negative men," Fierer says.
"There is reasonable data that HIV-negative men are not part of this
epidemic."
But that's not the case
for HIV-positive men, notes Lynn E. Taylor, MD, of
"We have robust
evidence of increasing HCV incidence among men who have sex with men who do not
inject drugs but do engage in high-risk sexual behaviors," Taylor, who was
not involved in the Fierer study, tells WebMD. "It is the new sexually
transmitted infection in this population. I am very concerned."
Schiff notes that when
HIV-positive men get HCV, they have much higher levels of the hepatitis C virus
in their blood. Taylor and Schiff warn that hepatitis C infection progresses
quickly in people with HIV infection.
"These men are
sitting ducks for liver cancer,"
Anal Sex, Methamphetamine
Linked to HCV
Fierer and colleagues gave
detailed questionnaires to 34 HIV-positive men with new hepatitis C infections,
as well as to 67 closely matched HIV-positive men who tested negative for HCV.
In detailed questioning and interviews, the men denied any form of intravenous
drug use -- even the use of prescription testosterone.
There was "quite a
laundry list" of behaviors linked to new HCV infections. But careful
statistical analysis revealed two factors that independently raised an
HIV-positive man's risk of HCV infection:
Receptive anal intercourse
with ejaculation of the partner increased HCV risk 23-fold.
Having sex while high on
methamphetamine increased HCV risk 28.5-fold.
"This is a smoking
gun for classic sexual transmission with semen," Fierer says.
Fierer warns that while
the study implicates semen, it does not suggest that anal sex without
ejaculation is safe. It isn't. And a troubling study of outbreaks of HCV among
HIV-positive German men suggested last March that prolonged or traumatic anal
intercourse often exposes both partners to infected blood.
As for methamphetamine,
Fierer says the problem is that it removes sexual inhibitions while prolonging
the sex act.
"
Sex-Spread HCV Threatens
New HCV Treatments
New HCV treatments make it
much more likely that a person can be cured of hepatitis C. But there's a catch.
Schiff notes that a person
can be infected with hepatitis C over and over again. He's already seen patients
who seem to be getting better with treatment, and then suddenly are reinfected.
That's going to be a
problem, he says, because powerful new hepatitis C drugs have an Achilles heel
-- the virus quickly becomes resistant. If a person is reinfected with HCV
during treatment with one of the new drugs, there's a good chance the virus will
acquire resistance to all similar drugs.
"If people are
re-exposed to HCV after treatment with new antivirals, there will be resistant
virus," he predicts.
"The rates of HCV
reinfection in HIV-positive men appear to be much higher than in other
groups," she says. "So just like syphilis, they come in with hepatitis
C again and again. ... [It is] a definite reality we are going to be dealing
with drug-resistant hepatitis C by the end of this year."
Gus
Published: 19 July 2011
Results from a study of
patients starting antiretroviral therapy in rural hospitals in Cameroon (Cohen)
indicate that, while sexual activity increased after the initiation of
treatment, and unprotected sex reverted back to baseline after an initial
decline, the increase in the proportion of patients with undetectable HIV, and
therefore much less infectious, more than compensated for an increase in
otherwise risky behaviour.
The other significant
finding in the study was that patients who reported poor communication with
their healthcare staff were nearly twice as likely to report not always using
condoms while having a detectable HIV viral load, though whether this is cause
or effect cannot be shown.
The Stratall ANRS
12110/ESTHER study was a French study of 459 patients, 70 of them women,
initiating antiretroviral therapy (ART) in rural hospitals in
An important aspect of the
Stratall ANRS 12110/ESTHER trial was that sexual behaviour in participants was
assessed too. Previously, there have been relatively few studies of the effect
of initiating HIV therapy on sexual and risk behaviour of patients in developing
countries.
A paper presented at the
International AIDS Conference in
This raised concerns about
the potential for increased access to HIV treatment to restart high rates of HIV
transmission. However, this paper did not factor in the reduced infectiousness
of patients with viral suppression.
The paper presented this
year added to this data. It measured sexual behaviour only in patients where
full data from every visit both on sexual behaviour and viral load were
available, a total of 290 patients.
It found that about a
third of patients at any one time had a detectable viral load (over 40
copies/ml), with this proportion declining slightly from 37% six months after
therapy initiation to 32% two years after.
In common with the
However, due to the
effects of treatment, the proportion of patients who were defined as
‘susceptible to transmitting HIV’ (STH), in other words using condoms
inconsistently while not being virally suppressed, remained steady through the
study. While 64% of patients at baseline were in this group, only 23% were at
month six and 22% at month 24. Increased levels of sexual activity were
therefore balanced out by an increased rate of viral suppression.
The investigators found
that treatment reduced an individual’s susceptibility to transmitting HIV by
86% at month six and 89% at month 24.
Other factors related to
being ‘STH’ included having more than one sexual partner (2.4 times the risk
of being STH) and having sex more than once a week (twice the risk). Another
risk factor was ‘limited readiness of health staff to listen’. All of these
factors were statistically significant.
The last factor was
assessed using a six-point multiple-choice patient questionnaire that asked
patients to rate the quality of their relationship with healthcare providers;
those rating the poorest quality of communication with healthcare staff were 80%
more likely to report susceptibility to transmitting HIV, though from this trial
it cannot be shown whether poor communication was responsible for sexual risk or
both were symptomatic of underlying factors like depression.
References
Cohen J, Spire B
(presenter) et al. Susceptibility to transmitting HIV in ART-treated
individuals: longitudinal analysis from Stratall ANRS 12110/ESTHER trial. Sixth
International AIDS Society Conference on HIV Pathogenesis, Treatment and
Prevention,
Kouanfack C et al. HIV
Viral Load, CD4 Cell Count, and Clinical Monitoring vs Clinical Monitoring Alone
for ART in Rural Hospitals in Cameroon: Stratall ANRS 12110/ESTHER Trial, a
Randomized Non-inferiority Trial. Eighteenth Conference on Retroviruses and
Opportunistic Infections,
Marcellin F et al. Sexual
activity and risk behaviours among HIV-infected patients initiating ART in rural
district hospitals in
By: JENNIE SMITH, Internal
Medicine News Digital Network
In addition, a third,
small study suggested that measurable HIV RNA may remain in the genital tracts
of some women taking antiretroviral therapy.
Dr. Craig R. Cohen of the
While previous studies had
demonstrated that women with BV are at a higher risk of acquiring HIV, Dr. Cohen
and his colleagues showed for the first time that BV also makes them more likely
to transmit it.
HIV incidence in men whose
infected female partner had BV 3 months prior to detecting seroconversion was
2.87/100 person-years (hazard ratio, 3.09), Dr. Cohen and his colleagues found,
compared with 0.88/100 person-years in men whose female partners had normal
vaginal flora.
After they controlled for
sociodemographic factors, sexual behavior, male circumcision, sexually
transmitted infections, pregnancy and plasma HIV in female partners, Dr. Cohen
and his colleagues still found an elevated risk associated with BV, with an
adjusted hazard ratio of 2.83.
The reasons for that were
unclear, Dr. Cohen said, though he added it was unlikely that BV increases
concentrations of HIV RNA in women. However, BV might affect male partners’
susceptibility, he said.
Bacterial vaginosis
affects between 15% and 20% of women in North America and as many as half of
women in sub-Saharan
Hormonal Contraception
Upped Risk
In a second study, the use
of hormonal contraception was shown not only to increase women’s
susceptibility to acquiring HIV but also to increase their chances of
transmitting it.
Renee Heffron of the
Ms. Heffron and her
colleagues found HIV acquisition rates and transmission rates alike to be
twofold higher among women using hormonal contraception. Previous studies had
demonstrated only higher acquisition rates for women.
Among 2,476 couples in
which the women were HIV positive, acquisition rates were 2.61/100 person-years
for male partners of women using hormonal contraception, compared with 1.51 for
partners of women who did not (HR 1.97, P = .02).
Acquisition incidence was
6.61/100 person-years among women using injected or oral hormonal contraception,
compared with 3.78 for those not using the methods (HR 1.98, P = .03). Most of
the women in the study were using injectable methods. The number of women using
oral contraceptives was not high enough for the findings regarding oral
contraceptives to reach statistical significance.
Ms. Heffron and her
colleagues also found significantly more HIV-RNA in the genital tracts of
infected women on hormonal contraception, suggesting a mechanism for
transmission.
The study used data
collected between 2004 and 2010, and none of the enrolled seropositive women
were eligible for antiretroviral therapy, according to their countries’
guidelines, at the time of enrollment.
Measurable HIV RNA Remains
The results of a third
study presented at the meeting suggested that even women taking antiretroviral
therapy (ART) have measurable HIV RNA in their genital tracts.
Dr. Anandi N. Sheth of
Emory University, Atlanta, presented findings from a small study in which she
and colleagues analyzed serum and cervicovaginal lavage (CLV) samples collected
twice weekly for 3 weeks from 20 HIV-positive women in the United States.
Though all the women in
the study were taking combination antiretroviral therapy (tenofovir,
emtricitabine, atazanavir/ritonavir) for at least 6 months and had undetectable
serum viral loads at enrollment, HIV-1 RNA was detected at low levels in CLV
samples from nine women (45%).
The results suggest that
the standard combination ART "does not completely inhibit local viral
replication and may not completely block sexual transmission," Dr. Sheth
said.
Dr. Sheth said that only
one of the women in her study was using hormonal contraception; another was
using an intrauterine device. An analysis of vaginal infections among the
enrolled women during the study period was in progress, she said, and could shed
more light on the findings.
The study presenters did
not provide conflict of interest information.
Gus
Published: 19 July 2011
The study, conducted by
Anandi Sheth from the
The other interesting
aspect of this small study was that samples were taken in the women six times
over a four-week period, thus sampling HIV viral load and drug levels at all
points of the menstrual cycle.
All of the women were on a
specific antiretroviral regimen of Truvada (tenofovir/FTC) plus boosted
atazanavir (ATV/r). All but one of the women was African-American, and all but
one had become HIV-infected through sexual contact. Seventeen of the women were
sexually active, 16 with only one sexual partner, and twelve (60%) were in a
serodiscordant sexual relationship. They had been, on average, HIV positive for
nine years, on their current antiretroviral regimen for 14 months, and had an
average current CD4 of 412 cells/mm3.
Counting from the first
day of each woman’s period, the first paired blood and cervico-vaginal fluid
sample was taken about eight days later or about four days after the end of her
period. Samples were then taken every two to four days to a total of six samples
over the next four weeks, with the last sample two to three days before the
woman started her next period. Between them, the 20 women provided 102 paired
blood/genital fluid samples.
Viral load was tested with
the Roche Amplicor viral load assay, whose ‘limit of quantification’ (LOQ)
is 50 copies/ml in blood and 500 copies/ml in cervico-vaginal fluid. Viral loads
below this would conventionally be called ‘undetectable’ but in fact assays
like this can detect the presence of lower levels of virus than this, they just
cannot quantify the number of copies reliably. Both blood and cervico-vaginal
fluid were tested for the levels of both viral RNA, indicating free viral
particles, and viral DNA, indicating cell-associated virus.
In blood, cell-associated
virus was detected in all samples, simply indicating that proviral HIV was still
present in some of the women’s cells despite antiretroviral treatment. Free
viral RNA was detected at 58% of visits in 80% of patients. However RNA above
the LOQ was only found in 11% of the 102 samples and never found in 60% of
patients.
The likelihood of viral
RNA being detected (at any count) varied through the month. RNA was detected in
70% of samples provided at the first and second visit, i.e. during the
follicular phase when the woman is reaching her peak fertility. It fell to about
50% during later visits, during the luteal phase when fertility is slowly
declining.
HIV was less likely to be
detected in cervico-vaginal fluid. Cell-associated HIV DNA was detected in 36%
of samples, and was never detectable in 30% of patients. Cell-free RNA was
detected in 16% of samples and never detected in 55% of patients but no samples
of RNA were found where the viral load was above the LOQ of 500 copies/ml.
Again, viral levels were higher in the early phase of the menstrual cycle, with
RNA found in 25% of the first two samples taken but 10% at later times in the
month. However this association with the position in the menstrual cycle was not
statistically significant. The only significant predictors of detectable RNA or
DNA in cervico-vaginal fluid was the presence of white cells (leukocytes) or
blood in the fluid.
Drug levels were higher in
all samples of cervico-vaginal fluid than in blood. FTC levels were 12.2 times
higher in CVF than in blood and tenofovir levels 3.4 times higher. These levels
are roughly in line with previous studies, though somewhat higher (a consensus
of results has found that FT levels roughly four times higher in CVF than in
blood and tenofovir levels about the same in both body fluids).
The surprise was
atazanavir; the consensus of previous studies having been that atazanavir levels
are only one-sixth as high in CVF as in blood, whereas in this study they were
2.5 times higher.
Drug levels did not vary
by position in the menstrual cycle, or by whether there was detectable virus in
the sample.
This was a study of
fundamentally healthy women on a stable ARV regimen with apparently 100%
adherence. In this population, although viral detectability did vary slightly
during the menstrual cycle, 89% of the women were conventionally
‘undetectable’ for HIV in blood and 100% in cervico-vaginal fluid, and all
had high drug levels.
While this does not rule
out that women in this position may be infectious, especially if infection via
cell-associated virus is common, it provides supporting evidence that HIV
treatment may reduce women’s infectiousness.
Reference
Sheth A et al. Genital
secretions of HIV-1 infected women on effective antiretroviral therapy contain
high drug concentrations and low amounts of cell-free virus. Sixth International
AIDS Society Conference on Pathogenesis, Treatment and Prevention,