SAATHII Electronic Newsletter

HIV/AIDS Updates

SOURCE: www.aidsmapnews@...,
http://www.kaisernetwork.org/dailyreports/hiv, nataphcvhiv@...

Posted on: 02.04.2008

COMPILED BY: Manish Soosai and Dr. Sai Subhasree Raghavan, SAATHII.

Note: this compilation contains news items about HIV/AIDS
published in the International Electronic Newsletters. Articles in this
and previous newsletters may also be accessed at
http://www.saathii.org/orc/elibrary

IN THIS EDITION…

1.Researchers Discover Genetic Circuit in HIV That Controls Whether Virus
Activates, Remains Dormant

2.Male Circumcision Does Not Offer Protection Against Some STIs

3.Anti-inflammatory drug could reduce heart disease risk in patients with HIV

4.Tenofovir has good concentrations and anti-HIV effect in semen

5.SSRI treatment improves adherence and outcomes in depressed HIV-positive
patients

6.Genetic Variations Might Be Causing Mutations to HIV, Making It Less Potent

7.Cotrimoxazole for children with HIV highly cost-effective

8.Discordant response to anti-HIV treatment increases risk of illness or death

9.Study confirms cost-effectiveness of STI management in HIV control

10.Researchers discover why salmonella is so dangerous for people with HIV
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1. Researchers Discover Genetic Circuit in HIV That Controls Whether Virus
Activates, Remains Dormant

http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=51040

Researchers from the University of California-San Diego and Oak Ridge National
Laboratory have discovered the genetic circuit in HIV that controls whether the
virus is activated or remains dormant, according to a study published in the
March 16 issue of the journal Nature Genetics, Xinhuanet reports (Xinhuanet,
3/18).For the study, Leor Weinberger, professor of chemistry and biochemistry at
UCSD, and colleagues examined HIV's genetic master circuit, called the Tat
circuit, by building upon previous research by Weinberger, IANS/Sify reports.
The previous research found that the circuit is driven by "cellular noise," or
random events, which activate the circuit for a limited amount of time before it
shuts off, according to IANS/Sify (IANS/Sify, 3/17). In the current study, the
researchers used the noise in the Tat circuit to measure how long HIV remained
activated in cells. The researchers found that the time the virus spent in the
active state determined
if it destroyed a cell or not. The researchers then increased the levels of the
cellular gene SirT1 -- a gene associated with aging -- to reduce the lifespan of
HIV, which forced cells infected with the virus to become dormant, the Press
Trust of India reports (Shourie, Press Trust of India, 3/17).According to
Weinberger, the findings are significant because "many researchers are
interested in determining which cellular processes generate biological noise."
He added that the researchers "asked if the cellular noise could tell us
anything about HIV and the cell -- and it did. What it told us is how a
developmental decision is made by HIV." Weinberger said the findings do not
indicate "how developmental decisions are made at the single-cell level" and
"whether noise can drive this decision." He added, "Surprisingly, viruses appear
to be good models for understanding this type of cellular decision-making."
Weinberger and colleagues are conducting further
studies on the feasibility of using this approach for HIV treatment, Xinhuanet
reports (Xinhuanet, 3/18). An abstract of the study is available online.
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2. Male Circumcision Does Not Offer Protection Against Some STIs, Study Finds

http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=51064

Although male circumcision has been found to offer men some protection against
HIV, the procedure does not protect against other common sexually transmitted
infections -- such as chlamydia, genital warts and genital herpes -- according
to a study published in the March issue of the Journal of Pediatrics, Reuters
Health reports. For the study, Nigel Dickson of the University of Otago Dunedin
School of Medicine and colleagues examined 499 men born in 1972 and 1973. About
40% of the participants had been circumcised in early childhood, Reuters Health
reports. The study found that up to age 32, there were no statistically
significant differences in rates of STIs other than HIV between the two groups,
with 23.4% and 23.5% of the circumcised and uncircumcised men, respectively,
reporting having had any type of STI. The most common STIs reported were genital
warts, chlamydia and genital herpes, the study found.According to the
researchers, there is "compelling
evidence" that male circumcision offers men a level of protection against HIV,
but it is unclear whether the procedure lowers the risk of other types of STIs.
The researchers noted that although another recent study found that circumcision
decreased the rate of STIs among men up to age 25 by 50%, the study was done in
a smaller group of participants with a lower rate of STIs than that reported in
the current study. In addition, fewer men in that study had been circumcised,
according to the researchers. "Although the reason for the different findings in
the two cohorts is unclear, when our findings are considered in the context of
other recent population-based studies in developed countries, it appears
unlikely that circumcision has a major protective effect against common [STIs]
in these populations, although a smaller effect cannot be ruled out," the
researchers concluded (Reuters Health, 3/19). An abstract of the study is
available online.
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3. Anti-inflammatory drug could reduce heart disease risk in patients with HIV
http://www.aidsmap.com/en/news/D169A39E-AF7A-4B05-852A-3F06290B0EFF.asp

Michael Carter, Friday, March 14, 2008

Treatment with the anti-inflammatory drug salsalate improves the function of key
cells in the blood vessels of HIV-positive individuals who aren’t taking
antiretroviral therapy, according to a study published in the March 12th edition
of AIDS. But treatment with salsalate was associated with abnormal liver
function in a large proportion of patients. The investigators call for further
studies using lower doses of salsalate or other anti-inflammatory drugs.

There is concern that HIV-positive patients may have an increased risk of heart
disease. Some (but by no means all) studies have suggested that antiretroviral
therapy can increase the risk of heart disease for some patients.

Furthermore, the SMART treatment interruption study was stopped early when it
was shown that patients who interrupted treatment were, amongst other things,
more likely to develop heart disease than patients who took treatment all the
time. It has also been suggested that inflammation caused by HIV can increase
the risk of heart disease, although the reasons for this are not yet fully
understood.

One possible reason is that HIV can cause long-term inflammation. This
inflammation can mean that the cells lining the blood vessels, endothelial
cells, don’t work properly, a condition called endothelial dysfunction. This
can make it harder for blood to flow through the veins, and endothelial
dysfunction often develops before hardening of the arteries, or atherosclerosis.

US investigators speculated that treatment with the anti-inflammatory drug
salsalate would, by reducing inflammation throughout the body, improve
endothelial function.

There is no information on the safety of salsalate in HIV-positive patients, so
the researchers designed a small pilot study to see if the drug is safe. They
hoped that this information would be of use in any later, larger studies.

A total of eleven patients were recruited to the study. All were 18 years or
older. None of the patients were taking antiretroviral therapy and all had a CD4
cell count above 350 cells/mm3, the current threshold for starting anti-HIV
therapy.

Treatment with an oral salsalate dose of 1500mg twice-daily was provided for
eight weeks.

Tests to assess the flow of blood through the veins were performed on entry to
the study and then after four and eights weeks of treatment. Other tests looking
at levels of inflammation were also performed, as were screens to determine the
safety of treatment.

Flow-mediated dilation, the diameter of blood vessels when blood flows through
them, was low in all the patients at 2.7%, showing the presence of endothelial
dysfunction.

Four weeks of treatment with salsalate lead to a slight improvement in flow
mediated dilation in nine patients. This improvement was significant at the end
of the eight week study in the eight patients who completed the trial (median
increase, 4.2%, p = 0.02).

Other tests showed that were was no change in HIV viral load or in any other
markers of inflammation.

But the investigators were concerned to see that one patient experienced a
severe deterioration in liver function after two weeks of treatment, as did a
second patient after three weeks. Both patients stopped salsalate treatment and
withdrew from the study, with liver function returning to normal. Two other
patients had mild elevations in their liver enzymes and reduced their dose of
salsalate to 750mg twice-daily.

“Our data provide support for the concept that HIV, via systemic inflammation,
may promote atherosclerosis independent of combination antiretroviral
therapy”, write the investigators.

The rate of liver toxicity seen in the study was higher than expected, and the
investigators think that this is may be because of the inflammation that HIV can
cause.

“This pilot study demonstrates that anti-inflammatory therapy has the
potential to improve endothelial dysfunction in HIV-infected subjects not
receiving combination antiretroviral therapy”, conclude the investigators,
adding, “further studies should evaluate either lower doses of salsalate or
other anti-inflammatory agents with the goal of reducing cardiovascular events
in this population.”

Reference

Gupta SK et al. Improvement in HIV-related endothelial dysfunction using the
anti-inflammatory agent salsalate: a pilot study. AIDS 22: 653 – 654, 2008.
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4. Tenofovir has good concentrations and anti-HIV effect in semen

http://www.aidsmap.com/en/news/8EBAE7EC-A258-4A71-8514-54C4484A48E2.asp

Michael Carter, Monday, March 17, 2008

Tenofovir (Viread) rapidly suppresses HIV in semen and could help prevent the
sexual transmission of HIV, according to a small study published in the March
1st edition of the Journal of Acquired Immune Deficiency Sydromes. Levels of
tenofovir in semen were several times those seen in blood.

The risk of the sexual transmission of HIV is associated with the level of HIV
in the male and female genital tract. There is also some evidence that the male
genital tract acts as a “reservoir” for HIV, with the virus reproducing
there independently to the blood . Therefore, anti-HIV treatment that gets into
the genital tract could reduce HIV viral load and the risk of transmission, and
also the help reduce the risk of drug drug-resistant HIV developing.

Tenofovir is a powerful anti-HIV drug that belongs to the nucleotide reverse
transcriptase inhibitor family of antiretrovirals. It is contained in the
combination pills Truvada and Atripla and is a popular choice for first-line
antiretroviral therapy.

Laboratory studies involving monkeys have shown that tenofovir works against HIV
in the female genital tract and studies are currently underway to assess its
safety and effectiveness as a microbicide. The drug is used in post-exposure
prophylaxis (PEP) regimes and is being invested as pre-exposure prophylaxis
(PREP).

But little is known about the ability of tenofovir to get into the male genital
tract and to reduce viral load in semen.

Investigators at the University of North Carolina therefore designed a small
study involving nine HIV-positive men to measure concentrations of tenofovir in
the genital tract after the first and then multiple doses, and to see the effect
of the drug on viral load in both the blood and semen.

The study was conducted between 2003 and 2005. All the men had an HIV viral load
above 200 copies/ml on entry to the study. Eight of the men were not taking any
antiretroviral therapy. These patients were provided with 14 days of tenofovir
monotherapy at a standard daily dose of 300mg and then started multi-drug
anti-HIV treatment. The remaining patient added tenofovir to an antiretroviral
regimen that was failing to suppress his viral load. The study lasted 28 days.
Paired blood and semen samples were obtained from the men throughout the study.

After the first dose, concentrations of tenofovir in semen were 4.4-fold higher
than those in blood. After subsequent doses tenofovir maintained a higher
concentration in semen than in plasma, this concentration being 5.1-fold higher
at the end of the study.

But tenofovir could only be detected in the cells of three of these men. In
these three patients intracellular concentrations of tenofovir in the genital
tract were 9-fold higher than those in peripheral blood mononuclear cells after
the first dose of tenofovir and 17.5-fold higher after the seventh dose.

After 14 days of treatment, median viral load was 866 copies/ml in blood and
below 400 copies/ml (the lower limit of detection) in semen in the eight men who
received monotherapy. The magnitude of the fall in viral load in blood and semen
from baseline was comparable at approximately 1 log10 copies/ml.

The single patient who added tenofovir to his existing antiretroviral regimen
had an undetectable viral load in his semen for the duration of the study. The
viral load in his blood was 366 copies/ml on entry to the study and 709
copies/ml at the end of the study.

Resistance tests were conducted in the four patients who had a tenofovir viral
load above 1000 copies/ml in blood (four patients) or semen (one patient). No
patient developed the K65R mutation that confers resistance to tenofovir.

On the basis of these findings the investigators conclude that tenofovir may
have the potential “to reduce the sexual transmission of HIV.”

Reference

Vourvahis M et al. The pharmacokinetics and viral activity of tenofovir in the
male genital tract. J Acquir Immune Defic Syndr 47: 329 – 333, 2008.
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5. SSRI treatment improves adherence and outcomes in depressed HIV-positive
patients

http://www.aidsmap.com/en/news/7E152406-9F69-4AF2-AF1A-D614DD9FC1D0.asp
Michael Carter, Wednesday, March 19, 2008

HIV-positive patients with depression have poorer adherence to antiretroviral
therapy than non-depressed individuals, according to a US study published in the
March 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The
study also showed that depressed patients were less likely to achieve good
suppression of HIV with anti-HIV treatment than non-depressed patients.

But the study also showed that treatment with SSRI (selective serotonin reuptake
inhibitor) antidepressants was of value, with their use improving adherence to
treatment. Furthermore, SSRI treatment boosted the chances of depressed patients
achieving good viral suppression and increases in CD4 cell count.

SSRI treatment for depressed individuals has recently been the subject of
controversy, with suggestions that the drugs are only of value for patients with
severe depression. The results of this study suggest that therapy with SSRIs may
also be of value to the estimated 30% of HIV-positive patients diagnosed with
depression.

Adherence is the single most important factor under a patient's control
influencing the success of their antiretroviral therapy. Mental health problems
can have a negative impact on adherence, and depression is considered to be a
risk factor for non-adherence to anti-HIV treatment.

Depression is widespread amongst patients with HIV and has also been shown to be
associated with earlier death.

Investigators wanted to see if treatment with SSRI antidepressants improved
adherence to antiretroviral therapy amongst depressed patients. They also wanted
to see if such treatment for depression had an effect on viral load and CD4 cell
counts.

They therefore performed a retrospective study involving patients who received
their HIV care from Kaiser Permanente and Group Health Cooperative facilities
between 2000 and 2003.

A total of 3359 patients were included in the investigators’ analysis. This
included 1398 patients (42%) who had a diagnosis of depression in their medical
records, and 508 of these patients had received treatment with an antidepressant
from the SSRI class.

Over twelve months, mean adherence for all patients was 81%. For non-depressed
patients mean adherence was 83%, compared to 79% for depressed patients who did
not receive treatment with an SSRI, a significant difference (p = 0.01).

But mean adherence was 81% for patients treated with an SSRI (comparable to that
seen in non-depressed individuals), and was 85% amongst those patients who were
also adherent to their SSRI treatment – significantly better than the mean
adherence seen amongst non-depressed patients (p = 0.01).

The investigators then looked at the impact of depression and SSRI treatment in
viral load and CD4 cell count.

They found that depressed patients without SSRI treatment were significantly
less likely to achieve an HIV viral load below 500 copies/ml after a year of
anti-HIV treatment than non-depressed patients (p = 0.02). However, depressed
patients who received SSRI therapy were just as likely to achieve this
virological outcome as non-depressed patients.

Mean CD4 cell count increased by 152 cells/mm3 for the entire cohort. Overall
there was no difference in CD4 cell increases between depressed and
non-depressed patients. But the investigators found that depressed patients who
had good adherence to SSRI therapy not only gained more cells than other
depressed patients, but 19 cells/mm3 more than patients who were not depressed,
a significant difference (p = 0.01).

Finally the investigators looked at the effect of SSRI therapy on patients who
changed antiretroviral therapy. None of these patients had taken SSRI therapy
before changing therapy. Taking SSRI treatment with a new antiretroviral regimen
was not associated with better adherence, or in better virological control or
improved CD4 cell gains.

“We demonstrate that a diagnosis of depression is associated with
significantly reduced adherence to HAART regimens”, comment the investigators,
adding that “depression was associated with significantly decreased odds of
achieving HIV RNA levels below 500 copies/ml.”

The investigators believe that factors other than adherence may affect viral
load in patients with depression and suggest “depression itself may affect
viral control. Viral control was improved among patients prescribed SSRI
medication, even more so if SSRI adherence is considered.”

They also draw attention to the superior gains in CD4 cell count seen in the
patients with good adherence to SSRIs. They write, “these results are
particularly important, because depression has been associated with earlier
mortality in HIV-positive patients.”

“Our results have clinical implications”, add the investigators. They
recommend that patients should be screened for depression, and that depressed
patients should be offered SSRI treatment, “because compliant SSRI medication
use was associated with improved HAART adherence and HIV laboratory
parameters.”

Reference

Horberg MA et al. Effects of depression and selective serotonin reuptake
inhibitor use on adherence to antiretroviral therapy and on clinical outcomes in
HIV-infected patients. J Acquir Immune Defic Syndr 47: 384 – 390, 2008.
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6. Genetic Variations Might Be Causing Mutations to HIV, Making It Less Potent,
Study Says

http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=51110

Genetic variations that might help people newly diagnosed with HIV control their
viral loads also could be causing a mutation in the virus that makes it less
potent, according to a study published Friday in PLoS Pathogens, Reuters
reports. Some people have versions of an immune system gene, called HLA, that
are "known to force HIV to tolerate mutations that damage its ability to
reproduce," according to Carolyn Williamson of the Centre for the AIDS Programme
of Research in South Africa and colleagues. The weakened virus also means lower
viral loads and slower disease progression in people with beneficial versions of
HLA, according to Reuters. The researchers found that the weakened virus might
be transmitted to and act in the same way in other people, even if they do not
have the HLA variation, Williamson said. The researchers followed 21 women in
South Africa who recently contracted a weakened strain of HIV. The women did not
have the beneficial HLA
variation, according to Reuters. The researchers followed the women for between
one to three years, Reuters reports. The researchers found the women had much
lower viral loads, compared with people carrying a strain of HIV that had not
mutated to a weakened state. The researchers also found that while the women's
viral loads decreased, their CD4+ T cell counts increased. "It is pretty well
established if you have certain HLA genes, you are better off," Williamson said,
adding, "It is very likely that the virus in the people who did not have the HLA
gene came from
individuals who did."According to Williamson, the "significant difference to
other studies is that this is showing the actual benefit is due to the genetic
composition of the virus." She added that the findings show "a survival
advantage with a virus containing specific genetic signatures associated with
lower replication."The researchers have not studied the women to see how much
slower they progress to AIDS but noted the findings could help researchers
looking for an effective vaccine through an improved understanding of why some
people living with the virus survive longer (Kahn, Reuters,3/20). The study is
available online.
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7. Cotrimoxazole for children with HIV highly cost-effective
http://www.aidsmap.com/en/news/79DBACD7-D9FA-4575-8D08-513029359282.asp
Keith Alcorn, Monday, March 31, 2008
Cotrimoxazole prophylaxis for children with HIV in Zambia is highly
cost-effective, according to an analysis of data from the CHAP trial, published
this month in AIDS.

The Children with HIV Antibiotic Prophylaxis trial, which reported its main
results in 2004, demonstrated that cotrimoxazole prophylaxis in children aged
one to 14 years reduced the risk of death by 43%, and also reduced
hospitalisation.

According to later analysis of the trial results, cotrimoxazole reduced the risk
of death and serious illness primarily by reducing the incidence of serious
bacterial lung infections, rather than by reducing the incidence of PCP
pneumonia (only one case of PCP was seen in the CHAP study).

Despite these findings, countries in sub-Saharan Africa have been slow to
implement cotrimoxazole prophylaxis for children. UNAIDS estimates that up to
four million children with HIV who could benefit from cotrimoxazole prophylaxis
do not receive it, either because they are undiagnosed or due to lack of access.

A major reason for lack of access, say the authors of the cost-effectiveness
review, is the competition for resources among many priorities.

In order to provide evidence that might encourage allocation of resources to
paediatric treatment, the authors used data from the CHAP study on the incidence
of illness, death and hospitalisation, together with CD4 cell percentage
measurements, to calculate the cost-effectiveness of cotrimoxazole treatment
compared with no prophylaxis.

Cost-effectiveness was measured in terms of quality-adjusted life years and
disability-adjusted life years saved by giving cotrimoxazole prophylaxis.

The incremental cost-effectiveness of an intervention represents the extra cost
of a health intervention compared with doing nothing, or continuing existing
practice, and this amount will vary from one setting to another according to
health system costs.

Cost-effectiveness is generally assumed if an intervention costs less than a
country’s GDP per life year saved.

In the case of Zambia, cotrimoxazole had an incremental cost-effectiveness ratio
of $72 per life-year saved, compared with a national GDP of $1019 per capita,
when delivered through hospital outpatient clinics.

However, it became even more cost-effective when delivered through primary
health care - $4 per life year saved – and the authors say that they found the
cost-effectiveness of cotrimoxazole to be highly sensitive to the cost of
outpatient visits, arguing for the deregulation of cotrimoxazole prescribing to
nurses and other cadres of health care workers.

In comparison one study has found that adult antiretroviral therapy (using data
derived from the Khayelitsha clinic cohort in South Africa in 2006) has an
incremental cost-effectiveness ratio of $984 per life-year saved, making it
cost-effective in the South African setting. No estimate of the
cost-effectiveness of antiretroviral therapy in children is available.

Reference

Ryan M et al. The cost-effectiveness of cotrimoxazole prophylaxis in
HIV-infected children in Zambia. AIDS 22: 749-757, 2008.
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8. Discordant' response to anti-HIV treatment increases risk of illness or death
http://www.aidsmap.com/en/news/A3892C1B-7660-4D6A-8D87-1429FC064C6B.asp
Michael Carter, Friday, March 28, 2008
HIV-positive patients who do not experience both an increase in their CD4 cell
count and a fall in their viral load to undetectable levels soon after starting
antiretroviral therapy are more likely to develop an AIDS-defining illness or
die than patients who have increases in their CD4 cell count and an undetectable
viral load, according to a US study published in the April 15th edition of the
Journal of Acquired Immune Deficiency Syndromes.

Antiretroviral therapy can mean a longer and healthier life for HIV-positive
individuals. The aim of anti-HIV treatment is to suppress viral load to
undetectable levels (the lower limit of detection is 50 copies/ml in the tests
used in most clinics), and this allows an increase in CD4 cell count. It is
possible to predict the long-term benefits of antiretroviral therapy by looking
at viral load and CD4 cell count three to nine months after anti-HIV therapy has
been started.

About 20% - 40% of patients starting antiretroviral therapy have what is called
a “discordant response.” This means that their viral load falls to
undetectable levels, but their CD4 cell count does not increase, or, their CD4
cell count increases but their viral load fails to become undetectable.

Investigators in the US wanted to see if patients who had a discordant response
to treatment had an increased risk of experiencing HIV disease progression or
death. They also wanted to see if any particular groups of patients had an
increased risk of experiencing a discordant treatment response.

Doctors at the University of Alabama therefore looked at the medical records of
404 patients starting antiretroviral therapy for the first time since 1995. The
majority of these patients (51%) were non-white, 76% were men, 51% became
infected with HIV through sex with another man, and the mean age was 38 years.

When anti-HIV treatment was initiated, mean CD4 cell count was 213 cells/mm3 and
mean viral load was 250,000 copies/ml.

Approximately six months after starting anti-HIV treatment, 71% of patients had
experienced both a fall in their viral load to undetectable levels and an
increase in their CD4 cell count. In all, 5% of patients had neither an
undetectable viral load nor an increase in their CD4 cell count. A significant
proportion of patients had a discordant response, with 9% achieving an
undetectable viral load but no increase in their CD4 cell count and 16% an
increase in their CD4 cell count without an undetectable viral load.

During a median of 38 months of follow-up, 35 (9%) patients developed a new
AIDS-defining opportunistic infection and 25 (6%) died.

Unsurprisingly, statistical analysis showed that patients who had both a fall in
their viral load to undetectable levels and an increase in their CD4 cell count
had the lowest risk of disease progression, and that patients with neither of
these outcomes had the highest risk of a new opportunistic infection or death.

Further analysis showed that compared to patients with both an immunological and
virological response to treatment, patients with a discordant response to
treatment were 2.24 times more likely to experience disease progression (95% CI:
1.3 – 4.), and patients with neither an undetectable viral load nor an
increase in their CD4 cell count were 4.83 times more likely to develop a new
opportunistic infection or die (95% CI: 2.1 – 11.1).

Non-white race was the only patient characteristic with a significant
association with either no response to treatment (odds ratio = 6.5; 95% CI: 1.7
– 24.7) or a discordant response to treatment (failure to suppress viral load,
but increase in CD4 cell count, OR = 2.83; 95% CI: 1.5 – 5.5).

The investigators call for further research to identify why non-whites are less
likely to have an early response to antiretroviral therapy.

Reference

Tan R et al. Clinical outcome of HIV-infected antiretroviral-naïve patients
with discordant immunologic and virologic responses to highly active
antiretroviral therapy. J Acquir Immune Defic Syndr 47: 553 – 558, 2008.
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9. Study confirms cost-effectiveness of STI management in HIV control
http://www.aidsmap.com/en/news/B72FE59E-B79C-44E9-90DA-F49E62B38345.asp Kelly
Morris, Wednesday, March 26, 2008
In sub-Saharan Africa, the management of sexually transmitted infections (STIs)
remains a cost-effective strategy for controlling HIV in a number of different
scenarios, report an international team of researchers in the March 1st edition
of the Journal of Acquired Immune Deficiency Syndromes. Even in mature epidemics
with substantial condom use, their study found that more than half of new HIV
infections may be attributable to STIs.

Previous research conducted in Mwanza, Tanzania, of syndromic management of STIs
- treatment of presenting symptoms according to guidelines - showed that STI
treatment was cost-effective in reducing HIV incidence. However, later African
trials failed to find a reduction in HIV incidence with such management.

Investigators from the London School of Hygiene and Tropical Medicine suggested
that “this may be because behavior change and the later stage of the HIV
epidemic reduce the role of curable STIs in HIV transmission”. These findings
have led some policy makers to question the role of STI treatment in tackling
generalised epidemics of HIV in Africa.

A multi-centre study published in 2001 identified two East African cities with
high HIV prevalence and two West African cities with relatively low HIV
prevalence. Notably, the prevalence of male circumcision was lower and the
prevalence of herpes simplex virus-2 (HSV-2) was higher in the cities with
higher HIV prevalence. However, sexual risk behaviours were not consistently
higher in the West African cities, and modelling confirmed that the different
prevalence rates were largely explainable by biologic factors, mainly male
circumcision.

Investigators extended this work to evaluate the proportion of new HIV
infections attributable to STIs (population-attributable fraction) and the
impact of syndromic STI treatment.

The investigators used a known statistical model to simulate the natural history
and transmission of HIV and STIs between individuals. The simulation has
previously been used and found to agree with data from large, randomised trials.

Data from the Tanzanian trial were used as a basis to simulate the effect and
costs of STI treatment. Factors such as condom usage and STI treatment effects
were then varied to model different scenarios. The potential impact on HIV
prevalence was modelled from the presumed start of the HIV epidemic in each city
for 16-20 years, until 2000-01.

The simulated impact of STIs on HIV incidence was 80-87% during years four to
five of the epidemics, and remained high at 50-70% in years 16-17.

While the impact of curable STIs fell over time, the impact of HSV-2 rose, which
explains why the effect of STI treatment decreased over time.

However, the authors write that “the absolute impact of syndromic management
remains high in generalized epidemics, and it remained cost-saving in three of
the four populations in which the cost per HIV infection averted ranged between
US $321 and $1665”.

These figures are lower than the estimated lifetime cost of treating HIV
infection in these areas, at around $3500. In the fourth city, STI treatment
might not be cost-effective due to the relatively low prevalences of curable
STIs and the low incidence of HIV.

The authors further suggest that in cities with low rates of male circumcision
and relatively high-risk sexual behaviours, STI treatment may be cost-effective
even with condom usage as high as 30-37.5% of casual contacts and 45% of sex
worker contacts or higher. STI treatment is virtually always cost-effective if
HIV prevalence was above 5.5%, they report.

However, in other scenarios, STI management has “important collateral public
health benefits, which effectively protects patients with STIs from the enhanced
risk of HIV acquisition and transmission,” the team concludes.

Reference

White RG et al. Treating curable sexually transmitted infections to prevent HIV
in Africa: still an effective control strategy?. J Acquir Immune Defic Syndr 47:
346 – 353, 2008.
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10. Researchers discover why salmonella is so dangerous for people with HIV
http://www.aidsmap.com/en/news/0EE5D496-1E08-4073-97CA-DABCAD039271.asp
Adam Legge, Tuesday, March 25, 2008
Researchers believe they have discovered why people with HIV are far more likely
to die of Salmonella food poisoning, compared to those without HIV who tend to
suffer a bout of diarrhoea.

Their study, published online in Nature Medicine, suggests the virus disrupts
the normal gastrointestinal lining, allowing the Salmonella bacteria to cross
into the bloodstream causing death.

The rise in numbers of people with AIDS in sub-Saharan Africa has been
associated with a big increase in cases of what is termed nontyphoidal
Salmonella serotype (NTS) infections.

NTS are a common cause of food-borne diseases across the world but tend to be
confined to the intestine, usually causing a week-long bout of diarrhoea. But up
to half of HIV-infected African people die after contracting NTS infection.

Now, US and UK researchers have looked at NTS infection in rhesus macaque
monkeys infected with simian immunodeficiency virus (SIV), which is similar to
HIV.

They have found that SIV infection leads to a depletion in the numbers of a type
of lymphocyte called T helper type 17 (TH17) in the walls of the ileum – the
final section of the small intestine. CD4+ cells are another type of T helper
lymphocyte.

TH17 cells produce a cytokine – or chemical messenger – called interleukin
17 (IL-17) which plays a pivotal role in the gut’s response to infection.

It is this reduction in IL-17 which is thought to allow the gut wall to become
‘leaky’, allowing the NTS bacteria to cross into and infect the bloodstream.

One of the researchers, Professor Satya Dandekar, chair of the department of
medical microbiology and immunology at the University of California at Davis
said: “We found that animals that had no SIV infection were able to generate
immediate responses to bacterial exposure, producing TH17 cells in large
amounts.”

But the SIV-infected animals had either a significantly lower response or failed
to produce measurable amounts of the cytokine, he said. “This muted TH17
response led to dissemination of Salmonella from the gut to the peripheral
blood.”

The data suggest TH17 may be a useful biomarker for monitoring HIV infection and
testing the efficacy of vaccines and other therapies. The authors also suggest
that efforts to enhance TH17 function could improve existing antiretroviral
treatments.

But the research also has wider implications, with this interruption in the
gut’s immune response possibly explaining how HIV can maintain reservoirs of
infection that evade drug treatment.

Reference

Raffatellu M et al. Simian immunodeficiency virus–induced mucosal
interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nature
Medicine, published online, 23rd March 2008.
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