Compiled by Robert Fieldhouse and Gus Cairns
reporting from the 13th Retrovirus Conference, Denver, Colorado, US
Illness common in people starting HAART
Doctors
are being urged to be extra vigilant about spotting problems associated with
immune system reconstruction during the first three months of HAART.
The warning came as a new study revealed immune reconstitution inflammatory
syndrome (IRIS) is common in the early months of HIV drug treatment.
IRIS is a term used to describe a wide range of symptoms which may develop
when our immune system begins to recover. Researchers at London’s King’s
College Hospital looked at the incidence and patterns of IRIS among 199, mainly
African people, starting HAART. Around one in five experienced a total of
51 IRIS events in the first six months of treatment. Typically, those who
developed IRIS experienced anogenital herpes simplex
virus (HSV) infection (22 patients), genital warts (10 patients), molluscum
contagiosum (four patients), and varicella-zoster virus infection (four patients).
Five patients developed a mycobacterial infection such as tuberculosis, four
had hepatitis B, one developed pneumocystis jirovecci infection, and one Kaposi’s
sarcoma. Half the IRIS incidents were new presentations of previously unrecognised
infections, while the other half represented a worsening or reoccurrence of
previously existing infections.
People who start therapy with a low CD4 cell percentage (less than 15 per
cent) appeared more likely to develop IRIS. Study lead Professor Philippa
Easterbrook said: “Physicians [should] be alert to the possibility of
IRIS, particularly in patients presenting with new events or clinical problems
in the initial three months after starting HAART.” They should also
discuss the possibility of IRIS occurring with their patients
to avoid them inappropriately discontinuing treatment as a result of feeling
discouraged by the development of symptoms, she added. Clinical Infectious
Diseases 2006; 42: 418-427
New microbicide is well-tolerated
A new study of a microbicide gel containing tenofovir has shown it to be safe
and well-tolerated by HIV positive and negative women alike. Eighty-four women
and 24 of their male partners were recruited to the study. Most women (87
per cent) reported mild side effects and one quarter reported genital itching.
None of the HIV positive women who used the gel over a two-week period developed
resistance to tenofovir.
Microbicide gels aim to reduce the likelihood of HIV transmission to their
partners.
AIDS 20: 543–551, 2006
Male circumcision to protect women?
A Ugandan study has found female partners of circumcised HIV positive men
are 30 per cent less likely to
get HIV. This follows a study that found circumcising men reduced their risk
of acquiring HIV by 75 per cent.
Baltimore’s Professor Tom Quinn said if a country adopted universal
circumcision, it could cut HIV by two-thirds. But he warned if men started
feeling they could have more sexual partners and more unsafe sex as a result,
it might make women more vulnerable and cancel out any beneficial effect.
Abstract 127*
Good outcome linked to early viral load control
Getting your viral load undetectable in the first six months of treatment
and keeping it there predicts
survival up to six years later, new research suggests.
A study of 2,046 people living with HIV split people into three groups based
on how long their viral load had remained undetectable during the first six
to 18 months after starting HAART.
CD4 counts rose more each month in people who achieved an undetectable viral
load, compared with those who did not. After six years, 92 per cent of patients
who achieved a viral load below 400 copies in the first six months of treatment
were still alive.
Researchers said doctors and patients should work together to get viral load
under control as quickly as possible, avoiding development of drug resistance
on therapy, which could affect long-term prognosis.
Clinical Infectious Diseases 2006; 42: 136-144
Aids-related deaths continue to fall…
The
death rate among people with HIV with access to antiretrovirals has continued
to fall during the HAART era, according to new UK research.
A team, led by Professor Caroline Sabin, of Royal Free and University College
Medical School, London, wanted to know why a small proportion of people living
with HIV at the Royal Free Hospital were still dying despite access to antiretrovirals.
They identified 121 HIV positive people in their database who had died since
1998. Most died from Aids (44.5 per cent). Others died from known side effects
to therapy (3.3 per cent), liver-related problems due to hepatitis B or C
coinfection (3.3 per cent), heart disease (2.5 per cent), or other known causes
(23.1 per cent).
The annual death rate between 2001 to 2003 was exactly half of that between
1998 and 2000. Almost two thirds (61.2 per cent) of those who died had received
HAART.
Half the deaths in people who had received HAART for more than six months
were due to HIV-related causes. A third occurred in people with well-controlled
viral replication, but whose average CD4 cell count was 28 at the time of
death. Twenty six patients had previously been tested for drug resistance.
Three quarters had at least one resistance mutation associated with reduced
susceptibility to currently available antiretrovirals.
Five of the 26 patients had at least one resistance mutation conferring reduced
susceptibility to the three most commonly used antiretroviral drug classes;
nucleoside analogues, NNRTIs and protease inhibitors.
A significant proportion
had high triglycerides (a type of blood fat), low haemoglobin, or low albumin
levels (a marker of liver function).
“Late presentation, delayed uptake of HAART, and the previous use of
treatment combinations now viewed as suboptimal have all contributed to high
levels of treatment exposure and drug resistance in this group,” the
Royal Free researchers wrote.
“While mortality rates among HIV-infected individuals at our centre
have fallen since 1988, the deaths that now occur are more diverse and are
the result of a number of factors,” the authors concluded.
JAIDS 2006; 20: 67-71
…and so do hospitalisations
Hospitalisations for opportunistic infections (OIs) have declined significantly
since the advent of HAART. That’s according to researchers at Johns
Hopkins University School of Medicine in the US.
However, treatment complications including diabetes, cardiovascular disease
and cerebrovascular problems increased between 1996 and 2000.
These conditions still only accounted for a small proportion of the total
number of HIV-related hospitalisations. Researchers looked at hospital admissions
data from 12 US states between 1996 and 2000 covering 317,000 HIV-related
admissions. Seven per cent of people died over the study period. Overall,
hospitalisations fell by a third and the proportion involving opportunistic
infections fell from 40 to 27 per cent.
The proportion of liver-related complications increased from eight to 13 per
cent while hepatitis C infection increased from one to five per cent. Diabetes
increased from three to five per cent and heart disease from 0.4 to 0.9 per
cent over the period of the study.
Journal of AIDS 2005; 40:
609-616
Once-weekly antiretroviral drugs in development
Roche has presented data on two new fusion inhibitor drugs that could eventually
succeed T-20 (Fuzeon).
Like T-20, TRI-999 and TRI-1144 also have to be injected, but stay in the
body four to six times longer, suggesting they might only have to be injected
once a week.
However, HIV also appears to slowly develop resistance to them. These drugs
won’t be along for a while yet; safety studies are just starting in
animals.
Another drug that may only have to be taken once every two weeks is nearer
reaching the clinics. TNX355 is a drug that surrounds T-cells and blocks HIV
from attaching itself to CD4 molecules on their surface.
A trial giving the drug as the sole HIV therapy for 24 weeks produced a sustained
15-fold drop in viral load in a group of experienced patients. This compars
with the viral load less than halving in patients on a placebo.
TNX355 has to be given as an intravenous drip, but patients might be prepared
to attend clinic once a fortnight to receive it.
Abstract 48*
Treatment breaks not so SMART
A major trial of treatment interruptions in people with HIV has been stopped
prematurely. This was because there were far more deaths and Aids cases in
people taking treatment interruptions, so-called ‘drug holidays’,
than in people on continuous treatment.
The SMART study was the largest HIV treatment study ever attempted. Participants
had to have a CD4 count over 350. One group of patients were put on continuous
treatment regardless of changes in their CD4. Another group was taken off
therapy when their counts went over 500, only restarting when they fell below
250.
The study was halted when they found the risk of developing Aids or dying
was 2.5 times greater in people interrupting treatment than in people who
stayed on the drugs.
One in 27 patients on treatment interruptions developed Aids or died compared
with one in 67 patients on continuous therapy. In total, 46 people interrupting
treatment died compared with 25 staying on treatment.
Prior to starting the study, experts thought that people who at some point
had had really low CD4 counts might do worse. But lowest-ever CD4 count made
no difference to the risk of developing Aids or dying.
Scientists are still analysing why people interrupting treatment faired worse.
One
theory is that the threshold for restarting therapy was too low.
However, most of the deaths were not due to classic Aids-defining illnesses
but due to other events like heart attacks. Another theory is that having
lots of HIV in the system is generally bad for you, revving up the immune
system in a way that damages other organs.
Whatever the cause, the findings imply that we may need to consider going
back to treating people earlier. Abstract 106LB*
One in 50 gets Aids illnesses with ‘protective’
CD4 count
A study of European patients with HIV has found about two per cent have developed
an Aids-defining illness at one time or another. That’s despite them
having a CD4 count considered high enough to protect them.
Altogether, 212 out of 11,229 patients developed CMV (cytomegalo virus), MAC
(mycobacterium avium complex), toxoplasmosis, PCP (pneumocystis carinii pneumonia),
active TB or oesophageal thrush at CD4 counts higher than expected.
Being on HAART made it three to four times less likely patients would get
these illnesses, regardless of their CD4. Abstract 783*
‘Serosorting’ may cut risk of
HIV by 40 per cent
A study of gay men attending an STI clinic in Seattle has found serosorting,
the practice of only having unprotected sex with people of your own HIV status,
cut the risk of HIV infection by about 40 per cent. By comparison, condom
use cut infection rates by 80 per cent.
The University of Washington’s Matthew Golden said the rate of new diagnoses
among clinic patients who serosorted (2.6 per cent) was midway between patients
who always tried to use condoms (1.5 per cent) and patients who took no precautions
(4.1 per cent).
Asked if serosorting should be promoted as an HIV prevention strategy, he
said: “Compared to what? Promoting condom use is better but in patients
who really don’t want to use them, it’s better than doing nothing.”
Abstact 163*
Nevirapine appears safe for most pregnancies
Most HIV positive pregnant women taking a combination therapy including nevirapine
show no ill effects from the drug, according to new research.
Dr Esaú Custódio João and colleagues at Hospital dos
Servidores do Estado, Rio de Janeiro, found nevirapine was “easy-to-take,
well tolerated and inexpensive”, and widely used in Brazil as part of
a three-drug regimen during pregnancy. However, the team acknowledged a few
reports of serious and even fatal side effects. Researchers conducted a retrospective
study of 197 women who had taken nevirapine for at least seven days after
becoming pregnant.
Side effects occurred in 11 patients (5.6 per cent). This led to seven of
them stopping the drug. One woman developed Stevens-Johnson Syndrome and another
grade-4 cholestasis (where bile excretion from the liver is blocked). Being
coinfected with hepatitis C was significantly associated with developing side
effects on nevirapine. Researchers saw toxic side effects in only a very small
proportion of patients and advise all pregnant women to screen for hep B and
C, if nevirapine is being considered.
American Journal of Obstetrics and Gynecology 2006; 194: 199-202
High viral load link to Aids-related cancer
Taking HAART for at least six months appears to reduce our risk of
developing non-Hodgkin’s lymphoma (NHL), a new study suggests.
But an uncontrolled viral load increases our risk of getting this common Aids-related
cancer. Dr Fabrice Bonnet, of Hopital Saint-Andre, Bordeaux, wanted to identify
which factors decreased the risk of NHL.
French researchers carried out a study of 55 patients with Aids-related NHL
with 145 controls matched for CD4 cell count, sex, and length of follow-up.
They found combination therapy taken for a minimum of six months was required
to prevent NHL, and that people with high HIV viral loads were at an increased
risk of developing it. Increased risk was not linked to age, how people were
infected, coinfection with hep B or C, peak levels of CD4 and CD8 cell count
or herpes virus.
Clinical Infectious Diseases 2006; 42: 411-417
Antiretrovirals may prevent HIV transmission
in monkeys
A
trial in monkeys designed to test the idea of giving antiretrovirals to prevent
HIV transmission has shown some success.
Six monkeys given tenofovir and FTC were protected from infection with a form
of HIV that can infect primates.
The virus was administered by rectal injection once a week to mimic human
anal sex. All but one of the six monkeys not receiving the pre-exposure prophylaxis
(PREP) were infected.
This study follows disappointing results from another using tenofovir alone
presented at last year’s conference.
In separate studies, the UK’s Andrew Hill calculated that tenofovir-based
PREP could be cost-effective in developing countries where the annual rate
of HIV infection was over three per cent. Researchers in Peru said they were
ready to begin the largest trial of the idea yet, attempted in 1,600 gay men
after intensive community consultation. Abstract 32LB*
Reminder about tenofovir and Truvada-containing regimens
Doctors are being reminded of the importance of closely following prescribing
guidelines to ensure renal safety in patients on tenofovir-containing regimes.
Under current recommendations, doctors should alter intervals between doses
of tenofovir or Truvada (tenofovir/FTC) when starting patients with kidney
abnormalities on these antiretrovirals. They should also establish creatinine
clearance in all patients starting these treatments.
Manufacturer Gilead Sciences issued the reminder to doctors and patients following
a request from the European Medicines Agency’s Committee for Medicinal
Products for Human use.
Despite current recommendations, Gilead has continued to receive reports of
kidney abnormalities in patients whose creatinine clearance was not established
before starting treatment. There have also been reports of failure to adjust
dose intervals in patients with kidney impairment taking tenofovir.
It was stressed this was a reminder letter; not a letter relating any new
safety concerns or data. The reminder to patients states: “If you are
taking either of these drugs you should have your kidney function monitored
(by calculating creatinine clearance and serum phosphate) before starting
tenofovir, every four weeks during the first year of treatment and every three
months thereafter.
“In patients at risk of, or with a history of, kidney dysfunction and
patients with renal insufficiency, more frequent monitoring of renal function
should be considered.
“If serum phosphate or creatinine clearance is decreased during treatment
with tenofovir, kidney function should be re-evaluated within one week, including
measurements of blood glucose, blood potassium and urine glucose concentrations.
“Your healthcare provider may have to alter the interval between each
dose or interrupt treatment with tenofovir or Truvada.
“If you have pre-existing kidney impairment or develop kidney problems
for any reason while on treatment, discuss the possibility of adjusting the
interval between each dose of tenofovir or Truvada with your healthcare provider.
“You should not use tenofovir with any drug shown to damage the kidneys.”
Gilead said it supported the distribution of the reminder letter to healthcare
professionals, to ensure broad awareness about renal guidelines and appropriate
use of tenofovir.
