Edwin J Bernard and Gus Cairns report from the 10th Conference on Retroviruses and Opportunistic Infections, held in Boston in February
A study at the 10th Retrovirus Conference appears to document an increased incidence of heart trouble in people on HIV drugs.
"Every
year you stay on current HIV medication is associated with a 27 per cent higher
risk of getting a heart attack," said presenter Dr Jens Lundgren.
The DAD study monitored heart attacks in 23,490 patients taking HIV drugs over a two-year period. During that time 1290 people had heart attacks and 31 per cent were fatal. This accounted for six per cent of all deaths.
Heart attacks occurred in people who had never taken HIV medication at a rate of 0.8 per 1,000 people per year. The rate for people who had taken it for two years was 2.2. If they had taken it for up to five years the rate was 5.5, which would imply an approximately one in 10 chance of a heart attack over the next 20 years.
Drug breaks - known as Structured Treatment Interruptions (STI) and Structured Intermittent Therapy (SIT) - are becoming more and more common. Evidence presented at the Retrovirus Conference shows that handled the wrong way, drug 'holidays' can lead to resistance and possible disease progression. But done right they can save your life - or save money.
A study from Thailand showed that if you had never had a CD4 count under 200, and had well over 350 CD4 cells, you could stop your drugs and start them again when you hit the 350 cell barrier without any health problems. The people who followed this approach spent a third as much time on HIV drugs as people who took them continually - and cost a third as much.
But if you're on efavirenz (Sustiva®) or 3TC (lamivudine, Epivir® - also in Combivir® and Trizivir®), beware. A European study found that in the week after you stop those drugs, the fact that they stay in the blood longer than other antiretrovirals means that your HIV can develop resistance to them. This also means that SIT or 'pulse therapy' - one week on, one week off - is not ready for prime time. The amount of drug resistance that emerged in a US SIT study - particularly to efavirenz and 3TC - was so high that they stopped the study early.
How about stopping drugs as a strategy when you've run out of options? This can work - as long as you don't stop for more than two months, and take between seven and nine drugs when you do start again.
Everyone in the French GIGAHAART trial was resistant to all known antiretrovirals, and many entered with a handful of CD4 cells. Four years later, the vast majority who took the two months off before starting their seven to nine-drug regime are doing well, and have not seen any more side-effects than if they were taking standard combos. Presenter Christine Katlama said: "I am convinced that the two month treatment interruption made the difference."
Right now, in the UK, the OPTIMA study is looking at this approach, and is still enrolling at 25 clinics. For more information check out the 'Clinical Trials' section at www.aidsmap.com
The 10th Retrovirus Conference heard a US study that indicated that HIV positive gay men were three times more likely to bareback with another positive man than with HIV-negative men. Dr Jeff McConnell from San Francisco found that some men are trying to take 'safer risks' by ensuring that the riskiest sex usually happens with sexual partners that they think have the same HIV status. When 'barebacking' did take place with partners of different HIV status (12 per cent of all sexual encounters), the HIV-positive partner was nearly always the bottom, which is slightly less risky than being the top.
Another study asking positive men whether knowing their partner's HIV status made a difference when it came to barebacking found that 19 per cent barebacked with a partner known to be HIV-negative, and 30 per cent had unprotected intercourse with a partner of unknown HIV status. Though only 13 per cent had been the exclusively active partner and 44 per cent exclusively receptive, 44 per cent had also been both 'top' and 'bottom' with partners.
A milestone was passed in the long march towards a vaccine against AIDS on 24th February. The first-ever large scale 'real world' trial of a vaccine announced its results.
It was widely predicted that the AIDSVAX vaccine would prove to be ineffective, so it was not too disappointing when its manufacturers Vaxgen inc. announced that it had failed to prevent HIV infection in the study group as a whole.
Unexpectedly, however, the data appeared to say that the vaccine helped prevent infection among people of black and Asian background. But community groups such as Gay Men's Health Crisis in New York have criticised Vaxgen for highlighting this finding, saying it could raise false hopes among people from ethnic minority backgrounds.
The study, which lasted three years, involved 5,009 HIV negative volunteers from 'high risk' groups: most were gay men, and six per cent minority were women. The predicted HIV infection rate among the group as a whole, based on their risk profile, was 2.7 new infections out of every 100 people per year without vaccination.
At the end of the study this was almost exactly what was observed. 86 new infections were observed when one would expect 90. Statistically speaking this signifies no difference at all.
However, there were fewer infections than expected among the 498 black and Asian volunteers, and especially among the 314 black volunteers. 13 ethnic minority people got HIV infections, nine receiving placebo and four receiving the vaccine.
Europeans with access to antiretroviral therapy (HAART) are thriving, according to two reports at the Retrovirus Conference.
The EuroSIDA study of 8,551 people with HIV shows that the incidence of Aids or death has declined consistently each six months since September 1998 by 10 per cent. The incidence had already declined from 44 cases a year per 100 patients to eight between 1996 and 1998.
This represents overall a nearly fifty-fold fall in the death and Aids rates since the introduction of HAART. Presenter Amanda Mocroft said: "As of 2002, the potential long-term adverse effects associated with HAART have not impacted on its success in this population."
Meanwhile, the Swiss HIV Cohort Study reported that, using the same criteria that life insurance underwriters use to assess suitability for cover, people who had a CD4 count over 250 - no matter what their lowest CD4 count was, and whether or not they had an undetectable viral load - were doing as well in the short term as successfully treated cancer patients - "a group which is able to obtain life insurance."
A study presented at the 10th Retrovirus Conference raised further concerns about the use of single-dose nevirapine to prevent mother to child HIV transmission (MTCT).
The study looked at 33 women from Zambia, all of whom had received a single dose of nevirapine at the onset of labour. HIV was detectable in the breast milk of women, with the average viral load 100 times lower than in blood.
However 13 of the 23 women had HIV in their breast milk that had one or more resistance mutations to nevirapine. Five of them did not have nevirapine-resistant HIV in their blood.
Altogether,
HIV resistant to nevirapine was about two-thirds more likely to be found in breast
milk than blood samples (65 per cent of samples resistant versus 40 per cent in
blood).
The most common resistance mutation was the 'K103N' mutation which also confers resistance to the two other currently-used non-nucleoside drugs, efavirenz and delavirdine.
Of the 33 babies born, six were infected with HIV, four in the womb but two after birth, one more than six months after birth indicating transmission through breast milk. These infection figures show that the nevirapine treatment cut the infection rate at birth by at least 50 per cent, as has been observed in other studies. Drug-resistance tests have not been performed on the babies, but other studies indicate that K103N-mutant HIV is just as easily transmitted as non-resistant HIV.
Single-dose nevirapine is the most commonly-used therapy to prevent MTCT in Africa.
Dr Constance Benson of the University of Colorado, a member of the Conference Scientific Committee, said: "This study raises concerns for me...we need to continue looking closely at nevirapine resistance in Africa."
