The 4th IAS (International AIDS Society) Conference was held in Sydney in July. More than 5,000 delegates from 133 countries came together for the four-day event to examine the latest developments in HIV related research. Much of the focus of the conference was on:
- The development of novel treatments that offer new hope to people who have developed resistance to existing medications.
- New biomedical prevention strategies available and others on the horizon, such as female-controlled microbicides, male circumcision and the use of pre-exposure prophylaxis (PrEP).
- New knowledge of HIV pathogenesis (origins and development) and the mechanisms through which HIV causes immune deficiency.
- Operations research detailing what we’ve learned, to date, about what is working on the ground in communities across the globe.
- Updates on the clinical implications of an aging population of people living with HIV, as well as on pediatric treatment issues.
Is HIV treatment actually reducing heart attack risk?
New study data reported at the conference indicates that HIV treatment—despite its often negative effects on blood lipid levels—may actually reverse artery hardening that can lead to a heart attack or stroke.
Research has shown that immune activation— and possibly HIV itself—can contribute to the formation of plaques inside blood vessel walls, possibly leading to artery hardening (arteriosclerosis). In turn, some investigators are now hypothesizing that antiretroviral (ARV) treatment may actually have positive effects on cardiovascular health—and there is a growing body of evidence suggesting that patients on treatment have less likelihood of getting cardiovascular disease than those are not on HIV medications.
Adding to the mounting data is a clinical trial comparing Efavirenz, Kaletra and both drugs combined in patients starting treatment for the first time. It found improvements in flow-mediated dilation (FMD), a cardiovascular test for arteriosclerosis that measures the ability of blood vessels to expand, in patients after six months of potent ARV therapy.
According to Francesca Torriani, MD, of the University of California, San Diego, it didn’t matter which treatment regimen patients were on—it was the reduction in viral load that had the positive effect on patients’ FMD scores.
HIV linked to higher skin cancer risk
Skin cancer rates are higher among HIV-positive people than among the general population, according. The new findings suggest that skin cancer screening should be a component of routine HIV care, even for those with healthy immune systems.
Nancy Crum-Cianflone, MD, and her colleagues with the TriService AIDS Clinical Consortium in Bethesda, Maryland, explained that skin cancer is more common among patients with compromised immune systems, notably organ transplant recipients receiving immunosuppressive drugs.
While there has been no shortage of research showing that rates of Kaposi’s sarcoma (KS) have dropped sharply over the past 10 years due to the widespread use of antiretroviral (ARV) treatment, there has been little data regarding the incidence of non-AIDS skin cancers.
To explore rates of melanoma and both squamous cell and basal cell carcinomas, Dr. Crum- Cianflone’s group evaluated data from a cohort of 4,507 HIV-positive patients. Enrolled between 1987 and 2006, the participants had been followed for an average of 5.4 years.
Comparing these data to those mined from U.S. cancer registries, the authors reported a 2.3-fold increased risk for basal cell carcinoma among HIV-positive patients and a 3.1-fold increased risk for malignant melanoma. The greater risk of skin cancer was not associated with immune suppression. The average CD4 count at the time of cancer diagnosis was 432 cells, suggesting an increased risk even among those in earlier stages of HIV disease. Similarly, there were no associations between skin cancer risk and having either a high viral load or a history of human papillomavirus infection—a major cause of squamous cell cancer.
In summary, Dr. Crum-Cianflone’s group wrote that, in light of the significant increase in basal cell carcinoma and malignant melanoma, “Implementation of skin cancer screening should be considered given the aging HIV population.
Aging with HIV: Are cancer, heart disease, dementia the new challenges?
With improved antiretroviral therapy (ART) bringing decades of extra life to the developed world, the impact of HIV on the aging process is beginning to become a pressing concern as researchers attempt to determine whether the giants of geriatric medicine - dementia, heart disease and cancer – will occur sooner or more frequently in HIV-positive people as they age.
Professor Brian Gazzard of the Chelsea and Westminster Hospital, London, explored these new challenges in a plenary presentation at the IAS Conference. Prevalence of HIV is increasing in older age groups. In the United Kingdom a third of all adults who are HIV-positive are 55 years or over. Life expectancy is improving year by year, thanks to improved ART, but in addition to longer life there is also the input of new seroconversions into older age groups.
Analysis of HIV-positive diagnoses in the UK shows that a growing number of people are being diagnosed with HIV at ages over 50 – up from around 5% of all new diagnoses in 1995 to just under 10% of gay men and heterosexual men in 2005. Data from CASCADE, the UK national HIV cohort, show that just over half of all HIV infections are estimated to have occurred after the age of 30.
But while these factors increase the number of people with HIV who are reaching old age, the expected life span is still short of that of the general population. The international Antiretroviral Cohort Collaboration estimated in 2005 that a person diagnosed with HIV at the age of 20 had a life expectancy of 33 years, compared to 58 years for an equivalent individual in the HIV-negative population.
The interrelationships between aging, HIV and the potential effects of ART are complex. Diseases of aging can be more common in those with HIV infection, have a worse prognosis and ultimately decrease life expectancy. While noting that some groups at risk of HIV may already have a greater risk of early death (giving the ‘dispossessed’ as an example), Professor Gazzard went on to explain how the effects of HIV were strongly related to aging.
While these parallels between the aging process and HIV progression may cause concern for some patients, Professor Gazzard compelled the audience to recognise that death is inevitable for us all. There is research still to be done and while meaningful improvements in outcome for people with HIV and increasing age might not be achievable beyond a certain point, these data could inform the origin and development of age-related diseases in everyone. www.aidsmap.com [4]
New drugs effective against HIV resistance
A combination of two new HIV drugs can reduce the virus to undetectable levels even in patients with a highly resistant strain, according to two studies presented at the conference.
In the DUET-1 and DUET-2 trials, researchers tested the new protease inhibitor darunavir (Prezista) against the combination of darunavir and emtravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI). In both arms of the trials, low-dose ritonavir was also given.
The proportion of patients reaching an undetectable level of HIV -- defined as fewer than 50 copies of HIV RNA per milliliter of blood -- was 17% higher for patients on the combination in DUET-1 and 18% higher in DUET-2, investigators reported at the International AIDS Society meeting.
A typical patient in the two parallel studies had been treated with up to a dozen drugs, had suffered one or more AIDS-defining illnesses, and had a CD4 cell count of about 100. “They were also harboring highly-resistant virus,” said Christine Katlama, of the Hôpital Pitié-Salpêtrière in Paris, who presented the studies. She noted that two-thirds of the patients had two or more mutations that caused resistance to NNRTIs and half had four or more mutations that generate resistance to protease inhibitors.
Usually, when patients need salvage therapy, “we don’t even think of the NNRTIs, because they will have usually developed resistance,” aid Jose Gatell, head of the infectious diseases and AIDS units of the University of Barcelona Hospital. “Now we will have something (in that class) available to us that works.” www.medpagetoday.com [5]
Hepatitis C clusters reveal international transmission among HIV-positive gay men
Clusters of acute hepatitis C in the United Kingdom and elsewhere in Europe provide further evidence that sexual transmission is occurring internationally among HIV-positive gay men, researchers reported.
Six years ago, sexual transmission of hepatitis C (HCV) among gay men was almost completely under the radar, with many physicians believing that it was a very rare occurrence. Beginning in the early 2000s, however, doctors in large cities in the UK and Europe (including the Netherlands, Germany and France) started seeing outbreaks of acute hepatitis C, mostly among HIV-positive men who have sex with men. There have now been nearly 400 such cases reported in London and Brighton alone, and similar outbreaks have since been observed in Australia and the United States.
These acute HCV infections appear to be sexually transmitted, and have been linked to risk factors including unprotected anal sex, fisting, multiple partners, group sex practices, concurrent sexually transmitted infections, and noninjection recreational drug use.
Given the mobility of gay men between European cities like London, Amsterdam and Berlin, an international group of researchers decided to investigate patterns of HCV transmission in northern Europe. Mark Danta from the UCL Institute of Hepatology in London and colleagues recruited 190 HIV-positive men who had been diagnosed with acute HCV infection between 2000 and 2006. Of these, 107 were from the UK, 51 were from the Netherlands, 24 were from Germany, and eight were from France.
All were men who have sex with men, with an average age of about 38 years. Between twothirds and three-quarters of the men in the various countries were taking HAART, and the mean CD4 cell count ranged from about 400 to about 600. Using blood samples, the researchers constructed phylogenetic trees to better understand the linkages between these cases. Phylogenetic testing compares viral gene sequences with a control group in order to determine the likelihood that samples from the study group are related. Although phylogenetic testing is not considered a reliable way to prove that one individual has infected another, it can provide suggestive information about clusters of infection.
The researchers concluded that this phylogenetic analysis reveals a large HCV transmission network among HIV-positive gay men in Europe, and that travel between countries presumably plays an important role in transmission. Further, they noted, international mixing increased with larger cluster size, indicating rapid spread of regional outbreaks to neighbouring countries.
They recommended that national public health agencies should implement targeted prevention strategies, including HCV screening for high-risk HIV-positive men who have sex with men, to reduce the spread of hepatitis C in this population www.aidsmap.com [4]
Sydney Declaration on research
The International AIDS Society released the Sydney Declaration, which calls for increased research funding to fight HIV/AIDS worldwide. The declaration proposes that donors allocate at least 10% of their HIV resources to research and states that “although funding remains insufficient to meet the increasing need for services, it is imperative that the global community does not lose sight of the future while responding to the immediate crisis.”
Conference participants added that this should be additional funding and not taken from existing resources. The research also needs to be planned and structured, with input from people living with HIV and affected communities.