CAPE TOWN, South Africa, July 20 — Patients in an experimental program suppressed human immunodeficiency virus (HIV) to undetectable levels over a full year of taking potent antiretroviral medications on a five-day on, two-day off (FOTO) schedule.

• The research was an experimental study that has not been replicated and all the patients in the study had suppressed viremia to be eligible for the study.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Lead researcher Cal Cohen, MD, medical director of the Community Research Initiative of Boston, suggested that the long half-life of the drugs — efavirenz (Sustiva), tenofovir (Viread), and emtricitabine (Emtriva) — give patients the opportunity to take brief drug holidays without creating virologic rebound.

“I don’t consider this a structured treatment interruption study,” Dr. Cohen said in a poster presentation at the International AIDS Society conference here. “I prefer to look at this as another way of taking medication, in this case using the pharmacokinetic properties to structure treatment.”

Of the 60 patients in the study, he said, all have maintained HIV suppression for a year, some of them for as long as 18 months.

Half the patients are on the five-days-on, two-days-off (FOTO) regimen while the other 30 are taking their regimen daily.

All the patients had suppressed HIV, with viral loads undetectable using the 50 copies/mL assay at the time they began the study.

He said the number of patients in the study was sufficient to show that FOTO was not inferior to daily treatment.

Because the treatment uses fewer drugs, he said the participants who are on the FOTO regimen use 28% less medication than the patients taking the drugs on a daily basis.

“That represents a savings of about $5,000 a year,” Dr. Cohen said. “If you think about 100,000 people on this regimen, the costs savings would be phenomenal.”

However, he said he would not recommend the treatment for initial therapy.

“You have to get the virus suppressed first, and then make sure your patients are compliant in staying on the drugs and maintaining that suppression. Then you can consider the FOTO regimen,” he said.

Others were even more cautious.

“This study only has 60 patients,” noted Pedro Cahn, MD, chief of infectious diseases and director of Fundacion Huesped in Buenos Aires, Argentina. “We really cannot recommend this type of trial unless we can be certain that it would apply to a larger group of patients.”

Dr. Cahn suggested that the FOTO study benefits from use of the “right drugs among the right patients” and that replication of the trial might be difficult.

Dr. Cohen said that he is actively seeking to collaborate with other institutions in a major clinical trial to test his hypothesis.

The FOTO trial has no financial support from industry, Dr. Cohen said. He and Dr. Cahn did not report financial conflicts: IAS does not require such disclosures.

Primary source: Conference Progamme 5^th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2009

Source reference:
Cohen C, et al “The FOTO study: The 48 week extension to assess durability of the strategy of taking efavirenz, tenofovir and emtricitabine Five days On, Two days Off (FOTO) each week in virologically suppressed patients,” Conference Progamme 5^th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2009. P. 49.

CAPE TOWN, South Africa, July 20 — From the female point of view, male circumcision is either no big deal or a positive improvement, Ugandan researchers said.

• Explain to interested patients that circumcision has been shown to reduce the risk of acquiring HIV for heterosexual men in Africa.
• Note that this study shows that an overwhelming majority of women think their own sexual satisfaction remains the same or even gets better after the procedure.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Among women whose partners took part in the landmark circumcision trial in Rakai, Uganda, only a handful reported that the procedure reduced their sexual satisfaction, according to Godfrey Kigozi, MD, of the Rakai Health Sciences Program.

The remaining 97% said their satisfaction was unchanged or improved, he said during a poster discussion session at the fifth International AIDS Society conference on pathogenesis, treatment, and prevention of HIV.

The Rakai circumcision trial is one of three studies that have shown that the procedure reduces the risk acquiring HIV for heterosexual men by more than 50%.

As a follow-up to the Rakai study, Dr. Kigozi and colleagues enrolled 455 women whose partners had the procedure during the trial and asked them to report their sexual satisfaction before and after.

Among the 2.9% who said their sexual satisfaction was reduced, the top two reasons — each reported by six of 13 participants — were lower levels of desire on both sides. (Participants could give multiple reasons, Dr. Kigozi said.)

Among the 39.8% who said things were better, the top reason — reported by 51 of 177 women — was better hygiene.

Interestingly, 45 of the 177 reported better sex because their partner took longer to achieve orgasm — the same reason two unhappy women gave for their dissatisfaction.

Among other reasons for better sex:

• 44 women said their partner wanted sex more often, a reason also given by one woman who was unhappy with her state of sexual satisfaction
• 26 said their partner had less or no difficulty maintaining an erection and 18 said he had less or no difficulty getting an erection in the first place
• 20 said they achieved orgasm more often

The findings are good news because they show that one possible barrier to the widespread use of circumcision to fight HIV — objections from women — doesn’t exist, according to Naomi Block, MD, of the CDC, who chaired a session at which the study was presented.

On the other hand, Dr. Block said, the result is not unexpected — more than a dozen earlier reports had said that women didn’t expect much to change after a partner’s circumcision.

“Women were very positive about it,” she said.

But those reports, she said, were based on interviews with women whose partners had not been circumcised, while the Rakai study involved women with experience both before and after the procedure.

Dr. Kigozi said the finding parallels earlier research on men’s opinions of sexual satisfaction after circumcision, with 97% saying it was either unchanged or better.

The study was supported by the Bill and Melinda Gates Foundation, the National Institute of Allergy and Infectious Disease, and Fogarty International. Dr. Kigozi reported no conflicts.

Primary source: IAS Conference on HIV Pathogenesis and Treatment

Source reference:
Kigozi G et al. “Sexual satisfaction of women partners of circumcised men in a randomized trial of male circumcision in Rakai, Uganda” IAS 2009; Abstract MOPDC104.

CAPE TOWN, South Africa, July 20 — At the opening of the second major international AIDS conference to be held in Africa, researchers and activists angrily lashed out at the developed world for failing to meet commitments to battle the HIV pandemic.

“We are appalled by the recent G8 meeting where there has been absolute silence when it comes to the ongoing commitment to HIV,” said Julio Montaner, MD, of the British Columbia Centre for Excellence in HIV/AIDS.

Dr. Montaner, who is president of the International AIDS Society, told reporters that such silence is “not only pathetic, it’s criminal.”

The society, which organizes the International AIDS Conference every two years and held the 2000 gathering in Durban, South Africa, is holding its fifth meeting on the pathogenesis of the virus here.

The pathogenesis conference, unlike the International AIDS Conference, usually focuses on the science of HIV, leaving the politics of the pandemic on the backburner.

But at the opening ceremony, Dr. Montaner and others expressed anger that the commitment of the developed world appears to have diminished since the 2005 G8 summit, where world leaders pledged to support the ambitious goal of universal access to HIV treatment by 2010.

“In four years, the need for bold leadership on AIDS has increased, while the voices of our political leaders have diminished,” he said. “This is a shame.”

Dr. Montaner said the universal access goal “is not going to happen.”

Stephen Lewis, the former UN Ambassador for AIDS, called on scientists to speak out — as did those involved in studying climate change — in order to put pressure on political leaders.

HIV researchers, he said, are “people who speak with unimpeachable scientific authority, and if they so wished, and brought advocacy to bear could move the mountains of resistance and inertia.”

“We need the scientific community as well to speak clearly, and unequivocally, boldly and evocatively to the power-brokers of this world,” Lewis said.

“Somehow, along with the science, we need the activism,” he added.

There is an increasing consensus, Dr. Montaner said, that effective HIV treatment, even in the absence of cure or a vaccine, can markedly slow the transmission of disease.

In that context, he said, meeting the ambitious goal of universal access to highly active anti-retroviral therapy (HAART) can be regarded not just as good medicine, but also as good public health policy.

Even the sole scientific presentation of the opening ceremony concluded with a warning that backing away from the goal of universal access would be dangerous.

Nobel laureate Françoise Barre-Sinoussi, PhD, of the Institut Pasteur in Paris, said recent research raises the possibility of eradicating HIV, rather than just controlling it. (See HIV Hiding Places Uncovered)

But, she added, there is still much research to be done before the research findings can be translated into clinical action.

In the meantime, she said, “reducing the international efforts on universal access to HAART because of the global recession would be a disaster.”

“HIV is not in recession,” added Dr. Barre-Sinoussi, who shared the 2008 Nobel prize in medicine for her work in discovering the human immunodeficiency virus.

Related Article(s):

• HIV Hiding Places Uncovered

CAPE TOWN, South Africa — There are significant differences in the demographics of patients who have late presentation of HIV infection and those diagnosed earlier in the disease process, doctors reported here.

• In areas of low prevalence, where HIV may not be the first diagnosis that comes to mind, doctors should remember that older individuals and women may have HIV infection especially if they are from a country where HIV is endemic.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Of 54 late-presenters, 13 (24%) were women compared with 26 of 251, or about 10% of the non-late group (P<0.01), according to Jurgen van Lunzen, MD, of the Universitatskilinkum Eppendorf in Hamburg, Germany.

“Late presenters tend to be older, they are more often women, and they are from high prevalence countries,” Dr. van Lunzen said in his poster presentation at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“Pre0

CAPE TOWN, South Africa, July 21 — In places like South Africa, starting anti-HIV treatment earlier than current WHO guidelines suggest for the developing world would save lives and reduce opportunistic infections, researchers said.

• Explain to interested patients that evidence is mounting that early treatment of HIV results in better clinical outcomes but that guidelines in Africa still suggest waiting until the disease is relatively advanced.
• Add that clinical trials aimed at seeing if earlier therapy would improve outcomes in sub-Saharan Africa are under way, but won’t report results for several years.
• Note that this study, using a mathematical model, suggests that in the meantime, clinicians should start treatment earlier.

Such a change in clinical practice would also be cost-effective, according to Rochelle Walensky, MD, of the Massachusetts General Hospital in Boston, and colleagues.

The conclusions are based on a mathematical model of the HIV epidemic in South Africa and are intended to guide clinical practice until several formal clinical trials studying the issue are complete, Dr. Walensky and colleagues reported in the Aug. 4 issue of the Annals of Internal Medicine.

The researchers also reached similar conclusions using data from Cote d’Ivoire and presented them in a poster here at the fifth International AIDS Society conference on pathogenesis, treatment, and prevention of HIV.

The current standard for starting HIV treatment in South Africa followed World Health Organization guidelines for the developing world — a patient is eligible for treatment when his or her CD4-positive T cell count falls below 200 per cubic millimeter of plasma or when there is an AIDS-defining illness.

But guidelines in the developed world now suggest starting at a higher level — 350 cells per cubic millimeter — and some recent studies have suggested that clinical outcomes would be even better if the threshold were set to 500 cells or more.

Clinical trials are under way in Africa to settle the issue, but they won’t report for another five years. In the meantime, Dr. Walensky and colleagues said, their model may provide guidance to clinicians.

The bottom line, they said, is that in all cases, starting therapy at the 350-cell threshold saved more lives, prevented more disease, and cost more, compared with a threshold of 250 cells.

The researchers estimated that such a threshold would mean 4.7 million people would be eligible for therapy in South Africa over the next five years.

Under the assumption that 10% of those patients would be identified and given care, Dr. Walensky and colleagues said, using the 350-cell threshold would result in 1,599,900 deaths compared with 1,622,000 for the lower level.

There would also be 1,664,500 opportunistic infections, compared with 1,689,700 using the lower threshold.

On the other hand, costs would increase by $141,977,100 (U.S.), they found.

At the other extreme, if all eligible patients were identified and linked to care, the higher threshold would avert 221,000 opportunistic diseases and 253,000 deaths.

The additional costs in that scenario would rise to $1.4 billion, the researchers said.

Either scenario would increase long-term survival by at least 7.9 years, with an average per-person life expectancy of 3.8 years with no therapy and 12.5 years at the 350-cell threshold.

Compared with the 250-cell threshold, starting at 350 had an incremental cost-effectiveness ratio of $1,200 per year of life saved, the researchers said.

“It is probably both effective and cost-effective” to allow therapy to start at the higher level, the researchers said.

The study was supported by the National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation. The researchers did not report conflicts.

Primary source: Annals of Internal Medicine

Source reference:

Walensky RP et al. “When to Start Antiretroviral Therapy in Resource-Limited Settings” Ann Intern Med 2009; 151.

CAPE TOWN, South Africa, July 21 — The nucleoside reverse transcriptase inhibitor abacavir (Ziagen) — suspected of causing heart attacks — may have gotten a bad rap, researchers said here.

• Explain to interested patients that the anti-HIV drug abacavir has been suspected of causing heart disease.
• Note that these studies suggest that the drug may not be responsible for the association seen in several large observational studies.
• Note that these studies were published as abstracts and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Confounding factors such as kidney disease may have been at the root of the association between the widely used anti-HIV drug and cardiovascular disease, according to Roger Bedimo, MD, of the VA North Texas Healthcare System in Dallas.

“Kidney disease is a bona fide risk factor for (myocardial infarction) in the HIV population,” Dr. Bedimo told attendees at the International AIDS Society conference on pathogenesis, treatment, and prevention of HIV.

And, he added, “the hazard ratios are much higher than anything we’ve seen with abacavir.”

The drug has been under a cloud since the observation — first in the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study and then in the so-called SMART trial — that cumulative use of abacavir was associated with an increased risk of heart attack. (See IAC: Abacavir (Ziagen) Linked Again with Higher Cardio Risk)

But other studies, especially those that excluded patients with kidney disease, found little or no effect, Dr. Bedimo said.

He and his colleagues analyzed medical records for 19,424 HIV-infected patients in the VA system, looking for associations between drugs and acute myocardial infarction and cerebrovascular accidents.

They broke the patient group down into four categories based on their use of antiretroviral drugs — those on three or more drugs including abacavir, those on three or more drugs with another nucleoside reverse transcriptase inhibitor (NRTI), those on therapy with fewer drugs, and those not on antiretrovirals.

All told, Dr. Bedimo said, the patient group recorded 278 heart attacks and 868 cerebrovascular accidents over the period from 1996 through 2004.

The researchers found that each year of abacavir use was associated with an unadjusted hazard ratio for heart attack of 1.27 and for cerebrovascular accident of 1.17.

Both hazard ratios approached but did not reach statistical significance, Dr. Bedimo said.

The traditional risk factors — age, hyperlipidemia, hypertension, diabetes, and smoking status — were significantly elevated among patients who suffered a heart attack, all at P<0.0001.

But, Dr. Bedimo said, chronic kidney disease — defined as an estimated glomerular filtration rate of less than 60 — was also associated with heart attack.

It turned out, he said, that the hazard ratio for heart attack among patients with kidney disease — compared with those without renal impairment — was 3.85, with a 95% confidence interval from 2.74 to 5.42, which was significant at P<0.0001.

When the researchers adjusted for those factors, he said, the link between abacavir and heart attack was even weaker.

The pattern was similar for cerebrovascular accidents, Dr. Bedimo said.

Interestingly, abacavir use was more common among patients with chronic kidney disease, which — it if were true in the other studies — might help account for the worrisome observations.

Indeed, he said, both the DAD and SMART studies accepted patients with chronic kidney disease, while three studies that did not show a link between abacavir and heart disease excluded those with kidney impairments.

“The preponderance of evidence at this time is not in favor of implicating abacavir in cases of MI,” Dr. Bedimo said. “Studies that show that effect have left out potential confounders that we have proven to be significant.”

He said proving a causal relationship needs three factors — a strong association, having all the evidence pointing in the same direction, and a plausible biological mechanism.

The first two do not hold, Dr. Bedimo said. The third was addressed by another study presented at the same session.

The BICOMBO study compares the efficacy and safety of two drug combinations — abacavir/lamivudine (Kivexa) and tenofovir/emtricitabine (Truvada).

But in a sub-analysis, the researchers looked at several blood biomarkers associated with an increased risk of cardiovascular disease, including such things as C-reactive protein, adiponectin, tumor necrosis factor-alpha, and insulin, according to Esteban Martinez, MD, of the University of Barcelona in Spain.

After 48 weeks, Dr. Martinez said, there were no significant differences from baseline between patients in each group in markers of inflammation, endothelial dysfunction, insulin resistance, or hypercoagulability.

The results “argue against the involvement of abacavir in any of these mechanisms,” he said.

But the jury is still out on the nucleoside reverse transcriptase inhibitors, said Dominique Costagliola, PhD, of the Universite Pierre et Marie Curie in Paris.

Dr. Costagliola, who was co-chair of the session, was also the principal investigator of a study of patients in the French HIV hospital database that found an association between abacavir and heart disease.

But despite that, she said, she’s not convinced that there’s solid evidence to convict abacavir or any nucleoside reverse transcriptase inhibitor.

“We’ve seen in our study a large amount of room for confounders,” she said. “I don’t believe there is a casual association with any NRTI.”

The findings presented here, though, will not settle the debate, she said.

Indeed, Dr. Costagliola said, probably only a very large study — all of the drug-naïve patients in the world who started NRTIs between 2006 and 2008 — could “clear the debate.”

Such an analysis, she said, would leave little room for confounders, while eliminating complications — such as dyslipidemia — arising from long-term use of antiretrovirals.

Dr. Bedimo did not report any external support for the research or any conflicts. Dr. Martinez said the study was supported by GlaxoSmithKline and Gilead Sciences. He e did not report any conflicts.

Primary source: IAS Conference on HIV Pathogenesis and Treatment

Source reference:
Bedimo R et al. “Abacavir use and risk of acute myocardial infarction and cerebrovascular disease in the HAART era” IAS 2009; abstract MOAB202.

Additional source: IAS Conference on HIV Pathogenesis and Treatment

Source reference:
Martinez E et al. “No evidence for recent abacavir/lamivudine use in promoting inflammation, endothelial dysfunction, hypercoagulability, or insulin resistance in virologically suppressed HIV-infected patients: a substudy of the BICOMBO randomized clinical trial (ISRCTN61891868)” IAS 2009; abstract MOAB203.

Related Article(s):

• IAC: Abacavir (Ziagen) Linked Again with Higher Cardio Risk

CAPE TOWN, South Africa — There are significant differences in the demographics of patients who have late presentation of HIV infection and those diagnosed earlier in the disease process, doctors reported here.

• In areas of low prevalence, where HIV may not be the first diagnosis that comes to mind, doctors should remember that older individuals and women may have HIV infection especially if they are from a country where HIV is endemic.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Of 54 late-presenters, 13 (24%) were women compared with 26 of 251, or about 10% of the non-late group (P<0.01), according to Jurgen van Lunzen, MD, of the Universitatskilinkum Eppendorf in Hamburg, Germany.

“Late presenters tend to be older, they are more often women, and they are from high prevalence countries,” Dr. van Lunzen said in his poster presentation at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“Prevention and testing strategies should try to take this into account,” Dr. van Lunzen said.

He and his colleagues compared 54 late-presenting cases with 251 patients who were diagnosed earlier in the disease process. Most late presenters had an AIDS-defining illness as their first diagnosis, Dr. Van Lunzen said, but also included in the definition were patients with CD4 counts below 100 cells/mm³ and those who had two months or less between diagnosis and start of HAART.

The researchers also discovered that 10 (19%) of the late presenters were from countries where more than 1% of the population is infected with HIV, compared with 18 (7%) of non-late presenters (P<0.01).

The late-presenters also were older — mean age 40.9 compared with 38.1 years (P=0.034).

“We basically found almost the same experience among late presenters,” said Gerrit Schreij, MD, of the University of Maastricht in the Netherlands.

“When we see women and older individuals in our area — which is much the same as western Germany — we just don’t think immediately about HIV or AIDS,” he said. “Consequently our diagnosis of the illness in these people is delayed.”

Dr. Schreij said that often older people in their 50s, 60s and 70s present late in the disease process because HIV infection is not foremost in clinicians’ minds. “Neither the doctor nor the patient is thinking in terms of HIV,” he said.

The researchers reviewed data collected among patients in the extended German Truvada cohort — patients receiving fixed dose combination of emtricitabine and tenofovir.

Despite the late presentation, Dr. van Lunzen said that treatment with combination therapy that included the combination pill plus either a non-nucleoside reverse transcriptase or a protease inhibitor succeeded in reducing HIV to undetectable levels similarly to that achieved among non-late presenters.

In fact, in his study 70% of the late presenters were able to achieve undetectable levels of virus using the assay with 50 copies/ml as the lower limits of detectability compared with 67% of the non-late presenters.

However, at 48 weeks mean CD4-postitive cell counts lagged in the late presenters. The baseline CD4-positive cell count was 64 in the late presenters compared with 237 in the non-late presenters.

By week 48, the late presenters registered a 271 CD4-positive cell count compared with 408 for the non-late presenters.

In addition, during the 48-week treatment period, 12 (22%) of the late presenters experienced an AIDS-defining event compared with 19 or 7.6% of the non-late presenters (P<0.05).

Dr. van Lunzen noted that late presenters were more likely to receive a protease inhibitor-based treatment (96%) than non-late presenters (50%).

The data was collected through a Gilead Sciences study, and Gilead supported the substudy on demographics in this report. Neither Dr. van Lunzen or Dr. Schreij reported conflict of interest. The IAS does not require reporting of possible conflicts of interest.

Primary source: Conference Progamme 5^th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2009

Source reference:
Van Lunzen J, et al “Late presentation is frequent in the elderly, in female and in patients from high prevalence countries in a German outpatient cohort,” Conference Progamme 5^th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2009. P. 49.