• Explain to interested patients that HIV infection attacks various targets, including the gut, leading to immune decline and poor nutritional status.
• Note that this study suggests that a nutritional supplement may blunt that HIV effect on the gut, slowing the immune system’s decline.
• 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.

SAN FRANCISCO — A nutritional supplement can slow the immune system decline in HIV patients not yet treated with antiretroviral drugs, a researcher said here.

In an international, randomized, placebo-controlled trial, patients taking the supplement — dubbed NR100157 — lost fewer CD4-positive T cells over a year than those getting a placebo, according to Pedro Cahn, MD, of Fundación Huésped in Buenos Aires.

But the study was stopped early when its data monitoring committee said there could be “no gain” in continuing, Cahn said in a late-breaker presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

All told, only 340 of the planned 800 patients had been enrolled and just 143 completed the full year on either the supplement or placebo. Despite that, Cahn said, the average 40-cell benefit over the year was significant at P=0.03.

But that was challenged during the discussion of the paper by Daniel Kuritzkes, MD, a prominent HIV researcher from Brigham & Women’s Hospital in Boston, who was not part of the study.

Kuritzkes said the recommendations of data monitoring committees should be followed when a safety issue is involved, but otherwise investigators should abide by established stopping rules.

Cahn responded that the investigators felt obliged to follow the recommendation of the committee.

Specifically, he said, the committee had reasoned that because of “a statistically significant difference between groups in primary outcome and no safety concerns, there is no further gain in continuing the trial.”

Later, Kuritzkes told MedPage Today that interim data analyses generally use a much lower level of significance to determine whether a trial should he halted.

“If you look at other studies that have been stopped for efficacy, typically the P-values are very very small,” he said, in order to avoid stopping for a “spurious positive result that may not persist to the end of the trial.”

He said the positive result reported by Cahn “may or may not have held up if they had enrolled all 800 patients.”

The study was aimed at showing that the product improved gut integrity, leading to immune preservation, a decrease in oxidative stress, and better nutrition, Cahn said.

It contains a mixture of micronutrients, long-chain polyunsaturated fatty acids, bovine colostrum, prebiotic oligosaccharides, and n-acetyl cysteine — ingredients that singly have shown benefits, Cahn said.

The product comes as a powder that can be mixed with liquid or added to food.

For the study, the researchers also used a placebo powder with the same amount of calories and proteins but none of the active ingredients, he said.

Of the 168 patients in the active arm of the study, 60 finished the year-long trial, 25 started antiretroviral therapy, 30 withdrew because of adverse events, 17 simply quit, and 20 were lost to follow-up. Sixteen volunteers did not complete for other reasons.

Of the 172 patients in the control arm, 83 finished, 29 started treatment, 14 withdrew because of adverse events, 20 just quit, and 17 were lost to follow-up. Another nine did not complete for other reasons.

Most of the adverse events in those who dropped out were gastrointestinal in nature, Cahn said.

Among those who completed the study, there was no difference in viral load between the groups. But there was a significant difference in the loss of immune cells:

• On average, those in the control arm lost 68 CD4 cells per cubic millimeter of blood per year.
• Those getting the supplement lost 28 cells, on average.

The findings show the “potential for nutritional-based strategies to become an integral part of disease management,” Cahn concluded, adding that more study is needed to establish the clinical relevance of the results.

Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy

Source reference:
Lange J, et al “Reduced CD4+ T cell decline and immune activation by NR100157: a specific multi-targeted nutritional intervention in HIV-1 positive adults not on antiretroviral therapy (BITE)” ICAAC 2009; Abstract H-1230b.

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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%).

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.

CAPE TOWN, South Africa, July 22 — In early trials, a novel integrase inhibitor produced “unprecedented” anti-HIV activity in patients who have never used a drug in the class, a researcher said here.

• Explain to interested patients that the integrase inhibitors are one of the new classes of anti-HIV drugs.
• Note that this study reports on a new member of the class, but caution that the data come from early studies and more research is needed.
• 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.

At the highest dose tested — 50 mg daily — the drug resulted in a 2.5-log₁₀ decline in HIV viral load, according to Sherene Min, MD, of GlaxoSmithKline .

That is a greater decline than is seen with either of the other two available integrase inhibitors, raltegravir (Isentress) and elvitegravir, Dr. Min said at the 2009 International AIDS Society conference on pathogenesis, treatment, and prevention of HIV.

Raltegravir is approved and is in clinical use, while elvitegravir is still in clinical trials. All three drugs block the integration of HIV genetic information into the host cell’s genome.

Dr. Min’s comparison of the drugs is based on a 35-patient randomized trial testing three doses of the new integrase inhibitor — so far known only as S/GSK1349572 — as monotherapy against placebo over a 10-day period.

But the comparison may be going a bit too far, according to Stefano Vella, MD, of the Istituto Superiore di Sanità in Rome, the Italian equivalent of the NIH. Dr. Vella, a former president of the AIDS society, chaired the session at which the research was presented.

“I think it’s a little premature to do this comparison,” Dr. Vella said. “Potency is very important, but we are already giving a score” even though only a handful of patients have been treated for a short period of time.

That said, Dr. Vella agreed the early results are “very encouraging. We need new generations, even of the new drugs.”

Dr. Min said the compound neither blocks nor enhances cytochrome p450, has a predictable exposure-response relationship, and does not have a significant food effect.

Also, she noted, there is “limited cross-resistance” to raltegravir and elvitegravir.

In the study, patients with a viral load of at least 5,000 copies of HIV RNA per milliliter of plasma and a CD4 cell count of at least 100 cells per cubic millimeter were randomized to a placebo or to 2, 10, or 50 mg of the drug daily.

After 10 days, only one of the patients in the two lower-dose groups had undetectable virus, defined as fewer than 50 copies per milliliter, compared with seven of the 10 patients getting 50 mg, Dr. Min said.

Adverse events were generally mild to moderate, including diarrhea, headache, and fatigue, Dr. Min said. Although there were four Grade 3 events, they were all different and there was no pattern of occurrence, she reported.

The data support longer studies, Dr. Min said, adding that a phase IIb trial will start later this month.

Primary source: IAS Conference on HIV Pathogenesis and Treatment

Source reference:
Lalezari J et al. “Potent antiviral activity of S/GSK1349572, a next generation integrase inhibitor (INI), in INInaïve HIV-1-infected patients” IAS 2009; abstract TUAB105.