Progress Continues In Treating HIV
By ED SUSMAN
KUALA LUMPUR, Malaysia – The splashy news from the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention surrounded discussion of the so-called “Boston Patients” – two individuals who appear to be free of human immunodeficiency virus (HIV) infection after undergoing bone marrow transplants as a treatment for lymphoma.
While many researchers expressed high enthusiasm about these cases and a handful of other similar situations in which the virus has been cleared due to remarkable treatments, the fact remains that these HIV “cures” are unlikely to be useful for the vast majority of the 30 million people worldwide who are infected with HIV – the pathogen that causes AIDS.
But for the rest of the people with the disease – primarily women, and those primarily living in sub-Saharan Africa, progress continues.
Quad Pill at 2 Years
For example, researchers reported that the so-called “quad” pill that combines elvitegravir-cobicistat-tenofovir-emtricitabine appears to perform as well as other standard of care regimens over two years.
David Cooper, MD, professor of medicine at the Kirby Institute, University of New South Wales, Sydney, Australia, said that:
When compared with the single tablet regimen of efavirenz, emtricitabine and tenofovir, 84 percent of patients on the single-tablet “quad” achieved undetectable viral load using the 50-copies.mm3 assay compared with 82 percent of the comparator regimen.
when compared with treatment with atazanavir/ritonavir plus the co-formulated emtricitabine-tenofovir regimen, 83 percent of patients on the “quad” had undetectable viral loads compared with 82 percent of the comparator group.
“This drug (quad) had a robust and durable effi cacy through Week 96,” Dr. Cooper said. “It was comparable to the other regimens, and was consistent across all demographic groups and when we stratified for HIV levels and CD4 cell counts.”
Long-term efficacy is important because new HIV-treatment guidelines suggest earlier initiation of antiretroviral drugs and treatment will be necessary for decades.
In his study, Dr. Cooper said efficacy was similar among patients younger than 40 and older than 40; in men and in women; in whites and in non-whites; in those with baseline HIV RNA levels above 100,000 copies/ml and in those with HIV RNA below 100,000 copies/ml; in those with CD4-positive cell counts 350 cells/mm3 or higher and those in patients with less than 350 cells/mm3; and there was similar efficacy if patients were adherence or less than 95 percent compliant in taking their medications, the researchers illustrated.
“We think that the overall efficacy, safety and tolerability support the use of this combination as a first line therapy in treatment naïve HIV patients,” Dr. Cooper said.
In the studies, researchers enrolled 701 patients on the “quad”; 352 patients were enrolled to efavirenz-based treatment and 355 patients were on atazanavir/ritonavir.
The study was sponsored by Gilead Sciences, Foster City, California.
Statins prevent cancer
Patients living with HIV have a markedly reduced risk of developing cancers if they are also on statin therapy.
After performing statistical analyses, the risk of developing cancer among HIV-infected individuals was decreased by 46 percent if the person was on statins compared with HIV-infected patients who were not treated with the anti-cholesterol drugs (p<.0001), said Vincenzo Spagnuolo, MD, a resident in infectious diseases at Ospedale San Raffaele, Milan, Italy.
“We performed a retrospective analysis of our patients who had HIV and we observed that 363 individuals out of 4,617 who were not on statins (7.9 percent) were diagnosed with cancer compared with 12 of 740 patients on statins (1.3 percent) (p<.0001),” he said at his poster presentation.
“We looked at more than 10 years of treatment records,” he said, “and we found that the protection of statins was even greater when we considered cancers that are considered AIDS-defining illnesses –non-Hodgkin lymphoma, Kaposi’s sarcoma and uterine cervical cancer.”
None of these cancers were observed in patients on statins; 194 of these cancers occurred among patients who were not on statins, he reported.
“Statin use has been recently associated with reduced cancer incidence and mortality both in the general population and among HIV-infected subjects,” Dr. Spagnuolo said. “Based on these encouraging results we hypothesized that statin use begun after the start of antiretroviral therapy and before a cancer diagnosis would be associated with reduced cancer occurrence.”
Dr. Spagnuolo and his research team reviewed medical records of patients at Ospedale San Raffaele, identifying 5,357 patients who were followed for an average of 10.3 years – totaling 52,663 person years of follow-up.
Overall, the crude cancer rate was 7.1 per 1,000 person-years of follow-up among all the patients included in the study. The incidence rate was 8.4 per 1,000 person-years of follow-up among those not on statins and 1.3 per 1,000 person-years of follow-up for those individuals who were assigned statin treatment.
Dr. Spagnuolo noted that the statin users were about 51.1 years of age, and the non-statin patients were about 45.7 years of age – a significant difference, favoring nonstatin use (p<0.001). The statin users were significantly more likely to be men (80 percent) and women (76 percent), (p=0.028). Patients were taking statins for a mean of 24.7 months, Dr. Spagnuolo said.
He determined that 107 patients were diagnosed with non-Hodgkin’s lymphoma, 73 were diagnosed with Kaposi’s sarcoma, and 14 women had uterine cervical cancer. Among the non-AIDS defi ning cancers, 44 patients had Hodgkin Lymphoma, 19 had liver cancer; 23 had anal cancer; 16 were diagnosed with lung cancer; 12 had skin cancers; 11 had head and neck cancers; 11 had urinary tract cancers; 34 other solid cancers were diagnosed and 11 patients had other cancers.
After 48 weeks of therapy with the protease inhibitor combination of darunavir/ritonavir, young children are able to extend suppression of HIV from 24 weeks to 48 weeks without encountering new toxicities, researchers said.
A key finding in the study, according to Avy Violari, MD, deputy executive director of the Perinatal HIV Research Unit at Chris Hani Baragwaneth Hospital, Soweto, South Africa, was that continued treatment resulted in more children achieving suppression of the virus using the more stringent 50 copies/ml assay than at 24 weeks.
“I think this is an important finding because a lot of us feel that if we do not achieve virologic suppression by 24 weeks we are not doing well,” said Dr. Violari in her oral presentation. In the Darunavir in Treatment Experienced Pediatric Population (ARIEL) study, after 24 weeks 57.1 percent of the children had achieved an undetectable HIV viral load, but after 48 weeks 81 percent of the 21 children aged 3 to 5 years had achieved that milestone, she said.
Dr. Violari reported also that CD4-positive cells counts had increased further from baseline with continued treatment. After 24 weeks, the mean CD4-positive cell counts had increased 109 cells/mm3; by 48 weeks the mean increased was 187 cells/mm3.
Three children experienced virologic failure at week 48, two of whom had never reached viral suppression and one who had rebounded, Violari reported.
“Over 48 weeks, treatment-experienced HIV-infected children aged 3 to less than 6 receiving darunavir/ritonavir and an optimized background regimen showed a high virologic response and a favorable safety profile,” she said.
“No new safety concerns were reported compared with the known safety profile of darunavir/ritonavir,” she reported. In the 24-week analysis, safety issues in the pediatric cohort were similar to that seen in adults. One child discontinued treatment in the 48-week study due to Grade 2 vomiting.
Dr. Violari also noted that in 48-week study no development of resistance to darunavir was observed. Most of the adverse events in the children were associated with childhood illnesses such as head colds.
The ARIEL trial was conducted in Argentina, Brazil, India, Kenya and South Africa. The researchers enrolled children who were 3 years of age and less than 6 years of age who weighed at least 10 kg but weighed less than 20 kg. All had been on highly active antiretroviral therapy for at least a year before entering the trial. They also had to have viral loads of at least 1000 copies/ml.
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