Abstract
Banana Chemical is Potent Inhibitor of HIV Infection
University of Michigan researchers have discovered a potent new inhibitor of HIV found in bananas. Lectin was found to be as potent as two antiretroviral medications currently on the market. Called BanLec, the lectin found in bananas may become a less expensive new component of applied vaginal microbicides.
The new study describes the complex actions of lectins and their ability to outsmart the HIV virus. Lectins are sugar-binding proteins that are able to identify viruses in the body and attach themselves to them. Ban Lec can inhibit HIV infection by binding to the sugar-rich HIV-1 envelope protein, gp120, and blockong its entry to the body. It is similar in potency to T-20 and maraviroc.
Currently, researchers are developing a process to molecularly alter BanLec to enhance its potential clinical utility. Clinical use is considered years away but researchers believe it could be used alone or with other anti-HIV drugs.
The findings were published in the March 19th issue of the Journal of Biological Chemistry, 2010;285(12):8646–8655.
Adherence Measure Predicts Viral Rebound
The use of a simple, routinely available measure of HAART adherence is helpful at predicting viral rebound at the next HIV viral load measurement in patients with viral suppression.
Researchers at the University College in London conducted their analysis on patients enrolled in the Royal Free HIV Cohort. A “drug-coverage-viral load episode” (DCVL episode) was defined for this study as a six-month period immediately before a viral load of ≤50 HIV-1 RNA copies/mL (time-zero). During the episode, the patient had been continuously on HAART, with all measured viral loads of ≤50 copies/mL. After time-zero, the next viral load was used to determine if a viral load rebound had occurred. This viral load rebound was defined as >200 copies/mL. The researchers used drug coverage as their measure of adherence. Drug coverage was calculated as the proportion of days in the six-month period covered by a valid prescription for at least three antiretrovirals.
Out of a total of 15,660 DCVL episodes, there were 376 (2.4 percent) viral load rebounds among 1,632 patients. Drug coverage was 100 percent for 32 percent of the episodes. Other drug coverage rates were 95–99 percent for 16 percent of episodes and ≤60 percent for 10 percent of episodes. A 10 percent increase in drug coverage was associated with a 0.93 risk ratio of rebound.
The study was published in HIV Medicine, 2010;11(3):216–224.
Minocycline Targets HIV-Infected Immune Cells
Researchers at Johns Hopkins have found that the common acne medicine minocycline effectively targets HIV-infected immune cells. Sine minocycline targets cellular pathways instead of viral proteins, drug resistance is less likely compared to existing antiretroviral agents.
According to the researchers minocycline does not target HIV directly. Instead, it reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression. Minocycline would be used as an adjunct to HAART. The approach is based on findings discovered in rheumatoid arthritis patients where minocycline was shown to have anti-inflammatory effects on T-cells. Hopkins researchers treated monkeys with SIV with minocycline. They found that the virus load in the cerebrospinal fluid, the viral RNA in the brain, and the severity of central nervous system disease were significantly decreased. In addition, minocycline was also shown to affect T-cell activation and proliferation. Although T-cell activation was reduced, there was no resulting impairment of the immune system.
Laboratory testing was next conducted to see if minocycline treatment affected latency in human T cells infected with HIV. Using cells from HIV-infected humans on HAART, the team isolated the “resting” immune cells and treated half of them with minocycline. The researchers counted how many virus particles were reactivated, finding completely undetectable levels in the treated cells versus detectable levels in the untreated cells. The drug has the ability to reduce HIV's capability to emerge from resting infected T-cells. It selectively interrupts certain specific signaling pathways critical for T-cell activation. Minocycline does not completely obliterate T-cells nor does it diminish their ability to respond to other infections or diseases.
The study was published in the April 15th issue of the Journal of Infectious Diseases, 2010;201(8):1132–1140.
HIV Drug Resistance is Common
According to researchers from the United Kingdom, the overall risk of virological failure and HIV drug resistance is fairly common. Specifically, after eight years, 28 percent of patients will have experienced at least one mutation.
A team at University College London analyzed 7,891 patients with HIV infection. All had initiated HAART containing a nucleoside backbone and either a NNRTI (82 percent) or a ritonavir-boosted PI (17 percent). The probability of detecting PI mutations in the ritonavir-boosted PI regimens was less than that observed for the NNRTI-based regimens used in the study. No differences were observed in the risk of detecting nucleoside resistance for either NNRTI or ritonavir-boosted PI regimens.
More details on this study can be found in May 1st issue of Clinical Infectious Diseases, 2010;50(9):1286–1287.
Greatest Uptake for New Antiretrovirals Occurs within First Year
After a new antiretroviral drug is approved, the uptake in usage is greatest within the first year following FDA approval. The finding comes from a study of new antiretroviral uptake in the Veterans Healthcare Administration (VHA) system. Three antiretrovirals were studied: atazanavir, darunavir, and tipranavir.
Veterans Affairs researchers evaluated VHA uptake of the three drugs along with lopinavir/ritonavir in each complete 90-day quarter since approval to December 2007. HIV Clinical Case Registry data was used to determine this uptake within four regions of the U.S.
A total of 6,551 veterans with HIV infection received the three new antiretrovirals. After the greatest uptake was seen in the first year after approval, it slightly declined and then plateaued. There was more early adoption of these new agents in the Western part of the U.S. A small percentage of prescribers were responsible for the new prescriptions of the three recently approved antiretrovirals. These tended to be infectious disease physicians who practiced in infectious disease clinics at medium-sized facilities. This was particularly true for darunavir and tipranavir. By the end of one year, providers at nearly half of the VHA facilities were prescribing these new agents.
The study was published in HIV Medicine, 2010;11(3):209–215.
Recent FDA Approvals and Changes
On April 6, 2010, the FDA granted tentative approval for generic tenofovir disoproxil fumarate tablets, 300 mg, under expedited review procedures for the President's Emergency Plan for AIDS Relief (PEPFAR). This generic formulation is manufactured by Hetero Drugs, Ltd.,of Hyberdad, India. FDA's tentative approval of this product means that while FDA cannot fully approve the product for sale in the United States because of existing patent protections, it has been shown to meet all of FDA's safety, efficacy and manufacturing quality standards. Tentative approval qualifies the product for purchase outside the United States using PEPFAR funds.
Also on April 6, 2010, the FDA granted approval for generic didanosine delayed-release capsules, 125 mg, 200 mg, 250 mg, and 400 mg, manufactured by Matrix Laboratories Limited, of Hyberdad, India. Although this Abbreviated New Drug Application (ANDA) was reviewed under the expedited review provisions for PEPFAR, this represents a generic product approval, meaning that this product is eligible for sale in the United States. This approval means that FDA has found the generic formulations of to be bioequivalent and, therefore, therapeutically equivalent to Videx EC Delayed-release Capsules, 125 mg, 200 mg, 250 mg, and 400 mg, respectively, made by Bristol Myers Squibb Company.
The FDA will hold an advisory committee meeting on May 27th to discuss the safety and efficacy of a new drug application (NDA) for Egrifta (tesamorelin acetate) to reduce excess visceral abdominal fat in HIV-related lipodystrophy. EGRIFTA (tesamorelin acetate) is a sterile lyophilized powder for injection developed by Theratechnologies, Inc. The drug is an analogue of growth hormone releasing hormone (GHRH). The proposed indication for EGRIFTA in this application is to induce and maintain a reduction of excess visceral abdominal fat in HIV-infected patients with lipodystrophy.
This will be a public meeting of its Endocrinologic and Metabolic Drugs Advisory Committee. The meeting will be held from 8 a.m. to 5 p.m, at The Inn and Conference Center, University of Maryland University College (UMUC). No registration is required. Background material can be found at
The FDA has approved revised labeling for Viread® (tenofovir disproxil fumarate) to expand the indication to include the treatment of HIV infection in combination with other antiretroviral agents in patients ages 12 to less than 18 years of age. These changes are being made based on 48-week clinical data from Study GS-US-104–0321.
For the treatment of HIV-1 in adolescents who are ≥12 Years of Age and ≥35 kg, the recommended dose is one 300 mg Viread tablet once daily taken orally, without regard to food. Assessment of bone mineral density (BMD) should be considered for adolescents who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained.
The safety of Viread in adolescent patients aged 12 to >18 years is supported by data from one randomized study in which Viread was administered to HIV-1 infected treatment-experienced subjects. In this study, the pharmacokinetic profile of Viread was similar to that found to be safe and effective in adult clinical trials. In Study 321, 87 treatment-experienced subjects 12 to >18 years of age were treated with Viread (N = 45) or placebo (N = 42) in combination with an optimized background regimen (OBR) for 48 weeks. The mean baseline CD4 cell count was 374 cells/mm3 and the mean baseline plasma HIV-1 RNA was 4.6 log10 copies/mL. At baseline, 90% of subjects harbored NRTI resistance-associated substitutions in their HIV-1 isolates. Overall, the trial failed to show a difference in virologic response between the Viread and placebo treatment groups. Subgroup analyses suggest the lack of difference in virologic response may be attributable to imbalances between treatment arms in baseline viral susceptibility to Viread and OBR. Although changes in HIV-1 RNA in these highly treatment-experienced adolescent subjects were less than anticipated, the comparability of the pharmacokinetic and safety data to that observed in adults supports the use of Viread in adolescent patients whose HIV-1 isolate is expected to be sensitive to the drug. The adverse reactions observed in adolescent subjects who received treatment with VIREAD were consistent with those observed in clinical trials in adults.