•  ANTIRETROVIRAL THERAPY

New Analysis of SMART Study Backs Continuing HAART Even With CD4 Above 350
Maintaining a CD4+ cell count over 350 cells/mm³ results in a lower risk of AIDS-related complications or death among HIV-infected patients, according to the results from an analysis of the SMART study that was published in the April 15 issue of the Journal of Infectious Diseases. The analysis showed that, over a mean 16 months of follow-up, patients who were taking HAART and had a CD4+ cell count above 350 were less than half as likely to experience an opportunistic infection or die than patients who were not taking HAART and had a CD4+ cell count above 350. The researchers attributed the difference to the presence of a higher HIV viral load among the patients who discontinued therapy.


Study Affirms Value of Initiating HIV Treatment Before CD4 Drops Below 350
In a separate analysis of SMART data published in the same issue of the Journal of Infectious Diseases, findings from other recent studies regarding the benefits of early HAART initiation were reaffirmed. Among a subset of SMART trial participants who were either antiretroviral naive or had not received therapy in the preceding six months, those who initiated HAART with a CD4+ cell count greater than 350 were found to be significantly less likely to develop an opportunistic infection, develop a serious non-AIDS-defining event or die than patients who initiated HAART when their CD4+ cell count dropped below 250.


Unusually High Immune Activation Could Present Danger for Some Elite HIV Controllers
Elite HIV controllers are an extremely fortunate subset of the HIV-infected population, due to their ability to control viremia for a seemingly indefinite period of time without the aid of antiretroviral therapy. However, there may be negative consequences to the unusually strong HIV-specific immune responses exhibited by some elite controllers, according to U.S. researchers. In this interview from the 15th Conference on Retroviruses and Opportunistic Infections, Peter Hunt, M.D., explains the results of his study, which found that some elite controllers may experience a CD4+ cell decline over time due to higher levels of immune activation.


Improving Immunologic Outcomes Among HIV-Infected Patients: A Talk With Steven Deeks, M.D.
The development of therapies that improve an HIV-infected patient's HIV-specific immune response has long been an area of interest for many HIV researchers. One of the foremost researchers in this field is Steven Deeks, M.D. Dr. Deeks recently sat down with Richard Jefferys of Treatment Action Group to discuss his most recent research in the field of immune-based HIV therapy.


Development Halted on Experimental CCR5 Antagonist
The flurry of new antiretroviral approvals in the United States over the past couple of years obscures the brutal reality of drug development: Many experimental drugs never make it to the application phase with the U.S. Food and Drug Administration. One drug at risk is INCB9471, a medication in the new CCR5 antagonist class whose development was halted last month. In spite of promising early studies, the drug's maker decided to stop researching INCB9471 -- a decision that, according to this report from Project Inform, may have been motivated in part by slow sales of maraviroc (Selzentry, Celsentri), the first and only CCR5 antagonist approved in the United States thus far.

•  COMPLICATIONS OF HIV/HAART

MI Incidence Has Not Increased Among HIV-Infected Patients, D:A:D Finds
Although cardiovascular risk has increased among HIV-infected patients over the past seven years, that increase has not translated into a marked rise in overall myocardial infarction (MI) incidence, according to results from the international D:A:D study published in the April 1 issue of Clinical Infectious Diseases. In fact, MIs may have become less common since 1999 as clinicians have taken more aggressive steps, such as prescribing lipid-lowering drugs, to reduce cardiovascular risk in at-risk HIV-infected patients, the researchers suggest. They warn, however, that cardiovascular risk has generally worsened among HIV-infected patients since 1999 (due at least in part to an aging of the population), and the reduction observed in MI risk over time was actually not as large as expected.


Specific Antiretroviral-Associated Adverse Events Vary by Race, Gender, Study Says
Race and gender may play a role in determining the adverse events HIV-infected patients experience while on antiretroviral therapy, according to a U.S. study published in the April 1 issue of JAIDS. In the study of 1,301 patients who initiated HAART between 1999 and 2002 and were followed for a median of five years, grade 4 cardiovascular and renal adverse events were found to occur 2.6 and 3.8 times as often, respectively, among black participants. Women were 2.3 times as likely as men to experience severe anemia. However, the researchers note that, in spite of the differential rates of some specific events, overall rates of adverse events, mortality and toxicity-related treatment discontinuation did not vary by race or gender.


HAART May Improve Survival in HIV-Infected Patients With Hodgkin's Lymphoma
Hodgkin's lymphoma, though not among the cancers included in the list of AIDS-defining illnesses, is nonetheless more common among HIV-infected individuals than among the general population. However, antiretroviral therapy appears to have a beneficial effect on HIV-infected patients with Hodgkin's lymphoma, suggesting that concurrent treatment of HIV and lymphoma may be wise to improve a patient's odds of recovery, according to the results of a study published in the April 1 issue of JAIDS. The 104-patient study found that patients treated with chemotherapy and HAART were significantly more likely to achieve complete remission of their lymphoma, and had a higher survival rate, than patients who received chemotherapy alone.


HIV Does Not Worsen Prostate Cancer, Study Finds
The prognosis of HIV-infected patients with prostate cancer appears no worse than among HIV-uninfected patients with the disease, according to the results of a nationwide U.S. study published on April 2 in the online edition of BJU International. The retrospective study of 17 male patients with HIV and prostate carcinoma (mean age: 59), most of whom were receiving HAART, found that HIV status did not appear to significantly impact a patient's PSA levels or clinical presentation with prostate cancer, nor did it impair a patient's response to cancer treatment. The researchers recommended that clinicians approach prostate cancer treatment in HIV-infected patients the same way they would for HIV-uninfected patients.

•  PATIENT EDUCATION

A Patient-Friendly Guide to Lipoatrophy, Lipohypertrophy and Metabolic Complications
Although much of the terminology surrounding body shape changes and metabolic complications in HIV-infected patients may be familiar to you, for your patients the topic can feel like a jungle of inaccessible gobbledygook. Fortunately, there are some quality educational materials online that your patients can use to help them better understand metabolic issues. This overview from AIDS InfoNet provides a down-to-earth discussion of the different types of body shape and metabolic changes that may be caused by HIV and antiretroviral therapy, and includes guidance on prevention and treatment. This guide is available at The Body, The Body PRO's sister site for the non-clinical HIV community.

For more patient-education materials regarding metabolic complications and gut-related adverse events, be sure to check out The Body's comprehensive, easy-to-read booklet.


A Guide to Immune Reconstitution Inflammatory Syndrome
Immune reconstitution inflammatory syndrome (IRIS) can be a difficult concept to explain to an HIV-infected patient: After all, the idea of experiencing a range of potentially serious adverse events triggered by the initiation of antiretroviral therapy may not be the most intuitive concept for the average patient. To help your patients better understand IRIS, refer them to this guide from Project Inform, which features an explanation of why IRIS may occur, the symptoms it may cause, and how those symptoms can be addressed should they occur. This guide is available at The Body, The Body PRO's sister site for the non-clinical HIV community.

•  HIV PATHOGENESIS

HIV May Reproduce Much Faster Than Previously Thought, Researchers Say
A single, HIV-infected immune cell may produce more than 50,000 copies of HIV during its life span, according to a new U.S. study. "Previous estimates, which just looked at a cell at a single point in time, suggested that 100 to 200 viruses might be made in each infected cell. That estimate was later raised to 1,000 to 2,000," said Alan Perelson, Ph.D., of Los Alamos National Laboratories, a leading investigator in the study. "But when we looked at a cell over its life span, we found each cell was making approximately 50,000 viruses -- and it looks like that's the minimum." The findings, although conducted in SIV-infected rhesus macaques, have potential implications for our understanding of HIV pathogenesis and disease progression.

•  IN THE NEWS

Some Physicians Say No to Pharmaceutical Fees
Is it ethically wrong for a physician to accept an honorarium for consulting with a pharmaceutical company, serving on its speakers bureau or accepting fees for assisting with research? It may be accepted practice within much of the medical community, but media attention and concerns about potential conflicts of interest have ballooned in recent years, leading some physicians to quietly bow out, The New York Times reports. "It is not worth it to be under suspicion," says Peter Libby, M.D., one of a number of physicians who have quietly opted out of taking money from food, drug and medical device companies in exchange for their services as consultants.

•  HIV TRANSMISSION

Tenofovir-Based nPEP Yields Fewer Discontinuations Than Zidovudine-Based nPEP, Study Suggests
Tenofovir (Viread)-based regimens for non-occupational post-exposure prophylaxis (nPEP) compare favorably to zidovudine (AZT, Retrovir)-based regimens, according to a U.S. study published in the April 1 issue of JAIDS. Approximately 100 study participants were prescribed either tenofovir + lamivudine (3TC, Epivir) or tenofovir + emtricitabine (FTC, Emtriva) following a high-risk non-occupational exposure to HIV. Their responses were compared to that of 122 historical controls who received zidovudine + lamivudine. Seventy-two percent of those who took tenofovir + emtricitabine and 87.5% of those who took tenofovir + lamivudine completed their nPEP course, compared to only 42.1% of historical controls. The researchers concluded that the far higher completion rate among tenofovir-based nPEP recipients was largely attributable to a much gentler adverse-event profile.

•  HIV TREATMENT IN DEVELOPING COUNTRIES

Symptoms Nearly as Effective as Labs in Determining Whether to Switch Treatment
In resource-limited regions of the world, where CD4+ cell tests and viral load monitoring can be hard to come by, clinicians can still gauge the success of a patient's antiretroviral regimen by closely monitoring the patient for symptoms of HIV disease progression, according to a study by European researchers published in the April 26 issue of The Lancet. The study divided patients on first-line therapy into three groups: Those monitored only with viral load tests, those monitored only with CD4+ cell count tests, and those who only received clinical monitoring (using World Health Organization definitions of stage 3 and 4 events). Although the researchers found that "viral load monitoring provided a moderate improvement in survival compared with other monitoring strategies," they also noted virtually no difference in survival outcomes among the three groups, nor did they note a "marked detrimental effect" on the development of HIV drug resistance due to a lack of laboratory monitoring. The study authors said the findings supported the expansion of HAART access in resource-limited areas irrespective of the availability of laboratory monitoring.