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HIV-Related Conditions

Prevention Task Force Recommends Wider Bone Screening for Older Women

The U.S. Preventive Services Task Force (USPSTF) this week issued revised guidelines, published in the January 17, 2011, advance online edition of Annals of Internal Medicine, recommending that all women age 65 and older should be screened for bone loss, along with younger women -- and presumably men -- who have equivalent risk. HIV and its treatment may raise the likelihood of bone loss, and experts recently recommended earlier bone screening for HIV positive women and men.

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Elevated Triglyceride Level Increases Likelihood of Peripheral Neuropathy

HIV positive people with higher blood triglyceride levels are more likely to develop peripheral sensory neuropathy, or nerve damage, according to a study described in the January 14, 2011 issue of AIDS. Investigators suggested that the relationship might be due to changes in mitochondria function associated with elevated triglycerides.

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AIDS 2010: Majority of HIV Positive People on Antiretroviral Therapy May Have Reduced Bone Density

About half of people with HIV taking antiretroviral therapy (ART) in a Spanish study had low bone mineral density, and another quarter had more severe bone loss, researchers reported at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. This study found that bone loss was associated with use of tenofovir and protease inhibitors, a finding also supported by results of the ACTG 5142 trial in the U.S.

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Risk Factors for Cancer Mortality among People with HIV

HIV positive people on antiretroviral therapy are more likely to die after cancer diagnosed if they have poor immune function as indicated by a low CD4 T-cell count or are unable to achieve undetectable viral load, according to a study published in the December 14, 2010 advance online edition of AIDS. Regular cancer screening starting at a younger age and prompt treatment could help improve survival in this population, investigators advised.

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Can Morphine Help Protect the Brain against HIV Neurotoxicity and Cognitive Impairment?

Morphine, a drug derived from opium poppies that relieves pain and often triggers addiction, may help protect the brain from damage due to HIV by interfering with the virus' ability to enter cells, according to a study in mice reported last week at the annual meeting of the Society of NeuroImmune Pharmacology. The researchers emphasized that people should not use morphine or similar drugs like heroin to protect the brain, but suggested these findings may offer clues for designing future therapies to prevent neurocognitive impairment in people with HIV.

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People with HIV Have Increased Bone Fracture Risk

HIV positive people in the HIV Outpatient Study were more likely to sustain bone fractures compared with the general population of the same age, according to a study described in the March 10, 2011, advance online edition of Clinical Infectious Diseases. In addition to known factors including hepatitis C coinfection, lowest-ever CD4 cell count was identified as a new risk factor for bone breaks.

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CROI 2010: Risk Factors for Neurocognitive Impairment among People with HIV

People with higher blood and cerebrospinal fluid viral load and lower CD4 cell count are more likely to develop neurocognitive impairment, according to studies presented in February at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) in San Francisco. In addition, researchers with the SMART study reported that cardiovascular risk factors predict poorer neurocognitive performance. But conflicting findings emphasize the need for further research. 

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Is Bone Loss Related to Immune Reconstitution in People on ART?

Immune system recovery and rising T-cell counts after starting antiretroviral therapy (ART) may contribute to bone loss among people with HIV, according to data from a small study presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston. A better understanding of early bone loss may allow for preventive therapies.

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CROI 2010: HIV/HCV Coinfected Patients Demonstrate Poorer Neurocognitive Performance, but No Difference in Neural Imaging

HIV/HCV coinfected individuals with good HIV suppression on performed more poorly than HIV monoinfected people on neurocognitive tests, but the 2 groups showed no significant differences in neural imaging measures, according to a study presented at the recent 17th Conference on Retroviruses and Opportunistic Infections in San Francisco (CROI 2010).

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Bone Loss and Low Vitamin D Levels Are Common among People with HIV

Nearly half of HIV positive people taking antiretroviral therapy (ART) in a Spanish study had low bone mineral density, and more than one-quarter experienced progressive bone loss, according to findings presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) last month in Boston. Two other studies found that HIV positive people are likely to have low levels of vitamin D, which is crucial for bone health.

Growth Hormone Releasing Factor Tesamorelin Reduces Visceral Fat in HIV Positive People with Lipodystrophy

The growth hormone releasing factor tesamorelin (brand name Egrifta, formerly TH9507)reduced the amount of visceral abdominal fat in HIV positive people with central fat accumulation and led to improved feelings about body image, researchers reported in the March 1, 2010 Journal of Acquired Immune Deficiency Syndromes. Tesamorelin lowered total cholesterol and did not cause significant side effects, including blood glucose abnormalities.

Abdominal fat accumulation -- an aspect of lipodystrophy syndrome -- is a concern for many HIV positive people, both in terms of body image and cardiovascular risk. Administration of human growth hormone has been shown to reduce visceral adipose tissue (fat deep within the abdomen), but it can lead to side effects including elevated blood glucose, swelling, bone pain, and carpal tunnel syndrome.

In contrast to administering growth hormone directly, tesamorelin is a growth hormone releasing factor that stimulates the pituitary gland in the brain to secrete more growth hormone. Investigators hypothesized that it might provide similar benefits with fewer adverse effects, and this was supported by initial studies.

Julian Falutz from McGill University School of Medicine and colleagues investigated the effects of tesamorelin in 404 HIV positive participants on antiretroviral therapy (ART) who had excess abdominal fat.

This double-blind Phase 3 trial consisted of 2 sequential parts. During the first 6 months, patients were randomly assigned (2:1) to receive daily subcutaneous injections of 2 mg tesamorelin or placebo. In the extension phase (months 6-12), participants initially receiving tesamorelin were randomly assigned (1:1) to either continue on the same tesamorelin regimen or switch to placebo, while patients initially randomized to placebo switched to tesamorelin.

The primary endpoint was changes in visceral adipose tissue, assessed with both CT and DEXA scans. Secondary endpoints included other body composition measurements, body image, levels of insulin-like growth factor-1 (a protein produced in response to growth hormone stimulation), and safety parameters.

Results

  • Visceral adipose tissue decreased by 10.9% (21 cm2 or about 1 kg) on average in the tesamorelin group versus a 0.6% (1 cm2 or about 0.2 kg) decrease in the placebo group during the first 6 months (P < 0.0001).
  • Trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-to-hip ratio (P = 0.001) all improved significantly, with no changes in limb or subcutaneous abdominal fat.
  • Patients reported significantly less distress about belly appearance in the tesamorelin group compared with the placebo group (P = 0.02).
  • Physicians' ratings of patient belly appearance also improved significantly (P = 0.02).
  • Among participants who continued on tesamorelin for 12 months, visceral adipose tissue decreased by 17.5% (P < 0.001).
  • However, the visceral adipose tissue improvements of the first 6 months were rapidly lost in patients who switched from tesamorelin to placebo.
  • Patients receiving tesamorelin did not experience a significant decrease in triglycerides compared with placebo (as was seen in a prior Phase 3 study), but there was a trend in this direction.
  • Participants who received tesamorelin for 12 months experienced a significant decrease in total cholesterol.
  • Tesamorelin was well-tolerated overall.
  • Levels of insulin-like growth factor-1 increased significantly, but there was no apparent change in glucose parameters.
  • About 4% of participants experienced hypersensitivity reactions, which were generally mild; a few discontinued therapy prematurely for this reason.

Based on these findings, the study authors concluded, "Tesamorelin reduces visceral fat by approximately 18% and improves body image distress in HIV-infected patients with central fat accumulation. These changes are achieved without significant side effects or perturbation of glucose."

With these new data, they added, "there are now consistent results from two large Phase 3, randomized, placebo-controlled studies to suggest that [tesamorelin] is a potentially useful clinical strategy to selectively reduce visceral adipose tissue and improve body image among HIV-infected patients with abdominal fat accumulation in the context of antiretroviral therapy."

Montreal-based developer Theratechnologies has requested approval of tesamorelin from the U.S. Food and Drug Administration; and the agency will told a public meeting on May 27, 2010 to discuss the topic.

Affiliations: Department of Medicine, Montreal General Hospital and McGill University School of Medicine, Montreal, Canada; Massachusetts General Hospital and Harvard Medical School, Boston, MA.

4/2/10

Reference

J Falutz, D Potvin, JC Mamputu, and others. Effects of Tesamorelin, a Growth Hormone-Releasing Factor, in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Placebo-Controlled Trial With a Safety Extension. Journal of Acquired Immune Deficiency Syndromes 53(3): 311-322. March 1, 2010.

Tesamorelin Growth Hormone-releasing Factor Reduces Visceral Fat in Diverse Patient Groups

Tesamorelin (TH9507, brand name Egrifta), a recombinant form of human growth hormone-releasing factor, decreased the amount of visceral abdominal fat over 1 year in a variety of sub-populations of HIV patients with lipodystrophy, according to research presented at the recent 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). A related study found that fat loss measured by CT scans was reflected in reduced waist size and improved patient-reported body image.

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CROI 2011: Low Vitamin D Levels Less Likely with Rilpivirine than Efavirenz

HIV positive people who use antiretroviral regimens containing the investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (TMC278) saw smaller changes in their vitamin D levels and were less likely to develop severe deficiency than people taking efavirenz, according to a presentation at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston.

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HIV Infection Linked to Increased Cardiovascular Risk Even in Long-term Non-progressors

Markers of endothelial dysfunction -- an early indicator of cardiovascular disease -- were elevated in HIV positive people who maintained a stable viral load and CD4 cell count without antiretroviral therapy (ART), and even among "elite controllers," according to a study presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) this week in Boston. This finding adds further evidence that factors other than waning CD4 T-cell function -- for example, persistent inflammation -- contribute to non-AIDS conditions in the ART era.

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CROI 2010: HIV Infection and HIV/HCV Coinfection Increased Risk of Strokes in Veterans Study

HIV positive veterans had about twice the risk of having a stroke as their HIV negative counterparts, and being coinfected with hepatitis C virus (HCV) further elevated the risk, but hepatitis C alone conferred an insignificant increase, according to a poster presented at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last month in San Francisco. The researchers suggested stroke death may have been underestimated in the past.

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Updated Recommendations for Prevention of Invasive Pneumococcal Disease

This new report from the U.S. Centers for Disease Control and Prevention (CDC) provides updated recommendations for prevention of invasive pneumococcal disease (IPD), which affects a broad spectrum of the U.S. population. The risk for IPD is highest among individuals who are immunocompromised, such as those with HIV infection or asplenia (e.g., sickle cell disease or congenital or surgical asplenia). Recommendations for revaccination among persons with immunocompromising conditions remain unchanged since the report issued in 1997. The indications for which vaccination is recommended now include smoking and asthma.

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CROI 2010: Quitting Smoking Lowers Risk of Cardiovascular Disease in People with HIV

Cigarette smoking was associated with a significantly higher rate of cardiovascular disease among people with HIV, but the risk began to decline after quitting and continued to fall over time, researchers reported at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last week in San Francisco. A similar pattern was not seen for overall mortality, however.

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People with CD4 Counts below 200 May Stop Pneumocystis Pneumonia Prophylaxis if Viral Load Is Undetectable

HIV positive people with a CD4 T-cell count between 100 and 200 cells/mm3 may be able to safely discontinue preventive medications for Pneumocystis jiroveci (formerly P. carinii) pneumonia, or PCP, if they maintain undetectable HIV RNA on combination antiretroviral therapy (ART), according to a report in the September 15, 2010 issue of Clinical Infectious Diseases.

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CROI 2010: HIV Raises Lung Cancer Risk, but Smoking Is a Much Stronger Predictor

HIV infection is significantly associated with lung cancer, increasing the risk by nearly 2-fold, but this was far overshadowed by tobacco smoking, which raised the risk by almost 10-fold, according to a study presented last week at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) in San Francisco. Smoking-related risk declined over time after quitting, but never fell to the level of people who never smoked.

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AIDS 2010: CHARTER Study Finds Neurocognitive Impairment Still Common in ART Era, Linked to Lowest CD4 Cell Count

Neurocognitive impairment ranging from subtle to severe remains common among people with HIV despite widespread use of effective combination antiretroviral therapy (ART), according to findings from the large CHARTER study presented at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. Impairment was associated with nadir or lowest-ever CD4 cell count, even among individuals whose immune function has since recovered on ART.

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Inflammatory Markers and Cardiovascular Risk in Treated and Untreated People with HIV

Two recently published studies shed further light on the relationship between inflammation and non-AIDS conditions in people with HIV. One study found that HIV positive people may have elevated levels of the inflammatory biomarker high-sensitivity C-reactive protein (CRP), even if they are on effective antiretroviral therapy (ART) and otherwise have a low cardiovascular risk. The second study found that people with untreated HIV infection had lower HDL (good) cholesterol and increased levels of inflammatory and coagulation markers compared with HIV negative individuals.

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