 |
|
|
| |
ID Week 2013: Co-morbidities
|
| |
| |
Report written for NATAP by David H. Shepp, MD Associate Professor of Medicine Hofstra North Shore-LIJ School of Medicine North Shore University Hospital - Manhasset, NY
Cardiovascular Disease (CVD). Many studies suggest HIV infection confers an increased risk of CVD even after accounting for traditional risk factors. HIV-infected patients are experiencing higher CVD rates at a time when morality from CVD is declining in the general population. The improvement in survival after CVD events in the general population over the past few decades has been attributed to more widely available and more aggressive use of invasive procedures and secondary prevention measures. Only more recently has it been appreciated that HIV-infected individuals have an increased rate of CVD, and with antiretroviral therapy (ART), a life expectancy that warrants aggressive interventions. Silverberg et al. used the Kaiser Permanente database to evaluate mortality in HIV-infected patients experiencing acute coronary syndrome (ACS) [1]. From 1996-2010, 226 HIV-infected patients and 66,321 HIV uninfected patients were identified. The HIV group was younger, had fewer females, were diagnosed more often in the later years of the study, were more likely to have an S-T elevation MI, had higher HDL and triglycerides and smoked more than the HIV-negative group. Raw mortality did not differ between groups, but after adjustment for multiple variables, HIV-infected patients had a 2.2 and 2.5-fold increase in mortality at one and three years, respectively. Compared to HIV-negatives, HIV-positive patients with a CD4 count <200 or 200-499 had a 5.6- and 2.5-fold adjusted increase in mortality, respectively. Mortality in those with a CD4 >500 did not differ from the HIV-negative group. Those on no ART or PI-based ART also had an adjusted increase in mortality (3.4 and 2.5-fold, respectively) compared to HIV-uninfected patients, while those on ART without a PI did not have significantly increased mortality. Data on CVD treatment utilization was not included in the presentation, so the observed differences in mortality might have resulted from differential use of interventions. Also, because the investigators could not ascertain cause of death, it remains uncertain if the increased mortality observed in the HIV group was due to cardiovascular disease, other comorbid conditions or HIV itself. Nevertheless, this study suggests ACS carries a more ominous prognosis in HIV and may warrant more aggressive treatment. Low CD4 counts and PI use have been linked previously to increased risk for development of CVD. This report suggests these factors also influence prognosis once clinical CVD event occur and support the current emphasis on earlier HIV diagnosis and treatment initiation.
ID Week: Higher Mortality With vs Without HIV After Acute Coronary, But Not With High CD4s - (10/10/13)
Hyperlipidemia is one of the most common metabolic disturbances occurring in HIV-infected individuals on antiretroviral (ARV) therapy. It may result from direct effects of certain ARVs or what has been termed "return to health". In reality, control of HIV infection with ARV therapy often returns the patient to same unhealthy lipid levels that would likely have been present in the absence of HIV infection, based on diet, lifestyle and genetics. Management of hyperlipidemia in HIV generally follows the same principles used in the general population, except drug-drug interactions between ARVs and lipid-lowering agents may limit efficacy, increase toxicity and reduce treatment options. Another difference is that patients receiving ARVs known to cause hyperlipidemia may sometimes be managed by switching to alternate ARVs. The SPIRIT study enrolled 476 participants with stable virologic control on an ART regimen anchored by a ritonavir-boosted protease inhibitor (PI) and randomized them to switch to the fixed-dose combination (FDC) of tenofovir DF, emtricitabine and rilpivirine (TDF/FTC/RIL), or remain on the baseline regimen. The primary outcome, reported previously, showed that switching was virologically non-inferior to continuing the PI-containing regimen at 24 weeks. At ID Week 2013, Tebas et al. presented the effects of switching on lipid profiles. At baseline, 41% of participants were on lopinavir or fosamprenavir, older PIs that have been associated with significant hyperlipidemia. Most of the rest were on atazanavir or darunavir, thought to cause less hyperlipidemia. Most were already taking tenofovir at baseline, although 13% were on abacavir, which causes somewhat more hyperlipidemia than tenofovir. After 24 weeks, the mean changes from baseline (mg/dL) in total cholesterol (TC), LDL, HDL and triglycerides (TG) for the switch and PI arms were were -25 and -1, -16 and 0, -4 and -1 and -54 and +3, respectively. With these changes, the proportion of participants in the switch group achieving a TC <200 increased from 59% to 84%, an LDL <100 from 29% to 45% and TG <150 from 59% to 84%, while the PI group had little change. After week 24, participants in the PI arm were switched to the rilpivirine-based FDC. Similar reductions were seen at study week 48 in the delayed switch group while the changes seen in the group originally randomized to switch to the FDC were sustained. No data on the distribution of baseline regimens in the two treatment arms or on use of lipid lowering agents was presented, although Dr. Tebas commented during Q & A that use was low and probably could not explain much of the observed changes. This study suggests patients switching from boosted PI regimens to the TDF/FTC/RIL FDC can gain moderate benefit to plasma lipids, potentially avoiding addition of lipid-lowering agents or allowing use of lower doses which may limit cost or potential for toxicity. Because the regimens used at baseline had varying potential to cause hyperlipidemia, a subgroup analysis according to baseline PI-use would help validate the findings.
ID Week: SPIRIT: Simplification to Rilpivirine/Emtricitabine/Tenofovir DF Single-Tablet Regimen from Boosted Protease Inhibitor Maintains HIV-1 Suppression and Improves Fasting Lipids at Week 48 - (10/10/13)
Bone Disease. Another comorbidity shown in many studies to be increased in HIV is osteoporosis. Traditional risk factors like smoking, alcohol and corticosteroid use, activity level and possibly vitamin D deficiency are important risk factors. Because patients with other chronic inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease also have increased risk for osteoporosis, the pathogenesis of bone mineral density (BMD) loss in HIV is presumed to be related to chronic inflammation as well. However, the mechanism is complex and incompletely understood. Initiation of ART reduces many components of inflammation but accelerates BMD loss. To better understand the relation between BMD and inflammation Hileman et al. measured BMD by DEXA and inflammatory markers over one year in 47 untreated individuals with early HIV (CD4>400) and 41 age, race and gender matched HIV-negative controls [3]. At baseline, BMD for the femoral neck, trochanter, total hip and spine was remarkably similar between groups, despite more smoking, hepatitis C, and higher levels of the inflammatory markers IL-6, sTNFR-II, sVCAM-1 and sICAM-1 in the HIV-infected group. Vitamin D and hsCRP levels were similar in both groups. After 48 weeks, there were no significant changes in the HIV-negative group and the differences between groups did not reach statistical significance. However, HIV-infected patients experienced losses from baseline of about 0.6% and 1.4% for total hip and trochanter BMD, which were statistically significant. More HIV-infected than uninfected individuals had BMD loss at the trochanter (73% vs. 49%, p=o.03) and more progressed to osteopenia or osteoporosis (21% vs. 6%, p=0.09). Multivariable analysis showed that among HIV-infected individuals, white race and elevated IL-6 were the only factors independently associated with progression. For the entire study population, HIV infection conferred a 2.8-fold risk of BMD loss at the trochanter (p=0.03). Adding inflammatory markers to the model partially attenuated the risk. The study findings prompt some additional questions. The average age of study participants was around 40. Is bone loss more significant in older HIV patients? [from jules: yes] Since HIV-infection was already present for a median of 4 years at baseline, why were the baseline BMD values so similar? Does the course of BMD loss accelerate over time? Since IL-6 appeared to be the marker best correlated with BMD loss, why does IL-6 decline while BMD loss worsens after ART initiation? This study confirms that modest BMD loss occurs over a one year time period in HIV-infected individuals not receiving ART and also suggests that inflammation is at least partly to blame. Because of its small size, the power to detect significant difference between groups and bone loss at other sites was limited. Larger studies with longer follow-up may help clarify the picture, although studies of untreated patients will be increasingly hard to do given the trend toward universal ART initiation.
ID Week: "ART-naïve HIV+ adults, but not controls, had BMD loss at the total hip and trochanter sites over 48 weeks" - ART-Naive Adults More Likely to Lose Trochanter BMD Than HIV-Negatives
1. Silverberg M, Hurley L. Prasad A et al. Mortality following hospitalization for acute coronary syndrome among HIV+ and HIV- patients. ID Week 2013, San Francisco, CA, October 2-6, 2013, abstract 759.
2. Tebas P, Palella F, Ruane P et al. SPIRIT: Simplification to Rilpivirine/Emtricitabine/Tenofovir DF Single-Tablet Regimen from Boosted Protease Inhibitor Maintains HIV-1 Suppression and Improves Fasting Lipids at Week 48. ID Week 2013, San Francisco, CA, October 2-6, 2013, abstract 672.
3. Hileman CO, Labbato DE, Storer NJ, McComsey GA. Inflammation, Vitamin D and Change in Bone Mineral Density (BMD) in Antiretroviral Therapy (ART)-Naive HIV-infected and Uninfected Adults-A 48-Week Matched Prospective Cohort Study. ID Week 2013, San Francisco, CA, October 2-6, 2013, abstract 674.
HCV at IDSA & ICAAC - 23 Reports - (10/11/13)
ID Week HIV Articles...
ID Week
October 2-6, 2013
San Francisco
|
| |
|
|
|
|
|
