Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
HIV & Hodgkin's Disease
- Kieran A Fernando (1 February 2009)
-
HIV and Bone Disease
- Thomas W Hamilton (3 February 2009)
-
HIV and COPD
- Ken M. Kunisaki (11 February 2009)
-
Re: HIV and COPD. Aging, viral infections and blood rheology.
- Les O. Simpson (13 February 2009)
|
|
|||
|
Kieran A Fernando, Specialist Registrar in GenitoUrinary/HIV Medicine Walsall Centre for Sexual Health, Walsall Hospitals NHS Trust, West Midlands WS2 9PS
Send response to journal:
|
Deeks & Phillips make valid comments on the association of advanced immunodeficiency and the risk of non-Hodgkin’s lymphoma.1 It is important to note, however, that the association of HIV and Hodgkin’s disease (HD) may not follow this pattern. An increased incidence of Hodgkin’s disease in the post-cART (combined antiretroviral therapy) era has been observed.2 It is hypothesised that in the setting of improved immunity, the malignant Reed-Sternberg cell of HD has an increased chance of survival and proliferation.2 Chemokines secreted by the Reed-Sternberg cell trigger an influx of CD4 lymphocytes to the local environment. The CD4 lymphocyte and the Reed-Sternberg cell act synergistically and results in inhibition of both apoptosis and further proliferation of the Reed- Sternberg cell.2 In the HIV setting a high degree of Epstein-Barr Virus (EBV) positivity is observed and mixed cellularity and lymphocyte depleted are the commonest HD subtypes, which unfortunately confer a worse prognosis. The recently published British HIV Association (BHIVA) guidelines on the management of HIV-associated malignancy recommend the use of cART in all patients with HIV associated HD.3 1. Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009;338:288-292. 2. Biggar RJ, Jaffe ES, Goedert JJ, et al. Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS. Blood 2006;108:3786-3791. 3. M Bower, et al. British HIV Association guidelines for HIV- associated malignancies 2008. HIV Med 2008;9:336–388. Competing interests: None declared |
|||
|
|
|||
|
Thomas W Hamilton, Academic Foundation Year Doctor John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU
Send response to journal:
|
As Deeks and Phillips note there is indeed emerging data on a link between bone disease, specifically osteoporosis and osteopenia, and HIV infection.[1] This data further highlights the complex interactions between lifestyle, disease and pharmacological factors in this patient group. A recent meta analysis of 20 studies demonstrated that HIV infected patients had a 6.4 fold increased odds of reduced bone mineral density (BMD) compared with HIV negative controls and 3.7 fold increased odds of osteoporosis.[2] Controls were matched for age and BMI with an increased incidence of smoking and amenorrhea noted in HIV infected patients. This difference in BMD had largely been attributed to chronic inflammation caused by HIV however recent in vitro studies have demonstrated that HIV envelope glycoprotein gp120 is capable of directly promoting osteoblast apoptosis as well as osteoclast proliferation, fusion and activation, via up-regulating TNF alpha, leading to unopposed bone re- absorption.[3, 4] This meta analysis also demonstrated that antiretroviral therapy (ART) itself may also directly promote bone demineralisation. When comparing patients treated with ART against ART naive individuals those receiving ART had a 2.5 fold increased risk of a reduced BMD and 2.4 fold increased risk of osteoporosis. This effect was more prevalent in patients treated with protease inhibitors (PI), with an odds ratio of a reduced BMD of 1.5, and of osteoporosis 1.6, fold higher compared to patients treated with an alternative class of antiretroviral drug. The mechanism by which ART, specifically PI, result in reduced BMD remains to be elucidated. Emerging studies suggest this may be a drug, not class, effect. In vitro the protease inhibitors ritonavir and saquinavir have been demonstrated to inhibit IFN gamma associated TNF alpha receptor associated factor 6 (TRAF6) degradation, in effect working synergistically with gp120 promotion of osteoclast activity.[4] This effect was not demonstrated in the PIs indinavir and nelfinavir which have not clinically been linked to bone loss. Longitudinal studies of HIV positive patients initiating ART are needed to delineate the impacts of lifestyle, disease and pharmacological therapy on BMD in this patient group as well as clarify the heterogeneous actions of different classes of ART. What is clear however is that we must take a holistic approach to HIV management, reducing traditional risk factors, managing HIV as well as being aware of the iatrogenic effects of therapy. [1] Deeks SG & Phillips AN. HIV infection, antiretroviral treatment, ageing and non-AIDS related morbidity. BMJ 2009;338:a3172. (31 January) [2] Brown TT & Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20:2165-2174. [3] Gibellini D, De Crignis E, Ponti C, Cimatti L, Borderi M, Tschon M, Giardino R & Re MC. HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNF alpha activation. Journal of Medical Virology 2008 80:1507-1514. [4] Fakruddin JM & Laurence J. Interactions among human immunodeficiency virus (HIV)-1, interferon-gamma and receptor of activated NF-kappa B ligand (RANKL): implications for HIV pathogenesis. Clinical Experimental Immunology 2004 137:538-45 Competing interests: None declared |
|||
|
|
|||
|
Ken M. Kunisaki, Staff Physician and Assistant Professor Minneapolis VA Medical Center and University of Minnesota, 55417
Send response to journal:
|
Deeks and Phillips note that HIV infection is associated with the premature development of multiple diseases that are more typically part of the normal ageing process [1]. I would like to add chronic obstructive pulmonary disease (COPD) as another similar disease for consideration. Humans reach peak lung function around the age of 25 years, after which lung function steadily declines throughout life. In persons who smoke cigarettes and are susceptible to COPD, this rate of decline is faster. Persons with HIV infection have been observed to experience a faster rate of lung function decline than would be predicted from aging alone [2]. Compared to similarly aged persons without HIV infection, they also have a higher prevalence of radiographic emphysema [3] and both diagnostic codes and self-report of COPD, even when stratified by smoking history [4]. Given the high rates of cigarette smoking in HIV-infected populations and the increased life expectancy of these patients, the topics of accelerated lung function decline and COPD in HIV infection are worthy of clinical consideration and further research. 1. Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009;338:288-292. 2. Morris AM, Huang L, Bacchetti P, et al. Permanent declines in pulmonary function following pneumonia in human immunodeficiency virus- infected persons. Am J Respir Crit Care Med. 2000;162:612-616. 3. Diaz PT, King MA, Pacht ER, et al. Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers. Ann Intern Med 2000;132:369-372. 4. Crothers K, Butt AA, Gibert CL, et al. Increased COPD among HIV- positive compared to HIV-negative veterans. Chest 2006;130:1326-1333. Competing interests: Recipient of an investigator-initiated research grant from GlaxoSmithKline (2005-2006) |
|||
|
|
|||
|
Les O. Simpson, retired experimental pathologist Dunedin, New Zealand 9077
Send response to journal:
|
Because of the reluctance of clinicians to accept that change in blood rheology has some pathophysiological significance, it is unlikely that they are aware of the effects of aging and viral infections on blood flow. In 1998, Ajmani and Rifkind (1) published an informative article titled, "Hemorheological changes during human aging", which showed that during the aging process, blood viscosity increased and red cell deformability decreased. In 2003 (2) we reported that immediately-fixed blood samples from subjects aged between 60 and 96 years had changed shape populations of red cells, which would explain the reduced red cell deformability reported by Ajmani and Rifkind. Changes in the internal environment associated with viral infections change the shape populations of red cells. Blinded blood samples provided by Westminster Hospital from HIV+ and AIDS patients showed that AIDS-related red cells were markedly different from HIV+ cells in terms of the cell shape populations. Given that the adverse effects on blood flow of the changes associated with AIDS will be additive to those related to aging, is it likely that COPD will be understood and treated effectively without taking cognisance of the changed blood rheology ? References. 1. Ajmani RS, Rifkind JM. Hemorheological changes during human aging. Gerontology 1998;44: 111-20. 2. Simpson, O'Neill DJ. Red cell shape changes in the blood of people 60 years of age and older imply a role for blood rheology in the aging process. Gerontology 2003;44:310-5. Competing interests: None declared |
|||