Archives of the Balkan Medical Union Copyright © 2013 CELSIUS
vol. 48, no. 4, pp. 447-451 December 2013
CASE REPORT
OSTEOPOROSIS IN A HIV-HCV COINFECTED PATIENT UNDER cART – CASE REPORT SIMONA CLAUDIA CAMBREA Infectious Diseases Clinic, Faculty of Medicine, “Ovidius” University Constanåa, Romania Children Infectious Diseases Department, Constanåa Clinical Infectious Diseases Hospital, Constanåa, Romania
S UMMARY
R ÉSUMÉ
Background: Recent studies have explored the apparent connection between HIV infection, combined antiretroviral therapy (cART) and osteoporosis, and some considered additional factors like coinfections with HCV. Results: In this article we present a case of a 24 years old HIV positive female diagnosed with osteoporosis in a screening evaluation. Patient presented a good adherence to antiretroviral treatments and in a period of 3 years she presented many episodes of pain in different articulations (hands, feet, and spine). After bone mineral density measurements (DEXA examination) we establish diagnosis of osteoporosis at lumbar spine and osteopenia for bilateral femoral neck. After one year of treatment with a combination of acidumalendronicum and colecalciferolum – 70 mg –one tablet/week clear improvement was recorded. Conclusions: It’s obvious that long term antiretroviral treatment can improve survival in HIV positive patients, but side effects as bone demineralization could be present. Key words: osteoporosis, DEXA, HIV, HCV, chronic inflammation
L’ostéoporose chez une patiente avec l’infection HIV associée au traitement anti-rétroviral (TARV)
I NTRODUCTION one is a living, growing material. Old bone is removed and new bone is added all the time. It is already known that in children and young adults, more bone is added than is removed. Also, after age of 30, more bone is removed than is added. Osteoporosis occurs when too much mineral is removed from
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Correspondence address:
Contexte: Des études récentes ont exploré le lien apparent entre l'infection VIH, associée au traitement antirétroviral (TARV) et l'ostéoporose aussi qu´aux certains autres facteurs considérés comme coïnfections avec VHC. Résultats: Dans cet article nous présentons le cas d'une femme de 24 ans positive au VIH, diagnostiquée avec ostéoporose dans une évaluation de dépistage. Le patient présentait une bonne adhérence aux traitements antirétroviraux et dans une période de 3 ans, elle a souffert de nombreux épisodes de douleur aux différentes articulations (mains, pieds et colonne vertébrale). Après avoir réalisé les mesurages de la densité minérale osseuse (examen DEXA), nous établissons un diagnostic de l'ostéoporose au rachis lombaire et de l'ostéopénie au col fémoral bilatéral. Après un an de traitement avec une combinaison de acidumalendronicum et colecalciferolum - 70 mg - un comprimé/semaine on a enregistré une amélioration visible. Conclusions: Il est évident que le traitement antirétroviral à long terme peut améliorer la survie chez les patients VIH positifs, mais des effets secondaires comme la déminéralisation osseuse pourraient être présents. Mots clés: ostéoporose, DEXA, le VIH, le VHC, l'inflammation chronique
the bone framework. Osteopenia is a mild or moderate loss of bone minerals. Metabolic and morphologic changes are frequent complications of HIV disease and its treatment, and may be associated with chronic inflammation. [1] Although there is no doubt about the benefits of combined antiretroviral therapy (cART) in prolonging life, on long term its adverse effects are still incompletely known.
Claudia Simona Cambrea MD, Ph.D. University lecturer, Faculty of Medicine, “Ovidius” University, Constanåa, Romania Castanilor Str., no. 19, Constanåa, Romania, 900190 E-mail:
[email protected]
OSTEOPOROSIS IN A HIV-HCV COINFECTED PATIENT UNDER CART - CAMBREA
Prevalence estimates of osteopenia and osteoporosis in HIV-infected patients and the role of cART vary in the literature. Many studies considered that HIV-positive patients who had been exposed to antiretroviral therapy or protease inhibitors had a higher rate of reduced bone mineral density and osteoporosis than non-exposed patients. [1, 2, 3] Most recent studies suggest that chronic viral hepatitis may also increase the risk of developing osteoporosis among people with HIV.[4]
M ATERIAL
AND
PRESENTATION
We present a case of a female patient, 24 years old, diagnosed with AIDS at age of 5. Possible route of HIV infection remains unknown because she was adopted when she was 3 years old. After adoption she presented no history of blood transfusions, just multiple hospitalizations and multiple parenteral treatments. From patient’s medical history we recall many opportunistic infections as we can see in table 1, some of them being indicator of AIDS (Kaposi’s sarcoma), some specific for HIV infection (hepatomegaly, lymphadenopathy,
Figure 1 - Evolution of CD4 count and Viral load – HIV
Table 1 - Medical history Medical history Hepatomegaly Lymphadenopathy Recurrent bacterial pneumonia Nose/ear/throat infections HIV parotiditis Height and Weight deficit Kaposi’s sarcoma Herpes zoster
Year 1989 1989 1989; 1993 1990 1991 1991 1998 2000
M ETHOD
We performed a retrospective study about clinical and paraclinical evaluation in a young female HIV positive with multiple osteoarticular symptoms. Blood examinations performed were: full blood count,inflammatory tests, liver transaminases, level of HIV-RNA, and CD4 count. HIV RNA was performed by polymerase chain reaction (PCR), using a real-time PCR method, ROCHE AMPLICOR. CD4 count was performed by Facs Count Becton Dickinson.Complementary bone investigations were: bone scintigraphy, and bone density, which was assessed by dual-energy X-ray absorptiometry - DEXA. Ethic comittee agreement was obtained in order to publish patient data and accompanying images. Written informed consent of patient was obtained regarding participation in medical teaching process and scientific interest.
C ASE
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Table 2 - Combined antiretroviral regimens cART
Period of time
Zidovudine+Lamivudine+Nelfinavir
20.02.1998 – 27.03.2000 27.03.2000 – 04.07.2000 22.09.2003 – in present
Zidovudine+Indinavir+Ritonavir Lopinavir/ritonavir + Zidovudine /Lamivudine
herpes zoster), and other suggestive for pediatric HIV (height and weight deficit and HIV parotiditis). Over the time patient received just 3 different antiretroviral regimens, as we can see in table 2. In the last 10 years she received an antiretroviral regimen based on boosted Lopinavir with ritonavir. After initial mild digestive side effects (nausea, watery stools, abdominal pain) patient had no other digestive symptoms. Her immunological and virusological evolution were very good as we presented in fig. 1. At the age of 13, patient presented at some routine evaluations levels of liver transaminases slightly increased and at the age of 14 these presented the highest peak of them. Also,occasionally patient presented short periods of fatigue and arthralgia in small articulations at hands and feet. We check viral etiology for chronic hepatitis B or C and we find total antibody for hepatitis C virus (HCV) positive and a RNA HCV of 552126 IU/L.
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Figure 2 - Bone scintigraphy
At 18 years old, there appeared first signs of lipoatrophy at her face and limbs. Concomitantly with these clinical obvious changes we noticed some changes in level of triglycerides and total cholesterol. These increased in lipids level were noticed after 6 years of different PIs based regimen (Nelfinavir, Indinavir, Lopinavir). Even if we recommend diet and exercises, the levels of triglycerides and total cholesterol decreased only under treatment with Rosuvastatin. After age of 19 years, over a period of 3 years she presented important pain in different articulations.Left sacroileitis was diagnosed after a bone scintigraphy at age of 20, which showed increased uptake of radiotracer at the level of joints of the spine (all regions), scapular-humeral joints, sacro-iliac joints, hip joints and knee joints (bilateral),due to inflammatory processes. All these changes were presented in fig. 2. All these pain episodes in moments of exacerbation were accompanied by increased levels of erythrocyte sedimentation rate (ESR), and C reactive protein. At age of 21 we performed a DEXA examination which revealed changes in bone mineral density (BMD) compatible with osteoporosis.First DEXA results evidenced a T score that highlights suggestive values for osteoporosis at lumbar spine and osteopenia for femoral neck bilaterally; the risk of fracture was high, as we can see in fig. 3. After one year value of BMD measured by DEXA shown an increase by 0.4% at the level of lumbar spine and by 2.0% at the level of
bilateral femoral neck.After one year of treatment with acidumalendronicum and colecalciferolum, even high risk of fracture persists; clear improvement was recorded, as we can see in fig. 4.
D ISCUSSION Recent reports showed a high frequency of osteopenia /osteoporosis in HIV-infected subjects. Patients with HIV have unusually high rates of low bone mineral density and broken bones. Mechanism of this alteration is still unclear, as the direct effect of virus, as consequence of chronic inflammation, or by some antiretroviral drugs used in HIV treatment.[5, 6] Even if our patient was adherent to cART, and viral load for HIV was undetectable chronic inflammation was present in our case. This chronic inflammation was evidenced by increased level of ESR and C reactive protein, and also at bones levels by bone scintigraphy. Brown and Qaqishin a meta-analytic review found that the prevalence of osteoporosis in HIV positive patients is more than three times greater compared with HIV uninfected. Patients exposed to cART and specially to PI had a higher prevalence of reduced BMD and osteoporosis, like in our case. The influence of other disease and treatment variables could not be determined in the reviewed articles. [2, 3] Our patient received antiretroviral therapy with three
OSTEOPOROSIS IN A HIV-HCV COINFECTED PATIENT UNDER CART - CAMBREA
Figure 3 - DEXA- first examination
Figure 4 - DEXA – second examination
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different PI’s. In a study by Tebaset et al., they found that osteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution. [3, 7] In our patient, as consequence of HIV treatment for more than 10 years, with Lopinavir, patient presented both lipoatrophy and reduced BMD. In a study by Bedimo R et al., they found that patients with cumulative exposure to TDF and, LPV/r were at increased risk of osteoporotic fracture in the cART era. [8] In our case the patient was diagnosed with osteoporosis as a result of DEXA screening examination and the patient received specific treatment. Thus in our case although osteoporosis was present there were no spontaneous fractures. In a multinational study performed by Hoy Jet et al., they randomized patients in two types of second-line regimens. In this study even there were registered less bone mineral density in regimens containing raltegravir and lopinavir/ritonavir compared with regimens containing NRTIs plus lopinavir/ritonavir, incidence of osteopenia or osteoporosis did not differ between the two treatment arms. [9] Some reports presented in IAS 2011 showed that the rate of fractures increased over the time among HIV positive patients. Also participants in the cART era (1996 - 2009) reported bone fractures at a rate that was 2.5 times higher than participants in the pre-cART era. Some additional analysis showed that use of Tenofovir or Lopinavir/ritonavir was associated with a 13 percent increased risk of bone fractures in the cART era. [10] In another study performed by Maouche and collab. osteoporosis was very common in a population of predominantly African-American HIV-HCV co-infected patients, particularly at the spine. Lower BMD was associated with controlled HIV replication, but not with liver disease severity. [4] According to this study in our case HIV – HCV coinfections represent an additional risk factor of osteoporosis.
C ONCLUSIONS Over 10 years of cART with boosted lopinavir a favorable virological and immunological evolution was noticed in our case. Side effects observed over the time such as reduced
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BMD, or dyslipidemia even were present in this case; they were partially corrected under specific treatment. In our case osteoporosis didn’t cause any spontaneous fracture. In our case chronic inflammation, antiretroviral treatment with Lopinavir,and HIV-HCV co-infection represent the main causes of osteoporosis.
R EFERENCES 1.
High sensitivity C-reactive protein (hs-crp) and body composition in a cohort of hiv-infected subjects from nutrition for healthy living,ConfRetrovir Opportunistic Infect 2006 Feb 58;13:abstract no. 752 2. Brown T.T., Qaqish R.B. – Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS, 2006; 20 (17): 2165 –74. 3. Tebas P, Powderly WG, Claxton S, Tantisiriwat W, Teitelbaum SL, Yarasheski KE. Accelerated bone mineral loss in HIVinfected patients receiving potent antiretroviral therapy. AIDS2000 Mar 10; 14 (4):F63–7. 4. Maouche DE, Mehta SH, Sutcliffe C, Higgins Y, Torbenson MS, Moore RD, Thomas DL, Sulkowski MS, Brown TT. Controlled HIV viral replication, not liver disease severity associated with low bone mineral density in HIV/HCV co-infection. Journal of Hepatology2011 Oct; 55 (4): 770-6. 5. Bongiovanni M, Fausto A, Cicconi P, Menicagli L, Melzi S, Ligabo VE, Cornalba G, Bini T, Sardanelli F, Monforte AD. Osteoporosis in HIV-infected subjects: a combined effect of highly active antiretroviral therapy and HIV itself? J Acquir Immune DeficSyndr 2005 Dec 1: 40(4) :503–4. 6. Mondy K, Yarasheski K, Powderly WG, Whyte M, Claxton S, DeMarco D, Hoffmann M, and Tebas P. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis 2003 Feb 15; 36:482–90. 7. Cambrea SC, Cambrea M, Raica A, Rugina CN, Rugina S. Coronary artery disease in an HIV+ adolescent.Archives of the Balkan Medical Union, 2009 Jul; 44.(2): 157-160; 8. Bedimo R, Maalouf NM, Zhang S, Drechsler H, Tebas P. Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents, AIDS 2012 Apr 24; 26(7):825-31. doi: 10.1097/QAD.0b013e32835192ae. 9. Hoy J, Martin A, Moore C, Mallon P, Emery S, Belloso W, Phanuphak P, Ferret S, Cooper D,. Boyd M. Changes in bone mineral density over 48 weeks among participants randomised to either lopinavir/ritonavir (LPV/r) + 2-3N(t)RTI or LPV/r + raltegravir as second-line therapy: a sub-study of the SECONDLINE trial. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract WELBB05. 10. April Clayton and Courtney McQueen. Role Of Antiretrovirals In Bone Fractures In People With HIV Remains Unclear (IAS 2011); Published: Jul 29, 2011 1:07 pm; http://www.aidsbeacon. com/news/2011/07/29/role-of-antiretrovirals-in-bone-fracturesin-people-with-hiv-aids-remains-unclear-ias-2011/
