Home Current Issue Previous Issues Published Ahead-of-Print Collections For Authors Journal Info
Skip Navigation LinksHome > April 13, 2001 - Volume 15 - Issue 6 > Indinavir and systemic hypertension
AIDS:
Research Letters

Indinavir and systemic hypertension

Cattelan, Anna Mariaa; Trevenzoli, Marcob; Sasset, Lolitaa; Rinaldi, Lucianoc; Balasso, Valentinaa; Cadrobbi, Paoloa

Free Access
Article Outline
Collapse Box

Author Information

aInfectious Diseases Department, General Hospital of Padua, Padua, Italy; bULSS 14 Veneto, Italy; and cResearch and Innovation, Padua, Italy.

Received: 4 January 2001; accepted: 30 January 2001.

The introduction of antiretroviral therapy that includes a protease inhibitor (PI) has changed dramatically the clinical perspectives for HIV-infected individuals [1]. Because the risk of HIV mortality is reduced, the importance of long-term side-effects associated with the use of PI has become a relevant issue [2,3]. Indinavir, one of the most widely used PI, has been associated with renal calculi and nephropathy [4,5]. Blood hypertension, as a consequence of indinavir treatment, has not been reported. The aim of this retrospective study was to evaluate the frequency of this side-effect in a cohort of HIV-infected patients receiving indinavir; individuals treated with other PI were used as a reference group. The study population was based on a cohort of HIV-infected patients receiving longitudinal care through the outpatient unit of the Division of Infectious Diseases of Padua, Italy, between January 1997 and June 2000. Inclusion criteria consisted of a duration of PI treatment of at least 6 months and no previous therapy with PI. Individuals with previous hypertension, and confirmed non-compliance (self-reported or drug-monitored) were excluded. According to an internal protocol, patients were followed at monthly clinical visits, at which time blood samples were drawn and blood pressure was taken. Biochemical parameters and urine analysis were monitored every 4 weeks, CD4 cell counts and HIV-RNA levels were monitored every 12 weeks. In the subset of patients in which hypertension was recorded, at least three repeated measurements of blood pressure were taken during a one month period. In addition, 24 h urine collection in order to check for creatinine clearance, protein and glucose excretion, the renin–angiotensin system, together with renal ultrasonography and a Doppler flow study were performed. Hypertension was defined as systolic blood pressure of 140 mmHg or higher, diastolic blood pressure of 90 mmHg or higher, or both [6].

A total of 198 patients were evaluated. Of these, five patients were excluded for the presence of hypertension at baseline, nine for non-compliance and three for lack of follow-up. A study population including 181 patients was thus observed; during a median follow-up period of 34 months (range 6–56), sixty-seven patients (37%) maintained the initial highly active antiretroviral therapy regimen for a median time of 26 months (7–45), whereas 114 patients (63%) changed their highly active antiretroviral therapy, with a median number of regimens of two (2–6). Indinavir was used in 104 patients (group 1) and other PI (nelfinavir, saquinavir, and ritonavir) were used in 77 patients (group 2), which was considered the control group. The baseline characteristics of the two patient groups were well matched for all the considered parameters (Table 1). At study entry both the mean systolic pressure and the mean diastolic pressure were similar in the two groups: 125 mmHg (110–130, SD ± 10.7) and 81 mmHg (60–85, SD ± 6.1) in group 1 versus 126 mmHg (105–135, SD ± 12.0) and 82 mmHg (70–85, SD ± 6.6) in group 2 (no significant differences were found using the Mann–Whitney test).

Table 1
Table 1
Image Tools

During the study period, 31 patients experienced stage 1 or greater blood hypertension: all patients belonged to group 1. The mean systolic pressure was 136 mmHg (105–180, SD ± 17.8) and the mean diastolic pressure was 91 mmHg (60–120, SD ± 12.3) in group 1 compared, respectively, with 125 mmHg (105–138, SD ± 13.0; P < 0.0001 Mann–Whitney test) and 80 mmHg (70–88, SD ± 7.5; P < 0.0001) in group 2. In the 31 patients with hypertension, the mean systolic pressure was 153 mmHg (120–180, SD ± 15.8) and mean diastolic pressure was 100 mmHg (95–120, SD ± 6.2) compared with baseline values of 120 and 80 mmHg, respectively, (P < 0.0001 Wilcoxon rank signed test) (Fig. 1). In six patients a stage 3 hypertension was recorded, in five a stage 2, and in 20 patients a stage 1. The proportion of cases with hypertension was higher in men than in women (M : F: 9 : 1), whereas no significant differences were observed between this subgroup of patients and group 2 in terms of age, CD4 cell count, HIV-RNA levels and type of nucleoside reverse transcriptase inhibitors used in the regimens. No significant changes in renal function were noted, whereas a positive family history for essential hypertension was reported in 18 out of 31 patients (58%).

Fig. 1
Fig. 1
Image Tools

Blood hypertension was effectively controlled with antihypertensive drugs in 18 patients, in nine indinavir was withdrawn (hypertension recovered in four, whereas it persisted in five cases), and in four patients specific therapy was refused because of mild hypertension.

This retrospective analysis showed that indinavir-containing regimens are significantly associated with blood hypertension. The pathogenesis of this side-effect remains unexplained. Further studies are needed to elucidate both the potential role of the prolonged use of previous antiretroviral therapies and the effects of a re-challenge with indinavir therapy. In addition, epidemiological variables such as obesity, alchohol, cigarette smoking, and the use of non-steroidal anti-inflammatory agents should be investigated.

Furthermore, it is of interest that more than half of our 31 patients had a positive family history of hypertension. We could speculate that indinavir, at least in some cases, may trigger latent hypertension, rather than directly cause this effect. These data are in agreement with the absence of renal abnormalities and the normal renin–angiotensin system found in our patients. Although the retrospective nature of the study did not allow us to confirm definitively the relationship between indinavir and hypertension, an important point emerges from this analysis: blood pressure needs to be carefully monitored in regimens that include indinavir. This is particularly important in patients with hypertension or a family history of hypertension, in whom indinavir should be considered as a second line PI antiretroviral therapy.

Anna Maria Cattelana

Marco Trevenzolib

Lolita Sasseta

Luciano Rinaldic

Valentina Balassoa

Paolo Cadrobbia

Back to Top | Article Outline

References

1. Palella FJ, Delaney KM, Moorman AC. et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998, 338: 853 –860.

2. Carr A, Samaras K, Burton S. et al. A syndrome of peripheral lipodistrophy, hyperlipidemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998, 12: F51 –F58.

3. Harrington M, Carpenter CC. Hit HIV-1 hard, but only when necessary. Lancet 2000, 335: 2147 –2152.

4. Brodie SB, Keller JK, Ewenstein BM. et al. Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients. AIDS 1998, 12: 2433 –2437.

5. Taschima KT, Horowitz JD, Rosen S. Indinavir nephropathy. N Engl J Med 1997, 336: 138 –140.

6. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure.Arch Intern Med 1997, 157:2413–2446.

Cited By:

This article has been cited 28 time(s).

Clinical Infectious Diseases
Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America
Gupta, SK; Eustace, JA; Winston, JA; Boydstun, II; Ahuja, TS; Rodriguez, RA; Tashima, KT; Roland, M; Franceschini, N; Palella, FJ; Lennox, JL; Klotman, PE; Nachman, SA; Hall, SD; Szczech, LA
Clinical Infectious Diseases, 40(): 1559-1585.

Hiv Clinical Trials
Update on HIV lipodystrophy
Kravcik, S
Hiv Clinical Trials, 5(3): 152-167.

Circulation
What a cardiologist needs to know about patients with human immunodeficiency virus infection
Hsue, PY; Waters, DD
Circulation, 112(): 3947-3957.
10.1161/CIRCULATIONAHA.105.546465
CrossRef
European Journal of Clinical Microbiology & Infectious Diseases
Prevalence of hypertension in HIV-positive patients on highly active retroviral therapy (HAART) compared with HAART-naive and HIV-negative controls: Results from a Norwegian study of 721 patients
Bergersen, BM; Sandvik, L; Dunlop, O; Birkeland, K; Bruun, JN
European Journal of Clinical Microbiology & Infectious Diseases, 22(): 731-736.
10.1007/s10096-003-1034-z
CrossRef
Drugs
Renal disease in patients with HIV infection - Epidemiology, pathogenesis and management
Fine, DM; Perazella, MA; Lucas, GM; Atta, MG
Drugs, 68(7): 963-980.

Hiv Clinical Trials
Elevated blood pressure in HIV-infected individuals receiving highly active antiretroviral therapy
Chow, DC; Souza, SA; Chen, R; Richmond-Crum, SM; Grandinetti, A; Shikuma, C
Hiv Clinical Trials, 4(6): 411-416.

Journal of Clinical Endocrinology & Metabolism
Carotid intimal medial thickness in human immunodeficiency virus-infected women: Effects of protease inhibitor use, cardiac risk factors, and the metabolic syndrome
Johnsen, S; Dolan, SE; Fitch, KV; Kanter, JR; Hemphill, LC; Connelly, JM; Lees, RS; Lee, H; Grinspoon, S
Journal of Clinical Endocrinology & Metabolism, 91(): 4916-4924.
10.1210/jc.2006-1140
CrossRef
Clinical Journal of the American Society of Nephrology
Cocaine use and hypertensive renal changes in HIV-infected individuals
Fine, DM; Garg, N; Haas, M; Rahman, MH; Lucas, GM; Scheel, PJ; Atta, MG
Clinical Journal of the American Society of Nephrology, 2(6): 1125-1130.
10.2215/CJN.02450607
CrossRef
Nephrology Dialysis Transplantation
Hypertension in HIV-1-infected patients and its impact on renal and cardiovascular integrity
Jung, O; Bickel, M; Ditting, T; Rickerts, V; Welk, T; Helm, EB; Staszewski, S; Geiger, H
Nephrology Dialysis Transplantation, 19(9): 2250-2258.
10.1093/ndt/gfh393
CrossRef
Drugs
Cardiovascular risk in patients with HIV infection - Impact of antiretroviral therapy
Bergersen, BM
Drugs, 66(): 1971-1987.

American Journal of Hypertension
Reversible posterior leukoencephalopathy secondary to indinavir-induced hypertensive crisis: A case report
Giner, V; Fernandez, C; Esteban, MJ; Galindo, MJ; Forner, MJ; Guix, J; Redon, J
American Journal of Hypertension, 15(5): 465-467.
PII S0895-7061(02)02264-1
CrossRef
AIDS
Clinical impact of HIV-related lipodystrophy and metabolic abnormalities on cardiovascular disease
Behrens, GMN; Meyer-Olson, D; Stoll, M; Schmidt, RE
AIDS, 17(): S149-S154.

Hiv Medicine
Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients. A prospective study in a cohort of naive patients
Palacios, R; Santos, J; Garcia, A; Castells, E; Gonzalez, M; Ruiz, J; Marquez, M
Hiv Medicine, 7(1): 10-15.

Clinical Pharmacokinetics
Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection
Fichtenbaum, CJ; Gerber, JG
Clinical Pharmacokinetics, 41(): 1195-1211.

Enfermedades Infecciosas Y Microbiologia Clinica
Hypertension, HIV infection, and highly active antiretroviric therapy
de la Serna, JIB; Zamora, FX; Montes, ML; Garcia-Puig, J; Arribas, JR
Enfermedades Infecciosas Y Microbiologia Clinica, 28(1): 32-37.
10.1016/j.eimc.2008.07.005
CrossRef
Janac-Journal of the Association of Nurses in AIDS Care
Cardiovascular considerations in patients treated with HIV protease inhibitors
Colagreco, JP
Janac-Journal of the Association of Nurses in AIDS Care, 15(1): 30-41.
10.1177/1055329003256922
CrossRef
Clinical Journal of the American Society of Nephrology
Highly active antiretroviral therapy and the kidney: An update on antiretroviral medications for nephrologists
Berns, JS; Kasbekar, N
Clinical Journal of the American Society of Nephrology, 1(1): 117-129.
10.2215/CJN.00370705
CrossRef
Antiviral Therapy
Predictors of hypertension and changes of blood pressure in HIV-infected patients
Thiebaut, R; El-Sadr, WM; Friis-Moller, N; Rickenbach, M; Reiss, P; Monforte, AD; Morfeldt, L; Fontas, E; Kirk, O; De Wit, S; Calvo, G; Law, MG; Dabis, F; Sabin, CA; Lundgren, JD
Antiviral Therapy, 10(7): 811-823.

International Journal of Std & AIDS
Antiretroviral therapy-induced hyperlipidaemia
Nair, D
International Journal of Std & AIDS, 16(): 2-10.

Expert Opinion on Drug Safety
Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients
Harris, M
Expert Opinion on Drug Safety, 7(4): 389-400.
10.1517/14740330802211423
CrossRef
American Journal of Physiology-Regulatory Integrative and Comparative Physiology
Inhibition of bilirubin metabolism induces moderate hyperbilirubinemia and attenuates ANG II-dependent hypertension in mice
Vera, T; Granger, JP; Stec, DE
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 297(3): R738-R743.
10.1152/ajpregu.90889.2008
CrossRef
American Journal of Hypertension
Hypertension in HIV-infected patients: Prevalence and related factors
Jerico, C; Knobel, H; Montero, M; Sorli, ML; Guelar, A; Gimeno, JL; Saballs, P; Lopez-Colomes, JL; Pedro-Botet, J
American Journal of Hypertension, 18(): 1396-1401.
10.1016/j.amjhyper.2005.05.016
CrossRef
Clinical Pharmacology & Therapeutics
Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers
Glesby, MJ; Aberg, JA; Kendall, MA; Fichtenbaum, CJ; Hafner, R; Hall, S; Grosskopf, N; Zolopa, AR; Gerber, JG
Clinical Pharmacology & Therapeutics, 78(2): 143-153.
10.1016/j.clpt.2005.04.005
CrossRef
Expert Opinion on Drug Safety
Cardiovascular & renal - Antiretroviral therapy and the kidney: balancing benefit and risk in patients with HIV infection
Wyatt, CM; Klotman, PE
Expert Opinion on Drug Safety, 5(2): 275-287.
10.1517/14740338.5.2.275
CrossRef
AIDS
The nephrologist in the HAART era
Izzedine, H; Deray, G
AIDS, 21(4): 409-421.
10.1097/QAD.0b013e328011ec40
PDF (168) | CrossRef
AIDS
Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy
Crane, HM; Van Rompaey, SE; Kitahata, MM
AIDS, 20(7): 1019-1026.
10.1097/01.aids.0000222074.45372.00
PDF (140) | CrossRef
AIDS
Cardiovascular disease risk factors in HIV patients – association with antiretroviral therapy. Results from the DAD study
for the DAD study group, ; Friis-Møller, N; Weber, R; Reiss, P; Thiébaut, R; Kirk, O; Monforte, Ad; Pradier, C; Morfeldt, L; Mateu, S; Law, M; El-Sadr, W; De Wit, S; Sabin, CA; Phillips, AN; Lundgren, JD
AIDS, 17(8): 1179-1193.

PDF (177)
Journal of Hypertension
Hypertension in an urban HIV-positive population compared with the general population: influence of combination antiretroviral therapy
Baekken, M; Os, I; Sandvik, L; Oektedalen, O
Journal of Hypertension, 26(11): 2126-2133.
10.1097/HJH.0b013e32830ef5fb
PDF (162) | CrossRef
Back to Top | Article Outline

© 2001 Lippincott Williams & Wilkins, Inc.

Login