An Editorial. Aging with Human Immunodeficiency Virus Infection and the Impact of Long-term Anti-retroviral Therapy
Main Article Content
Abstract
The world is now well into the third decade of use of effective anti-retroviral therapy (ART) that provides sustained control of HIV-1 viremia (viral loads <200 copies of HIV RNA/microliter). With few exceptions, control of HIV in individual patients is predictable and long lasting. Only a short time ago, the prevailing opinion was that HIV infection ‘physiologically aged’ an individual by ten years or more compared to uninfected subjects and could lead to premature frailty.1-4 Whereas these findings may have accurately characterized the untreated HIV-infected individual, they do not apply to those on ART. We discuss these concepts and show why they have not held up to scrutiny since clinical and cellular evidence contradict these statements. Theories about aging in HIV-positive patients arose in the early 2000’s5 about the time we began to study the course of HIV infection in our clinics, measuring frailty as well as obtaining and preserving blood samples from HIV- and healthy, age-matched control patients that allowed us to study cellular aging and immunity as well as the molecular features of HIV genes in viral quasispecies suppressed by ART.
Keywords:
HIV infection, Long-term antiretroviral therapy (ART), Aging with HIV, HIV-associated frailty
Article Details
How to Cite
KLOTZ, Stephen A.; AHMAD, Nafees.
An Editorial. Aging with Human Immunodeficiency Virus Infection and the Impact of Long-term Anti-retroviral Therapy.
Medical Research Archives, [S.l.], v. 12, n. 9, sep. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5703>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i9.5703.
Section
Editorial
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2. Desquilbet L, Margolick JB, Fried LP, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50(3):299-306.
3. Onen NF, Agbebi A, Shacham E, Stamm KE, Onen AR, Overton ET. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009;59(5):346-352.
4. TerzianAS,HolmanS,NathwaniN,etal.Factorsassociatedwith preclinical disability and frailty among HIV-infected and HIV- uninfected women in the era of cART. J Womens Health (Larchmt). 2009;18(12):1965-1974.
5. Martin CP, Fain MJ, Klotz SA. The older HIV-positive adult: a critical review of the medical literature. Am J Med. 2008 Dec;121(12):1032-7. doi: 10.1016/j.amjmed.2008.08.009. PMID: 19028193.
6. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56(3):M146-M156.
7. Rees HC, Ianas V, McCracken P, Smith S, Georgescu A, Zangeneh T, Mohler J, Klotz SA. Measuring frailty in HIV-infected individuals. Identification of frail patients is the first step to amelioration and reversal of frailty. J Vis Exp. 2013 Jul 24;(77):50537. doi: 10.3791/50537. PMID: 23912098; PMCID: PMC3846283.
8. Fried LP, Cohen AA, Xue QL, Walston J, Bandeen-Roche K, Varadhan R. The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nat Aging. 2021 Jan;1(1):36-46. doi: 10.1038/s43587-020-00017-z. Epub 2021 Jan 14. PMID: 34476409; PMCID: PMC8409463.
9. Ahmed N, Mandel R, Fain MJ. Frailty: an emerging geriatric syndrome. Am J Med. 2007 Sep;120(9):748-53. doi: 10.1016/j.amjmed.2006.10.018. PMID: 17765039.
10. Ianas V, Berg E, Mohler MJ, Wendel C, Klotz SA. Antiretroviral therapy protects against frailty in HIV-1 infection. J Int Assoc Provid AIDS Care. 2013 Jan-Feb;12(1):62-6. doi: 10.1177/1545109712457241. Epub 2012 Oct 4. PMID: 23042791.
11. Veeravelli S, Najafi B, Marin I, Blumenkron F, Smith S, Klotz SA. Exergaming in Older People Living with HIV Improves Balance, Mobility and Ameliorates Some Aspects of Frailty. J Vis Exp. 2016 Oct 6;(116):54275. doi: 10.3791/54275. PMID: 27768079; PMCID: PMC5092148.
12. Rees HC, Meister E, Mohler MJ, Klotz SA. HIV-Related Frailty Is Not Characterized by Sarcopenia. J Int Assoc Provid AIDS Care. 2016 Mar-Apr;15(2):131-4. doi: 10.1177/2325957414553848. Epub 2014 Oct 15. PMID: 25320145.
13. Radloff L. The CES_D Scale: a self report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401.
14. Klotz SA and MJ Mohler. Contemporary HIV patients and the frailty syndrome. A short Review. Austin J Infect Dis. 2014; 1(2): 2
15. Shioda T, Levy JA, Cheng-Mayer C: Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature 1991;349:167–169.
16. Behrens NE, Love M, Bandlamuri M, Bernhardt D, Wertheimer A, Klotz SA, Ahmad N. Characterization of HIV-1 Envelope V3 Region Sequences from Virologically Controlled HIV-Infected Older Patients on Long Term Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2021 Mar;37(3):233-245. doi: 10.1089/AID.2020.0139. Epub 2021 Jan 12. PMID: 33287636.
17. Love, M., Samora,L., Barker, D., Zukosky, P., Kummet, N., Ahmad, N., Bernhardt, D., Tripathi, M., Klotz, K. Ahmad, N. Genetic Analysis of HIV-1 vpr Sequences from HIV-Infected Older Patients on Long Term Antiretroviral Therapy. Current HIV Research September 2022.
18. Behrens NE, Wertheimer A, Klotz SA, Ahmad N. Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy. PLoS One. 2018 Jun 13;13(6):e0199101. doi: 10.1371/journal.pone.0199101. PMID: 29897981; PMCID: PMC5999291.
19. Klotz SA, Bradley N, Smith S, Ahmad N. HIV Infection-Associated Frailty: The Solution for Now Is Antiretroviral Drugs: A Perspective. J Int Assoc Provid AIDS Care. 2019 Jan-Dec;18:2325958219831045. doi: 10.1177/2325958219831045. PMID: 30803299; PMCID: PMC6748472.
20. Behrens NE, Wertheimer A, Love MB, Klotz SA, Ahmad N. Evaluation of HIV-specific T-cell responses in HIV-infected older patients with controlled viremia on long-term antiretroviral therapy. PLoS One. 2020 Sep 17;15(9):e0236320. doi: 10.1371/journal.pone.0236320. PMID: 32941433; PMCID: PMC7498024
21. Love, Maria, Nicole Behrens-Bradley, Ahmad, Aasm, Wertheimer, Anne, Klotz, Stephen and Ahmad, Nafees. "Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy." Viral Immunology 37, no. 4 (2024): 202-215.
22. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: From Clinical Significance to Quantification. Adv Sci (Weinh). 2021 Aug;8(15):e2004433. doi: 10.1002/advs.202004433. Epub 2021 Jun 10. PMID: 34114369; PMCID: PMC8336501.
23. Osuji FN, Onyenekwe CC, Ahaneku JE, Ukibe NR. The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects. J Biomed Sci. 2018 Dec 3;25(1):88. doi: 10.1186/s12929-018-0490-9. PMID: 30501642; PMCID: PMC6276218. Levels go down with ART within a year
24. Wiche Salinas TR, Gosselin A, Raymond Marchand L, Moreira Gabriel E, Tastet O, Goulet JP, Zhang Y, Vlad D, Touil H, Routy JP, Bego MG, El-Far M, Chomont N, Landay AL, Cohen ÉA, Tremblay C, Ancuta P. IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells. iScience. 2021 Oct 7;24(11):103225. doi: 10.1016/j.isci.2021.103225. PMID: 34712922; PMCID: PMC8531570.
25. Klotz SA, Egurrola C, Love M, Miller MN, Bradley N, Smith SN, Najafi B, Ahmad N. Phenotypic frailty in people living with HIV is not correlated with age or immunosenescence. Int J STD AIDS. 2022 May;33(6):597-603. doi: 10.1177/09564624221091455. Epub 2022 Apr 4. PMID: 35377254; PMCID: PMC9024027.
26. Toosizadeh N, Wendel C, Hsu CH, et al. Frailty assessment in older adults using upper-extremity function: index development. BMC Geriatr 2017 Jun 2; 17(1): 117PMC5457588.
27. Toosizadeh N, Najafi B, Reiman EM, et al. Upper-extremity dual-task function: an innovative method to assess cognitive impairment in older adults. Front Aging Neurosci 2016; 8: 167.
28. Klotz SA, Nguyen HC, Van Pham T, Nguyen LT, Ngo DT, Vu SN. Clinical features of HIV/AIDS patients presenting to an inner city clinic in Ho Chi Minh City, Vietnam. Int J STD AIDS. 2007 Jul;18(7):482-5. doi: 10.1258/095646207781147265. PMID: 17623507.
29. Klotz SA, Chan CB, Bianchi S, Egurrola C, York LD. The Genie Is Out of the Bottle: Telemedicine Is More Effective Than Brick-and-Mortar Clinics in the Care of HIV-Infected Outpatients. Am J Med. 2023 Apr;136(4):360-364. doi: 10.1016/j.amjmed.2022.11.012. Epub 2022 Dec 8. PMID: 36495936; PMCID: PMC9910587
2. Desquilbet L, Margolick JB, Fried LP, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50(3):299-306.
3. Onen NF, Agbebi A, Shacham E, Stamm KE, Onen AR, Overton ET. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009;59(5):346-352.
4. TerzianAS,HolmanS,NathwaniN,etal.Factorsassociatedwith preclinical disability and frailty among HIV-infected and HIV- uninfected women in the era of cART. J Womens Health (Larchmt). 2009;18(12):1965-1974.
5. Martin CP, Fain MJ, Klotz SA. The older HIV-positive adult: a critical review of the medical literature. Am J Med. 2008 Dec;121(12):1032-7. doi: 10.1016/j.amjmed.2008.08.009. PMID: 19028193.
6. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56(3):M146-M156.
7. Rees HC, Ianas V, McCracken P, Smith S, Georgescu A, Zangeneh T, Mohler J, Klotz SA. Measuring frailty in HIV-infected individuals. Identification of frail patients is the first step to amelioration and reversal of frailty. J Vis Exp. 2013 Jul 24;(77):50537. doi: 10.3791/50537. PMID: 23912098; PMCID: PMC3846283.
8. Fried LP, Cohen AA, Xue QL, Walston J, Bandeen-Roche K, Varadhan R. The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nat Aging. 2021 Jan;1(1):36-46. doi: 10.1038/s43587-020-00017-z. Epub 2021 Jan 14. PMID: 34476409; PMCID: PMC8409463.
9. Ahmed N, Mandel R, Fain MJ. Frailty: an emerging geriatric syndrome. Am J Med. 2007 Sep;120(9):748-53. doi: 10.1016/j.amjmed.2006.10.018. PMID: 17765039.
10. Ianas V, Berg E, Mohler MJ, Wendel C, Klotz SA. Antiretroviral therapy protects against frailty in HIV-1 infection. J Int Assoc Provid AIDS Care. 2013 Jan-Feb;12(1):62-6. doi: 10.1177/1545109712457241. Epub 2012 Oct 4. PMID: 23042791.
11. Veeravelli S, Najafi B, Marin I, Blumenkron F, Smith S, Klotz SA. Exergaming in Older People Living with HIV Improves Balance, Mobility and Ameliorates Some Aspects of Frailty. J Vis Exp. 2016 Oct 6;(116):54275. doi: 10.3791/54275. PMID: 27768079; PMCID: PMC5092148.
12. Rees HC, Meister E, Mohler MJ, Klotz SA. HIV-Related Frailty Is Not Characterized by Sarcopenia. J Int Assoc Provid AIDS Care. 2016 Mar-Apr;15(2):131-4. doi: 10.1177/2325957414553848. Epub 2014 Oct 15. PMID: 25320145.
13. Radloff L. The CES_D Scale: a self report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401.
14. Klotz SA and MJ Mohler. Contemporary HIV patients and the frailty syndrome. A short Review. Austin J Infect Dis. 2014; 1(2): 2
15. Shioda T, Levy JA, Cheng-Mayer C: Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature 1991;349:167–169.
16. Behrens NE, Love M, Bandlamuri M, Bernhardt D, Wertheimer A, Klotz SA, Ahmad N. Characterization of HIV-1 Envelope V3 Region Sequences from Virologically Controlled HIV-Infected Older Patients on Long Term Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2021 Mar;37(3):233-245. doi: 10.1089/AID.2020.0139. Epub 2021 Jan 12. PMID: 33287636.
17. Love, M., Samora,L., Barker, D., Zukosky, P., Kummet, N., Ahmad, N., Bernhardt, D., Tripathi, M., Klotz, K. Ahmad, N. Genetic Analysis of HIV-1 vpr Sequences from HIV-Infected Older Patients on Long Term Antiretroviral Therapy. Current HIV Research September 2022.
18. Behrens NE, Wertheimer A, Klotz SA, Ahmad N. Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy. PLoS One. 2018 Jun 13;13(6):e0199101. doi: 10.1371/journal.pone.0199101. PMID: 29897981; PMCID: PMC5999291.
19. Klotz SA, Bradley N, Smith S, Ahmad N. HIV Infection-Associated Frailty: The Solution for Now Is Antiretroviral Drugs: A Perspective. J Int Assoc Provid AIDS Care. 2019 Jan-Dec;18:2325958219831045. doi: 10.1177/2325958219831045. PMID: 30803299; PMCID: PMC6748472.
20. Behrens NE, Wertheimer A, Love MB, Klotz SA, Ahmad N. Evaluation of HIV-specific T-cell responses in HIV-infected older patients with controlled viremia on long-term antiretroviral therapy. PLoS One. 2020 Sep 17;15(9):e0236320. doi: 10.1371/journal.pone.0236320. PMID: 32941433; PMCID: PMC7498024
21. Love, Maria, Nicole Behrens-Bradley, Ahmad, Aasm, Wertheimer, Anne, Klotz, Stephen and Ahmad, Nafees. "Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy." Viral Immunology 37, no. 4 (2024): 202-215.
22. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: From Clinical Significance to Quantification. Adv Sci (Weinh). 2021 Aug;8(15):e2004433. doi: 10.1002/advs.202004433. Epub 2021 Jun 10. PMID: 34114369; PMCID: PMC8336501.
23. Osuji FN, Onyenekwe CC, Ahaneku JE, Ukibe NR. The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects. J Biomed Sci. 2018 Dec 3;25(1):88. doi: 10.1186/s12929-018-0490-9. PMID: 30501642; PMCID: PMC6276218. Levels go down with ART within a year
24. Wiche Salinas TR, Gosselin A, Raymond Marchand L, Moreira Gabriel E, Tastet O, Goulet JP, Zhang Y, Vlad D, Touil H, Routy JP, Bego MG, El-Far M, Chomont N, Landay AL, Cohen ÉA, Tremblay C, Ancuta P. IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells. iScience. 2021 Oct 7;24(11):103225. doi: 10.1016/j.isci.2021.103225. PMID: 34712922; PMCID: PMC8531570.
25. Klotz SA, Egurrola C, Love M, Miller MN, Bradley N, Smith SN, Najafi B, Ahmad N. Phenotypic frailty in people living with HIV is not correlated with age or immunosenescence. Int J STD AIDS. 2022 May;33(6):597-603. doi: 10.1177/09564624221091455. Epub 2022 Apr 4. PMID: 35377254; PMCID: PMC9024027.
26. Toosizadeh N, Wendel C, Hsu CH, et al. Frailty assessment in older adults using upper-extremity function: index development. BMC Geriatr 2017 Jun 2; 17(1): 117PMC5457588.
27. Toosizadeh N, Najafi B, Reiman EM, et al. Upper-extremity dual-task function: an innovative method to assess cognitive impairment in older adults. Front Aging Neurosci 2016; 8: 167.
28. Klotz SA, Nguyen HC, Van Pham T, Nguyen LT, Ngo DT, Vu SN. Clinical features of HIV/AIDS patients presenting to an inner city clinic in Ho Chi Minh City, Vietnam. Int J STD AIDS. 2007 Jul;18(7):482-5. doi: 10.1258/095646207781147265. PMID: 17623507.
29. Klotz SA, Chan CB, Bianchi S, Egurrola C, York LD. The Genie Is Out of the Bottle: Telemedicine Is More Effective Than Brick-and-Mortar Clinics in the Care of HIV-Infected Outpatients. Am J Med. 2023 Apr;136(4):360-364. doi: 10.1016/j.amjmed.2022.11.012. Epub 2022 Dec 8. PMID: 36495936; PMCID: PMC9910587