Skip to main content
Erschienen in: Current HIV/AIDS Reports 2/2018

05.03.2018 | Co-infections and Comorbidity (S Naggie, Section Editor)

Serious Non-AIDS Conditions in HIV: Benefit of Early ART

verfasst von: Jens D. Lundgren, Alvaro H. Borges, James D. Neaton

Erschienen in: Current HIV/AIDS Reports | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose of review

Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions.

Recent findings

Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function.

Summary

HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.
Literatur
1.
Zurück zum Zitat • Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384(9939):241–8. International cohort collaboration demonstrating marked reduction in last 15 years in fatal AIDS and SNA-related events incl those caused by cardiovascular and liver pathologies but not non-AIDS cancers. Whereas reduction in AIDS conditions were associated with gradually increasing CD4+ lymphocyte count, this was not the case for the SNA conditions, but perhaps better quality of care . CrossRefPubMed • Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384(9939):241–8. International cohort collaboration demonstrating marked reduction in last 15 years in fatal AIDS and SNA-related events incl those caused by cardiovascular and liver pathologies but not non-AIDS cancers. Whereas reduction in AIDS conditions were associated with gradually increasing CD4+ lymphocyte count, this was not the case for the SNA conditions, but perhaps better quality of care . CrossRefPubMed
2.
Zurück zum Zitat The Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.CrossRef The Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.CrossRef
4.
Zurück zum Zitat Lifson AR, Belloso WH, Davey RT, Duprez D, Gatell JM, Hoy JF, et al. Development of diagnostic criteria for serious non-AIDS events in HIV clinical trials. HIV Clin Trials. 2010;11(4):205–19.CrossRefPubMedPubMedCentral Lifson AR, Belloso WH, Davey RT, Duprez D, Gatell JM, Hoy JF, et al. Development of diagnostic criteria for serious non-AIDS events in HIV clinical trials. HIV Clin Trials. 2010;11(4):205–19.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat May MT, Vehreschild J, Trickey A, Obel N, Reiss P, Bonnet F, et al. Mortality according to CD4 count at start of combination antiretroviral therapy among HIV-infected patient followed for up to 15 years after start of treatment: collaborative cohort study. Clin Infect Dis. 2016;62:1571–7.CrossRefPubMedPubMedCentral May MT, Vehreschild J, Trickey A, Obel N, Reiss P, Bonnet F, et al. Mortality according to CD4 count at start of combination antiretroviral therapy among HIV-infected patient followed for up to 15 years after start of treatment: collaborative cohort study. Clin Infect Dis. 2016;62:1571–7.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Baker JV, Peng G, Rapkin J, Krason D, Reilly C, Cavert WP, et al. Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. J Acquir Immune Defic Syndr. 2008;48:541–6.CrossRefPubMedPubMedCentral Baker JV, Peng G, Rapkin J, Krason D, Reilly C, Cavert WP, et al. Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. J Acquir Immune Defic Syndr. 2008;48:541–6.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Achhra AC, Amin J, Law MG, Emery S, Gerstoft J, Gordin FM, et al. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS. 2010;24(12):1877–86.CrossRefPubMedPubMedCentral Achhra AC, Amin J, Law MG, Emery S, Gerstoft J, Gordin FM, et al. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS. 2010;24(12):1877–86.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat •• Grund B, Baker JV, Deeks SG, et al. Relevance of interleukin-6 and D-dimer for serious non-AIDS morbidity and death among HIV-positive adults on suppressive antiretroviral therapy. PLoS One. 2016;11:e0155100. Combined cohort analysis demonstrating persisting prognostic impact from initial levels of interleukin-& and D-dimer. These observations were confirmed in the START cohort (Baker JV, Sharma S, Grund B, et al. Association of inflammation and coagulation with clinical risk in the START Trial. Abstract, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington, 2017) . CrossRefPubMedPubMedCentral •• Grund B, Baker JV, Deeks SG, et al. Relevance of interleukin-6 and D-dimer for serious non-AIDS morbidity and death among HIV-positive adults on suppressive antiretroviral therapy. PLoS One. 2016;11:e0155100. Combined cohort analysis demonstrating persisting prognostic impact from initial levels of interleukin-& and D-dimer. These observations were confirmed in the START cohort (Baker JV, Sharma S, Grund B, et al. Association of inflammation and coagulation with clinical risk in the START Trial. Abstract, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington, 2017) . CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009;360:1815–26.CrossRefPubMedPubMedCentral Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009;360:1815–26.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, et al. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1 infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet. 2009;373:1352–63.CrossRefPubMed Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, et al. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1 infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet. 2009;373:1352–63.CrossRefPubMed
11.
Zurück zum Zitat CASCADE Collaboration, Jonsson M, Fusco JS, Cole SR, Thomas JC, Porter K, et al. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med. 2011;171:1560–9.CrossRef CASCADE Collaboration, Jonsson M, Fusco JS, Cole SR, Thomas JC, Porter K, et al. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med. 2011;171:1560–9.CrossRef
12.
Zurück zum Zitat Cain LE, Logan R, Robins JM, Sterne JA, Sabin C, Bansi L, et al. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study. Ann Intern Med. 2011;154:509–15.CrossRefPubMed Cain LE, Logan R, Robins JM, Sterne JA, Sabin C, Bansi L, et al. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study. Ann Intern Med. 2011;154:509–15.CrossRefPubMed
13.
Zurück zum Zitat • The HIV-Causal Collaboration, Lodi S, Phillips A, Logan R, Olson A, Costagliola D, et al. Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study. Lancet HIV. 2015;2:e335-e-345. Most recent report to address whether statistical analysis of observational studies can predict the benefit from earlier initiation of ART. The predicted benefit (3–20%) was smaller than what was observed in the START study . • The HIV-Causal Collaboration, Lodi S, Phillips A, Logan R, Olson A, Costagliola D, et al. Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study. Lancet HIV. 2015;2:e335-e-345. Most recent report to address whether statistical analysis of observational studies can predict the benefit from earlier initiation of ART. The predicted benefit (3–20%) was smaller than what was observed in the START study .
14.
Zurück zum Zitat Lane HC, Neaton JD. When to start therapy for HIV infection: a swinging pendulum in search of data. Ann Intern Med. 2003;138(8):680–1.CrossRefPubMed Lane HC, Neaton JD. When to start therapy for HIV infection: a swinging pendulum in search of data. Ann Intern Med. 2003;138(8):680–1.CrossRefPubMed
15.
Zurück zum Zitat Lundgren JD, Babiker AG, Gordin FM, et al. When to start antiretroviral therapy: the need for an evidence base during early HIV infection. BMC Med. 2013;11:148.CrossRefPubMedPubMedCentral Lundgren JD, Babiker AG, Gordin FM, et al. When to start antiretroviral therapy: the need for an evidence base during early HIV infection. BMC Med. 2013;11:148.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat •• TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):808–22. Single country (Ivory Coast) randomised controlled trial demonstrating clinical benefit from starting ART earlier rather than later in course of early HIV infection. Benefit was due to reduced risk of tuberculosis and invasive bacterial infections (44% reduction) . CrossRef •• TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):808–22. Single country (Ivory Coast) randomised controlled trial demonstrating clinical benefit from starting ART earlier rather than later in course of early HIV infection. Benefit was due to reduced risk of tuberculosis and invasive bacterial infections (44% reduction) . CrossRef
17.
Zurück zum Zitat •• The INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795–807. Large, geographical diverse randomised controlled trial demonstrating clinical benefit from starting ART earlier rather than later in course of early HIV infection. Benefit was due to reduced risk of opportunistic infections and cancer (57%) . CrossRefPubMedCentral •• The INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795–807. Large, geographical diverse randomised controlled trial demonstrating clinical benefit from starting ART earlier rather than later in course of early HIV infection. Benefit was due to reduced risk of opportunistic infections and cancer (57%) . CrossRefPubMedCentral
18.
Zurück zum Zitat INSIGHT Strategic Timing of AntiRetroviral Treatment (START) Study Group, Lundgren J, Babiker A, Gordin F, Emery S, Fätkenheuer G, et al. Why START? Reflections that led to the conduct of this large long-term strategic HIV trial. HIV Med. 2015;16(Suppl 1):1–9. https://doi.org/10.1111/hiv.12227.CrossRef INSIGHT Strategic Timing of AntiRetroviral Treatment (START) Study Group, Lundgren J, Babiker A, Gordin F, Emery S, Fätkenheuer G, et al. Why START? Reflections that led to the conduct of this large long-term strategic HIV trial. HIV Med. 2015;16(Suppl 1):1–9. https://​doi.​org/​10.​1111/​hiv.​12227.CrossRef
19.
Zurück zum Zitat Babiker AG, Emery S, Fätkenheuer G, et al. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study. Clin Trials. 2013;10(1 Suppl):S5–S36.CrossRefPubMed Babiker AG, Emery S, Fätkenheuer G, et al. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study. Clin Trials. 2013;10(1 Suppl):S5–S36.CrossRefPubMed
20.
Zurück zum Zitat • Lodi S, Sharma S, Lundgren JD, Phillips AN, Cole SR, Logan R, et al. The per-protocol effect of immediate versus deferred antiretroviral therapy initiation. AIDS. 2016;30(17):2659–63. Analysis of the START cohort with aim to assess the benefit from earlier ART if all had all the trial participants adhered to the protocol. The ITT effect estimate (as reported in the N Engl J Med main article) may underestimate the benefit of immediate ART initiation by 23%.CrossRefPubMedPubMedCentral • Lodi S, Sharma S, Lundgren JD, Phillips AN, Cole SR, Logan R, et al. The per-protocol effect of immediate versus deferred antiretroviral therapy initiation. AIDS. 2016;30(17):2659–63. Analysis of the START cohort with aim to assess the benefit from earlier ART if all had all the trial participants adhered to the protocol. The ITT effect estimate (as reported in the N Engl J Med main article) may underestimate the benefit of immediate ART initiation by 23%.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Molina JM, Grund B, Gordin F, et al. Who benefited most from immediate treatment in START? A subgroup analysis. Abstract THAB0201, AIDS 2016, Durban, South Africa; 2016. Molina JM, Grund B, Gordin F, et al. Who benefited most from immediate treatment in START? A subgroup analysis. Abstract THAB0201, AIDS 2016, Durban, South Africa; 2016.
22.
Zurück zum Zitat Lifson AR, Grund B, Gardner EM, Kaplan R, Denning E, Engen N, et al. Improved quality of life with immediate versus deferred initiation of antiretroviral therapy in early asymptomatic HIV infection. AIDS. 2017;31(7):953–63.CrossRefPubMed Lifson AR, Grund B, Gardner EM, Kaplan R, Denning E, Engen N, et al. Improved quality of life with immediate versus deferred initiation of antiretroviral therapy in early asymptomatic HIV infection. AIDS. 2017;31(7):953–63.CrossRefPubMed
23.
Zurück zum Zitat • Babiker A, Grund B, Sharma S, et al. The role of HIV RNA and T cell counts, percent and ratio in explaining the benefit of immediate ART initiation in HIV+ individuals with high CD4+ counts. Abstract, AIDS 2016, Durban, South Africa; 2016. Analysis of the START study focusing on which immunological parameters could explain benefit from earlier ART initiation. Whereas changes in absolute CD4 count over follow-up only explained a small fraction of benefit (15%), changes in the CD4:CD8 ratio was a better predictor (45%). • Babiker A, Grund B, Sharma S, et al. The role of HIV RNA and T cell counts, percent and ratio in explaining the benefit of immediate ART initiation in HIV+ individuals with high CD4+ counts. Abstract, AIDS 2016, Durban, South Africa; 2016. Analysis of the START study focusing on which immunological parameters could explain benefit from earlier ART initiation. Whereas changes in absolute CD4 count over follow-up only explained a small fraction of benefit (15%), changes in the CD4:CD8 ratio was a better predictor (45%).
24.
Zurück zum Zitat Mocroft A, Furrer HJ, Miro JM, Reiss P, Mussini C, Kirk O, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/μL in the post-combination antiretroviral therapy era. Clin Infect Dis. 2013;57(7):1038–47.CrossRefPubMed Mocroft A, Furrer HJ, Miro JM, Reiss P, Mussini C, Kirk O, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/μL in the post-combination antiretroviral therapy era. Clin Infect Dis. 2013;57(7):1038–47.CrossRefPubMed
25.
Zurück zum Zitat • O'Connor J, Vjecha MJ, Phillips AN, Angus B, Cooper D, Grinsztejn B, et al. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial. Lancet HIV. 2017;4(3):e105–12. Analysis in START cohort of how earlier ART reduced substantially (61%) the risk of contracting a composite endpoint of severe bacterial infection (including bacterial pneumonia, pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death). This benefit was partially explained by how earlier ART increased CD4+ lymphocyte count.CrossRefPubMedPubMedCentral • O'Connor J, Vjecha MJ, Phillips AN, Angus B, Cooper D, Grinsztejn B, et al. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial. Lancet HIV. 2017;4(3):e105–12. Analysis in START cohort of how earlier ART reduced substantially (61%) the risk of contracting a composite endpoint of severe bacterial infection (including bacterial pneumonia, pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death). This benefit was partially explained by how earlier ART increased CD4+ lymphocyte count.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat • Borges AH, Neuhaus J, Babiker AG, et al. Immediate antiretroviral therapy reduces risk of infection-related cancer during early HIV infection. Clin Infect Dis. 2016;63:1668–76. Detailed analysis of cancer emerging in the START cohort, and how earlier initiation of ART reduced risk of both infectious-related and un-related types of cancers. Intriguingly, adjusted for time-updated HIV-RNA levels (but not CD4+ count) attenuated the observed benefit from earlier initiation of ART, but this effect was not observed for infectious-related, suggesting that the anti-cancer benefit from earlier ART initiation is not solely attributable to suppression of HIV replication.CrossRefPubMedPubMedCentral • Borges AH, Neuhaus J, Babiker AG, et al. Immediate antiretroviral therapy reduces risk of infection-related cancer during early HIV infection. Clin Infect Dis. 2016;63:1668–76. Detailed analysis of cancer emerging in the START cohort, and how earlier initiation of ART reduced risk of both infectious-related and un-related types of cancers. Intriguingly, adjusted for time-updated HIV-RNA levels (but not CD4+ count) attenuated the observed benefit from earlier initiation of ART, but this effect was not observed for infectious-related, suggesting that the anti-cancer benefit from earlier ART initiation is not solely attributable to suppression of HIV replication.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Reekie J, Kosa C, Engsig F, Monforte AD, Wiercinska-Drapalo A, Domingo P, et al. Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies. Cancer. 2010;116(22):5306–15.CrossRefPubMed Reekie J, Kosa C, Engsig F, Monforte AD, Wiercinska-Drapalo A, Domingo P, et al. Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies. Cancer. 2010;116(22):5306–15.CrossRefPubMed
28.
Zurück zum Zitat Kersten MJ, Van Gorp J, Pals ST, Boon F, Van Oers MH. Expression of Epstein-Barr virus latent genes and adhesion molecules in AIDS-related non-Hodgkin’s lymphomas: correlation with histology and CD4-cell number. Leuk Lymphoma. 1998;30(5–6):515–24.CrossRefPubMed Kersten MJ, Van Gorp J, Pals ST, Boon F, Van Oers MH. Expression of Epstein-Barr virus latent genes and adhesion molecules in AIDS-related non-Hodgkin’s lymphomas: correlation with histology and CD4-cell number. Leuk Lymphoma. 1998;30(5–6):515–24.CrossRefPubMed
29.
Zurück zum Zitat Arvey A, Ojesina AI, Pedamallu CS, Ballon G, Jung J, Duke F, et al. The tumor virus landscape of AIDS-related lymphomas. Blood. 2015;125(20):e14–22.CrossRefPubMedPubMedCentral Arvey A, Ojesina AI, Pedamallu CS, Ballon G, Jung J, Duke F, et al. The tumor virus landscape of AIDS-related lymphomas. Blood. 2015;125(20):e14–22.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat • Friis-Møller N, Ryom L, Smith C, Weber R, Reiss P, Dabis F, et al. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: the dData-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Eur J Prev Cardiol. 2016;23(2):214–23. Updated version of the D:A:D study predictor of absolute underlying risk of cardiovascular disease in HIV+ populations. This and risk prediction tools for chronic kidney disease are available for online use at http://www.chip.dk/Tools .CrossRefPubMed • Friis-Møller N, Ryom L, Smith C, Weber R, Reiss P, Dabis F, et al. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: the dData-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Eur J Prev Cardiol. 2016;23(2):214–23. Updated version of the D:A:D study predictor of absolute underlying risk of cardiovascular disease in HIV+ populations. This and risk prediction tools for chronic kidney disease are available for online use at http://www.chip.dk/Tools .CrossRefPubMed
34.
Zurück zum Zitat Kuller LH, Tracy R, Belloso W, Wit SD, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203.CrossRefPubMedPubMedCentral Kuller LH, Tracy R, Belloso W, Wit SD, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Baker JV, Neuhaus J, Duprez D, et al. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. J Acquir Immune Defic Syndr. 2011;56:36–43.CrossRefPubMedPubMedCentral Baker JV, Neuhaus J, Duprez D, et al. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. J Acquir Immune Defic Syndr. 2011;56:36–43.CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat • Baker JV, Sharma S, Achhra AC, Bernardino JI, Bogner JR, Duprez D, et al. Changes in cardiovascular disease risk factors with immediate versus deferred antiretroviral therapy initiation among HIV-positive participants in the START (Strategic Timing of Antiretroviral Treatment) Trial. J Am Heart Assoc. 2017;6(5). Analysis in START cohort of how earlier ART initiation impact traditional cardiovascular risk factors, iincluding worsening dyslipidaemia (in part depending on type of antiretroviral drug used), but decreased use of blood pressure medications, leading to an overall projected clinically insignificant impact on cardiovascular risk. Risk of new onset diabetes was not affected. • Baker JV, Sharma S, Achhra AC, Bernardino JI, Bogner JR, Duprez D, et al. Changes in cardiovascular disease risk factors with immediate versus deferred antiretroviral therapy initiation among HIV-positive participants in the START (Strategic Timing of Antiretroviral Treatment) Trial. J Am Heart Assoc. 2017;6(5). Analysis in START cohort of how earlier ART initiation impact traditional cardiovascular risk factors, iincluding worsening dyslipidaemia (in part depending on type of antiretroviral drug used), but decreased use of blood pressure medications, leading to an overall projected clinically insignificant impact on cardiovascular risk. Risk of new onset diabetes was not affected.
38.
Zurück zum Zitat • Ghehi C, Gabillard D, Moh R, Badje A, Kouamé GM, Oouttara E, et al. High correlation between Framingham equations with BMI and with lipids to estimate cardiovascular risks score at baseline in HIV-infected adults in the Temprano trial, ANRS 12136 in Côte d’Ivoire. PLoS One. 2017;12(6):e0177440. Analysis of the TEMPRANO study using the Framingham equation, assessing temporal trends during follow-up and between the two randomised arms of the trial. No effect of earlier ART initiation affected this outcome.CrossRefPubMedPubMedCentral • Ghehi C, Gabillard D, Moh R, Badje A, Kouamé GM, Oouttara E, et al. High correlation between Framingham equations with BMI and with lipids to estimate cardiovascular risks score at baseline in HIV-infected adults in the Temprano trial, ANRS 12136 in Côte d’Ivoire. PLoS One. 2017;12(6):e0177440. Analysis of the TEMPRANO study using the Framingham equation, assessing temporal trends during follow-up and between the two randomised arms of the trial. No effect of earlier ART initiation affected this outcome.CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat • Baker JV, Hullsiek KH, Engen NW, Nelson R, Chetchotisakd P, Gerstoft J, et al. Early antiretroviral therapy at high CD4 counts does not improve arterial elasticity: a substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial. Open Forum Infect Dis. 2016;3(4):ofw213. Substudy in START assessing whether earlier ART affects changes in arterial elasticity (a marker of arterial wall disease which in general population studies are closely linked with risk of cardiovascular disease). No benefit from earlier ART was observed in this study.CrossRefPubMedPubMedCentral • Baker JV, Hullsiek KH, Engen NW, Nelson R, Chetchotisakd P, Gerstoft J, et al. Early antiretroviral therapy at high CD4 counts does not improve arterial elasticity: a substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial. Open Forum Infect Dis. 2016;3(4):ofw213. Substudy in START assessing whether earlier ART affects changes in arterial elasticity (a marker of arterial wall disease which in general population studies are closely linked with risk of cardiovascular disease). No benefit from earlier ART was observed in this study.CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Trullas JC, Mocroft A, Cofan F, Tourret J, Moreno A, Bagnis CI, et al. Dialysis and renal transplantation in HIV-infected patients: a European survey. J Acquir Immune Defic Syndr. 2010;55(5):582–9.CrossRefPubMed Trullas JC, Mocroft A, Cofan F, Tourret J, Moreno A, Bagnis CI, et al. Dialysis and renal transplantation in HIV-infected patients: a European survey. J Acquir Immune Defic Syndr. 2010;55(5):582–9.CrossRefPubMed
41.
Zurück zum Zitat Ryom L, Lundgren JD, Ross M, Kirk O, Law M, Morlat P, et al. Renal impairment and cardiovascular disease in HIV-positive individuals: the D:A:D study. J Infect Dis. 2016;214(8):1212–20.CrossRefPubMedPubMedCentral Ryom L, Lundgren JD, Ross M, Kirk O, Law M, Morlat P, et al. Renal impairment and cardiovascular disease in HIV-positive individuals: the D:A:D study. J Infect Dis. 2016;214(8):1212–20.CrossRefPubMedPubMedCentral
42.
43.
Zurück zum Zitat • Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016;3(1):e23–32. International cohort study demonstrating dose-response association between duration of tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir usage and gradually increasing risk of developing chronic kidney disease. This finding did in relative terms not interact with patients underlying risk of contracting this outcome, implying that this complication is relatively common in those with elevated predicted underlying risk (i.e. a low number needed to harm).CrossRefPubMed • Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016;3(1):e23–32. International cohort study demonstrating dose-response association between duration of tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir usage and gradually increasing risk of developing chronic kidney disease. This finding did in relative terms not interact with patients underlying risk of contracting this outcome, implying that this complication is relatively common in those with elevated predicted underlying risk (i.e. a low number needed to harm).CrossRefPubMed
44.
Zurück zum Zitat Mocroft A, Lundgren J, Ross M, Law M, Reiss P, Kirk O, et al. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. PLoS Med. 2015;12:e1001809.CrossRefPubMedPubMedCentral Mocroft A, Lundgren J, Ross M, Law M, Reiss P, Kirk O, et al. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. PLoS Med. 2015;12:e1001809.CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Achhra AC, Mocroft A, Ross M, Ryom-Nielson L, Avihingsanon A, Bakowska E, et al. Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. Int J Antimicrob Agents. 2017. Achhra AC, Mocroft A, Ross M, Ryom-Nielson L, Avihingsanon A, Bakowska E, et al. Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. Int J Antimicrob Agents. 2017.
46.
Zurück zum Zitat Kunisaki KM, Niewoehner DE, Collins G, Nixon DE, Tedaldi E, Akolo C, et al. Pulmonary function in an international sample of HIV-positive, treatment-naïve adults with CD4 counts > 500 cells/μL: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015;16(Suppl 1):119–28.CrossRefPubMedPubMedCentral Kunisaki KM, Niewoehner DE, Collins G, Nixon DE, Tedaldi E, Akolo C, et al. Pulmonary function in an international sample of HIV-positive, treatment-naïve adults with CD4 counts > 500 cells/μL: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015;16(Suppl 1):119–28.CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat •• Kunisaki KM, Niewoehner DE, Collins G, Aagaard B, Atako NB, Bakowska E, et al. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial. Lancet Respir Med. 2016;4(12):980–9. Substudy from START study, assessing whether earlier ART affects longitudinal pulmonary function over a 2 year period. No such effect was found, irrespective of smoking status, which by itself markedly affected the course of pulmonary function.CrossRefPubMedPubMedCentral •• Kunisaki KM, Niewoehner DE, Collins G, Aagaard B, Atako NB, Bakowska E, et al. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial. Lancet Respir Med. 2016;4(12):980–9. Substudy from START study, assessing whether earlier ART affects longitudinal pulmonary function over a 2 year period. No such effect was found, irrespective of smoking status, which by itself markedly affected the course of pulmonary function.CrossRefPubMedPubMedCentral
48.
Zurück zum Zitat Hoy J, Grund B, Roediger M, Ensrud KE, Brar I, Colebunders R, et al. Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy. J Bone Miner Res. 2013;28(6):1264–74.CrossRefPubMedPubMedCentral Hoy J, Grund B, Roediger M, Ensrud KE, Brar I, Colebunders R, et al. Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy. J Bone Miner Res. 2013;28(6):1264–74.CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat • Hoy JF, Grund B, Roediger M, Schwartz AV, Shepherd J, Avihingsanon A, et al. Immediate initiation of antiretroviral therapy for HIV infection accelerates bone loss relative to deferring therapy: findings from the START bone mineral density substudy, a randomized trial. J Bone Miner Res. 2017;32:1945–55. https://doi.org/10.1002/jbmr.3183. Substudy from START study, assessing whether earlier ART affects changes in bone mineral density over a 2 year period. Earlier ART reduced density more so in the first but not the second year, and this initial decline was not linked to type of ART used.CrossRefPubMed • Hoy JF, Grund B, Roediger M, Schwartz AV, Shepherd J, Avihingsanon A, et al. Immediate initiation of antiretroviral therapy for HIV infection accelerates bone loss relative to deferring therapy: findings from the START bone mineral density substudy, a randomized trial. J Bone Miner Res. 2017;32:1945–55. https://​doi.​org/​10.​1002/​jbmr.​3183. Substudy from START study, assessing whether earlier ART affects changes in bone mineral density over a 2 year period. Earlier ART reduced density more so in the first but not the second year, and this initial decline was not linked to type of ART used.CrossRefPubMed
50.
Zurück zum Zitat Borges ÁH, Hoy J, Florence E, Sedlacek D, Stellbrink HJ, Uzdaviniene V, et al. Antiretrovirals, fractures, and osteonecrosis in a large international HIV cohort. Clin Infect Dis. 2017;64(10):1413–21.CrossRefPubMed Borges ÁH, Hoy J, Florence E, Sedlacek D, Stellbrink HJ, Uzdaviniene V, et al. Antiretrovirals, fractures, and osteonecrosis in a large international HIV cohort. Clin Infect Dis. 2017;64(10):1413–21.CrossRefPubMed
51.
Zurück zum Zitat Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009;73(5):342–8.CrossRefPubMedPubMedCentral Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009;73(5):342–8.CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Wright E, Grund B, Robertson K, Cysique L, Collins G, Brew B et al. No difference between the effects of immediate versus deferred ART on neuropsychological test performance in HIV-positive adults with CD4+ cell counts > 500 cells/μL. 15th European AIDS Conference (EACS), Barcelona, October 2015. Wright E, Grund B, Robertson K, Cysique L, Collins G, Brew B et al. No difference between the effects of immediate versus deferred ART on neuropsychological test performance in HIV-positive adults with CD4+ cell counts > 500 cells/μL. 15th European AIDS Conference (EACS), Barcelona, October 2015.
53.
Zurück zum Zitat •• Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375(9):830–9. Follow-up report to original HPTN 052 report documenting substantial reduction (93%) in risk of linked HIV transmission from placing HIV+ person on ART. Whereas no linked transmission was observed while index HIV+ person was on fully suppressive ART, a total of 8 linked transmissions were observed after initiation of ART stressing that full adherence is required.CrossRefPubMedPubMedCentral •• Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375(9):830–9. Follow-up report to original HPTN 052 report documenting substantial reduction (93%) in risk of linked HIV transmission from placing HIV+ person on ART. Whereas no linked transmission was observed while index HIV+ person was on fully suppressive ART, a total of 8 linked transmissions were observed after initiation of ART stressing that full adherence is required.CrossRefPubMedPubMedCentral
54.
Zurück zum Zitat •• Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using supportive antiretroviral therapy. JAMA. 2016;316:171–81. International study assessing the risk of HIV transmission in serodiscordant relationships having condom-less sex, and where the initial HIV+ person was on fully suppressive ART. No linked transmissions were observed after 40,000+ sexual intercourses. Supports claim that fully suppressive ART renders the person no longer able to transmit HIV.CrossRefPubMed •• Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using supportive antiretroviral therapy. JAMA. 2016;316:171–81. International study assessing the risk of HIV transmission in serodiscordant relationships having condom-less sex, and where the initial HIV+ person was on fully suppressive ART. No linked transmissions were observed after 40,000+ sexual intercourses. Supports claim that fully suppressive ART renders the person no longer able to transmit HIV.CrossRefPubMed
55.
Zurück zum Zitat Jean K, Boily MC, Danel C, Moh R, Badjé A, Desgrées-du-Loû A, et al. What level of risk compensation would offset the preventive effect of early antiretroviral therapy? Simulations from the TEMPRANO trial. Am J Epidemiol. 2016;184:755–60.CrossRefPubMed Jean K, Boily MC, Danel C, Moh R, Badjé A, Desgrées-du-Loû A, et al. What level of risk compensation would offset the preventive effect of early antiretroviral therapy? Simulations from the TEMPRANO trial. Am J Epidemiol. 2016;184:755–60.CrossRefPubMed
56.
Zurück zum Zitat • Sereti I, Gulick RM, Krishnan S, et al. ART in HIV persons with pre-treatment viremia ≤ 3000 c/mL: the START study. Abstract 984, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington, 2017. Subgroup analysis of START cohort, focused on those entering the study with low HIV RNA viral load. Earlier ART raised CD4+ lymphocyte count and reduced risk of HIV viral rebound . No power was available to assess impact on clinical events from earlier initiation of ART. • Sereti I, Gulick RM, Krishnan S, et al. ART in HIV persons with pre-treatment viremia ≤ 3000 c/mL: the START study. Abstract 984, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington, 2017. Subgroup analysis of START cohort, focused on those entering the study with low HIV RNA viral load. Earlier ART raised CD4+ lymphocyte count and reduced risk of HIV viral rebound . No power was available to assess impact on clinical events from earlier initiation of ART.
57.
Zurück zum Zitat The SPARTAC Trial Investigators, Fidler S, Porter K, Ewings F, Frater J, Ramjee G, et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med. 2013;368:207–17.CrossRefPubMedCentral The SPARTAC Trial Investigators, Fidler S, Porter K, Ewings F, Frater J, Ramjee G, et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med. 2013;368:207–17.CrossRefPubMedCentral
58.
Zurück zum Zitat Crowell TA, Hatano H. Clinical outcomes and antiretroviral therapy in ‘elite’ controllers: a review of the literature. J Virus Erad. 2015;1:72–7.PubMedPubMedCentral Crowell TA, Hatano H. Clinical outcomes and antiretroviral therapy in ‘elite’ controllers: a review of the literature. J Virus Erad. 2015;1:72–7.PubMedPubMedCentral
59.
Zurück zum Zitat Borges AH, Neuhaus J, Sharma S, et al. Benefit of continuous/immediate ART on disease risk: SMART & START combined analysis. Abstract 793, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington; 2017. Borges AH, Neuhaus J, Sharma S, et al. Benefit of continuous/immediate ART on disease risk: SMART & START combined analysis. Abstract 793, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington; 2017.
60.
Zurück zum Zitat Mocroft A, Phillips AN, Gatell J, Ledergerber B, Fisher M, Clumeck N, et al. Normalization of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational study. Lancet. 2007;370:407–13.CrossRefPubMed Mocroft A, Phillips AN, Gatell J, Ledergerber B, Fisher M, Clumeck N, et al. Normalization of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational study. Lancet. 2007;370:407–13.CrossRefPubMed
Metadaten
Titel
Serious Non-AIDS Conditions in HIV: Benefit of Early ART
verfasst von
Jens D. Lundgren
Alvaro H. Borges
James D. Neaton
Publikationsdatum
05.03.2018
Verlag
Springer US
Erschienen in
Current HIV/AIDS Reports / Ausgabe 2/2018
Print ISSN: 1548-3568
Elektronische ISSN: 1548-3576
DOI
https://doi.org/10.1007/s11904-018-0387-y

Weitere Artikel der Ausgabe 2/2018

Current HIV/AIDS Reports 2/2018 Zur Ausgabe

The Science of Prevention (JD Stekler and J Baeten, Section Editors)

PrEP Stigma: Implicit and Explicit Drivers of Disparity

The Science of Prevention (JD Stekler and J Baeten, Section Editors)

Genetic Cluster Analysis for HIV Prevention

HIV Pathogenesis and Treatment (AL Landay and N Utay, Section Editors)

Quarter Century of Anti-HIV CAR T Cells

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.