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Published in: BMC Infectious Diseases 1/2023

Open Access 01-12-2023 | Human Immunodeficiency Virus | Research article

Heavily treatment-experienced people living with HIV in the OPERA® cohort: population characteristics and clinical outcomes

Authors: Ricky K. Hsu, Jennifer S. Fusco, Cassidy E. Henegar, Vani Vannappagari, Andrew Clark, Laurence Brunet, Philip C. Lackey, Gerald Pierone Jr., Gregory P. Fusco

Published in: BMC Infectious Diseases | Issue 1/2023

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Abstract

Background

Multi-class resistance, intolerance, and drug–drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH.

Methods

Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan–Meier methods; cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described.

Results

A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load [VL] ≥ 50 copies/mL) were less likely to achieve undetectability (VL < 50 copies/mL; 24-month cumulative probability: 80% [95% Confidence Interval 77–82]) than their non-HTE counterparts (85% [84–86]). No difference was observed in the probability of maintaining VLs < 200 copies/mL over the first 48 months after achieving suppression (< 50 copies/mL). HTE PLWH were less likely than non-HTE PLWH to maintain CD4 cell counts ≥ 200 cells/µL (24-month cumulative probability: 95% HTE [91–93]; 97% non-HTE [97–97]), and more likely to change regimens (45% HTE; 41% non-HTE). Incident non-AIDS defining event (ADE) morbidities were common in both populations, though more likely among HTE PLWH (45%) than non-HTE PLWH (35%). Incident ADE morbidities and deaths were uncommon among HTE (ADEs 5%; deaths 2%) and non-HTE (ADEs 2%; deaths 1%) PLWH.

Conclusions

HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.
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Literature
1.
go back to reference Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS. 2016;11(5):492–500.CrossRefPubMedPubMedCentral Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS. 2016;11(5):492–500.CrossRefPubMedPubMedCentral
2.
go back to reference Laprise C, de Pokomandy A, Baril JG, Dufresne S, Trottier H. Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation. Clin Infect Dis. 2013;57(10):1489–96.CrossRefPubMed Laprise C, de Pokomandy A, Baril JG, Dufresne S, Trottier H. Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation. Clin Infect Dis. 2013;57(10):1489–96.CrossRefPubMed
3.
go back to reference WHO Expert Consultation. ART failure and strategies for switching ART regimens in the WHO European region. Copenhagen. 2007. WHO Expert Consultation. ART failure and strategies for switching ART regimens in the WHO European region. Copenhagen. 2007.
4.
go back to reference Borroto-Esoda K, Waters JM, Bae AS, Harris JL, Hinkle JE, Quinn JB, et al. Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz. AIDS Res Hum Retrovir. 2007;23(8):988–95.CrossRefPubMed Borroto-Esoda K, Waters JM, Bae AS, Harris JL, Hinkle JE, Quinn JB, et al. Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz. AIDS Res Hum Retrovir. 2007;23(8):988–95.CrossRefPubMed
5.
go back to reference Al-Dakkak I, Patel S, McCann E, Gadkari A, Prajapati G, Maiese EM. The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: a systematic review and meta-analysis. AIDS Care. 2013;25(4):400–14.CrossRefPubMed Al-Dakkak I, Patel S, McCann E, Gadkari A, Prajapati G, Maiese EM. The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: a systematic review and meta-analysis. AIDS Care. 2013;25(4):400–14.CrossRefPubMed
7.
go back to reference Temesgen Z, Cainelli F, Poeschla EM, Vlahakis SA, Vento S. Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults. Lancet Infect Dis. 2006;6(8):496–507.CrossRefPubMed Temesgen Z, Cainelli F, Poeschla EM, Vlahakis SA, Vento S. Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults. Lancet Infect Dis. 2006;6(8):496–507.CrossRefPubMed
8.
go back to reference Henegar C, Vannappagari V, Viswanathan S, DeKoven M, Clark A, Ackerman P, et al. Identifying heavily treatment-experienced patients in a large administrative claims database. In: International AIDS Society (IAS) conference on HIV science in Mexico City, Mexico, July 21–24, 2019. 2019. Henegar C, Vannappagari V, Viswanathan S, DeKoven M, Clark A, Ackerman P, et al. Identifying heavily treatment-experienced patients in a large administrative claims database. In: International AIDS Society (IAS) conference on HIV science in Mexico City, Mexico, July 21–24, 2019. 2019.
9.
go back to reference Hsu R, Henegar C, Fusco J, Vannappagari V, Llamoso C, Lackey P, et al. Identifying heavily treatment-experienced patients in the OPERA Cohort [Poster THPEB044]. In: 22nd international AIDS conference, Amsterdam, the Netherlands. 2018. Hsu R, Henegar C, Fusco J, Vannappagari V, Llamoso C, Lackey P, et al. Identifying heavily treatment-experienced patients in the OPERA Cohort [Poster THPEB044]. In: 22nd international AIDS conference, Amsterdam, the Netherlands. 2018.
10.
go back to reference Pelchen-Matthews A, Borges AH, Reekie J, Rasmussen LD, Wiese L, Weber J, et al. Prevalence and outcomes for heavily treatment-experienced individuals living with human immunodeficiency virus in a European cohort. J Acquir Immune Defic Syndr. 2021;87(2):806–17.CrossRefPubMed Pelchen-Matthews A, Borges AH, Reekie J, Rasmussen LD, Wiese L, Weber J, et al. Prevalence and outcomes for heavily treatment-experienced individuals living with human immunodeficiency virus in a European cohort. J Acquir Immune Defic Syndr. 2021;87(2):806–17.CrossRefPubMed
11.
go back to reference Grover D, Copas A, Green H, Edwards SG, Dunn DT, Sabin C, et al. What is the risk of mortality following diagnosis of multidrug-resistant HIV-1? J Antimicrob Chemother. 2008;61(3):705–13.CrossRefPubMed Grover D, Copas A, Green H, Edwards SG, Dunn DT, Sabin C, et al. What is the risk of mortality following diagnosis of multidrug-resistant HIV-1? J Antimicrob Chemother. 2008;61(3):705–13.CrossRefPubMed
12.
go back to reference Zaccarelli M, Tozzi V, Lorenzini P, Trotta MP, Forbici F, Visco-Comandini U, et al. Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients. AIDS. 2005;19(10):1081–9.CrossRefPubMed Zaccarelli M, Tozzi V, Lorenzini P, Trotta MP, Forbici F, Visco-Comandini U, et al. Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients. AIDS. 2005;19(10):1081–9.CrossRefPubMed
13.
go back to reference Smith CJ, Phillips AN, Dauer B, Johnson MA, Lampe FC, Youle MS, et al. Factors associated with viral rebound among highly treatment-experienced HIV-positive patients who have achieved viral suppression. HIV Med. 2009;10(1):19–27.CrossRefPubMed Smith CJ, Phillips AN, Dauer B, Johnson MA, Lampe FC, Youle MS, et al. Factors associated with viral rebound among highly treatment-experienced HIV-positive patients who have achieved viral suppression. HIV Med. 2009;10(1):19–27.CrossRefPubMed
14.
go back to reference Lalezari JP, Henry K, O’Hearn M, Montaner JS, Piliero PJ, Trottier B, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348(22):2175–85.CrossRefPubMed Lalezari JP, Henry K, O’Hearn M, Montaner JS, Piliero PJ, Trottier B, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348(22):2175–85.CrossRefPubMed
15.
go back to reference Khanna N, Klimkait T, Schiffer V, Irigoyen J, Telenti A, Hirschel B, et al. Salvage therapy with abacavir plus a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor in heavily pre-treated HIV-1 infected patients. AIDS. 2000;14(7):791–9.CrossRefPubMed Khanna N, Klimkait T, Schiffer V, Irigoyen J, Telenti A, Hirschel B, et al. Salvage therapy with abacavir plus a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor in heavily pre-treated HIV-1 infected patients. AIDS. 2000;14(7):791–9.CrossRefPubMed
16.
go back to reference Imaz A, Falco V, Ribera E. Antiretroviral salvage therapy for multiclass drug-resistant HIV-1-infected patients: from clinical trials to daily clinical practice. AIDS Rev. 2011;13(3):180–93.PubMed Imaz A, Falco V, Ribera E. Antiretroviral salvage therapy for multiclass drug-resistant HIV-1-infected patients: from clinical trials to daily clinical practice. AIDS Rev. 2011;13(3):180–93.PubMed
17.
go back to reference Brown ST, Tate JP, Kyriakides TC, Kirkwood KA, Holodniy M, Goulet JL, et al. The VACS index accurately predicts mortality and treatment response among multi-drug resistant HIV infected patients participating in the options in management with antiretrovirals (OPTIMA) study. PLoS ONE. 2014;9(3): e92606.CrossRefPubMedPubMedCentral Brown ST, Tate JP, Kyriakides TC, Kirkwood KA, Holodniy M, Goulet JL, et al. The VACS index accurately predicts mortality and treatment response among multi-drug resistant HIV infected patients participating in the options in management with antiretrovirals (OPTIMA) study. PLoS ONE. 2014;9(3): e92606.CrossRefPubMedPubMedCentral
18.
go back to reference Benzie AA, Bansi LK, Fau-Sabin CA, Portsmouth S, Fau-Hill T, Johnson M, Fau-Gilson R, et al. Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures. AIDS. 2007;21(11):1423–30.CrossRefPubMed Benzie AA, Bansi LK, Fau-Sabin CA, Portsmouth S, Fau-Hill T, Johnson M, Fau-Gilson R, et al. Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures. AIDS. 2007;21(11):1423–30.CrossRefPubMed
19.
go back to reference Mocroft A, Ledergerber B, Viard JP, Staszewski S, Murphy M, Chiesi A, et al. Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group. J Infect Dis. 2004;190(11):1947–56.CrossRefPubMed Mocroft A, Ledergerber B, Viard JP, Staszewski S, Murphy M, Chiesi A, et al. Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group. J Infect Dis. 2004;190(11):1947–56.CrossRefPubMed
20.
go back to reference Lataillade M, Lalezari JP, Kozal M, Aberg JA, Pialoux G, Cahn P, et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. Lancet HIV. 2020;7(11):e740–51.CrossRefPubMed Lataillade M, Lalezari JP, Kozal M, Aberg JA, Pialoux G, Cahn P, et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. Lancet HIV. 2020;7(11):e740–51.CrossRefPubMed
21.
go back to reference Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1. N Engl J Med. 2018;379(7):645–54.CrossRefPubMed Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1. N Engl J Med. 2018;379(7):645–54.CrossRefPubMed
22.
go back to reference Molina JM, Segal-Maurer S, Stellbrink HJ, Castagna A, Berhe M, Richmond GJ, et al. Efficacy and safety of long-acting subcutaneous lenacapavir in phase 2/3 in heavily treatment-experienced people with HIV: week 26 results (Capella study). J Int AIDS Soc. 2021;24(S4): e25755. Molina JM, Segal-Maurer S, Stellbrink HJ, Castagna A, Berhe M, Richmond GJ, et al. Efficacy and safety of long-acting subcutaneous lenacapavir in phase 2/3 in heavily treatment-experienced people with HIV: week 26 results (Capella study). J Int AIDS Soc. 2021;24(S4): e25755.
23.
go back to reference Potard V, Goujard C, Valantin MA, Lacombe JM, Lahoulou R, Cheret A, et al. Impact of etravirine on hospitalization rate between 2005 and 2011 among heavily treated HIV-1-infected individuals on failing regimens. BMC Infect Dis. 2018;18(1):326.CrossRefPubMedPubMedCentral Potard V, Goujard C, Valantin MA, Lacombe JM, Lahoulou R, Cheret A, et al. Impact of etravirine on hospitalization rate between 2005 and 2011 among heavily treated HIV-1-infected individuals on failing regimens. BMC Infect Dis. 2018;18(1):326.CrossRefPubMedPubMedCentral
24.
go back to reference Colin X, Lafuma A, Costagliola D, Lang JM, Guillon P. The cost of managing HIV infection in highly treatment-experienced, HIV-infected adults in France. PharmacoEconomics. 2010;28(Suppl 1):59–68.CrossRefPubMed Colin X, Lafuma A, Costagliola D, Lang JM, Guillon P. The cost of managing HIV infection in highly treatment-experienced, HIV-infected adults in France. PharmacoEconomics. 2010;28(Suppl 1):59–68.CrossRefPubMed
Metadata
Title
Heavily treatment-experienced people living with HIV in the OPERA® cohort: population characteristics and clinical outcomes
Authors
Ricky K. Hsu
Jennifer S. Fusco
Cassidy E. Henegar
Vani Vannappagari
Andrew Clark
Laurence Brunet
Philip C. Lackey
Gerald Pierone Jr.
Gregory P. Fusco
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2023
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-023-08038-w

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