Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Bruno Ledergerber; Jens D Lundgren; A Sarah Walker; Caroline Sabin; Amy Justice; Peter Reiss; Cristina Mussini; Ferdinand Wit; Antonella d'Arminio Monforte; Rainer Weber; Gregory Fusco; Schlomo Staszewski; Matthew Law; Robert Hogg; Fiona Lampe; M John Gill; Francesco Castelli; Andrew N Phillips; PLATO Collaboration

doi:10.1016/s0140-6736(04)16589-6

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Bruno Ledergerber, Jens D Lundgren, A Sarah Walker, Caroline Sabin, Amy Justice, Peter Reiss, Cristina Mussini, Ferdinand Wit, Antonella d'Arminio Monforte, Rainer Weber, Gregory Fusco, Schlomo Staszewski, Matthew Law, Robert Hogg, Fiona Lampe, M John Gill, Francesco Castelli, Andrew N Phillips, PLATO Collaboration

73 Citations (Scopus)

Abstract

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5·5 per 100 person-years; 3-year mortality risk 15·3% (95% CI 13·5-17·3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15·8 (95% CI 9·28-27·0) for counts below 50 cells per μL versus above 200 cells per μL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1·5 log₁₀copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per μL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1·5 log₁₀copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

Original language	English
Journal	Lancet
Volume	364
Issue number	9428
Pages (from-to)	51-62
Number of pages	12
ISSN	0140-6736
DOIs	https://doi.org/10.1016/s0140-6736(04)16589-6
Publication status	Published - 3 Jul 2004

Keywords

Adult
Anti-Retroviral Agents
CD4 Lymphocyte Count
Cohort Studies
Female
Follow-Up Studies
HIV Infections
HIV Protease Inhibitors
HIV-1
Humans
Male
Middle Aged
Proportional Hazards Models
Reverse Transcriptase Inhibitors
Risk Factors
Treatment Failure
Viral Load

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/s0140-6736(04)16589-6

Cite this

Ledergerber, B., Lundgren, J. D., Walker, A. S., Sabin, C., Justice, A., Reiss, P., Mussini, C., Wit, F., d'Arminio Monforte, A., Weber, R., Fusco, G., Staszewski, S., Law, M., Hogg, R., Lampe, F., Gill, M. J., Castelli, F., Phillips, A. N., & PLATO Collaboration (2004). Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet, 364(9428), 51-62. https://doi.org/10.1016/s0140-6736(04)16589-6

Ledergerber, B, Lundgren, JD, Walker, AS, Sabin, C, Justice, A, Reiss, P, Mussini, C, Wit, F, d'Arminio Monforte, A, Weber, R, Fusco, G, Staszewski, S, Law, M, Hogg, R, Lampe, F, Gill, MJ, Castelli, F, Phillips, AN & PLATO Collaboration 2004, 'Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes', Lancet, vol. 364, no. 9428, pp. 51-62. https://doi.org/10.1016/s0140-6736(04)16589-6

@article{b57034ff33e24a2c8de8529acea8aa5c,

title = "Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes",

abstract = "Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5·5 per 100 person-years; 3-year mortality risk 15·3% (95% CI 13·5-17·3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15·8 (95% CI 9·28-27·0) for counts below 50 cells per μL versus above 200 cells per μL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1·5 log10copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per μL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1·5 log10copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.",

keywords = "Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cohort Studies, Female, Follow-Up Studies, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, Proportional Hazards Models, Reverse Transcriptase Inhibitors, Risk Factors, Treatment Failure, Viral Load",

author = "Bruno Ledergerber and Lundgren, {Jens D} and Walker, {A Sarah} and Caroline Sabin and Amy Justice and Peter Reiss and Cristina Mussini and Ferdinand Wit and {d'Arminio Monforte}, Antonella and Rainer Weber and Gregory Fusco and Schlomo Staszewski and Matthew Law and Robert Hogg and Fiona Lampe and Gill, {M John} and Francesco Castelli and Phillips, {Andrew N} and {PLATO Collaboration}",

year = "2004",

month = jul,

day = "3",

doi = "10.1016/s0140-6736(04)16589-6",

language = "English",

volume = "364",

pages = "51--62",

journal = "Lancet",

issn = "0140-6736",

publisher = "TheLancet Publishing Group",

number = "9428",

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TY - JOUR

T1 - Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

AU - Ledergerber, Bruno

AU - Lundgren, Jens D

AU - Walker, A Sarah

AU - Sabin, Caroline

AU - Justice, Amy

AU - Reiss, Peter

AU - Mussini, Cristina

AU - Wit, Ferdinand

AU - d'Arminio Monforte, Antonella

AU - Weber, Rainer

AU - Fusco, Gregory

AU - Staszewski, Schlomo

AU - Law, Matthew

AU - Hogg, Robert

AU - Lampe, Fiona

AU - Gill, M John

AU - Castelli, Francesco

AU - Phillips, Andrew N

AU - PLATO Collaboration

PY - 2004/7/3

Y1 - 2004/7/3

N2 - Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5·5 per 100 person-years; 3-year mortality risk 15·3% (95% CI 13·5-17·3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15·8 (95% CI 9·28-27·0) for counts below 50 cells per μL versus above 200 cells per μL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1·5 log10copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per μL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1·5 log10copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

AB - Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5·5 per 100 person-years; 3-year mortality risk 15·3% (95% CI 13·5-17·3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15·8 (95% CI 9·28-27·0) for counts below 50 cells per μL versus above 200 cells per μL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1·5 log10copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per μL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1·5 log10copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

KW - Adult

KW - Anti-Retroviral Agents

KW - CD4 Lymphocyte Count

KW - Cohort Studies

KW - Female

KW - Follow-Up Studies

KW - HIV Infections

KW - HIV Protease Inhibitors

KW - HIV-1

KW - Humans

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Reverse Transcriptase Inhibitors

KW - Risk Factors

KW - Treatment Failure

KW - Viral Load

U2 - 10.1016/s0140-6736(04)16589-6

DO - 10.1016/s0140-6736(04)16589-6

M3 - Journal article

C2 - 15234856

SN - 0140-6736

VL - 364

SP - 51

EP - 62

JO - Lancet

JF - Lancet

IS - 9428

ER -

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Abstract

Keywords

UN SDGs

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