Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study

Tomas O. Jensen; Shweta Sharma; Anchalee Avihingsanon; Joseph Lutaakome; Indira Brar; William Burman; Ploenchan Chetchotisakd; Nathalie de Castro; Juan-Francisco Galán-Herrera; Nagalingeswaran Kumarasamy; Roger Paredes; Rene Ridzon; Michael Sciaudone; Kanal Singh; Alison Uriel; Jens Lundgren; Cavan Reilly; Gail Matthews

doi:10.1016/j.ijid.2025.107911

Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study

Tomas O. Jensen^*, Shweta Sharma, Anchalee Avihingsanon, Joseph Lutaakome, Indira Brar, William Burman, Ploenchan Chetchotisakd, Nathalie de Castro, Juan-Francisco Galán-Herrera, Nagalingeswaran Kumarasamy, Roger Paredes, Rene Ridzon, Michael Sciaudone, Kanal Singh, Alison Uriel, Jens Lundgren, Cavan Reilly, Gail Matthews

^*Corresponding author for this work

Abstract

OBJECTIVES: Deferring antiretroviral therapy (ART) until a CD4 count below cells/mm3 or other clinical indication in people with HIV (PWH) carries an increased risk of severe bacterial infections and tuberculosis (TB). It is not known if this increased risk is reversed after ART initiation.

METHODS: We analyzed 4684 adult PWH with CD4 cell counts above 500 cells/mm3 who were randomized to immediate or deferred ART in the Strategic Timing of AntiRetrovial Treatment trial. In May 2015, the deferred group was offered ART and follow-up continued until December 2021. Cox proportional hazards models were used to compare the risks of severe bacterial infections including TB in the immediate and deferred groups before and after ART initiation in the deferred group.

RESULTS: A total of 217 (4.6%) participants experienced a severe bacterial infection during the entire follow-up period. Pre-2016, the immediate group had a lower rate of severe bacterial infections compared to the deferred group (hazard ratio [HR] 0.38; 95% CI 0.26, 0.55). During 2016-2021, there was no longer a statistically significant difference (HR 0.75; 95% CI 0.49, 1.16). No differences were observed between clinical or demographic subgroups.

CONCLUSION: The increased risk of severe bacterial infections seen after deferring ART is reversed once ART is initiated.

Original language	English
Article number	107911
Journal	International Journal of Infectious Diseases
Volume	156
ISSN	1201-9712
DOIs	https://doi.org/10.1016/j.ijid.2025.107911
Publication status	Published - Jul 2025

Keywords

Adult
Anti-HIV Agents/therapeutic use
Anti-Retroviral Agents/therapeutic use
Bacterial Infections/epidemiology
CD4 Lymphocyte Count
Female
HIV Infections/drug therapy
Humans
Male
Middle Aged
Proportional Hazards Models
Prospective Studies
Risk Factors
Time-to-Treatment
Tuberculosis/epidemiology
Bacterial
Pneumonia
Anti-retroviral agents
Bacterial infections
Tuberculosis
HIV

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Jensen, T. O., Sharma, S., Avihingsanon, A., Lutaakome, J., Brar, I., Burman, W., Chetchotisakd, P., de Castro, N., Galán-Herrera, J.-F., Kumarasamy, N., Paredes, R., Ridzon, R., Sciaudone, M., Singh, K., Uriel, A., Lundgren, J., Reilly, C., & Matthews, G. (2025). Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study. International Journal of Infectious Diseases, 156, Article 107911. https://doi.org/10.1016/j.ijid.2025.107911

Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study. / Jensen, Tomas O.; Sharma, Shweta; Avihingsanon, Anchalee et al.
In: International Journal of Infectious Diseases, Vol. 156, 107911, 07.2025.

Research output: Contribution to journal › Journal article › Research › peer-review

Jensen, TO, Sharma, S, Avihingsanon, A, Lutaakome, J, Brar, I, Burman, W, Chetchotisakd, P, de Castro, N, Galán-Herrera, J-F, Kumarasamy, N, Paredes, R, Ridzon, R, Sciaudone, M, Singh, K, Uriel, A, Lundgren, J, Reilly, C & Matthews, G 2025, 'Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study', International Journal of Infectious Diseases, vol. 156, 107911. https://doi.org/10.1016/j.ijid.2025.107911

@article{5ed939fc902b42f491cf00b04ba19a1f,

title = "Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study",

abstract = "OBJECTIVES: Deferring antiretroviral therapy (ART) until a CD4 count below cells/mm3 or other clinical indication in people with HIV (PWH) carries an increased risk of severe bacterial infections and tuberculosis (TB). It is not known if this increased risk is reversed after ART initiation.METHODS: We analyzed 4684 adult PWH with CD4 cell counts above 500 cells/mm3 who were randomized to immediate or deferred ART in the Strategic Timing of AntiRetrovial Treatment trial. In May 2015, the deferred group was offered ART and follow-up continued until December 2021. Cox proportional hazards models were used to compare the risks of severe bacterial infections including TB in the immediate and deferred groups before and after ART initiation in the deferred group.RESULTS: A total of 217 (4.6\%) participants experienced a severe bacterial infection during the entire follow-up period. Pre-2016, the immediate group had a lower rate of severe bacterial infections compared to the deferred group (hazard ratio [HR] 0.38; 95\% CI 0.26, 0.55). During 2016-2021, there was no longer a statistically significant difference (HR 0.75; 95\% CI 0.49, 1.16). No differences were observed between clinical or demographic subgroups.CONCLUSION: The increased risk of severe bacterial infections seen after deferring ART is reversed once ART is initiated.",

keywords = "Adult, Anti-HIV Agents/therapeutic use, Anti-Retroviral Agents/therapeutic use, Bacterial Infections/epidemiology, CD4 Lymphocyte Count, Female, HIV Infections/drug therapy, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors, Time-to-Treatment, Tuberculosis/epidemiology, Bacterial, Pneumonia, Anti-retroviral agents, Bacterial infections, Tuberculosis, HIV",

author = "Jensen, \{Tomas O.\} and Shweta Sharma and Anchalee Avihingsanon and Joseph Lutaakome and Indira Brar and William Burman and Ploenchan Chetchotisakd and \{de Castro\}, Nathalie and Juan-Francisco Gal{\'a}n-Herrera and Nagalingeswaran Kumarasamy and Roger Paredes and Rene Ridzon and Michael Sciaudone and Kanal Singh and Alison Uriel and Jens Lundgren and Cavan Reilly and Gail Matthews",

note = "Copyright {\textcopyright} 2025. Published by Elsevier Ltd.",

year = "2025",

month = jul,

doi = "10.1016/j.ijid.2025.107911",

language = "English",

volume = "156",

journal = "International Journal of Infectious Diseases",

issn = "1201-9712",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy

T2 - a multicenter, prospective, cohort study

AU - Jensen, Tomas O.

AU - Sharma, Shweta

AU - Avihingsanon, Anchalee

AU - Lutaakome, Joseph

AU - Brar, Indira

AU - Burman, William

AU - Chetchotisakd, Ploenchan

AU - de Castro, Nathalie

AU - Galán-Herrera, Juan-Francisco

AU - Kumarasamy, Nagalingeswaran

AU - Paredes, Roger

AU - Ridzon, Rene

AU - Sciaudone, Michael

AU - Singh, Kanal

AU - Uriel, Alison

AU - Lundgren, Jens

AU - Reilly, Cavan

AU - Matthews, Gail

PY - 2025/7

Y1 - 2025/7

N2 - OBJECTIVES: Deferring antiretroviral therapy (ART) until a CD4 count below cells/mm3 or other clinical indication in people with HIV (PWH) carries an increased risk of severe bacterial infections and tuberculosis (TB). It is not known if this increased risk is reversed after ART initiation.METHODS: We analyzed 4684 adult PWH with CD4 cell counts above 500 cells/mm3 who were randomized to immediate or deferred ART in the Strategic Timing of AntiRetrovial Treatment trial. In May 2015, the deferred group was offered ART and follow-up continued until December 2021. Cox proportional hazards models were used to compare the risks of severe bacterial infections including TB in the immediate and deferred groups before and after ART initiation in the deferred group.RESULTS: A total of 217 (4.6%) participants experienced a severe bacterial infection during the entire follow-up period. Pre-2016, the immediate group had a lower rate of severe bacterial infections compared to the deferred group (hazard ratio [HR] 0.38; 95% CI 0.26, 0.55). During 2016-2021, there was no longer a statistically significant difference (HR 0.75; 95% CI 0.49, 1.16). No differences were observed between clinical or demographic subgroups.CONCLUSION: The increased risk of severe bacterial infections seen after deferring ART is reversed once ART is initiated.

AB - OBJECTIVES: Deferring antiretroviral therapy (ART) until a CD4 count below cells/mm3 or other clinical indication in people with HIV (PWH) carries an increased risk of severe bacterial infections and tuberculosis (TB). It is not known if this increased risk is reversed after ART initiation.METHODS: We analyzed 4684 adult PWH with CD4 cell counts above 500 cells/mm3 who were randomized to immediate or deferred ART in the Strategic Timing of AntiRetrovial Treatment trial. In May 2015, the deferred group was offered ART and follow-up continued until December 2021. Cox proportional hazards models were used to compare the risks of severe bacterial infections including TB in the immediate and deferred groups before and after ART initiation in the deferred group.RESULTS: A total of 217 (4.6%) participants experienced a severe bacterial infection during the entire follow-up period. Pre-2016, the immediate group had a lower rate of severe bacterial infections compared to the deferred group (hazard ratio [HR] 0.38; 95% CI 0.26, 0.55). During 2016-2021, there was no longer a statistically significant difference (HR 0.75; 95% CI 0.49, 1.16). No differences were observed between clinical or demographic subgroups.CONCLUSION: The increased risk of severe bacterial infections seen after deferring ART is reversed once ART is initiated.

KW - Adult

KW - Anti-HIV Agents/therapeutic use

KW - Anti-Retroviral Agents/therapeutic use

KW - Bacterial Infections/epidemiology

KW - CD4 Lymphocyte Count

KW - Female

KW - HIV Infections/drug therapy

KW - Humans

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Factors

KW - Time-to-Treatment

KW - Tuberculosis/epidemiology

KW - Bacterial

KW - Pneumonia

KW - Anti-retroviral agents

KW - Bacterial infections

KW - Tuberculosis

KW - HIV

UR - https://www.scopus.com/pages/publications/105005498285

U2 - 10.1016/j.ijid.2025.107911

DO - 10.1016/j.ijid.2025.107911

M3 - Journal article

C2 - 40268134

SN - 1201-9712

VL - 156

JO - International Journal of Infectious Diseases

JF - International Journal of Infectious Diseases

M1 - 107911

ER -

Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: a multicenter, prospective, cohort study

Abstract

Keywords

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