title: The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania.
abstract: Background.  Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers' confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods.  A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI. Results.  Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2-.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1-4.3). Conclusion.  Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.
authors.affiliation: Kilimanjaro Christian Medical Centre, Moshi; Tanzania; Department of Epidemiology, University of North Carolina, Chapel Hill.
authors.forename: Habib O
authors.initials: HO
authors.lastname: Ramadhani
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, and; Duke Global Health Institute, Durham, North Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Bartlett
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, and; Duke Global Health Institute, Durham, North Carolina.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Thielman
authors.affiliation: Department of Epidemiology , University of North Carolina , Chapel Hill.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pence
authors.affiliation: Duke Global Health Institute , Durham, North Carolina.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kimani
authors.affiliation: Kilimanjaro Christian Medical Centre , Moshi ; Tanzania.
authors.forename: Venance P
authors.initials: VP
authors.lastname: Maro
authors.affiliation: Mawenzi Regional Hospital .
authors.forename: Mtumwa S
authors.initials: MS
authors.lastname: Mwako
authors.affiliation: Machame Designated District Hospital .
authors.forename: Lazaro J
authors.initials: LJ
authors.lastname: Masaki
authors.affiliation: Kilema Designated District Hospital , and.
authors.forename: Calvin E
authors.initials: CE
authors.lastname: Mmbando
authors.affiliation: Kibosho Designated District Hospital , Moshi , Tanzania.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Minja
authors.affiliation: Kibosho Designated District Hospital , Moshi , Tanzania.
authors.forename: Eileen S
authors.initials: ES
authors.lastname: Lirhunde
authors.affiliation: Department of Epidemiology , University of North Carolina , Chapel Hill.
authors.forename: William C
authors.initials: WC
authors.lastname: Miller
keywords: HIV; immunological failure; opportunistic infection; second-line ART; switching