Markers of rapid HIV progression among untreated Argentinean seroconverters
M.E. Socías, O. Sued, N. Laufer, H. Mingrone, C. Acuipil, E. Loiza, L. Amante, C. Remondegui, M. Lázaro, D. Pryluka, M. Cabrini, M.I. Figueroa, G. Turk, A. Gun, M.B. Bouzas, M.C. Iannella, H. Salomón, A. Krolewiecki, H. Pérez, P. Cahn, on behalf of Grupo Argentino de Seroconversión Study Group
Grupo Argentino de Seroconversión
FRAX0104
Grupo Argentino de Seroconversión
Background
• Diagnosis of Primary HIV Infection (PHI) has important clinical and public health implications.
• Indication of treatment at this stage remains controversial.
• Understanding early host-virus interactions may help develop new treatment and prevention strategies.
Grupo Argentino de Seroconversión
Cohort description• Multicenter Registry of PHI
patients started in 2008• 16 centers• 152 patients
HIV/AIDS in Argentina• 120,000 PLWHA• 60,000 know their status• 44% live in Buenos Aires city
and surroundings
Grupo Argentino de Seroconversión
Objectives
• To describe clinical and immunological outcomes and identify potential predictors of progression during the first year of infection among Argentinean seroconverters.
Grupo Argentino de Seroconversión
Material & Methods• Inclusion Criteria:
– >16 years old– Confirmed acute or recent HIV infection:
• Negative or Indeterminate WB plus positive virological test
• Positive WB plus negative HIV test within the previous 6 months
– HIV diagnosis between 1997-2008– ≥ 1 year of follow-up
Grupo Argentino de Seroconversión
Material & Methods• Definitions:
– “Symptomatic” PHI: ≥ 1 symptom associated with Acute Retroviral Syndrome (ARS).
– “Severe symptomatic” PHI: B or C events, or other non-AIDS related serious events at the time of seroconversion.
– HIV progression: • Clinical criteria: B or C event, or death• Immunological criteria: CD4 cell count < 350
cells/L
Grupo Argentino de Seroconversión
Baseline characteristics (n=134)• Sex: 109 male (81%), 25 female (3 pregnant)• Age, median: 32 years old (IQR 25-39)• Risk: MSM 53 %
Heterosexual 37%
IDU 1%
• HIV-test: Negative WB 9%
Indeterminate WB 40%
Seroconversion 51%
• 28 cases with HIV-positive partner• Median Viral load: 4.87 log copies/ml (IQR 4.11-5.51)• Median CD4: 479 cells/L (IQR 341-682)
Requested by patients in 33%
Grupo Argentino de Seroconversión
Morbidity and mortality associated with acute HIV infection
• Symptomatic PHI: 99 patients (74%)• Severe symptomatic PHI: 26 patients
– 7 Opportunistic infections– 9 B events– 10 non-AIDS defining serious events
• Hospital admission: 35 patients (26%)• 1 death (disseminated histoplasmosis)
Factors Associated with Severe Symptomatic PHI
Grupo Argentino de Seroconversión
n=26
Risk Factor OR 95%CI p
Age > 30 years 1.36 0.63-2.92 0.495
Male sex 2.52 0.63-10.04 0.246
Diagnosis ≥ 2005 0.79 0.37-1.70 0.619
MSM 1.14 0.51-2.55 0.58
HIV RNA > 100,000 copies/mL 3.72 1.58-8.77 0.001
CD4 cell-count < 350 cells/l 3.72 1.83-7.58 0.001
Diagnosis based on physician suspicion 5.06 1.83-14.04 <0.001
Grupo Argentino de Seroconversión
12-month follow-up
134 PHI patients
Initiated HAART
42
Progressed*
3 (7%)
Untreated
92
Progressed*: 24 (26%)
- Clinical: 12 (1 death)
- Immunological: 12
* HIV progression:- Clinical: B or C event, or death.- Immunological: CD4 < 350 cells/l.
p=0.01
Risk FactorUnivariate model Multivariate model
HR 95%CI p HR 95%CI p
Male sex 1.07 0.89-1.29 0.752 3.33 0.16-67.54 0.433
Diagnosis ≥ 2005 0.81 0.61 - 1.09 0.146 2.10 0.20-21.99 0.537
Age > 30 1.40 0.93-2.10 0.159 4.42 0.91-21.47 0.065
MSM 1.38 1.02-1.86 0.081 0.99 0.11-8.64 0.995Baseline CD4 cell-count ≤ 350 cell/l 3.81 1.64-8.86 0.002 3.14 0.47-20.78 0.236
Baseline HIV RNA ≥ 100,000 copies/mL 1.91 1.08-3.39 0.043 16.4 1.74-154.6 0.015
HIV RNA at 6 months ≥ 100,000 copies/mL
9.88 1.30-75.20 0.008 2.24 0.19-26.14 0.520
Symptomatic PHI 1.40 0.48-4.03 0.742 9.23 1.2-72.4 0.034
Predictors of Disease Progression in untreated patients
Grupo Argentino de Seroconversión
n=92
Grupo Argentino de Seroconversión
Time to Progression of HIV Disease Among Untreated Patients
n=92
13%
34%
p=0.04
Grupo Argentino de Seroconversión
Conclusions• In our cohort, PHI was associated with
significant morbidity.• One quarter of untreated patients would
require HAART during the first year of HIV infection.
• Symptomatic PHI and high baseline VL were associated with more rapid HIV progression within the first year of infection.
• HAART should be considered in PHI-patients with ARS or high baseline VL.
Grupo Argentino de Seroconversión
SITESHospital FernándezFundación HuéspedCentro Médico HuéspedHospital MuñizHospital San Antonio de ArecoSanatorio OtamendiHospital de BarilocheHospital San Roque de JujuyNexo Asociación CivilSanatorio TrinidadHospital Aeronáutico de CórdobaSanatorio San LucasHospital de GuernicaAclires
LABORATORIESCNRSHoracio SalomónManuel Gomez CarrilloGabriela TurkDario DilerniaFUND HUESPEDAna GunH. MUÑIZM Belén BouzasInés ZapiolaH. FERNANDEZOsvaldo Cando
PHYSICIANSLorena AbusamraMarcela AcostaCarolina AcuipilViviana AlonsoLiliana AmanteGraciela BenAriel BravermanMercedes CabriniPedro CahnCecilia CánepaDaniel Cangelosi Juan CastelliMariana CeriottoCarina CesarMaría CollinsFabio CrudoAndrea DuarteGustavo EcheniqueM Inés FigueroaValeria Fink
Claudia GallosoPalmira GardaAlejandro KrolewieckiNatalia LauferMarita LázaroAlberto LeoniEliana LoizaHoracio MingroneMarcela OrtizPatricia PattersonHéctor PérezNorma PorteiroDaniel PrylukaCarlos Remondegui Raúl RománM. Eugenia SocíasOmar SuedJ Gonzalo TomásJavier YaveCarlos Zala
Grupo Argentino de Seroconversión Study Group
We are in debt to all the patients of Grupo Argentino de Seroconversión.
Financial Support: Partially funded by Fogarty International Center (Grant # D43 TW 001037).
Grupo Argentino de Seroconversión
Thank you for your attention!!!
If you need more information please contact:
“Protocolo PHI”: Eugenia Socías