Outcomes of HAART in HIV infected individuals in Argentina

Carlos Zala, Robert Hogg, Horacio Salomon, Keith Chan,

Mariana Ceriotto, Marcelo Beltran, Miriam Burgos,

Pedro Cahn, JSG Montaner

and the PUMA study group

Buenos Aires, Argentina

BC Center for Excellence in HIV/AIDS. Vancouver, BC. Canada

PUMA

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19861987198819891990199119921993199419951996199719981999200020012002200320042005

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Number of people living with HIV

AIDS epidemic update, December 2005

Number of people living with HIV in Latin America and Caribbean, 1986–2005

Latin America and Caribbean

Background

• The Argentinean government has made a commitment to provide free HAART to eligible individuals (IAS-USA guidelines)

• Limited data are available on subjects who initiates HAART in Argentina

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Potential limitations of HAART use in Argentina

• Use of generic ARVs• Limited or restricted use of newer drugs• Endemic OIs

– High TB prevalence• Lack of drug resistant testing• Physicians have variable experience with HAART• Heterogeneous sources of HIV care

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Prospective evaluation in the Use and Monitoring of

Antiretrovirals in Argentina:

The The PUMAPUMA Cohort Cohort

Ongoing multi-site based cohort at HIV clinics throughout Argentina

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Objective (1)

• To evaluate baseline plasma HIV RNA, CD4 T cell counts among ARV naïve HIV positive subjects initiating HAART at selected public hospitals

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Objective (2)

• To describe AIDS related morbidity and mortality, changes in plasma HIV RNA and CD4 T cell counts among patients who initiated HAART

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Eligibility Criteria

• All consecutive ARV naïve HIV infected

individuals seeking treatment or care

• Age 18 or older

• Known data of initiation of HAART

• HIV RNA and CD4 within 3 mo from BSL

• CDC clinical stage (pre-HAART)

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Treatment, labs and follow-up

• HAART: any boosted-PI or NNRTI + 2 NRTI

• Free access to routine lab monitoring

• Lost to follow-up: missing laboratory values > 6

months

• AIDS related death (CDC)

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Data collection

• Prospective/ standardized data collection

at 10 sites

• Data entry at a single Coordinating Center

• Anonymous data pooled for analysis

• IRB approval

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Types of data collected

• Sociodemographic data

• HAART treatment history

• Laboratory tests, including CD4 and HIV RNA

• Reasons for interruption, switching and failure

• AIDS defining illnesses/ death

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• 605 participants enrolled from Jan 03 to Dec 05

• 299 (49%) initiated HAART upon entering the program

• 93 (36%) initiated HAART during follow-up

• Median follow-up 17.8 months (IQR: 6.6-26.4)

• 85 (14 %) lost to follow up

Results Results

• 605 participants enrolled from Jan 03 to Dec 05

• 299 (49%) initiated HAART upon entering the program

• 93 (36%) initiated HAART during follow-up

• Median follow-up 17.8 months (IQR: 6.6-26.4)

• 85 (14 %) lost to follow up

Results Results

PUMA: Baseline (n = 605)

Characteristic n (%)

Males 437 (72%)

Age* 35 (29-41)

HCV serology 60/392 tested (15%)

CD4 T cell count* 223 (75-431)

HIV RNA (copies/ml)* 48,116 (5,523-200,153)

AIDS (+) 141 (23%)

PI based-regimen 105 (17%)

NNRTI-based regimen 184 (30%)

* Median (interquartile range); (+) according ot CDC 1987 case definition

Baseline HAART Variable Treatment p-value

No (n=306)n (%)

Yes (n=299)n (%)

Gender Male Female

227 (74) 79 (26)

208 (70) 91(30) 0.206

Age** 35 (28-40) 35 (31-42) 0.010*

Risk Group MSM IDU Heterosexual

114 (37) 29 (9)

139 (45)

107 (36) 39 (13) 121 (40)

0.7080.1650.218

AIDS No Yes

270 (88) 36 (12)

194 (65)105 (35) <0.001

CD4** 377 (236-581) 105 (36-217) <0.001*

Viral Load** 30,507 (5,932-122,286)

89,629(3,390-315,000)

0.005*

* Wilcoxon Rank Sum Test ** median (interquartile range)

Time to start of HAART

Unadjusted Hazard Ratio (95% CI)

Adjusted Hazard Ratio (95% CI)

Gender (M vs. F) 1.23 (0.77-1.97) 0.87 (0.50-1.49)

Age (per 10 years) 1.30 (1.06-1.59) 1.26 (1.00-1.61)

MSM Risk (Yes vs. No) 0.90 (0.59-1.37)

IDU Risk (Yes vs. No) 2.42 (1.33-4.40) 2.21 (1.09-4.48)

AIDS (Yes vs. No) 5.70 (3.44-9.41) 3.34 (1.78-6.26)

Baseline pVL* (per log increase) 2.81 (1.94-4.06) 2.42 (1.64-3.58)

Baseline CD4* (per 100 cell increase)

1.00 (0.99-1.01)

* at baseline

Most common OIs at entry

Opportunistic infections N (%)

TB 25

PCP * 24

Esophageal candidiasis 14

CNS Toxoplasmosis 11

Cryptococcosis 5

CMV 5

Kaposi’s sarcoma 3

PML 2

Histoplasmosis 2

* (includes presumptive and confirmed cases)

Most common initial regimen (%)

NNRTIs Efavirenz 44

Nevirapine 20

PIs Saquinavir/r 17

Indinavir/r 6.5

Others (*) 12.5

backbone NRTIs ZDV + 3TC (**) 49

d4T + 3TC 17

* LVP/r, Atazanavir/r; ** Generic of Combivir

Reasons for switching first HAART regimen

• 96/387 (25%)– Gastrointestinal (25%)– Intolerance (21%)– Anemia (11 %)– Skin reactions (8.5 %)– Physician indication (8.5 %)– Virologic failure (3.5 %)– CNS (1.7 %)

Switching of first HAART Unadjusted Hazard

Ratio (95% CI)Adjusted Hazard Ratio

(95% CI)

Gender (M vs. F) 0.98 (0.63-1.51) 0.85 (0.54-1.32)

Age (per 10 years) 1.23 (1.01-1.51) 1.27 (1.04-1.58)

MSM Risk (Yes vs. No) 0.97 (0.64-1.46)

IDU Risk (Yes vs. No) 1.05 (0.59-1.89)

AIDS* (Yes vs. No) 1.70 (1.01-2.87)

pVL* (per log increase) 1.07 (0.90-1.26)

CD4* (per 100 cell increase) 0.91 (0.79-1.04)

NNRTI* (Yes vs. No) 0.54 (0.36-0.80) 0.51 (0.34-0.77)

PI* (Yes vs. No) 1.81 (1.21-2.70)

* at start of first therapy.** as part of first therapy.

Lost to follow-upTime to start of Therapy

Unadjusted Hazard Ratio (95% CI)

Adjusted Hazard Ratio (95% CI)

Gender (M vs. F) 1.36 (0.83-2.25) 1.43 (0.86-2.36)

Age (per 10 years) 0.63 (0.48-0.84) 0.62 (0.47-0.82)

MSM Risk (Yes vs. No) 0.94 (0.60-1.46)

IDU Risk (Yes vs. No) 0.79 (0.38-1.64)

AIDS* (Yes vs. No) 0.15 (0.06-0.37) 0.34 (0.14-0.84)

pVL* (per log increase) 0.84 (0.70-0.99)

CD4* (per 100 cell increase) 1.00 (0.99-1.01)

ARV* (Yes vs. No) 0.03 (0.01-0.08) 0.04 (0.01-0.10)

NRTI* (Yes vs. No) 0.03 (0.01-0.09)

NNRTI* (Yes vs. No) 0.09 (0.03-0.24)

PI* (Yes vs. No) -

Plasma HIV RNA and CD4 change (baseline to 12 months)

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Virologic response (< 50 copies/ml x 2)

Unadjusted Hazard Ratio (95% CI)

Adjusted Hazard Ratio (95% CI)

Gender (M vs. F) 0.90 (0.59-1.38) 1.01 (0.65-1.59)

Age (per 10 years) 1.16 (0.96-1.41) 1.27 (1.04-1.55)

MSM Risk (Yes vs. No) 0.92 (0.62-1.37)

IDU Risk (Yes vs. No) 1.36 (0.77-2.38)

AIDS* (Yes vs. No) 0.94 (0.50-1.75)

pVL* (per log increase) 0.86 (0.75-0.98) 0.84 (0.74-0.97)

CD4* (per 100 cell increase) 0.91 (0.80-1.04)

NNRTI** (Yes vs. No) 1.72 (1.14-2.60) 1.85 (1.18-2.89)

PI** (Yes vs. No) 0.69 (0.46-1.05)

* at start of first therapy.** as part of first therapy.

• Histoplasmosis 1• LNH 3• TB 1• Toxoplasmosis 1• SK 1• Cryptococosis 2• SK 1• LMP 1• ESLD 2• UNK 2

AIDS related deaths (n=15)

• Lack of active follow-up procedures

• No tracking lost to follow up patients

• Death reported only if occurred at the

participating institutions

• Evaluation of Adherence

Limitations

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• First prospective HAART cohort in Argentina

• Initiation of HAART was associated with advanced HIV disease

• Proportion of patients with early virologic response similar to that reported in other cohorts

• Urgent efforts are needed to optimize timing of initiation of HAART in this setting

Conclusions

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• The PUMA study group - Argentina

Acknowledgments

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Hospital de San Isidro (Marcelo Beltran)

Hospital Tornu (Miriam Burgos/Viviana Rodriguez)

Hospital Alberdi (Raul Bortolozi)

Hospital de Neuquen (Liliana Calani)

Helios Salud (Isabel Cassetti)

Hospital Cecilia Grierson (Mariana Ceriotto)

Hospital San Juan de Dios (Jorge Contarelli)

Hospital de Mar del Plata (Alejandro Ferro)

Hospital Misericordia (Angel Minguez)

Hospital de San Fernando (Fernando Murano)

Funcei (Gustavo Lopardo)

Hospital Velez Sarfield (Daniel Pryluka)

Hospital de Jujuy (Carlos Ramondegui)

CNRS (Horacio Salomon)

Hospital Paroissien (Eduardo Warley)

Hospital Fernandez (Carlos Zala/Pedro Cahn)

• Center for Excellence in HIV/aids – Vancouver, BC. Canada

Robert Hogg

Keith Chan

Nada Gataric

Julio SG Montaner

Statistics

• Categorical variables were compared between

groups using Pearson’s chi-squared test and

Fisher’s exact test.

• Comparisons of continuous variables were

carried out using Wilcoxon’s rank-sum test.

• Kaplan Meier methods and Cox proportional

hazard regression were used to analyze time to

event outcomes.

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Quarterly accrual 2003-2005

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