1. IMPLEMENTATION OF THE BRAZILIAN HIV/AIDS ANTIRETROVIRAL PROGRAM AT A PUBLIC HEALTH POST: ADHERENCE TO PRESCRIBING GUIDELINES AND TREATMENT CONTINUITY Carmody ER*; Diaz T**; Starling P***; Beruth dos Santos AP***; Sacks HS* *Mount Sinai School of Medicine, New York, NY, USA **Global AIDS Program, CDC, PAHO, Rio de Janeiro, Brazil ***Centro de Saude Vasco Barcelos de Nova Iguaçu

2. Abstract IMPLEMENTATION OF THE BRAZILIAN HIV/AIDS ANTIRETROIVRAL PROGRAM AT A PUBLIC HEALTH POST: ADHERENCE TO PRESCRIBING GUIDELINES AND TREATMENT CONTINUITY. Authors: Carmody E, Diaz T, Starling P, Beruth dos Santos AP, Sacks HS. Institutions: Mount Sinai School of Medicine, New York, NY, USA; Global AIDS Program, CDC, PAHO, Rio de Janeiro, Brazil; Centro de Saude Vasco Barcelos de Nova Iguaçu. Problem Statement: Since 1996, the Brazilian health system has undertaken a national drug distribution program to provide antiretroviral (ARV) therapy for all HIV+ individuals needing viral suppressive treatment. Objectives: To determine practitioner adherence to ARV prescribing guidelines, to assess whether prescriptions were refilled within appropriate intervals, to outline which patient characteristics were associated with treatment lapses, and to improve a public health post’s ARV program. Design: Retrospective pilot study. Setting and Population: One public health post in a low-income suburb of Rio de Janeiro. Year 2000 data were abstracted from all non-archived adult patients first registered for HIV care from 1/00-6/00. Interventions: Subsidized by the Brazilian National Treasury, ARVs are produced in national laboratories or purchased from private international companies, then distributed from the Ministry of Health to health care facilities. Outcome Measures: % patients on HAART (highly active antiretroviral therapy) vs two-drug therapy, % regimens prescribed according to Brazilian guidelines, % patients with medication lapses >1 month during the year 2000. Results: 59 of 67 patients (88.1%) were prescribed ARV treatment. 42 regimens (71.2%) were HAART vs. 17 (28.8%) two-drug regimens. No combinations were prescribed that were contraindicated to guidelines, but 33 patients (55.9%) were prescribed ARVs before CD4+ levels and/or viral loads were obtained. There were delays between health post’s request and receipt of initial CD4+/viral load results, ranging from 25-107 (mean 66) and 33-139 (mean 86) days respectively. 14 patients on ARV treatment lacked a supply of medication for >1 month at least once during the year. 11 of these had interruption of treatment due to failure to pick up medications, and 3 due to drug stock shortages. Medication lapses were associated with being female, hospitalized in 2000, and having >2 drugs in regimen. Lapses were not associated with age, CD4+ level or previous use of ARVs. Conclusions: Brazilian practitioners at this health post adhered to prescribing guidelines in the new ARV distribution program, but demonstrated conservative prescription of HAART therapy. Delays in disease monitoring were identified as a source of potential mismatch between clinical status and treatment. Problems with preserving treatment continuity were based primarily on patient inability to collect drug refills within appropriate intervals, but drug shortages also provoked treatment lapses. Study funded by: Mount Sinai School of Medicine, New York, and CDC. Abstract is based upon our published work: An evaluation of antiretroviral HIV/AIDS treatment in a Rio de Janeiro public clinic. Tropical Medicine and International Health, 2003; 8:378-385.

3. Background and Setting: Brazilian public health system provides free, universal access to antiretroviral (ARV) therapy for people infected with HIV 95,000 received ARV in 2000 at cost $303 million Drugs are purchased from international companies and produced in national laboratories Program evaluation is necessary to ensure optimal drug delivery, prevent treatment failure, curb viral resistance, assess as a model for low-income countries with high HIV burden Study was conducted in poor suburb of Rio de Janeiro at public outpatient clinic with onsite pharmacy and four HIV/AIDS physicians Municipality of study ranked 18 th for number of AIDS cases in Brazil (1998)

4. Study Objectives: Assess feasibility of collecting medical record and pharmacy data to evaluate ARV provision Describe type of ARV therapy used Determine practitioner adherence to Brazilian ARV treatment guidelines Assess whether prescriptions were refilled within appropriate intervals; explore patient characteristics associated with treatment lapses Improve a public health post’s ARV program

5. Methods: Design: Retrospective pilot study Data collection: Year 2000 medical record and pharmacy dispensation review of all active patients who first registered at clinic for HIV/AIDS care from 1/00-6/00 (n=67 of total 115 registered) Data analyses: Frequency analyses, chi-square association tests, and logistic regression Outcome measures: % patients on HAART, % drug regimens prescribed according to guidelines, % patients with medication lapses >1 month in 2000

6. Characteristics of 67 HIV-infected Patients From Vasco Barcelos Health Post, Nova Iguaçu, 2000 Characteristic Gender Male Female No. (%) 39 (58.2) 28 (41.8) Age (years) Mean 20-29 30-39 40-49 50-79 34.9 (SD=10.1) 21 (31.3) 28 (41.8) 15 (22.4) 3 (4.5) Education None (Analfabeto) <8 years 9-12 years N/A 22 (32.8) 3 (4.5) 32 (47.7) 10 (14.9) AIDS (Brazilian definition) Yes No N/A 1 (1.5) 54 (80.6) 12 (17.9) Hospitalized in 2000 Yes No or N/A 25 (37.3) 42 (62.7) Previous use of ARVs Yes No N/A 1 (1.5%) 9 (13.4) 57 (85.1)

7. Type of ARV Therapy Initiated 59 of 67 patients prescribed ARV therapy in 2000 Dual combination: 28.8% HAART: 71.2% Regimen changed during 2000: 30.5% NRTI=nucleoside analogue reverse transcriptase inhibitor, NNRTI=non-nucleoside reverse transcriptase inhibitor, PI=protease inhibitor

8. Practitioner Adherence to Treatment Guidelines No contraindicated regimens were prescribed 3.4% of total sample received regimens inadequate for immunologic measures (n=2) 55.9% patients were prescribed ARV before both immunological or virological parameters known (n=33) Delays in monitoring averaged 64 days between request and notification of first CD4+ level, and 86 days for first viral load

9. Treatment Lapses 23.7% of sample lacked medication for >1 month (n=14) 5 –Example: patient recorded as picking up 30 day supply of meds 3/4/00 did not return until after 5/4/00 Medication insufficiencies due to both patient failure to pick up prescriptions (n=11) and pharmacy shortages (n=3)

10. Associations between patient characteristics and treatment lapses of 59 patients, Vasco Barcelos Health post, Nova Iguaçu, Brazil 2000 CharacteristicStratumn (total number in stratum) n (number and % with insufficiency) Odds ratio and 95% CI P value GenderMale Female 36 23 4 (11.1%) 10 (43.5%) 1 6.15 (1.63-23.19)0.004 Hospitalization in 2000 Not hospitalized  1 hospitalization 35 24 5 (14.3%) 9 (37.5) 1 3.60 (1.12-12.65)0.039 Number of drugs 2 >2 17 42 1 (5.9%) 13 (31.0%) 1 7.17 (0.86-59.97)0.040 Age20-29 30-39 40-49 50-70 18 24 15 2 6 (33.3%) 6 (25.0%) 2 (13.3%) 0 (0%) 1 0.67 (0.17-2.56) 0.31 (0.05-1.83) N/A 0.554 0.181 0.329 CD4+ count (n=52) <200 200-349 350-500 >500 20 22 5 6 (30.0%) 4 (18.2%) 2 (40.0%) 1 (20.0%) 1 0.52 (0.12-2.20) 1.56 (0.54-2.52) 0.58 (0.05-6.37) 0.369 0.668 0.656 Prior ARV UseARV naïve ARV prior use 50 9 11 (22.0%) 3 (33.3%) 1 1.73 (0.37-8.06)0.483

11. Discussion: Conservative prescription of HAART in proportion to dual combination therapy: –Nova Iguaçu: 70% HAART –New York City: 89% HAART in 1998 (Sackoff JE et al, 2000) High practitioner adherence to ARV guidelines –Nova Iguaçu: correct therapy in 57 of 59 initial treatments –U.S.: 85% provider adherence (Kaplan JE et al, 1999) Medication insufficiencies suggest adherence short of 90-95% needed for optimal viral suppression, women more at risk for treatment lapse than men According to pharmacist, adherence hampered by frequent changes in drug packaging, leading to patient confusion Limitations of study include small sample size, significant number of archived patients among initial registrants, and liberal measure for medication insufficiencies

12. Conclusions and Implications: Brazilian public health system is providing ARV treatment according to guidelines at this health post Delays in monitoring identified as source of potential mismatch between clinical status and treatment; improved lab capabilities may shorten monitoring delays Problems exist with maintaining treatment continuity, largely secondary to patient non-adherence Some evidence obtained that resource-poor countries can deliver successful HIV treatment provided that antiretroviral drugs are made available

13. References: Carmody ER, Diaz T, Starling P, Beruth dos Santos AP, Sacks HS. An evaluation of antiretroviral HIV/AIDS treatment in a Rio de Janeiro public clinic. Tropical Medicine & International Health, 2003; 8: 378-385. Ministerio da Saude. Recomenda ç oes para terapia antiretroviral em adultos e adolescentes infectados pelo HIV—1999. Coordena ç ao Nacional de DST e AIDS, Brasilia. (http://www.aids.gov.br/assistencia, accessed 7 Jan 2003).http://www.aids.gov.br/assistencia Sackoff JE, McFarland JW, Shin SS. Trends in prescriptions for highly active antiretroviral therapy in four New York City HIV clinics. Journal of AIDS, 2000; 23: 178-183. Kaplan JE, Parham DL, Soto-Torres L et al. Adherence to guidelines for antiretroviral therapy and for preventing opportunistic infections in HIV- infected adults and adolescents in Ryan White-funded facilities in the Unites States. Journal of AIDS, 1999; 21: 228-235.