IMPLEMENTATION OF THE BRAZILIAN HIV AIDS ANTIRETROVIRAL PROGRAM AT

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 Saúde Vasco Barcelos de Nova Iguaçu

Background: • Since 1996, Brazilian public health system has provided free, universal access to antiretroviral (ARV) therapy for people infected with HIV • 95, 000 patients received ARV in 2000 at $303 million • Drugs purchased from international companies and produced in national laboratories

Background (continued): Evaluation necessary to: • ensure optimal delivery of medicines • prevent drug resistance at individual and population levels • appraise program as model for low to lowmiddle income countries with high HIV burden

Setting: Centro de Saúde Vasco Barcelos de Nova Iguaçu • Public outpatient health post in suburb of Rio de Janeiro with onsite pharmacy and four HIV physicians • Patient population drawn from low socioeconomic status • Nova Iguaçu ranked 18 th among municipalities for number of AIDS cases in Brazil

Centro de Saúde Vasco Barcelos de Nova Iguaçu, Brazil

Study Objectives: • Assess feasibility of collecting medical record and pharmacy data to evaluate the provision of ARVs • Determine practitioner adherence to Brazilian ARV treatment guidelines • Assess whether prescriptions were refilled in timely manner; explore patient characteristics associated with treatment lapses • Improve a public health post’s ARV program

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

Results: Patient Demographics • 58. 2% male (n=39); 41. 8% female (n=28) • Age: mean=34. 9; Range=20 to 70 • Education: 4. 5% none; 48% 1 -8 years; 15% 9 -12 years; 33% n/a • Most common occupations: domestic servant, mechanic, carpenter, homemaker, manicurist, unemployed

Patient Clinical Characteristics • 80. 6% of sample had AIDS: clinical symptoms or CD 4<350 as per Brazilian definition (n=54) • 85. 1% were ARV naïve • Date of HIV+ diagnosis: – 2000: 50. 7% – 1999: 38. 8% – 1998 or earlier: 7. 5%; N/a 3% • Mean initial CD 4+ level 276 cell/mm 3, initial viral load 237, 517 copies/ml

Antiretroviral Use • 88. 1% of patients sampled were prescribed ARV in 2000 (n=59) • 30. 5% of patients prescribed ARV changed regimens during 2000 (n=18)

Type of Initial ARV Therapy • Dual combination: 28. 8% • HAART: 71. 2% NRTI=nucleoside analogue reverse transcriptase inhibitor, NNRTI=non-nucleoside reverse transcriptase inhibitor, PI=protease inhibitor

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 immunologic or virologic parameters known (n=33)

Average Monitoring Delays Between Request and Notification of Lab Results

Treatment Lapses • 23. 7% of sample lacked medication for >1 month (n=14) – Example: patient recorded as picking up 30 -day supply 3/4/00 did not return until after 5/4/00 • Medication insufficiencies primarily due to patient failure to pick up prescriptions (n=11), less so to pharmacy shortages (n=3)

Predictors of Medication Insufficiency in Multivariate Analysis • Women nearly 6 times more likely to experience medication insufficiencies than men (OR=5. 81, CI 1. 41 -23. 86) • Univariate association between medication insufficiencies and hospitalization in 2000 not significant in multivariate analysis • Not associated with patient age, baseline CD 4 count, or prior ARV use in univariate or multivariate logistic regression models

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

Discussion: Factors Contributing to Medication Insufficiencies as Discussed with Practitioners and Pharmacist: • Patient non-adherence – Use of multiple drug manufacturers led to frequent changes in packaging, creating patient confusion • Drug shortages – Transportation hurdles – Manual feedback system to estimate demand (delays, calculation errors)

Study Limitations: • Small sample size • High proportion of archived initial registrants (35%) • Liberal, non-specific measure for medication insufficiencies

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

Recommendations: • Improved lab capabilities are needed to shorten monitoring delays • Adherence interventions addressing women may reduce treatment lapses • Standardization of labeling may facilitate medication use • Further adherence research using more standard markers is required

• 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: 378385. • Ministerio da Saude. Recomendaçoes para terapia antiretroviral em adultos e adolescentes infectados pelo HIV— 1999. Coordenaçao Nacional de DST e AIDS, Brasilia. (http: //www. aids. gov. br). • Sackoff JE, Mc. Farland 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.