Antiretroviral treatment in resource-poor settings: the Brazilian experience.

The Brazilian HIV/AIDS drug policy has been highly debated and even criticized, particularly at the time of its implementation by the Government in early 90s. However, after more than a decade of action, the success of the Brazilian response to HIV is evident and recognized worldwide, lying upon a concerted early governmental response, a strong and effective participation of the civil society, a multisectoral mobilization, a balanced prevention and treatment approach and the advocacy of human rights in all strategies, particularly with the policy of wide access to antiretroviral drugs. This policy made highly active anti-retroviral therapy (HAART) universally available since 1996, with logistic and criteria distribution based on regularly updated national guidelines. Approximately 140,000 patients now receive antiretroviral (ARV) treatment through the public health system. As a result there has been a significant fall in morbidity/mortality rates, hospital admissions and costs of treatment, with significant growth in demand for outpatient services and decrease for hospital, home and day-care services. It has also led to improvements in the quality of life for HIV+ individuals and savings in the medical costs, while economic and social related costs also have fallen. The policy of universal access to combined antiretroviral treatment (ART)' in Brazil has been shown to be cost-effective and the financial resources devoted to this initiative represents an economically viable investment. This experience also shows that a well-designed and supported international effort to reduce drug prices and improve health infrastructure could overcome many obstacles in middle-income and limited-resource countries.

Dramatic improvement in survival among adult Brazilian AIDS patients.

BACKGROUND: Since the last study of survival time among Brazilian AIDS patients, care has improved steadily, culminating in a controversial policy of universal free access to triple antiretroviral treatment since 1996. This large, national study examined how these changes have impacted survival. METHODS: Using national data for cases diagnosed in 1995 and 1996, we randomly selected 3930 adult AIDS cases from 18 cities in seven states representing all regions of Brazil. Trained abstracters reviewed medical records, determining dates of diagnosis and death or last contact, exposure category, treatment, and demographics. After review, 2821 cases met the inclusion criteria and were available for Kaplan-Meier and proportional hazards analysis. Data from the earlier study were re-analyzed for comparison. RESULTS: Median survival was 5 months for cases diagnosed in the 1980s, 18 months for those diagnosed in 1995, and 58 months for those diagnosed in 1996. Predictors of longer survival in univariate analysis included antiretroviral treatment, year of diagnosis, higher education, sexual exposure category, female sex, and Pneumocystis carinii pneumonia prophylaxis. In multivariate analysis, the predictive value of most of these was attenuated or disappeared, leaving antiretroviral treatment as the main predictor of survival. CONCLUSIONS: Survival time has increased substantially for adult Brazilian AIDS patients. The timing of these gains and analysis of the predictors of survival both indicate antiretroviral treatment as the cause. These findings demonstrate that universal access to antiretroviral treatment in a developing country can produce benefits on the same scale as in richer countries.

Brazilian Network for HIV Drug Resistance Surveillance (HIV-BResNet): a survey of chronically infected individuals.

OBJECTIVE: To study the prevalence of HIV drug resistance mutations and subtype distribution in a Brazilian drug-naive population. Asymptomatic, drug-naive HIV-1-infected individuals were targeted in 13 voluntary counseling and testing centers spread around the country. METHODS: Plasma viral RNA was extracted from 535 HIV-1-positive subjects. Protease (PR) and reverse transcriptase (RT) genomic regions were sequenced for subtype determination and analysis of drug resistance mutations. RESULTS: Eight samples (2.24 %) showed primary mutations related to protease inhibitor (PI) resistance, eight (2.36%) to nucleoside reverse transcriptase inhibitors (NRTI) and seven (2.06%) to non-nucleoside reverse transcriptase inhibitors (NNRTI). Accessory mutations were found in the PR gene at the following positions: L63P/V/T/A/I [153/345 (44.3%)], M36I/L [149/345 (43.2%)], L10I/F/V [82/345 (23.8%)], V77I [60/345 (17.4%)], A71V/T [11/345 (3.2%)], K20M/R [10/345 (2.9%)], and V82I [4/345 (1.2%)]. Mutations known to be associated with reduced sensitivity to NRTI or NNRTI (V118I, E44D, K219R, T69A, and V75L) were found in a low prevalence (0.6-2.4%). A high proportion of the isolates from subtype C was found in the southern states. Subtype F-related viruses were the main non-B variant in the rest of the country. CONCLUSIONS: Brazil has a low prevalence of drug-resistant strains circulating among recently diagnosed individuals. However, there was an increase in these rates compared with similar studies performed with samples collected in Brazil from 1996 to 1998. Continued surveys are required to detect trends in these rates, but routine genotypic testing in the drug-naive population prior to antiretroviral initiation is not required in Brazil.

A specific subtype C of human immunodeficiency virus type 1 circulates in Brazil.

OBJECTIVE: To characterize the subtype C strains of HIV type 1 that circulate in Brazil, especially those originated from the southern part of the country. DESIGN AND METHODS: One hundred and twelve HIV-1-positive subjects had their plasma viral RNA extracted. Protease (PR) and reverse transcriptase (RT) genomic regions were polymerase chain reaction-amplified and sequenced for subtype determination. Subtype C strains were selected and compared to other strains of this subtype from the database, and specific amino acid signature patterns were searched. RESULTS: Brazilian subtype C viruses form a very strong monophyletic group when compared to subtype C viruses from other countries and presented specific signature amino acids. Recombinants between subtype C and B viruses have been documented in areas of co-circulation. The incidence of primary PR and RT inhibitor resistance mutations in drug-naïve subjects was observed. An increasing number of secondary resistance mutations was also seen, some of which are characteristic of subtype C-related sequences. CONCLUSIONS: Introduction of subtype C of HIV-1 in Brazil was likely a single event of one or a mixture of similarly related strains. Recombination between subtype C and B viruses is an ongoing process in the country. Primary and secondary drug resistance mutations were observed, although some of the secondary mutations could be associated with subtype C molecular signatures. Subtype-specific polymorphisms of PR and RT sequences found in this subtype C Brazilian variant might influence this emergence and have an impact on HIV treatment and on vaccine development in the country.

Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART.

BACKGROUND: Current guidelines for antiretroviral (ARV) therapy recommend at least triple-drug combination, the so-called highly active antiretroviral therapy (HAART). Not all patients respond to HAART and the development of drug resistance remains one of the most serious obstacles to sustained suppression of HIV. OBJECTIVE: In an attempt to correlate the HIV therapeutic failure with reverse transcriptase (RT) and protease resistance mutations, we describe the ARV resistance profile in patients failing HAART in Brazil. We studied 267 Brazilian HIV-1 infected patients failing HAART looking for mutations in RT and protease genes. The mutation profile of the viruses infecting these individuals were deduced and correlated to laboratorial parameters. STUDY DESIGN: Two different HIV-1 genomic regions were targeted for PCR amplification, the protease (pro) and pol RT (palm finger region) genes. The mutations related to drug resistance in RT gene was analyzed using a line probe assay (LIPA(R)) and pro amino acids positions 82 and 90 were screened through RFLP using HincII restriction digestion. RESULTS: There was strong correlation between the mutation in the pro and RT genes and therapeutic failure. The main mutation found in RT gene was the M184V (48%) followed by T69D/N (47%), T215Y/F (46%), M41L (39%), and L74V (7%). In the pro gene the main mutation found was L90M (26%) followed by dual substitution in L90M and V82A (6%). All mutations profiles matched very well with the patients drug regimen. CONCLUSIONS: This study has shown that 84.7% of HIV infected subjects failing HAART for more than 3 months presented viral genomic mutations associated with drug resistance.