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The Chilean AIDS Cohort

A Model for Evaluating the Impact of an Expanded Access Program to Antiretroviral Therapy in a Middle-Income Country-Organization and Preliminary Results

Wolff, Marcelo J, MD*; Beltrán, Carlos J, MD*; Vásquez, Patricia, MD*; Ayala, Marisol X, MD*; Valenzuela, Miguel, MD*; Berríos, Gloria, RN; Arredondo, Anabella, MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2005 - Volume 40 - Issue 5 - p 551-557
doi: 10.1097/01.qai.0000185573.98472.f8
Clinical Science
Free

Chile, middle-income country with 15 million people, began an expanded access program (EAP) to antiretroviral therapy (ART) in 2001. EAP provides ART, monitoring, and funding for management of associated complications in 32 points of care. A national cohort (Chilean AIDS Cohort [ChiAC]), enrolling 98% of these patients, was created for standardized treatment and impact evaluation. Information exchange is mainly through the Internet. By December 2004, the ChiAC had 4365 participants (83.3% male). At baseline, 47.5% had clinical AIDS, 26.2% were asymptomatic, 80.2% had a CD4 count <200 cells/mm3 and 58.2% were ART naive; in these patients, the most frequent regimen is zidovudine, lamivudine, and efavirenz. A 6-month follow-up in 1057 patients showed a global mortality of 5% (0.5% if patients were asymptomatic at baseline and 8.3% if patients had baseline AIDS). There was a similar risk of death if the baseline CD4 count was 100 to 200 cells/mm3 or >200 cells/mm3 (∼1%), but this increased to 4.8% (relative risk [RR] = 5.2) and 10.7% (RR = 11.5) if the CD4 count was 51 to 100 cells/mm3 or ≤50 cells/mm3, respectively. Discontinuation occurred in 7.7% of patients because of drug toxicity, and progression occurred in 2.9%. A successful EAP to ART with the resources of a middle-income country is possible. Early results are similar to those of industrialized countries. A national cohort allows better implementation and evaluation of the program and may be a useful model for other countries.

From the *Chilean AIDS Group, Santiago, Chile, and †National AIDS Commission, Santiago, Chile.

Financed by the Global Fund to Fight AIDS, Tuberculosis, and Malaria; and the National Fund for Health Research (FONIS).

M. J. Wolff and C. J. Beltrán contributed equally to this report.

Reprints: Marcelo Wolff, 23 de Febrero 8630-N, Santiago, Chile (e-mail: mwolff@vtr.net).

The AIDS epidemic, which affected between 35.9 and 44.3 million people worldwide at the end of 2004, has become the leading cause in the world of adult mortality attributable to infectious diseases.1 Effective treatment to control the disease, which is in use for most people known to be infected in the industrialized world, has reduced AIDS complications and mortality dramatically.1-5 This treatment is almost nonexistent in the countries hit most hard by the epidemic, however. Altogether, treatment is being provided to less than 5% of the world's HIV-infected population, and almost all untreated people live in developing countries. There is a growing consensus that proper treatment availability must be greatly expanded to include patients in the so-called “Third World” and that developed countries should commit themselves to support expanded access to AIDS treatment in the poorer and most severely affected countries, mainly in sub-Saharan Africa and, increasingly, in certain regions of Asia. The World Health Organization's goal is to reach the so-called “3 by 5” goal: treatment of 3 million people from these regions by 2005.6

A sizable number of middle-income countries, led by Brazil and including countries from Asia, Latin America, and Eastern Europe, are trying to expand access to treatment using their own resources. For the most part, they have the social network, health infrastructure, human resources and expertise, and political commitment to carry out this endeavor.7 Although useful, the experience of industrialized countries is not totally applicable in these countries. For this reason, it is of utmost importance for them to evaluate their own experience in AIDS treatment to optimize the use of scarce resources; minimize errors; and, most importantly, evaluate the effect of the program on morbidity, mortality, social rehabilitation, transmission, and progression of the epidemic. These are precisely the topics for which adequate scientific information from limited-resource settings is limited.

Chile, a middle-income country, recently began an expanded access program (EAP) to antiretroviral therapy (ART). The Chilean experience organizing the EAP and its impact has been carefully monitored. Sharing this experience with countries of similar economic capacity, epidemic status, and commitment to treatment should be extremely useful. Some poorer countries that are just beginning to expand access to ART could also benefit from this experience.8 The purpose of this report is to describe the Chilean EAP and the model for evaluating its impact, the Chilean AIDS Cohort (ChiAC), with its preliminary results.

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METHODS

Basic epidemiologic data were obtained from epidemiology bulletins published by the National Commission on AIDS (CONASIDA). A general description of the Chilean EAP is presented, including its organizational structure, human resources, treatment guidelines, and funding mechanisms. The main characteristics of the ChiAC database are described. A patient was considered to be a member of the cohort and reported here after having a treatment request approved by the central office and initiating treatment under the EAP.

All patients from the cohort with complete baseline data by July 2004 were included for analysis. Descriptive statistics included biodemographic, immunologic, and clinical data. Clinical outcomes were assessed at 6 months of follow-up. Participants were classified according to Centers for Disease Control and Prevention (CDC) stage, CD4 cell count, and whether they were treatment naive or not. Overall mortality was calculated for each stratum using CDC category A and stage 1 as the reference group; crude relative risks of death were estimated for groups B and C and compared by χ2 test. Among survivors, absolute risk of clinical progression and incidence of opportunistic infections (OIs) were calculated and compared with baseline data. Finally, we calculated the adverse event rates and toxicities associated with each drug.

Tests of significance were 2-sided, and a P value less than 0.05 was considered significant.

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RESULTS

Chile, a South American country with a population of 15.5 million, has a current annual per capita income of approximately US $5000. The HIV epidemic is of moderate proportion, and close to 0.2% of the general population was estimated to be infected (33,000 people) as of December 2002; 94% acquired the infection sexually, mainly in homosexual or bisexual men, but heterosexual transmission and HIV cases in women have been steadily increasing recently (female/male ratio increased from 1:12 in the 1980s to 1:7 in early 2000s).9 The growth rate of reported cases is 15% per year and stable. It is estimated that approximately 6000 people (5000 from the public health system [PHS] sector) now require therapy; 85% of the HIV-infected population receives treatment from the PHS, which is otherwise responsible for health assistance of 70% of the nation's population (Table 1).

TABLE 1

TABLE 1

In late 2001, the EAP began providing free highly active ART to patients cared for by the PHS. It was financed with national public funds, and services were delivered throughout the country by a network of 32 points of care associated with public hospitals staffed by multiprofessional teams. Thirty percent of the medical staff members are infectious disease specialists or immunologists, and 70% are general practitioners or internists with a variable degree of HIV care training. Specialists are concentrated in the major urban centers, where most patients are seen.

The Ministry of Health, through CONASIDA, is responsible for providing the following:

  1. Antiretrovirals on a patient-by-patient basis, meaning that individual records of each therapy are kept
  2. Viral load testing (Nuclisens), performed in 2 centers in the country at a cost of US $45 per test
  3. CD4 count determinations (flow cytometry), performed in 2 centers at a cost of US $18 per test
  4. Genotyping testing, performed in 1 center at a cost of US $250 per test
  5. Supplementary budget for the management of OIs requiring more than standard care drugs and calculated according to the patient load per center. Lately, there has been a shift in the utilization of this budget from OIs to therapy-associated complications and cancer therapy. Local AIDS care centers and associated hospitals cover the remaining health care expenses.

Before initiating the EAP, CONASIDA released national guidelines for ART,10 developed by an advisory expert group, to be followed by practitioners participating in the program. Treatment has been recommended for all symptomatic patients (CDC C and most B categories) and asymptomatic patients with a CD4 count ≤200 cells/mm3; treatment for patients with a CD4 count between 200 and 350 cells/mm3 is considered on an individual basis favoring initiation if there is a rapidly declining CD4 count or viral load >55,000 copies/mL. No asymptomatic patients with a CD4 count >350 cells/mm3 are treated under the program.

Recommendations for treatment-naive patients include the use of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Recommendations for treatment-experienced patients and cases of failure are dealt with on an individual basis. Genotyping is available on a limited basis after second failure. No generic drugs are used, and CONASIDA has negotiated price reductions with the pharmaceutic industry. The stock of currently available drugs includes zidovudine, lamivudine, stavudine, didanosine, abacavir, nevirapine, efavirenz, indinavir, nelfinavir, ritonavir (only for boosting), and, under the restriction of previous failures, lopinavir/ritonavir. Other drugs can be obtained in special circumstances.

Centers telefax a request to CONASIDA for a therapeutic regimen on an individual basis using a special form containing pertinent information in accordance with guidelines; physicians are free to choose the individual drugs to be used. The information is checked for administrative data; pooled forms are sent to members of the advisory group, who check the appropriateness of the request and its concordance with the national guidelines, and requests are approved, modified, or postponed because of the need for more information. The decision is sent back to CONASIDA, which instructs the pharmaceutic companies to deliver the medications directly to the pharmacies of the points of care. Orders for measurement of CD4 cell counts and viral loads are made directly from the centers to the reference laboratories under specific guidelines. Genotyping testing is requested of CONASIDA and is approved by an advisory group. Time limits for all parties involved have been established to ensure the prompt resolution of the requests and initiation of therapies (Fig. 1).

FIGURE 1

FIGURE 1

As of July 2004, CONASIDA had approved therapies for 5048 patients and 4454 had initiated ART. Under a similar program, approximately 100 children nationwide are receiving free ART.

The ChiAC is a prospective observational cohort made up of patients managed by a network of HIV-treating physicians and nonmedical professionals carrying out the EAP in the PHS: the Chilean AIDS Group. It was created in 2002 as an initiative of the Chilean Society for Infectious Diseases and with the support of (but independent from) CONASIDA. A grant from the Global Fund to Fight AIDS, Tuberculosis, and Malaria allowed the hiring of personnel and the setting up of an administrative office. Participation is voluntary, but once a center is enrolled, information on all its patients for whom therapy has been requested is mandatory to avoid enrollment bias. By July 2004, 29 (90.6%) of 32 centers were participating and 4365 patients had been enrolled (98% of EAP patients). There is a central office for administration with 2 coordinators, 2 associates, and a registered nurse. The ChiAC database is fed with information requested by CONASIDA to provide ART, plus additional baseline and follow-up information requested by the cohort headquarters regarding clinical, immunologic, and virologic results; toxicities; and treatment discontinuations and changes during every 6-month period. Centers are contacted periodically to update their information. There is a team in charge of verifying the quality of the information sent, which checks up on all the follow-up forms and conducts random reviews of a number of cases. The main purpose of the ChiAC is to evaluate the results of the EAP with the largest possible number of patients and to obtain information and experience validated in the country in which it is being implemented. It is postulated that results obtained here could be useful to other middle-income countries with a similar epidemic scenario and a similar commitment to an EAP to therapy.

An interactive electronic database was created, including a ChiAC Web page (www.sidachile.cl), e-mail for all members, and other online exchanges between headquarters and centers as well as electronic real-time capture and correction of the data.11 Direct exchange of clinical and laboratory information between the centers, CONASIDA, the cohort central office, and the laboratories performing the CD4 cell count, viral load, and resistance testing is being planned for the near future. Confidentiality of patient information is retained through coded files.

There are primary and secondary objectives for the cohort. Primary objectives include morbidity and mortality; clinical, immunologic and virologic outcomes; and overall feasibility of the program. Secondary objectives include results according to ART regimens; impact of therapy on tuberculosis and other highly prevalent complications; and toxicity, treatment compliance, and results according to gender, sociodemographic characteristics of the population, and characteristics of points of care.

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Baseline Characteristics

As of July 31, 2004, the ChiAC had complete baseline information for 4365 patients on ART (83.4% male, with a mean age of 38 years). The group initiated ART for advanced disease, which included 80.2% of patients with a CD4 count <200 cells/mm3 (Fig. 2) and 47.5% with clinically defined AIDS (Fig. 3).

FIGURE 2

FIGURE 2

FIGURE 3

FIGURE 3

The main OIs before ART were oral or esophageal candidiasis (36.8% of patients), Pneumocystis jiroveci pneumonia (20.5% of all patients and 42.4% of those in category C), and tuberculosis (8.0% of all patients and 16.4% of those in category C, one third with extrapulmonary disease). Characteristics of 2479 ART-naive patients (58.2% of the total) included 53.4% having initiated therapy with a CD4 count <100 cells/mm3 and 30.9% with a CD4 count from 100 to 199 cells/mm3; the mean CD4 count was 96 cells/mm3. Background ART in naive patients has been lamivudine plus zidovudine (84.2%) or stavudine (12.5%) plus nevirapine (29.9%), efavirenz (39.5%), or single or boosted indinavir (21.6%). The choice of efavirenz increased from 26.4% in 2002 to 61.5% in late 2003 (Table 2).

TABLE 2

TABLE 2

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Preliminary Results

At 6 months of follow-up in 1057 patients12,13 5.3% (5.0%) had died: 5.9% in the ART naive-group and 3.3% in the non-naive-group. Mortality according to baseline CDC classification is shown in Table 3 and Figure 4. Mortality according to baseline CD4 cell count is shown in Table 3 and Figure 5.

FIGURE 4

FIGURE 4

FIGURE 5

FIGURE 5

TABLE 3

TABLE 3

At 6 months of follow-up, 83.1% of all patients were still on initial therapy and 63.5% of them had a viral load <80 copies/mL. Clinical progression while on therapy was seen in 31 (2.9%) patients and followed a similar pattern as mortality with regard to baseline CD4 count: 1.3% if the baseline CD4 count was >200 cells/mm3, 1.0% if the baseline CD4 count was 101 to 200 cells/mm3, 3.6% if the baseline CD4 count was 51 to 100 cells/mm3, 4.5% if the baseline CD4 count was 11 to 50 cells/mm3, and 6.8% if the baseline CD4 count was ≤10 cells/mm3. The incidence of OIs at 6 months of therapy is shown in Table 4 in comparison to the baseline cumulative incidence of these complications.

TABLE 4

TABLE 4

Toxicity was the leading cause for ART discontinuation in that period: 81 patients (7.7%) stopped ART because of toxicity. Severe toxicity was almost twice as high among women (12.6% of women, 6.5% of men). Main toxicities requiring therapy discontinuation are shown in Figure 6.

FIGURE 6

FIGURE 6

Discontinuation was also required in 1% of cases because of lactic acidosis from stavudine; in 1.2% of cases because of abacavir hypersensitivity; in 1.2% of cases because of hepatitis from nevirapine; in 1.1% and 0.7% of cases because of efavirenz-induced rash and neurologic symptoms, respectively; and in 1.4% and 1.1% of cases because of nephrolithiasis from unboosted and boosted indinavir, respectively.

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DISCUSSION

We have presented the model of the EAP to ART in a middle-income country (Chile), the national system established to evaluate its results (the ChiAC), and preliminary data on results. In late 2001, the government undertook the task of providing free, potent, state-of-the-art HIV therapy to patients cared for by the PHS with its own resources and aiming at 100% coverage. By mid-2003, and with the financial support of the Global Fund to Fight AIDS, Tuberculosis, and Malaria, a small gap was closed and the aim was reached. There is, however, still no free or subsidized ART for the 15% of the HIV-infected nonindigent population cared for by other systems or without any coverage. New health legislation should soon change this situation.

This is a centralized program trying to unite the complex management of a complex disease in a situation in which many health care providers are not specialists. The program not only provides antiretroviral drugs and monitoring tests but, interestingly, a supplementary budget for special medications involved in the nonantiretroviral care of HIV disease, with the purpose of not forcing hospitals, with already austere budgets, to bear the extra burden of these patients and becoming reluctant to undertake their care. The program is not without difficulties: its centralized nature carries unavoidable bureaucracy and delays, and centers do not have a general uncommitted stock of drugs; instead, drugs are allocated to specific and previously defined patients, with modifications of previously approved regimens requiring further approval. There are still few sites performing monitoring tests, and many samples need to be transported long distances. The ministerial AIDS commission, CONASIDA, is still greatly involved in operational activities, taking time and effort from its main regulatory role. Despite all this, the program has been largely successful; after a short waiting period, PHS patients needing therapy do get their treatment. The program uses no generic drugs, which are less expensive, but through price reductions negotiated by the government, the annual cost of a first-line regimen (zidovudine or lamivudine plus nevirapine or efavirenz) is approximately US $2300 (but US $6000 for other regimens after more than 1 failure). No such price reduction is available to patients not participating in this program. In comparison, the annual cost for similar regimens in Argentina, which also has its own EAP and uses mainly generic drugs, are US $1250 and US $2500, respectively (J. Lazovsky, MD, 2005, personal communication). In Brazil, full generic first-line treatments cost between US $606 and $925 (J. Mendonça, MD, 2005, personal communication).

The central authority has limited capability to evaluate the results of the program beyond gross mortality, AIDS-related hospitalizations, and global use of antiretrovirals. This difficulty may explain the scarcity of reports on the results of this kind of program in middle-income countries that have begun treatment of their patients. To fill this gap, among other goals, the ChiAC was created. Interestingly, health care providers from AIDS care centers responded enthusiastically; at this time, more than 90% of doctors and nurses involved in AIDS care in the PHS are voluntarily participating, having enrolled practically all patients on treatment through the EAP. Participants are highly motivated, and many, especially those living distant from major cities, have manifested their satisfaction at participating in a national project and having their opinion considered. This was an unexpected finding, considering the usual reluctance of people to respond to centrally generated inquiries. The active participation of health care providers has allowed a small and low-budget central administrative office to collect a large amount of data in a relatively short time. The Internet has been used to develop a communication system for the cohort. The interactive nature of the cohort study group, still in its infancy, permits the exchange of information and consultations; in the near future, it is expected that ART requests, laboratory results, and drug stocks may be incorporated into the system. The cost of implementing this has been minimal. This massive participation has reduced enrollment bias to a minimum, which is different from the situation in other large cohorts, with voluntary participants providing information not mandatory from all their patients.

The epidemic in Chile is fairly typical of many middle-income nontropical countries. The major mode of transmission is sexual, affecting mainly adult homosexual or bisexual men, with a growing number of women affected, most of whom are regular, long-term, and exclusive partners of infected men, and the disease remains mainly an urban problem. A major difference may be the small impact of drug abuse as a risk factor for infection (<5%).

More than 4300 patients receiving treatment have been included and have provided complete baseline information, which is a larger number than that of cohorts from many industrialized countries14,15 and involves as many naive patients as other multicountry cohorts.16,17 This cohort is likely to be one of the largest from a middle-income country. Most patients were treatment naive, had advanced disease, and were severely immunosuppressed at the beginning of ART. There are still a large number of symptomatic patients not presently under health care, who, now that they are aware of the program, are seeking treatment; thus, it is expected that advanced disease will still predominate for some time.

Background dual therapy for treatment-naive patients has been zidovudine and lamivudine in more than 80% of cases; severe anemia and/or neutropenia requiring a regimen change occurred only in 6.9%, validating this combination as the first choice. The third drug used varied: indinavir was used much more frequently at the beginning of the program, but efavirenz and, in second place, nevirapine are now the first choices, with the former becoming the leading associated third drug mainly because of its lower incidence of adverse effects observed in this cohort and increasing concerns regarding the safety of the latter. Nevirapine and indinavir (especially if boosted with ritonavir) required discontinuation in more than 10% of patients, and efavirenz required discontinuation in approximately 2%. More toxicity was observed in women than in men; the significance of this finding requires confirmation with more patients and longer follow-up. Preliminary results at 6 months of follow-up, although obtained from a quarter of the cohort population, are numerous enough to foresee trends, and these are similar to those obtained in other large cohorts: low toxicity and important reductions in mortality and opportunistic complications of highly active ART. This first report is from a short follow-up period, but the data are clear enough to set a definitive pattern: prompt reduction of major and frequent complications.

Not surprisingly, mortality and clinical failure were higher in patients with more advanced disease clinically or immunologically, but it is worth pointing out the finding of similar mortality in patients with a wide range of baseline CD4 cell counts and a significant increase only when the count was less than 100 cells/mm3 and, more markedly, less than 50 cells/mm3. Similar findings were previously reported in studies involving a smaller number of naive patients with similarly advanced HIV disease.18,19 In settings in which therapy might not be available to everybody, an approach with priorities for therapy initiation according to this finding may be used. Longer follow-up is underway, immunologic and virologic data are being prepared, and substudies with secondary objectives are being undertaken. The preliminary results have already had an impact on the national program: new guidelines have just been released, which include a stronger recommendation for efavirenz than the previous one, exclusion of indinavir, some nevirapine safety warnings, a CD4 count reduction for consideration of therapy initiation in asymptomatic and non-high-viral-load patients from 350 to 250 cells/mm3, and a fast track for initiating therapy for those patients with CD4 counts <100 cells/mm3.20

In summary, an EAP in middle-income countries with only local resources or some minor foreign aid is possible, and clinical results are more than encouraging.

Proper evaluation of the impact and results of such programs is of the utmost importance. The cohort model presented here may be one of these systems. Results of evaluations such as the one presented here may also be useful in other countries with similar epidemic and economic scenarios that are committed to expanded access to therapy.21 The follow-up standard reporting forms in Spanish are available on the ChiAC Web site (www.sidachile.cl).

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REFERENCES

1. World Health Organization. Global Summary of the AIDS Epidemic. Geneva: World Health Organization; 2005. Available at: http://www.unaids.org/wad2004/EPI_1204_pdf_en/Chapter0-1_intro_en.pdf.
2. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853-860.
3. Messeri P, Lee G, Abramson DM, et al. Antiretroviral therapy and declining AIDS mortality in New York City. Med Care. 2003;41:512-521.
4. Moore RD, Chaisson RE. Natural history of HIV infection in the era of combination antiretroviral therapy. AIDS. 1999;13:1933-1942.
5. Egger M, May M, Chene G, et al. ART Cohort Collaboration prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet. 2002;360:119-129.
6. World Health Organization. Treat 3 Million by 2005 (3 by 5) Initiative. Geneva: World Health Organization; 2004. Available at: http://www.unaids.org/en/treat+3+million+by+2005+initiative.asp.
7. Brazilian Ministry of Health. The impact of antiretroviral therapy. Secretariat for Special Health Projects. National coordination for DST/AIDS, July 17, 2004. Available at: http://www.aids.gov.br/antiretrov_therap.htm.
8. Katzenstein D, Laga M, Moatti JP. The evaluation of the HIV/AIDS drug access initiatives in Cote d'Ivoire, Senegal and Uganda: how access to antiretroviral treatment can become feasible in Africa. AIDS. 2003;17(Suppl 3):S1-S4.
9. Comisión Nacional de SIDA. Caracterización epidemiológica de la infección por VIH/SIDA en Chile: Diciembre de 2003. Rev Chil Infectol. 2005;22:169-202.
10. Comisión Nacional del SIDA. Guía Clínica para la Atención de las Personas Adultas que viven con VIH/SIDA. Gobierno de Chile, Ministerio de Salud, Octubre 2001.
11. Wolff M, Beltrán C, Gallardo D, et al, for the ChiAC Group and CONASIDA. A national antiretroviral therapy expanded-access-program and the Chilean AIDS cohort: a model for ART in a middle-income country. Presented at: 43th ICAAC Conference; 2003; Chicago.
12. Vasquez P, Beltrán C, Gallardo D, et al, for the Chilean AIDS Study Group, CONASIDA. Efficacy of HAART in patients with extremely advanced HIV disease in a middle income country. Chilean AIDS Cohort. Presented at: Ninth European Congreso Europeo on AIDS; 2003; Warsaw.
13. Beltrán C, Wolff M, Morales R, et al, for the Chilean AIDS Cohort and CONASIDA. A national cohort model for assessing the effect of an expanded program to antiretroviral therapy and the short-term predictors for efficacy in a middle-income country. Presented at: 11th Conference on Retroviruses and Opportunistic Infections; 2004; San Francisco.
14. Petoumenos K. Australian HIV observational database. The role of observational data in monitoring trends in antiretroviral treatment and HIV disease stage: results from the Australian HIV observational database. J Clin Virol. 2003;26:209-222.
15. Perez-Hoyos S, del Amo J, Muga R, et al. GEMES (Spanish Multicenter Study Group of Seroconverters). Effectiveness of highly active antiretroviral therapy in Spanish cohorts of HIV seroconverters: differences by transmission category. AIDS. 2003;17:353-359.
16. Paredes R, Mocroft A, Kirk O, et al. Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe. Results from the EuroSIDA Study. Arch Intern Med. 2000;160:1123-1132.
17. Lundgren J, Mocroft A, Gatell J, et al. A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA Study. J Infect Dis. 2002;185:178-187.
18. MacArthur RD, Perez G, Walsmley S, et al. CD4+ cell count is a better predictor of disease progression than HIV RNA level in persons with advanced HIV infection on highly active antiretroviral therapy [abstract 203]. Presented at: Eighth Conference on Retroviruses and Opportunistic Infections; 2001; Chicago.
19. Miller V, Mocroft A, Reiss P, et al. Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA Study. Ann Intern Med. 1999;130:570-577.
20. Ministry of Health, Chile. Clinical Guidelines: Acquired Immunodeficiency Syndrome. Santiago: Ministry of Health; 2005.
21. Reynolds SJ, Bartlett JG, Quinn TC, et al. Antiretroviral therapy where resources are limited. N Engl J Med. 2003;348:1806-1809.
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APPENDIX

The members of the Chilean AIDS Study Group are Carlos Gallo, Roxana Galvez, David Wachter, Patricia Sarabia, Marcela de Andraca, Patricia Pavez, Patricia Carrasco, Lorena Berna, Carmen Aguayo, Marisol Ayala, Viviana Turi, Luis Montes, Eduardo Hermosilla, Gladys Varela, M. Eugenia Madariaga, Erna Ripoll, Elizabeth Barthel, M. Inés Sánchez, M. Teresa de Mateo, Werner Jensen, Rodrigo Ahumada, Alvaro Covarrubias, Luis Bavestrello, Sylvia Gómez, A. Burdiles, P. Rodas, Katty Zúñiga, Marcelo Wolff (coordinator), Rebeca Northland, Teresa Bidart, Jeanette Dabanch, Claudia Bustamante, Patricia Alvarez, Ingrid Flores, Patricia Vásquez, Marisol Bustos, Claudia Ledesma, Juan Ballesteros, Alexis Diomedi, Rinna Ortega, Jeannette Sobarzo, Jorge Pérez, Martín Lasso, Ana M. Fernández, Aurora Garín, Enna Zunino, Laura Bahamondes, Patricia Olea, Lucía Aguad, M. Moreno, Cristian Montenegro, C. Valdés, Margarita Enberg, J. López de Maturana, R. Pizarro, M. Quezada, Gregorio Ramírez, Johanna Bravo, Erika Molina, Carlos Beltrán (coordinator), Ricardo Morales, David Gallardo, J. M. Arancibia, Amalia Adasme, Miguel Valenzuela, Johanna Huerta, Diana Yanine, Silvia Arredondo, Manuel Amigo, Mauricio Maturana, M. Angélica Olivares, Luis Uribe, Eugenia Rodríguez, Ricardo Vásquez, Eva Woldarsky, Elizabeth Daube, Rodrigo Blamey, M. Eugenia Cancino, M. Elena Novoa, José Carreño, M. Isabel Mendoza, Carolina Chahín, Claudia Molina, Mario Calvo, Mónica Hering, Alicia Rebolledo, Jorge Mardones, Sara Villalobos, Iván Becerra, Ana M. Sáez, Carmen Toro, Lucía Atala, Stanko Karelovic, and Tatiana Navarro as well as Alejandra Valdovinos, Angélica Carrasco, and Omar Morales (staff).

Keywords:

resource-limited countries; cohort studies; antiretroviral therapy; expanded access to therapy; impact evaluation

© 2005 Lippincott Williams & Wilkins, Inc.