Elsevier

The Lancet

Volume 367, Issue 9513, 11–17 March 2006, Pages 817-824
The Lancet

Articles
Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

https://doi.org/10.1016/S0140-6736(06)68337-2Get rights and content

Summary

Background

Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings.

Methods

18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22 217, respectively, treatment-naïve adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses.

Findings

Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per μL vs 234 cells per μL), were more likely to be female (51% vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70% vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per μL vs 103 cells per μL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76% vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20 532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4·3 (95% CI 1·6–11·8) during the first month to 1·5 (0·7–3·0) during months 7–12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0·23; 95% CI 0·08–0·61).

Interpretation

Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Introduction

The increasingly widespread use of highly active antiretroviral therapy (HAART) since 1996 has substantially improved the prognosis of HIV-infected patients who have access to these drugs.1, 2, 3, 4 In resource-poor settings in Africa, Asia, and South America, where 90% of people with HIV/AIDS live, access to HAART is limited. With falling prices of proprietary drugs, the increasing availability of generic formulations and the launch of initiatives by international agencies, including the World Health Organization's (WHO's) “3 by 5” programme (to get 3 million HIV patients on antiretrovirals by 2005), the Global Fund to fight AIDS, Tuberculosis and Malaria, and the US President's Emergency Plan for AIDS Relief (PEPFAR), this situation is changing. The WHO estimates that as of June, 2005, about 1 million people were receiving HAART, although this number still only represents 15% of the estimated 6·5 million people in urgent need of antiretroviral therapy in low-income and middle-income countries.5

Several factors could limit the effectiveness of HAART in resource-poor settings. Interruptions in supply at the programme level or patients' limited financial resources might compromise adherence and treatment efficacy. The high prevalence of co-infections, notably with tuberculosis and other bacterial diseases might also affect prognosis.6, 7, 8 Here we report on the Antiretroviral Therapy in Lower Income Countries (ART-LINC) Collaboration, a network of treatment programmes in Africa, Asia, and South America.9 Our objective was to compare early mortality and immunological and virological response in patients starting HAART in these settings with outcomes in patients participating in a similar collaboration of cohort studies in high-income countries, the ART Cohort Collaboration (ART-CC).1

Section snippets

Participants

Treatment programmes in low-income countries were identified by searching published scientific reports, including abstracts from recent conferences, and by consulting with colleagues. Site assessments were done with a standardised questionnaire. Programmes that collected prospective data on patient characteristics and outcomes were eligible for inclusion in ART-LINC. 23 treatment programmes were approached, 19 agreed to participate, and 18 of these contributed data to this analysis.

Information

Results

The ART-LINC dataset has 6498 treatment-naïve patients with a known date of starting HAART and at least one follow-up; 4810 (74%) patients also had a CD4 count at baseline, and were thus included in the analysis. Compared with treatment-naive patients starting HAART without an immunological assessment, those with a documented baseline CD4 count were less likely to be male and more likely to be treated in publicly funded centres or programmes offering free care.9 The characteristics of the

Discussion

Mortality rates of HIV-infected patients from low-income settings in Africa, South America, and Asia fell substantially within the first few months of HAART, and approached those seen in Western Europe and North America after 4–6 months. Patients in low-income settings started treatment with considerably more advanced immunodeficiency than those from industrialised countries, but virological and immunological response to HAART were similar in both settings, a finding that tallies with results

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