CD4 cell count increases sustained up to five years in developing-world treatment programmes

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According to a large-scale collaborative analysis reported in AIDS, antiretroviral programmes have led to significant and sustained increases in CD4 cell counts among people in low-income countries who are able to remain on therapy. Among nearly 20,000 people receiving antiretroviral therapy (ART) in African, Latin American, and Asian study cohorts, median CD4 cell counts increased from a baseline of 114 cells/mm3 to 395 cells/mm3 after five years on treatment.

Data for this collaborative report was gathered from cohorts participating in the ART-LINC (Antiretroviral Therapy in Low Income Countries) Collaboration of the International Epidemiologic Databases to Evaluate AIDS (IeDEA). Results from this analysis were presented earlier this year at the Fifteenth Conference on Retroviruses and Opportunistic Infections; key points and further discussion from the published paper are reported here.

The analysis was based on data from treatment-naive adults and adolescents (15 years or older) who started ART during 1995 or later through one of 27 African, Latin American, and Asian treatment programmes. Out of 35,010 potential participants, 14,779 (42%) were excluded due to missing data or having less than six months of follow-up, and 264 for having baseline CD4 cell counts over 500 cells/mm3. This left a final study population of 19,967 patients, equivalent to 39,200 person-years. The median age was 35, and 60% of the patients were women. The median baseline CD4 count was 114 cells/mm3, and most (57%) were at an advanced clinical stage of HIV disease. Most (81%) were in treatment programmes in Africa (22 programmes), 12% were from two Asian programmes, and 7% were from three Latin American programmes.

Glossary

low income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. While the majority of the approximately 30 countries that are ranked as low income are in sub-Saharan Africa, many African countries including Kenya, Nigeria, South Africa and Zambia are in the middle-income brackets. 

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

immunologic response

The effect of treatment on the immune system, particularly on the CD4 cell count.

The median CD4 cell count of the entire study population increased steadily with time on ART, from 114 cells/mm3 at baseline to 263 cells/mm3 at one year, 336 cells/mm3 at two years, 372 cells/mm3 at three years, 377 cells/mm3 at four years, and 395 cells/mm3 at five years. The numbers of patients in follow-up decreased with time: 820 patients from eight clinics were being actively followed at the five-year mark.

While women had faster and greater CD4 cell increases than men in univariate analysis, women also had higher baseline CD4 cell counts than men (121 vs. 104 cells/ mm3), and this difference in response essentially disappeared in multivariate analysis. In full multivariate analyses, baseline CD4 cell count was the most important predictor of outcomes, with better responses at higher baseline counts. Age was also a predictor, with younger participants showing greater increases.

These encouraging large-scale results demonstrate "robust CD4 responses to ART that are sustained over several years," consistent with long-term findings in developed countries. Although there were significant differences in baseline characteristics between cohorts, "the overall finding (substantial improvements in CD4 cell counts after ART initiation) was consistent across the diversity of geographical settings." However, the authors stress that the results are drawn only from those who remained on ART for the duration of the study and for whom follow-up data were available, which excluded a substantial proportion of the total population.

Given that higher baseline CD4 counts were the best predictor of a good response, this underscores the need to implement wider CD4 cell count testing, which would identify more people in need of treatment and "likely… improve treatment outcomes considerably," say the investigators. Most participants in the ART-LINC cohorts were already at advanced immunologic and/or clinical stages of disease; only 6% had less advanced clinical disease and CD4 cell counts above 200 cells/mm3 when they were started on treatment. The investigators note that CD4 counts at the start of ART, "although still low in most of the [ART-LINC] cohorts, have increased in recent years."

Reference:

Nash D et al. Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies.AIDS 22:2291–2302, 2008.