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Factors that also interfere in CD4 levels and can be considered on analyzing the effect of age on immunological response of antiretroviral therapy

Rocha, Bruno S. da; Duarte, Daniele W.; Wolff, Fernando H.; Barcellos, Nêmora T.

doi: 10.1097/QAD.0b013e328359aa89

Postgraduate Studies Program in Epidemiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2400 – second floor, Porto Alegre, Rio Grande do Sul, Brazil.

Correspondence to Bruno Simas da Rocha, Av. Ipiranga 2752, 203, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS – Brasil CEP 90610-000, Brazil. E-mail:

Received 14 June, 2012

Accepted 23 August, 2012

We read with great interest the article ‘Effect of age on immunological response in the first year of antiretroviral therapy (ART) in HIV-1-infected adults in West Africa’ [1]. The increasing life expectancy of HIV-infected patients due to aging of general population and large-scale access to ART is a reality we now face also in resource-limited countries. Data from Europe and USA had already shown lower immunological response to ART in older patients, and this article now brings information of paramount importance from sub-Saharan Africa, a population with very particular features that were not well investigated in previous studies.

The results were, in accordance with the other studies, pointing to a lower response to ART in African patients that rises with aging. However, some important factors that interfere in CD4 levels that were not taken into account could have been addressed in the analysis. In this context, we highlight the effect of tuberculosis (TB) coinfection in CD4 response to ART. According to some studies, TB coinfection was associated with poor CD4 response to ART [2–4], being also associated with CD4+ lymphocytopenia even in HIV-seronegative patients [5]. Analyzing the IeDEA West-African cohort profile [6], in which the present study was based, one of the objectives mentioned was describing important comorbities and coinfection in HIV infection, including malaria, TB and cancer. According to this publication, these data are collected in most sites of the cohort. Moreover, most of the facilities in West Africa have tuberculin skin test, sputum smear and – at least some of them – have access to culture for Mycobacterium tuberculosis, which could provide data from TB infection that could have been included in analysis.

Another factor that was not considered and can also influence CD4 levels after ART is the time of disease. Related to this last issue, we point out a study that investigated the prognosis of highly active antiretroviral therapy (HAART) treatment in patients in Serbia. This article showed that, if the treatment is initiated during primary HIV infection, it takes a shorter time to achieve a favorable response comparing to patients who began HAART in chronic HIV stages. Furthermore, a higher proportion of patients with primary HIV infection achieved a favorable response to HAART compared to those treated in the chronic phase [7]. Additionally, the authors of a nationwide Denmark cohort study concluded that prolonged periods of immune deficiency prior to successful HAART are a risk factor for incomplete CD4 cell recovery [8]. Thereby, we believe that controlling the analysis for these important aspects of HIV treatment could provide a more accurate result of the real impact of aging in ART response in these patients.

Finally, the impressive number of patients enrolled in the study draws attention; nonetheless, the high percentage of those lost for the second point of CD4 measurement raises concern. The primary outcome of the study was analyzing the difference between median CD4 12 months after initiation of ART and the baseline CD4 levels [1]. However, according to the results of the study, only 42.3% of the sample measured the second CD4 after 12 months of treatment, leading to a loss of 57.7% for these data [1]. There was no information from these losses in the article. We believe that maybe this high number of losses was due to the fact that the study was planned in 2006, but it was based in a cohort (IeDEa) that began previously [6], and were not designed specifically for measuring the present study outcomes. It would be important to describe the features of these patients lost for the second CD4 measurement, considering them in the analysis to be sure that this would not change the study results. If the points mentioned were clarified, certainly the information presented by this study would have greater impact for a better understanding of how aging affects the immune response to the ART in adults infected by HIV in West Africa.

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Conflicts of interest

There are no conflicts of interest.

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