Like CD4 cell count, CD4 percentage at baseline was lower in Côte d'Ivoire than in France (P < 0.01), and the difference did not vary (P = 0.20) during follow-up (Table 3). In both cohorts, low cell-associated HIV-1 DNA was associated with a higher CD4+ percentage at enrollment but not with CD4+ percentage decline (Fig. 2D). The association of HIV RNA and CD4+ percentage did not reach statistical significance. Age was not associated with CD4+ percentage. The effect of gender differed between cohorts (interaction term P = 0.04): male gender was associated with a lower CD4+ percentage at enrollment in the French cohort only (Fig. 2C).
Comparing 2 cohorts of HIV-infected adults in Côte d'Ivoire and in France and taking into account the time since estimated seroconversion, we showed that CD4+ cell count and percentage were lower in Cote d'Ivoire than in France by around 86 CD4 cells per cubic millimeter and 4%, respectively. These differences were already observed during early infection although the rate of CD4+ decline was similar between the 2 cohorts (−63 cells/year). The difference in CD4 between the 2 settings remained similar after adjustment for viral markers.
Although analyses were performed among HIV seroconverters, the delay between the estimated date of seroconversion and enrollment in the cohort (defining the availability of the first measurements of the markers) prevented a valid estimate of baseline CD4 value, that is, before HIV infection. Hence, estimated differences between baseline values represent differences established very early after primary infection. It would be interesting to confirm these results with different datasets comparing African and non-African HIV-infected subjects prospectively followed since before seroconversion. We censored the follow-up at 2 years after seroconversion to reasonably exclude selection bias that may result from informative lost-to-follow-up due to AIDS or deaths.21
Studies comparing the decline in CD4 cell count after seroconversion between high-income and low-income settings are scarce. Our data are in agreement with data from other cohorts of seroconverters. In Brazil, CD4 cell counts are lower than in the North American Multicenter AIDS Cohort Study (MACS) studies with the same time after seroconversion.12 Among individuals followed in France, those originating from sub-Saharan Africa had a lower CD4+ after seroconversion than non-Africans.13
Our results indicate that the differences in CD4 levels between the 2 settings are established early during HIV infection. This may be the consequence of pathophysiological mechanisms such as higher cell activation resulting in faster decrease in CD4 cell count in the first weeks of HIV infection.22,23 This phenomenon has been attributed to be more frequent in HIV-infected adults living in Africa who are exposed to various infections.24 Several other factors may also play a role in these differences between both settings. The level of CD4 may have been lower in African adults before seroconversion.25 To our knowledge, there is no evidence of differential evolution according the HIV subtype as long as the recombinant CRF02_AG predominant in Cote d'Ivoire is concerned.26 Moreover, several nonmeasurable individual or environmental characteristics may influence CD4 count or evolution.
CD4+ variability was partly explained by differences in HIV DNA and in HIV RNA in both settings. The percentage of variability explained by these viral markers was higher in our study, which considered early viral measurements, than in studies considering patients at later stages of HIV infection.27 The differences in viral markers that we observed between the 2 cohorts may be related to technical reasons, sera or plasma samples for HIV RNA, and Roche or real-time polymerase chain reaction for HIV DNA.
Previous studies showed that cell-associated HIV DNA after seroconversion was associated with spontaneous disease progression, independently of HIV RNA and CD4+.19,28 We found here that the difference at baseline in CD4 cells per cubic millimeter according to the level of HIV DNA persisted in both settings during the whole follow-up period because there was no association between HIV DNA level at baseline and the rate of CD4+ decline. This also argues for an early role of HIV DNA on the disease course. Alternatively, HIV DNA levels may also have an effect on CD4 decrease that could be demonstrated during a longer follow-up period.
The association between male gender and lower baseline CD4 count in the SEROCO cohort was present in univariate analysis and was not evidenced when virologic markers were taken into account. In fact, men had higher HIV RNA and HIV DNA in our study. Higher HIV RNA in men has been previously reported in other settings.32 Concerning the percentage analysis, the association of male gender and low CD4 persisted in adjusted analysis.
Other predictors of the decrease in CD4 cell count have been identified. For instance, a study performed in Abidjan among adults whose date of seroconversion was unknown showed the role of body mass index.33 Nevertheless, this study was performed among individuals with a more advanced disease than the patients in our study.
Our results have several implications. First, there is a need to further study acute HIV infection in Africa to better understand the mechanisms that lead to a lower CD4+ count observed at an early stage of HIV infection. Second, these results argue for the need of an early HIV diagnosis, particularly in settings such as Africa, to follow patients before their need of prophylactic and antiretroviral treatments. Of note, cotrimoxazole prophylaxis is recommended in Africa when CD4 cell count is <350 cells per cubic millimeter34 and is prescribed when CD4 cell count is <500 cells per cubic millimeter in countries like Côte d'Ivoire. Nevertheless, case management of HIV infection often starts at a symptomatic stage or when CD4+ cell count is below 200 cells per cubic millimeter.35 Moreover, the monitoring of CD4+ before antiretroviral treatment in Africa should be at least as frequent than in the North.36
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