Gender Differences in Immune Reconstitution: A Multicentric Cohort Analysis in Sub-Saharan Africa
et al. (2012) Gender Differences in Immune Reconstitution: A Multicentric Cohort
Analysis in Sub-Saharan Africa. PLoS ONE 7(2): e31078. doi:10.1371/journal.pone.0031078
Gender Differences in Immune Reconstitution: A Multicentric Cohort Analysis in Sub-Saharan Africa
David Maman 0
Mar Pujades-Rodriguez 0
Fabien Subtil 0
Loretxu Pinoges 0
Megan McGuire 0
Rene Ecochard 0
Jean-Franc ois Etard 0
Landon Myer, University of Cape Town, South Africa
0 1 Epicentre, Me decins Sans Frontie`res , Paris, France, 2 Hospices Civils de Lyon , Service de Biostatistique , Lyon, France, 3 TransVIHMI, UMI 233, Montpellier , France , 4 Universite de Lyon , Lyon, France, 5 Universite Lyon I, Villeurbanne, France, 6 CNRS UMR5558 , Laboratoire de Biome trie et Biologie Evolutive , Equipe Biostatistique Sante , Pierre-Be nite , France
Background: In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution. Methods/Principal Findings: Antiretroviral-nave adults who received ART for at least 9 months in four HIV programs in subSaharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART. A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85-206] for women and 125 cells/mL [IQR 63-187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/mL per year on average (95% CI 16-23; P,0.001). Up to 6 years after ART start, patients with low initial CD4 levels experienced similar gains compared to patients with high initial levels, including those with CD4.250cells/mL (difference between patients with ,50 cells/mL and those with .250 was 284 cells/mL; 95% CI 272-296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150-200 cells/mL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4-2.5) and men after 4.5 years (95% CI 4.1-4.8) of ART use. Conclusion: Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men.
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According to UNAIDS, more than 3.9 million patients were
receiving antiretroviral therapy (ART) in sub-Saharan Africa at the
end of 2009. This represents 37% of those in need of treatment and
an increase of one million patients in one year [1]. Early initiation of
ART in the course of disease is associated with better survival [2,3]
and better long-term immune reconstitution [4,5]. Indeed, in 2009,
the World Health Organization (WHO) raised the recommended
CD4 threshold for ART initiation to 350 cells/mL [1,6].
Immune recovery after ART initiation follows two phases: a
rapid increase during the first months, followed by a slower one
thereafter [7,8,9]. They correspond to different biological
mechanisms: the first phase of rapid CD4 cell increase is linked
to the relapse of pre-trapped CD4 cells [10], while the second
phase corresponds to a proliferation of new CD4 cells, related to
thymus reactivation, which progressively reconstitutes stocks of
CD4 cells [11]. The feasibility of complete reconstitution remains
unknown, as do influencing factors.
Most of large cohort studies describing long-term immune
reconstitution have been performed in North American cohorts
[12,13]. In sub-Saharan Africa, the gender differences at ART
start are important. In these settings, more women than men are
infected [14,15], as the majority of infections happen through
heterosexual transmission. Furthermore, men are frequently
underrepresented in ART cohorts, and they initiate ART at a
more advanced stage of the disease with a lower CD4 cell counts.
[16,17,18] In addition, they experience higher early mortality
compared with women [17,19,20,21].
This study explored gender differences in immune
reconstitution after the first 9 months of ART, to focus on the second phase
of immune reconstitution, in four sub-Saharan African HIV
programs supported by Medecins Sans Frontie`res (MSF).
Data Analysis and Study Population
In collaboration with national Ministries of Health, MSF began
providing free HIV care and antiretroviral therapy (ART) in four
programs in Malawi, Uganda, and Kenya between March 2001
and July 2002. A standardized surveillance system was
implemented to collect routine demographic, clinical, and treatment
data (FUCHIA software, Epicentre, Paris, France). Data
consistency checks were implemented to ensure the data quality.
The databases used for the analysis were locked on 30
November 2009. ART initiation was based on 2003 and 2006
WHO recommendations. Patients received non-nucleoside reverse
transcriptase inhibitor-based first-line therapy in the form of
fixeddose combinations. Adherence supp (...truncated)