Women have a greater immunological response to effective virological HIV-1 therapy

In HIV-1 infection, the HIV-1-RNA viral load and CD4 T-cell counts are used as prognostic indicators, which serve as the bases for recommending antiviral therapy [1]. In addition, in individuals whose HIV-1 viral load significantly decreases on combination antiviral therapy, CD4 T-cell peripheral blood counts usually increase [2]. These observations have been made in clinical studies that primarily enrolled adult males [3]. A few studies have recently shown that average viral loads at given CD4 T-cell counts were lower in women than in men [4,5]. We are not aware of any studies that specifically evaluate the sex difference in the immunological responses of patients who have a sustained virological response to therapy. To address this issue, we compared the immunological responses of men with those of women in patients who had achieved sustained virological suppression (< 400 copies HIV-1-RNA/ml) at 24 weeks. We retrospectively collected data on all patients of an inner city clinic. A patient was considered eligible if: (i) he or she had a pre-therapy viral load greater than 400 copies/ml on more than two consecutive measurements; (ii) his or her viral load decreased to less than 400 copies/ml and remained undetectable at 24 weeks after the initiation of therapy; and (iii) he or she had CD4 T-cell counts performed within 2 weeks before initiating therapy and then 24 weeks after initiating therapy. Exclusion criteria included a failure to sustain virological suppression, an antiretroviral regimen change during the study period secondary to documented resistance, and incomplete laboratory values. HIV-1 viral loads (using reverse transcriptase–polymerase chain reaction methodology) and CD4 T-cell counts were routinely performed by LabCorp (CD4 T cells: Raritan, NJ, USA; and HIV plasma RNA viral loads: Research Triangle Park, NC, USA). Statistics were calculated using SAS version 8.0 (SAS Systems Inc., Cary, NC, USA). We reviewed 450 charts and excluded 337 individuals, on the basis of the criteria listed above. Data from 53 women and 60 men were analysed (Table 1). Demographically, 49% of patients were African American, 30% were Hispanic, and 21% were Caucasian. The majority of women, 70%, acquired HIV through heterosexual contact; 32% of male patients had sex with men as their risk factor; 0.5% acquired HIV through infected blood products. All others were former intravenous drug users. Thirty per cent of both groups were naive to anti-HIV therapy.Table 1: Sex differences in CD4 cell response.The initial CD4 T-cell count and viral load averages were similar in both groups (Table 1). However, the mean of the CD4 T-cell count change (ΔCD4+), was much higher in women than in men (women, 170 cells/μl versus men, 100 cells/μl). The difference in ΔCD4+ was statistically significant (P = 0.0074 as determined by the Wilcoxon rank sum test). Multivariable analyses were carried out using regression, and included the patient's age and entry viral load. These analyses failed to show any contribution by these variables. In addition, the initial viral load, the initial CD4 T-cell count, and the final CD4 T-cell count were not statistically different between the two sexes, by rank sum test. All patients received combination antiviral therapy. Thirty per cent of both groups were treated with a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors; 5% were treated with three nucleoside reverse transcriptase inhibitors. Protease inhibitors were used in 61% of men and women. Studies on the differences in sex response in other disease states have been carried out on animals and humans [6]. However, no report known to us has suggested that there is a sex difference in response to therapy of an infectious disease. Our data reveal that, among virological responders, women have a greater immunological response. The reasons for this difference are not clear. As shown, no other obvious variable could explailain the observed immunological response difference. Age, initial CD4 T-cell count, and initial viral load were similar in the two groups. The therapies used were similar. Therefore, sex is the only variable in this study that correlates with the immunological response difference. The average CD4 T-cell increase in men is 100 cell/μl. Perhaps the immunological response difference seen in this study is secondary to an unexplained factor that reduced the immunological response in men. However, in previous studies that measured CD4 T-cell count changes over time, an average increase of approximately 100 cells/μl was also seen at 24 weeks after initiating therapy [7]. Therefore, it is unlikely that the difference observed in our study is secondary to a reduced immunological response in the group of male patients. This study is the first to analyse the immunological response difference between women and men in patients who respond virologically. The larger increase in CD4 T-cells seen in women suggests that significant pathological differences may exist between the two sexes. Our findings warrant further investigation of the immunological differences between the two sexes.