Lack of sex difference in CD4 to HIV-1 RNA viral load ratio
Authors: Richard D Moore, Laura Cheever, Jeanne C Keruly, Richard E Chaisson
Journal: The Lancet (1999)

Recent data suggested that HIV-1 RNA viral load measures are 38–65% lower in women than in men with a similar CD4 count.1Farzadegan H Hoover DR Astemborski J et al.Sex differences in HIV-1 viral load and progression to AIDS.Lancet. 1998; 352: 1510-1514Summary Full Text Full Text PDF PubMed Scopus (353) Google Scholar These differences were found in frozen specimens from HIV-1-seropositive injecting-drug users (IDUs) at a baseline visit when the median CD4 was 518 cells/μL in both men and women, and 4 years later when the median CD4 had declined to about 400 cells/μL for both sexes. One earlier study also suggested a difference between men and women in the CD4 to HIV-1 RNA viral load ratio at a mean CD4 count of 345 cells/μL.2Katzenstein DA Hammer SM Hughes MD et al.The relation of virologic and immunologic markers to clinical outcomes after nucleoside analogue therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter: AIDS Clinical Trials Group Study 175 Virologic Study.N Engl J Med. 1996; 335: 1091-1098Crossref PubMed Scopus (459) Google Scholar A second study failed to show a significant sex difference in mean CD4 count of 211 cells/μL.3Bush CE Donovan RM Markowitz N et al.Gender is not a factor in serum human immunodeficiency virus type 1 RNA levels in patients with viremia.J Clin Microbiol. 1996; 34: 970-972PubMed Google Scholar Since 1989, we have collected longitudinal clinical and sociodemographic data on patients receiving primary HIV-1 care at Johns Hopkins in Baltimore, Maryland.4Moore RD Understanding the clinical and economic outcomes of HIV therapy: the Johns Hopkins HIV Clinical Practice Cohort.J Acquir Immune Defic Syndr. 1998; 17: S38-S41Crossref Scopus (144) Google Scholar Since September, 1996, HIV-1 viral load has been measured in fresh blood specimens by Roche Amplicor reverse transcriptase PCR assay. CD4 counts have been measured with flow cytometry. We analysed our data to determine the association between CD4 count and HIV-1 viral load. We stratified CD4 count into several ranges (<100, 100–200, 201–350, 350, 500, 500–750, >750) and calculated the mean and median log10 transformed HIV-1 viral load within each stratum for men and women. This analysis was done for all men and women irrespective of HIV-1 transmission risk behaviour, and again for only men and women who were IDUs. Other variables used to further stratify the analysis included antiretroviral combination therapy and ethnic origin. HIV-1 viral load used was the first obtained for each patient with the Roche Amplicor assay. The CD4 count was that value obtained closest in time to the viral load but not preceding by more than 30 days or following by more than 7 days. Analyses were repeated on HIV-1 viral load and associated CD4 counts obtained for each patient at the time closest to 1 year after their first viral-load measure (within a window of ±60 days). The table shows our results. For all men and women, there was no difference in the HIV-1 viral load within any of the CD4 strata for the first obtained viral load or for the subsequent viral loads obtained after 1 year. When we limited our analysis to IDUs only (67% of patients), again there were no significant differences between men and women in HIV-1 viral load in any of the CD4 strata (data not shown). In a multivariate regression analysis, we assessed whether there were any significant interactions between sex and HIV-1 viral load for CD4 counts of greater than 750, 500–750, 200–500, and below 200/μL, adjusting for combination antiretroviral drug use (18% of patients for the first obtained value and 53% of patients at 1 year), ethnic origin (white vs African-American) and IDU. There were no significant interactions between sex and HIV-1 viral load for any of the CD4 ranges with the first obtained or 1-year measures, supporting the findings shown in the table of no difference between men and women in the CD4 to HIV-1 viral load ratio.TableHIV-1 viral load by CD4 strataWomenMenp*Comparing women with men by the Wilcoxon rank sum test.First1 yearFirst1 yearFirst1 yearCD4 count >750N61256735Viral load (mean)3·512·973·572·92Viral load (median)3·412·603·522·600·620·37CD4 (mean)1015961934980CD4 (median)9848528928780·120·40CD4 count 500–750N1015615986Viral load (mean)3·573·213·623·160·870·29Viral load (median)3·642·803·492·60CD4 (mean)6026096046040·680·55CD4 (median)583608586594CD4 count 350–500N1125220462Viral load (mean)3·883·553·993·310·220·12Viral load (median)3·983·634·082·70CD4 (mean)4264364224250·410·13CD4 (median)423447422424CD4 count 200–350N12163254123Viral load (mean)4·103·614·133·520·860·37Viral load (median)4·203·594·243·16CD4 (mean)2752692812770·170·21CD4 (median)294260268274CD4 count 100–200N7539186100Viral load (mean)4·363·834·313·900·420·85Viral load (median)4·653·924·504·08CD4 (mean)1491621501540·950·29CD4 (median)153163148158CD4 count <100N10660327163Viral load (mean)4·774·544·744·280·620·46Viral load (median)5·044·884·944·64CD4 (mean)373837400·780·71CD4 (median)25312935All CD4 counts are per μL.* Comparing women with men by the Wilcoxon rank sum test. Open table in a new tab All CD4 counts are per μL. Our results suggest that the mean half-log difference found by Farzadegan et al1Farzadegan H Hoover DR Astemborski J et al.Sex differences in HIV-1 viral load and progression to AIDS.Lancet. 1998; 352: 1510-1514Summary Full Text Full Text PDF PubMed Scopus (353) Google Scholar may reflect early variations in load setpoints after seroconversion in men and women. With progression of HIV-1 infection, any sex differences in the CD4 to HIV-1 viral load ratio seems to diminish. We did not find sex differences in the CD4 count to viral load ratio in patients with CD4 counts above 500/μL. However, particularly at a CD4 count greater than 750/μL, our sample size is fairly small and differences may exist that are difficult for us to detect. Among patients who are candidates for antiretroviral therapy based on CD4 levels, we found no differences in viral load by sex. Therefore, we would caution against recommendations to change the guidelines for the use of antiretroviral therapy. We believe that further corroboration and a better understanding of possible sex difference in HIV-1 viral load response is needed before making a change in guidelines. Supported by the National Institute on Drug Abuse (RO1-DA-11602), the Agency for Health Care Policy and Research (RO1 HS07809), and the Food and Drug Administration (FD-U-000977).