Sex differences in HIV-1 viral load and progression to AIDS

Abstract

Homayoon Farzadegan and colleagues (Nov 7, p 1510)1Farzadegan H Hoover DR Astemborski J et al.Sex differences in HIV-1 viral load and progression to AIDS.Lancet. 1998; 352: 1510-1513Summary Full Text Full Text PDF PubMed Scopus (350) Google Scholar examine sex differences in HIV-1 viral load and disease progression in 650 HIV-infected injection-drug users (IDUs). In univariate analysis they showed a lower viral load in women than in men but no differences in the rate of progressing to AIDS. Multivariate analysis showed that, at the same level of viral load, women had a higher rate of disease progression. The investigators suggest that thresholds for initiation of antiretroviral therapy should be revised downwards for women. We examined this issue in the Swiss HIV Cohort Study (SHCS), a national community cohort with many female participants.2Egger M Hirschel B Francioli P et al.Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study.BMJ. 1997; 315: 1194-1199Crossref PubMed Scopus (567) Google Scholar No stringent inclusion and exclusion criteria exist and the cohort includes a large proportion of people with HIV.3Gebhardt M Rickenbach M Egger M for the Swiss HIV Cohort StudyImpact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland.AIDS. 1998; 9: 1195-1201Crossref Scopus (46) Google Scholar Viral load measurements with a reverse transcriptase PCR assay (Roche Diagnostics, Basle, Switzerland), were introduced in June, 1995. We compared viral load values among patients free of AIDS and not treated with combination therapies at the time of the first viral load measurement. All patients infected via IDU or heterosexual contact who had a CD4 cell count within 3 months of the viral load measurement were included in the analysis. Like Farzadegan et al we assigned half the lower detection limit (200 copies/mL) to undetectable viral load values. Viral load values were log10 transformed for analysis. A total of 1337 patients were analysed, 456 men and 286 women who were IDUs and 234 men and 361 women who were heterosexually infected. In IDUs, median viral load was slightly lower in women than men (4·20 vs 4·43 log copies/mL, p=0·009 by Mann-Whitney test) and median CD4 cell count tended to be higher in women (327 vs 307 cells/·L, p=0·14). Results were similar among heterosexually infected patients: median viral loads and 4·11 log copies/mL and 4·15 in women and men, respectively (p=0·21), and median CD4 cell counts were 360 and 313 cells/·L, respectively (p=0·028). We examined the relation between viral load and CD4 cells in linear regression models and obtained similar equations for women and men, and IDUs and individuals infected heterosexually. We also replicated Farzadegan and colleagues Cox regression models of progression rates to AIDS. Our analysis was based on 102 AIDS diagnoses in 1933 patient-years of follow-up. Contrary to these workers” findings, we showed no sex differences in disease progression, both in crude models and models controlled for CD4 cell count and HIV-1 viral load. Results were similar among IDUs and patients infected by the heterosexual route (table). Finally, the predictive value of viral load was not determined by sex (p for interaction terms >0·25 in all models).TableRelative hazard of developing AIDS for women compared with men among Swiss HIV Cohort Study participants infected via IDU or heterosexual contactsPredictor variablesIntravenous drug use (n=742)Heterosexual contact (n=595)All patients*Controlled for transmission group. (n=1337)Model 1Female vs male0·91 (0·55–1·50)0·84 (0·43–1·63)0·86 (0·58–1·29)Model 2Female vs male1·00 (0·61–1·66)0·92 (0·47–1·78)0·96 (0·64–1·43)100 cell decrease in CD4 cell count2·02 (1·66–2·46)2·19 (1·68–2·86)2·10 (1·79–2·46)Model 3Female vs male1·02 (0·62–1·68)0·86 (0·44–1·66)0·96 (0·64–1·43)100 cell decrease in CD4 cell count1·62 (1·33–1·98)1·83 (1·38–2·41)1·81 (1·45–2·00)10-fold increase in viral load2·22 (1·56–3·17)2·12 (1·31–3·43)2·17 (1·63–2·88)Hazard ratios (95% CI) are shown.* Controlled for transmission group. Open table in a new tab Hazard ratios (95% CI) are shown. Farzadegan and colleagues note that many cohort studies have failed to show sex differences in disease progression, and therefore postulate a different relation of viral load and risk of AIDS. Our findings do not support this hypothesis. The reasons for this discrepancy remain unclear, but selection bias in either cohort is a possible explanation. We conclude that data from other cohorts should be considered before recommendations for treatment of HIV infection in women are changed. Sex differences in HIV-1 viral load and progression to AIDSAuthors” reply Full-Text PDF