When To Begin Therapy

Initial HIV-1 plasma RNA level after seroconversion does not predict progression to AIDS in women

A number of studies have suggested that viral load for women is 50% lower than for men earlier in the course of disease progression, but this evens out after 4-5 years and there has been no noticeable difference in disease progression between men and women. Tim Sterling from Johns Hopkins University reported at a late breaker oral session on this retrospective analysis on the relationship between a person's initial viral load after HIV-1 sero-conversion and it's use in predicting progression to AIDS. Progression to AIDS was defined as an AIDS-defining opportunistic infection (OI). Sterling said initial HIV-1 plasma RNA level (VL) after seroconversion (SC) predicts progression to AIDS in men, but this has not been well-studied in women. Several recent studies have demonstrated lower VL in women than men at the time of sero-conversion and sex differences in HIV-1 viral dynamics.

Sterling measured plasma VL among all HIV-1 seroconverters enrolled in a longitudinal cohort study of injection drug users (IDU) and correlated the initial VL with the subsequent development of AIDS. 3,380 IVDUs were enrolled and followed every 6 months between March 1989-December 1998. VL was subsequently quantified for each visit after HIV-1 SC. Inclusion criteria for this study were HIV-1 SC within 12 months of last sero-negative visit and before 12/1/97, and > 2 plasma VL's after SC. VL was determined by RT-PCR (Roche).

There were 295 sero-converters, of whom 202 met the inclusion criteria; women were not disproportionately excluded. Although 29/156 (19%) male and 15/46 (33%) female sero-converters progressed to AIDS, time to AIDS did not differ by sex (p = 0.19). Time between SC and 1st VL did not differ by sex (median = 4 mos; p = 0.8).

Among male seroconverters, initial median VL was 77,822 copies/ml among those who progressed to AIDS, compared to 40,634 copies/ml among those who did not (p = 0.009). Among female seroconverters, initial median VL was 17,149 copies/ml among those who progressed to AIDS, compared to 12,043 copies/ml among those who did not (p = 0.21).

Sterling concluded initial VL after SC did not predict progression to AIDS in women but did in men, but this may be related to the low number of women in the analysis (n=46). Initial CD4 did not differ between progressors and nonprogressors among both men and women. These results are consistent with a sex difference in viral dynamics and suggests that these data should be incorporated into treatment guidelines for women.

In addition, when looking at risk of progression to AIDS, by 1 log changes in the entire population (not in an individual), there was an increase risk progression to AIDS (AIDS defining OI) of 1.5 (hazard ratio) for women and men (not statistically significant either).

Comments: The gender viral load differences suggest differences in pathogenesis which ought to be addressed in clinical trials. Potential differences in response to therapy by gender and race should also be further explored in clinical trials.