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.