- Modeling the Impact of Revised DHHS HIV Treatment Guidelines on Survival in Women
Authored by Teresa L. Kauf, D. C. Gibbons, T. L. Kirkland, G. Capuano, J. M. Tolson, D. Goodwin, (GlaxoSmithKline, Inc., Research Triangle Park, NC).
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It is believed that some illnesses, including HIV, may follow a different clinical course in males than in females. The possibility that a gender difference may influence the manifestation and progression of HIV has been a concern over the past few years.
Although some cohort studies have only found minor differences, others have reported significantly lower HIV RNA levels in females than in males. This lower HIV RNA level may potentially result in a delay in initiation of therapy that may put this group of patients at risk for HIV-related complications. Furthermore, the current U.S. guidelines for initiation of therapy have been constructed utilizing data from predominantly male cohorts.
These issues raise the concern that the current treatment guidelines may not be appropriate for females. This is particularly disturbing now that females account for an increasing proportion of new HIV infections in the U.S.
With these controversial issues in mind, investigators at GlaxoSmithKline designed a model of HIV progression that estimates the possible impact of the revised HIV treatment guidelines with regards to women. For this model they used some disease progression parameters from the LIVE Study. The LIVE Study is a large longitudinal cohort of seroconverters, in which approximately 23 percent were women (which matches the current estimates of seroconversion across the nation). To further feed information into this model, investigators also used data from other cohorts such as MACS and a meta-analysis from more than 1,000 HIV-1-infected women enrolled in several Glaxo clinical trials.
The study design required that a gender adjustment be made with the assumption that an HIV RNA of 15,000 to 20,000 copies/mL in women was equivalent to an HIV RNA of 50,000 to 55,000 copies/mL in men. After this adjustment was made, the female groups were re-assigned to new categories following both the previous HIV guidelines and the new revised HIV guidelines to determine eligibility to begin HAART and the possibility of disease progression.
The study analysis concluded that the estimated survival of women with HIV under the revised guidelines was significantly lower than with the previous guidelines. This survival was lower regardless of whether the HIV RNA gender adjustment was taken into consideration. It was estimated that the average life expectancy for a woman without treatment under the current guidelines was 5.47 years. When the HIV RNA gender adjustment was taken into account, that survival decreased to 5.31 years.
As expected, in this model the use of HAART significantly improved the average survival under both the old and new guidelines. If the HIV RNA gender adjustment was taken into consideration in women treated with HAART, survival increased from 1.19 to 2.43 years using the revised guidelines. For the old guidelines, survival with HAART increased from 4.31 to 5.35 years after the HIV RNA gender adjustment.
What this study is trying to say is that some manifestations of HIV are different in men than in women. One of these differences is the lower amount of HIV RNA in women. Using the current guidelines for initiation of therapy, women may have an overall decrease in life span when compared to the life span they may have by using the previous guidelines.
The problem I have with this study is that it is too hypothetical. Although I do agree that there may be some small but important differences in the manifestations of HIV between men and women, the impact of those differences, if significant, is probably impossible to calculate. This study is based on data that is taken from too many different cohorts to feed a completely hypothetical scenario. The cohorts used may not appropriately reflect the true epidemic of HIV in female patients across the U.S. The model of disease progression can be influenced by too many variables, most of them related to treatments that change quite rapidly. Also the calculations for the estimates of HIV RNA gender adjustment were not clear.
What is important about this work is the recognition of the importance of gender when studying populations of HIV-infected patients. Given the fact that there may be potential gender differences in respect to HIV progression, the cohort used to establish treatment guidelines should be appropriately balanced to reflect the increase in the incidence of HIV infection in women.