1st International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment
July 7-11, 2001
Buenos Aires, Argentina
Gender Differences in Morphologic Alterations (Body Changes or Lipodystrophy)
Galli and colleagues from Milan, Italy, studied the correlation between gender and morphologic alterations (MAs) in a group of 2258 patients, of whom approximately 30% were women. A total of 750 patients (33.2%) developed at least 1 MA. Of interest, female gender was the strongest independent factor associated with an increased risk of MA (adjusted odds ratio [OR] = 2.019, P = .001) in a multivariate analysis that included duration of antiretroviral therapy, age, viral load, and use of combination antiretroviral therapy prior to study enrollment. The prevalence of various morphologic abnormalities is presented in Table 3.
Table 3. Gender Differences in Morphologic Alterations in HIV-Infected Patients
|Specific Morphologic Alteration||Women||Men||P Value|
|Fat loss only||9.3%||12.2%||NS|
|Fat accumulation only||10.1%||7.7%||.0008|
|Both fat loss and fat accumulation||22.4%||9.7%||.0001|
The timing of the development of lipodystrophy among HIV-infected women was addressed by Carpenter and colleagues in a 2.5-year follow-up study of a group of 21 women who reported morphologic changes after institution of HAART. These women were compared with 21 controls who were also receiving HAART but reported no such morphologic alterations. The mean duration of HAART at baseline in the cases was 12 months vs 15 months in the comparators. Of interest, the morphologic changes remained stable in cases over time in 10 of 14 cases, while 3 experienced modest improvement and 1 developed a dorsal fat pad. In the comparators, who had no morphologic changes at baseline, only 2 of 21 developed such changes. Serum lipid values were elevated at baseline in both cases and comparators, and did not change over time.
This study would indicate that the morphologic and/or lipid changes that occur with HAART are likely to occur within the first 12-18 months of therapy, with very few additional cases over time. In this regard, these data are similar to those from the Multicenter AIDS Cohort Study presented at the 8th Conference on Retroviruses and Opportunistic Infections in February 2001, in which the prevalence of lipodystrophy among HIV-infected men rose steadily during the first 2 years of potent antiretroviral therapy use but appeared to stabilize thereafter. (Editorial note: I differ with this conclusion. major changes in body co0mposition occurred within the first 1-2 years in the MACS study but minor changes continued to occur. And these data are preliminary. and the data from the studies above show a small percentage of people developing lipodystrophy after 15 months).
In a subsequent plenary session, David Cooper, MD, from Sydney, Australia, summarized the current state of knowledge of the lipodystrophy syndrome, including morphologic alterations. He acknowledged that there is no currently validated definition of lipodystrophy syndrome, leading to confusion and some lack of comparability of data; a multinational prospective case definition study is currently underway which should serve to clarify this issue. Summarizing data from 7 cohort studies that evaluated HIV-associated lipodystrophy, he concluded that the use and duration of therapy with PIs or NRTIs were associated with development of the syndrome. (Editorial note: a number of leading researchers suggest that HIV and immune restoration by HAART may play role in lipodystrophy [indirect role of ART]. Anecdotal reports are that patients with lower cd4s who have the best responses to HAART (god cd4 increases and undetectable viral load) appear to be more likely to develop body changes).
However, there does not appear to be an association between CD4+ cell counts and the development of the syndrome. Data regarding viral load and the likelihood of lipodystrophy have been disparate, with 3 of the 7 studies showing that lower plasma HIV-1 RNA levels were associated with lipodystrophy, while the other 4 showed no relationship. While concluding that antiretroviral therapy is the most likely etiology of this complication, he acknowledged that other factors may also play a role. These include increasing age, weight loss prior to HAART, and female gender. In explaining the possible role of gender in the development of lipodystrophy, however, his explanation was simply that women have more body fat than men, and that fat loss was thus more noticeable in men, while fat gain would be more noticeable in women. Clearly, further work will be required to ascertain the precise role of hormones and other factors in the development of lipodystrophy in women.
Thanks to Alexandra Levine, MD, and Medscape for this article.