Women and HIV

Effect of HIV infection or antiretroviral therapy on oral glucose tolerance and insulin sensitivity in overweight women

Study Question: Is diabetes more common among HIV-infected women compared to HIV-uninfected women of similar body mass index (BMI)? Is insulin resistance greater in HIV-infected women compared to HIV-negative women?

Study Participants: A total of 258 women-88 HIV-negative, 74 HIV-positive and not on HAART, and 96 HIV-positive and on HAART-were enrolled in this study which is a cross-section substudy of the Women's Interagency HIV Study (WIHS).

Study Methods:

	Each woman had a standard oral glucose tolerance test (OGTT). Prediabetes and diabetes were defined using the criteria of the American Diabetes Association for fasting and 2-hour blood glucose levels.
	The BMI of each woman was calculated based on her weight and height.

Study Findings:

	The mean and median BMIs were in the overweight range for all three groups.
	The HIV-negative women were younger, had a higher BMI and were somewhat more likely to smoke.
	The BMI was higher among women with HIV who were not on HAART.
	Higher BMI was associated with prediabetes and diabetes and insulin levels.
	When the OGTT data were adjusted for BMI, age, race and menopausal status, no significant differences were noted among the HIV-positive and HIV-negative women or among the HIV-positive women in different treatment categories. No significant difference was observed in the prevalence of prediabetes or diabetes among the three groups of women.

Limitations: Participants in this study were different from those in other studies of HIV and diabetes: all were women, 81% were African American or Latina, 72% were overweight or obese, in general had a CD4 cell count >300 cells, and had been on HAART longer than other studies. The timing of ingesting antiretroviral medications was not standardized within the study.

The authors caution that although they did not find more frequent abnormalities of glucose metabolism in the women with HIV compared to the controls, the study may not have been large enough to detect smaller differences between the groups.

Lessons Learned:

	This study of HIV-positive women and HIV-negative women matched on demographic characteristics and BMI found no association between HIV serostatus or antiretroviral regimen and the frequency of diabetes or prediabetes. The only feature significantly associated with diabetes and prediabetes was BMI.
	The authors urge lifestyle changes in eating and exercise habits and maintenance of normal body weight particularly for those at increased risk for cardiovascular complications such as the overweight African American and Latina women in this study.

Source: Danoff A, Shi Q, Justman J, Mulligan K, Hessol N, Robison E, Lu D, Williams T, Wichienkuer P, Anastos K; Women's Interagency HIV Study (WIHS). Oral glucose tolerance and insulin sensitivity are unaffected by HIV infection or antiretroviral therapy in overweight women. J Acquir Immune Defic Syndr. 2005 May 1;39(1):55-62.

Hormonal contraceptive use and the effectiveness of HAART

Study Question:Is there an association between hormonal contraceptive use and immunologic and virologic responses to HAART?

Study Participants:This study compared 77 HIV-positive women who used hormonal contraceptives prior to starting HAART with 77 women who initiated HAART, but did not use hormonal contraceptives. Participants were a subset of the women enrolled in the larger Women's Interagency HIV Study (WIHS) and had one study visit every six months.

Study Methods:

	Because many factors can affect responses to HAART, the two groups of women were matched using a propensity score method. This method combines many behavioral and demographic variables into a single score in order to adjust for these variables in the analyses. This approach allowed researchers to more accurately examine the effect of hormonal contraceptive use on the observed outcomes.
	Co-variants included in the propensity score were race, age, illicit drug use, viral load, CD4+ cell count, prior use of antiretrovirals, and education, among many others.

Study Findings:

	HAART regimens did not differ significantly between the two groups. Seventy-nine percent of the women were on a regimen that included a protease inhibitor and no NNRTIs.
	Both hormonal contraceptive users and non-users had an overall positive increase in CD4+ cell response to HAART initiation. The mean CD4+ cell count and the mean change in CD4+ cell count at or after HAART initiation were not significantly different between users and non-users. There were no significant differences between the groups when the mean percent changes in CD4+ cell count was assessed.
	Overall, there were no statistically significant differences in mean changes in log viral load between users and non-users, except at one isolated visit.
	Over the entire follow-up period, 74% of non-users and 58% of non-users obtained an increase in CD4+ cell count of >= 100 cells/mm3 after HAART initiation. Hormonal contraceptive use was not a significant predictor of achieving an increase in CD4+ cell count. By the fourth visit, 65% of women using hormonal contraceptives had stopped taking them.

Limitations:The use of hormonal contraceptives among women in the WIHS cohort was rather limited, perhaps because women were already using condoms or they were reluctant to add to their pill burden. Although not a randomized study, the propensity scores successfully matched hormone users and non-users on baseline characteristics. The study was not able to assess adherence to HAART because these data were not initially recorded in the WIHS. However, WIHS adherence data collected later found that 76% of women reported adherence at above 95%.

Lessons Learned:

	HIV-infected women who used hormonal contraceptives and those who did not use hormonal contraceptives did not differ significantly in the immunologic and virologic responses to HAART suggesting that the overall effectiveness of HAART was not altered by hormonal contraceptive exposure.
	Although studies have found that female sex hormones, estrogen and progesterone, may influence responses to HIV infection and disease progression, this study found no association between hormonal contraceptive use and changes in both CD4+ cell count and viral load after initiation of HAART. These findings may alleviate some concerns regarding suspected negative effects of hormonal contraceptive use on the response to HAART.

Source:Chu JH, Gange SJ, Anastos K, Minkoff H, Cejtin H, Bacon M, Levine A, Greenblatt RM. Hormonal contraceptive use and the effectiveness of highly active antiretroviral therapy. Am J Epidemiol. 2005 May 1;161(9):881-90.

Cardiovascular disease risk indices in HIV-infected women

Study Question:How do indices of cardiovascular risk compare between HIV-positive and HIV-negative women?

Study Participants: 100 HIV-positive women and 75 HIV-negative women were recruited from hospitals and communities across Massachusetts. Women were between 18 and 60 years of age and met other criteria regarding not being on certain medications or having had an infection recently.?

Study Methods:

	All participants were given 75mg of oral glucose following a 12-hour fast and their glucose level was measured at 0 and 120 minutes.
	Other possible risk factors for cardiovascular disease (CVD) were also measured including C - reactive protein (CRP), interleukin-6 (IL-6), adiponectin, and lipid levels.
	Body composition was examined using CT scan to assess for abdominal fat, dual-energy x-ray absorptometry (DXA) to assess total fat, and measurements of hip and waist.

Study Findings:

	Although similar in age, weight, and racial composition, HIV-positive women demonstrated higher CRP, IL-6, triglyceride, 2-hour glucose after oral glucose challenge, and fasting insulin and lower high-density lipoprotein cholesterol and adiponectin levels compared with the HIV-negative women.
	HIV-positive women had more abdominal visceral fat and less extremity fat by CT and DXA scan and demonstrated a higher waist-to-hip ratio (WHR) than the HIV-negative women.
	Using a regression model, researchers found that WHR was the most significant variable associated with several indices of cardiovascular risk-CRP, adiponectin, fasting insulin, 120 minute glucose, and HDL cholesterol
	Antiretroviral drug exposure (or use of individual antiretroviral agents) was not associated with cardiovascular risk indices.

Limitations:The sample size is relatively small and was a convenience sample although the control group was well-matched. As a cross-sectional study, conclusions as to causes are limited but the modeling approach strongly suggest that WHR and changes in body composition more than other factors are associated with abnormal CVD risk indices.

Lessons Learned:

	CRP is a strong independent risk marker for CVD in uninfected women, and the relationship to CVD in women with HIV (who had significantly higher CRP than controls) needs to be investigated.
	CVD risk indices are strongly related to body composition in HIV-infected women as measured by the sophisticated techniques such as CT and DXA, but also by the simpler measure of WHR. WHR functions as a marker of overall fat distribution which may contribute to CVD. The data suggest that changes in body composition associated with HAART, not the medication itself or HIV status, contribute to abnormal CVD risk.
	The HIV-positive women had an increased IL-6 concentration in association with increased WHR. IL-6 has been found to be associated with coronary artery disease in non-infected women. Women with HIV also had lower levels of adiponectin, which has also been found to be associated with coronary artery disease in HIV-negative men.
	The study also found the women with HIV demonstrated traditional CVD risk factors including increased triglyceride and reduced HDL cholesterol, as well as increased fasting insulin and impaired glucose tolerance.
	Studies are needed to determine whether increased cardiovascular risk indices translate into increased cardiovascular events. In addition, treatment strategies are needed to modify CVD risk and improve abnormal fat distribution.

Source: Dolan SE, Hadigan C, Killilea KM, Sullivan MP, Hemphill L, Lees RS, Schoenfeld D, Grinspoon S. Increased cardiovascular disease risk indices in HIV-infected women. J Acquir Immune Defic Syndr. 2005 May 1;39(1):44-54.