Conference has strong emphasis on women

1 April 2003. Related: Conference reports, Women's health, Lipodystrophy and metabolic complications, Cancer and HIV, CROI 10 (Retrovirus) 2003.

Polly Clayden, HIV i-Base

The conference had a surprisingly strong emphasis on women and these sessions were extremely well attended. This in turn was much commented on – session chair Professor James McIntyre from Soweto chairing the “lone session on women and paediatrics” remarked that “I thought I’d be sitting here alone.”

However, there was still only limited data reported on women over and beyond their role in mother to child transmission. Chairing the session on HIV and Women, Dr Judith Currier emphasised: “Half of the new infections in the world are in women, yet we spend so little time discussing issues unique to prevention, pathogenesis and treatment as it pertains to their health.”

Women and HIV in India and Africa

Dr Suniti Solomon painted a grim picture of the position of women – and in particular HIV positive women – living in India [1]. She discussed the limitations of prevention strategies in a society where infanticide is not uncommon following the birth of a girl, every 34 minutes a woman is raped, every 93 minutes a woman is burned to death over a dowry and 1,000 child marriages were still reported in a single day in the year 2003.

Their vulnerability to HIV can only be enhanced by beliefs such as that sex with a virgin can cure sexually transmitted diseases and by a system where monogamy is often unilateral (in one study 95% of HIV positive women were married, 81% housewives and 88% report monogamy ). Lack of economic autonomy and job opportunities means that women are frequently forced to remain in a marriage where they are at risk or to support themselves through sex work.

Dr Solomon described their prevention needs, which include: empowering women, encouraging men to admit that they are vulnerable; gender sensitising programmes; engaging men in the process of changing gender norms and initiating structural changes. In other words reconstructing the culture in which, as Dr Solomon pointed out at the beginning of her talk, the “social construct of gender has evolved for several hundred years.” In a society where, she estimates, seroprevelance is greater than 5% among women of chid bearing age within a population of over a billion, the potential threats and challenges seem insurmountable. “How on earth does she get out of bed in the morning to all that?” wondered my colleague.

Leaving her audience completely stunned, Dr Solomon concluded that: “It is not flattering that it takes a ruthless epidemic to awaken the world to the needs and condition of her women.”

In a session on international strategies Dr Dorothy Mbori-Ngacha from Kenya outlined the situation for women in Africa where “as the epidemic has matured the vulnerability of women has come to the fore.” [2] Current UNAIDS figures indicate that women constitute 58% of all people living with HIV on the continent of Africa and women are more vulnerable to HIV acquisition for a variety of social, cultural, economic and biological reasons.

In the USA

Dr Ruth Greenblatt from the Women’s Interagency HIV Study (WIHS) and Dr Kate Squires from the University of Southern California both described the current situation in the USA [3,4]. Here HIV is still the greatest cause of death among women of colour between 25 and 44 years old, and women living with HIV, and those at high risk, remain a demographically distinctive group.

Dr Squires gave an overview of sex/gender differences, and both speakers emphasised how little we actually know and the need for more trials that address these differences and women specific research programmes. Dr Greenblatt was emphatic that “we need to address research related to women much more aggressively.’

And there were a few reports addressing women’s health presented at this meeting…

Osteopenia and fat redistribution

There is no current consensus of the effect of HIV and/or antiretroviral use on the prevalence or course of osteopenia in HIV positive women, particularly older women.

Two oral presentations evaluated bone mineral density in HIV positive women [5,6]. Dr Jacobsen and colleagues from Tufts University, Boston looked at the association between HAART use and other demographic variables on bone mineral density in a cohort of 141 women over nine-18 months and 21-27 months of follow up (42 women were followed for two years). This cohort is 33% Caucasian, 52% African American, and 22% other with a median age of 39 years.

The median total BMD at first DXA scan was 1.09 gm/cm2 (25th% 1.04; 75th% 1.16). After adjusting for age and weight, neither HAART use nor demographic variables were significantly associated with total BMD.

In this study the median BMD was not found to change over two years. The investigators report: “However, in individuals loss of BMD is associated with loss of lean body mass.”

They also found that “osteopenia is prevalent in HIV-positive Caucasian women”, and that “smoking and injection drug use may increase the risk of osteopenia”.

Dr Arnsten from the Montefiore Medical Centre evaluated the incidence of osteopenia in a cohort of 284 older (above 35 years, median 45 years) peri- and post menopausal HIV positive (n=144) and negative women (n=140)

Using DXA, they analysed BMD of the lumbar spine, hip, and total body, and in addition they also analysed the impact of protease-inhibitor (PI) use on BMD.

Controlling for race, physical inactivity, smoking, and HIV status, the researchers found that osteoporosis was more prevalent in post-menopausal (OR = 6.8, p < 0.001), physically inactive (OR = 3.9, p = 0.04), and white (OR = 3.5, p = 0.04) women. HIV infection was not associated with either osteopenia or osteoporosis.

In contrast with previous studies, the investigators also reported that women who had used PIs for more than one year were significantly less likely to have osteopenia than women who had used PIs for less than one year or not at all (OR = 0.3, p < 0.01). They concluded: “PI use among older HIV-infected women may protect against bone mineral loss by modifying cytokine-mediated disturbances in the synchronised bone-remodelling process.”

A poster from Dr Yin and colleagues evaluated the prevalence of osteoporosis and HIV associated risk factors for low bone density (BMD) in 32 postmenopausal HIV-positive women [7].

The mean age of this cohort was 56 years, and mean time since onset of menopause 10 years. Eighty-eight per cent of women had used HAART for a mean of five years. Thirty-six per cent had experienced all three classes of drugs, 36% to nucleosides plus PIs and 7% to nucleosides plus NNRTIs. Seventy-two per cent were Hispanic and 25% African American.

An assessment by DEXA was conducted at the lumber spine and femoral neck.

In this small study the investigators found the prevalence of osteoporosis to be considerably higher among African American and Hispanic women with HIV than in comparable HIV-negative women. They reported that lower BMD was more strongly associated with generally accepted osteoporosis risk factors (higher weight, time since menopause and use of HRT) but not with HIV and treatment related factors. They noted that “Hispanics and African Americans account for over 80% of HIV-positive women over age 50 in New York. As the female HIV population increases and ages, diagnosis and treatment of osteoporosis should play a more prominent role in their long-term management.”

A poster from Dr Howard and colleagues from the Montefiore Medical Centre evaluated fat distribution in a cohort of HIV-positive (n=105) and negative (n=120) women and evaluated the impact of antiretroviral use and demographic factors on regional adiposity [8]

Of this group the mean age was 45 years; 45% were African American, 36% Hispanic and 15% white. HIV-positive women were younger and more likely to be African American and obesity was greater in HIV-negative women. Regional body composition was measured by DXA scan. Among the HIV-positive women studied 129 (66%) were using PIs for a median duration of 27 months and 110 (56%) used d4T for a median of 24 months.

The investigators found that in this group of older, predominately obese women after controlling for age, CD4 and PI use in a multivariant analysis, HIV was associated with decreased body mass index (BMI) and percentage of body fat but not with fat redistribution. Amongst the women with HIV, d4T use was associated with an increase in truncal fat and decreased extremity fat, but PI use was not.

Cervical cancer

Likewise there is still no consensus on the effect of HAART use on the course of HPV (human papillomavirus) related cervical pathology in HIV-positive women. In response to contrasting reports in the literature Dr Ubert-Foppa and colleagues from Milan assessed the long-term (mean 36.4 months + or – 10.4 months) effect of HAART on persistent HPV infection and histological cervical lesions in 154 HIV-positive women (mean age 37.3 years) receiving two nucleosides, HAART or no treatment [9].

Women were assessed every six-12 months using PAP smear and coploscopy (with biopsy if indicated) and high grade cervical lesions were treated with loop electrosurgical incision.

Unsurprisingly CD4 levels significantly increased in the HAART-receiving women (p = 0.017) and in those switching to more potent HAART (p = 0.0001), but this was not associated with a decreased persistence of HPV. A significant reduction of positive biopsies though was found only in women on long term HAART (p = 0.00006).

However, the investigators found that in this cohort they could establish no beneficial effect of long term HAART on HPV persistence and related cervical disease and that these conditions persisted in a high proportion of women. They explained that HPV-related histological lesions are significantly reduced only in women with stable clinical and virological picture including those untreated or treated with two NRTIs or with HAART. HPV pathology persists particularly in those with the longest history of HIV infection, suggesting that, regardless of antiretroviral regimen and its effect on HIV replication, the crucial aspect is the number (and probably the competence) of CD4 cells.

They recommend continued monitoring and “strict surveillance of patients is still the best preventive scheme for HPV-related cervical lesions, also in the era of HAART.”

A poster from the WIHS describes the magnitude of incidence of cervical cancer in this cohort of HIV-positive and at risk women (n= 2,133 women – 463 HIV-negative, 1,662 HIV-positive, and eight seroconverters) followed prospectively from October 1994 through September 2001. Women with a history of cervical cancer or hysterectomy were excluded.

Cervical cytology was obtained at six-month intervals and cervical disease treatment was individualised. They found cases of invasive cervical cancer were observed in the HIV-negative women during 2,380 years of observation – an incidence rate of 0/10,000 woman-years. During 8,260 woman-years of observation, eight cases of cervical cancer were identified in HIV-positive women but only two were confirmed. They found no significant difference in incidence rates between HIV-positive and negative women.

The investigators noted that this low incidence could not be generalised to women who are not under a regular screening and prevention programme or to women not receiving HAART.

Neurological disease

Finally, a poster from Dr Hall and colleagues, in response to previous chart review data suggesting a higher incidence of HIV neurological disease and differences in progression in women and men, reported findings from a longitudinal study evaluating gender differences in nervous system decline [11].

In this prospective longitudinal study of 48 HIV-positive, 48 HIV-negative women and 52 HIV-positive men undergoing standard neurological exams by a neurologist and controlling for factors such as antiretroviral use, the investigators found no evidence that nervous system decline was more likely in one gender than the other.

References:

Unless stated otherwise, all references are to the Programme and Abstracts of the 10th Conference on Retroviruses and Opportunisitc Infections (CROI), 10–14 February 2003, Boston.

http://www.retroconference.org/2003/

1. Solomon S. Stopping HIV infection before it begins in women. Abstract 114
2. Mbori-Ngacha D. Prevention and care of HIV-infected women in Sub-Saharan Africa. Abstract 47
3. R M Greenblatt Natural history of HIV-1 infection in women—findings from the Women’s Interagency HIV Study. Abstract 115
4. Squires K. The impact of sex/gender and antiretroviral therapy and its complications. Abstract 117
5. Jacobson D, Knox T, Shevitz A. et al Low bone mineral density in HIV-infected women. Abstract 102
6. Arnsten JH, Freeman R, Santoro N, et al. HIV infection and protease inhibitor use are not associated with reduced bone mineral density in older HIV-infected women. Abstract 103
7. Yin MT. Dobkin JF, Brudney KF et al. Osteoporosis in postmenopausal HIV+ women. Abstract 766
8. Howard AA, Freeman R, Santoro N et al. Body composition and antiretroviral use in older HIV-infected women. Abstract 735
9. Uberti-Foppa C, Ferrari D,. Lodini S. Long-term effect of highly active antiretroviral therapy on histological cervical squamous intra-epithelial lesions among HIV+ women. Abstract 767
10. Massad LS, Seaberg E, Bitterman P et al. Incidence of invasive cervical cancer among women with HIV. Abstract 768
11. Hall C, Robertson W, Fiscus S et al. No gender differences in progression of HIV-related neurological disease. Abstract 703