RESOURCE CENTRE

Teresa Branco, Margaret Johnson, Karine Lacombe, Anne-Mette Lebech, Mona Loutfy, Angelina Namiba, Maria Jesús Pérez Elías and Sharon Walmsley on behalf of Women for Positive Action.

Women are one of the fastest growing population groups at risk for HIV infection, however research among this group is limited. Women for Positive Action aims to highlight the need for enhanced inclusion of women’s needs into HIV research and care.

A number of recent and ongoing studies are focussed on investigating the challenges facing women living with HIV and the healthcare professionals involved in their care, as well as women who have a partner with HIV. The Women for Positive Action faculty feel that this research is of importance to all those involved in the care of women living with HIV and have summarised findings from these studies, in addition to providing their perspective of the impact of these findings.

Antiretroviral treatment to prevent the sexual transmission of HIV: Findings from the HPTN 052 study

Topical pre-exposure prophylaxis (PrEP) for prevention of HIV transmission

Oral pre-exposure prophylaxis (PrEP) for prevention of HIV transmission

Use of hormonal contraceptives and risk of HIV transmission

Sexual transmission of HIV: Questions for consideration

 

Antiretroviral treatment to prevent the sexual transmission of HIV: Findings from the HPTN 052 study

The HPTN 052 study1 investigated if the risk of transmitting HIV to sexual partners can be reduced through the earlier initiation of oral antiretroviral therapy. The study assessed HIV transmission in 1,763 serodiscordant couples (one partner HIV positive, the other one negative) across 13 sites in nine countries. HIV-positive partners with CD4 cell counts of 350-550/mm3 were randomised to receive either immediate antiretroviral therapy or delayed therapy (defined as CD4 count declining to <250/mm3 or development of an AIDS-defining illness). Half of the HIV-positive participants were women.

Over the follow-up period (median 1.7 years), there were 28 linked transmissions to the HIV-negative partner in those who delayed therapy compared to one transmission in the group who started antiretroviral therapy immediately. This represented a highly statistically significant reduction in the risk of transmission of 96% (p<0.001). The majority of transmissions (60%) were estimated to have occurred when the partner with HIV had a higher CD4 cell count (>350/mm3).

Statistical analysis showed that a higher viral load at the beginning of the study was the strongest predictor of transmission in both groups (those who delayed therapy and those who began treatment immediately). Furthermore, study participants who stated that they used condoms consistently were reported to be at a reduced risk for HIV transmission.

Couples who reported 100% condom use at study entry had a 67% lower risk of HIV transmission than couples who reported less than 100% condom use. However, the study findings show that the protective effect of antiretroviral therapy was independent of condom use.

 

Topical pre-exposure prophylaxis (PrEP) for prevention of HIV transmission

The topical administration of antiretroviral drugs for pre-exposure prophylaxis (PrEP) (where antiretroviral drugs are used to reduce the likelihood of contracting HIV by protecting an individual prior to possible HIV exposure) has been a key area for research recently and to date there are a number of studies ongoing.

Initial research into the use of microbicide-containing antiretrovirals looked at 1% tenofovir gel in human cervical tissue samples, and provided pre-clinical support for the effectiveness of topical antiretroviral therapies against HIV infection.2 However, in early human studies the first generation of topical microbicides using gel formulations showed either no benefit or an increased risk of infection in women. This may have been related to irritation to the genital mucosa.

The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial3, published in 2010, studied the effectiveness and safety of 1% tenofovir gel for the prevention of HIV infection in South African women. CAPRISA was the first study to demonstrate a positive effect on HIV transmission. When used intravaginally both before and after sex, 1% tenofovir gel reduced the incidence of HIV infection among women by 39% overall and by up to 54% in highly adherent subjects (i.e. those with >80% adherence). Approximately a 51% reduction in herpes simplex virus type 2 (HSV-2) was also observed. Despite an adherence support program and high gel acceptability, about 40% of the women in this study had <50% gel adherence, with declining rates of adherence observed over the course of the study.

The VOICE (Vaginal and Oral Interventions to Control the Epidemic) study (also known as MTN-003)4 is an ongoing, safety and effectiveness study comparing daily use of 1% tenofovir gel, oral tenofovir and oral emtricitabine/tenofovir for the prevention of HIV infection in women. The study, which began in September 2009, has enrolled 5,029 sexually active HIV-negative women at sites in Zimbabwe, Uganda and South Africa. In September 2011 the tenofovir arm of the study was terminated by the Data and Safety Monitoring Board because it had already answered the research question that oral tenofovir tablets were no more effective in preventing HIV than placebo tablets. In November 2011 the study group using the 1% tenofovir gel daily was discontinued as the gel was shown to be no more effective than placebo. The study arm containing oral emtricitabine/tenofovir will continue and results are expected by 2013.

The Follow-on African Consortium for Tenofovir Studies 001 (FACTS 001) trial is another study in the field, which has recently began recruitment. This is a large scale, placebo-controlled trial to test the safety and effectiveness of vaginal tenofovir gel used before and after sex to protect women against HIV infection and also against HSV-2. The FACTS 002 study is designed to test the safety and acceptability of tenofovir gel in 16- and 17-year-old South African women. Implementation of the strategy of PrEP in the clinical setting will be dependent upon the results of ongoing clinical trials. However, with regard to assessing the feasibility and effectiveness of providing tenofovir gel in a clinic setting, the three-year CAPRISA 008 study, which follows on from CAPRISA 004, will begin to provide information about implementation, demonstrating how the gel can be provided and monitored as part of family planning services.

Looking to the future, new microbicides are already in development. Dapivirine, an NNRTI, is in Phase I or I/II development in Europe and Africa either alone or in combination with the CCR5 antagonist maraviroc, in gel or vaginal ring form. Other antiretrovirals such as integrase inhibitors have been used in exploratory studies and raltegravir has been shown to prevent vaginal transmission of simian HIV (found in monkeys) even when applied three hours after viral exposure in macaques, which could mean that microbicides could also be used as post exposure prophylaxis.

 

Oral pre-exposure prophylaxis (PrEP) for prevention of HIV transmission

Recent research has focussed on the role of antiretrovirals as a preventive option for transmission of HIV; both as post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). In animal models, both tenofovir and emtricitabine were shown to be protective when animals were challenged with HIV virus and a combination of drugs may lead to increased protection.5

Based on animal models5-8, and observational studies9, the Centers for Disease Control and Prevention (CDC) developed HIV prevention guidelines for occupational, non-occupational and high-risk exposure to HIV.10,11 One of the limitations of PEP is that efficacy is based upon the proximity between contact with the HIV virus and starting treatment. To date a number of studies have investigated the effectiveness of oral PrEP.

It has been reported that PrEP is effective for slowing the spread of HIV in men who have sex with men however studies in women are limited. A phase II trial of tenofovir for PrEP among women in Ghana, Cameroon and Nigeria indicated, that the approach was safe, but could not assess the effectiveness due to the small number of infections seen during the study which was prematurely halted.12 The FEM-PrEP study of oral PrEP in women compared a once-daily dose of oral emtricitabine/tenofovir with placebo. The study was conducted at four sites across Africa where a high prevalence of HIV was reported.13 FEM-PrEP was prematurely stopped when the Independent Data Monitoring Committee advised that the study would be unable to demonstrate effectiveness of emtricitabine/tenofovir in preventing HIV infection. As of the 18 February 2011 the study had enrolled 1,951 participants and a total of 56 new infections were reported (equal numbers in both arms). Family Health International (FHI) which was responsible for implementation of the FEM-PrEP clinical trial along with research groups in Africa, decided to initiate orderly closure of the study.14 Thus, collection of primary end-point data continued to August 2011 with the final analysis scheduled for the end of 2011.

The VOICE (Vaginal and Oral Interventions to Control the Epidemic) study4 is comparing daily use of oral emtricitabine/tenofovir, oral tenofovir and 1% tenofovir-based vaginal gel for safety and effectiveness in preventing male to female HIV transmission. The study outcome raises some important issues regarding drug availability in the vagina and rectum after oral dosing and ancillary studies to explain these differences are urgently needed. To date the study groups receiving oral tenofovir and tenofovir gel have been discontinued as these treatments have been shown to be no more effective than placebo. Results from the study group receiving oral emtricitabine/tenofovir are expected in 2013.

The Partners PrEP study, evaluated transmission-prevention in HIV-serodiscordant couples.15 In this study of 4,747 couples in Uganda and Kenya, the HIV-negative partners were randomised to receive tenofovir alone, emtricitabine/tenofovir, or placebo as daily oral PrEP. Results showed that PrEP substantially decreased the risk of transmission to both men and women compared with placebo, whether tenofovir was used alone (62% decrease; p=0.003) or with emtricitabine (73% decrease; p<0.0001).

Another study, TDF2, was conducted in heterosexually active young adults in Botswana.16 A total of 1,219 individuals, aged 18 to 39 years, were randomised to receive daily oral emtricitabine/tenofovir or a matched placebo. All individuals received monthly HIV testing, and those who tested positive went on to receive counselling and treatment. Individuals who tested HIV negative were given their next month’s supply of emtricitabine/tenofovir and continued in the study. Significantly fewer HIV infections were observed in the active PrEP arm; 9 vs 24 in the placebo arm, which resulted in a 62.6% (p=0.0133) efficacy rate for emtricitabine/tenofovir.

 

Use of hormonal contraceptives and risk of HIV transmission

Heffron et al. recently reported the results of a study assessing the association between hormonal contraceptive use and risk of contracting HIV-1 in women and HIV-1 transmission from HIV-1 positive women to their male partners.17 The 3,790 serodiscordant couples (i.e. one partner with HIV-1 infection and one partner without) were recruited either as part of the Partners in Prevention cohort or for the Couples Observational Study - two large prospective cohort studies in HIV-1 carried out across seven African countries.

In two-thirds of couples the woman was HIV-positive, and in the other third, the man was HIV-positive. The partners with HIV had no history of AIDS-defining disorders, had CD4 counts of <250 cells/mm3 and were not using antiretroviral therapy. Rates of HIV-1 acquisition by women and HIV-1 transmission from women to men were compared among injectable and oral hormonal contraceptive users and non-users. The primary outcome measure was development of antibodies to HIV-1 (seroconversion).

Results showed that during the course of the study, hormonal, injectable or oral contraception was used at least once by 21%, 16% and 7% of women without HIV respectively. Among the 1,314 couples in which the HIV-negative partner was female, rates of HIV-1 transmission were 6.61 per 100 person-years in women who used hormonal contraception and 3.78 per 100 person-years in those who did not (p=0.03). Among 2,476 couples in which the HIV-negative partner was male, rates of HIV-1 transmission from women to men were 2.61 per 100 person-years in couples in which women used hormonal contraception and 1.51 per 100 person-years in couples in which women did not use hormonal contraception (p=0.02).

After adjusting for confounding factors (such as age and viral loads), women using any hormonal method had twice the risk of acquiring HIV as other women. This statistical analysis also reported that men whose HIV-positive partners used any form of hormonal contraceptive had twice the risk of contracting HIV as other men. Findings were particularly driven by injectable hormone contraception.

 

Sexual transmission of HIV: Questions for consideration

If a person living with HIV assumes that having an undetectable viral load means they are unlikely to transmit the virus and so have unprotected sex, who is responsible if transmission occurs?

Engaging in a sexual relationship is a matter of shared responsibility. The decision to not use condoms based on the results of research studies and advice given by healthcare professionals must be discussed with both partners during reproductive counselling and a mutual decision taken. To help a couple make an informed choice healthcare professionals must also provide up to date information from recent published research studies in a way that can be clearly understood by patients, in addition the importance of adherence to therapy for preventing transmission should be highlighted. If all those conditions are fulfilled, it is difficult to blame either partner if transmission occurs. However, in the case of multiple partnerships it should be considered that transmission may occur with another sexual partner than the “official” positive partner.

If a person living with HIV assumes that having an undetectable viral load means they are unlikely to transmit the virus, then how often should their viral load be monitored to ensure that their partner is not at risk?

All patients are statistically at risk of experiencing viral blips, which renders the significance of a transient positive viral load difficult to interpret, in terms of risk of transmission. We could reasonably assume from the Swiss Statement that a partner with HIV and an undetectable viral load for more than 2 or 3 years has a level of viral reservoir excretion sufficiently low and even virtually nonexistent. If adherence is optimal and viral load controlled for some years, it is not necessary to shorten the recommended delay for viral load check i.e. 3 to 6 months.

Considering the results of the Partners trial, showing an increased risk of HIV transmission from both women to men and men to women, should hormonal contraception (and especially injecting contraception) be avoided and replaced by mechanical contraception?

It is commonly recognised that injectable contraceptives (e.g. subcutaneous) delivering progestogen, increase the risk of hypermenorrhea, and therefore the risk of contracting HIV or transmitting HIV through infected blood. Oral contraception may be a suitable alternative option in cases of hypermenorrhea, but in all cases, dual contraception (use of both condoms and hormonal contraception) should be advised. During reproductive counselling it should be stressed that hormonal contraception should not be abandoned as it is one of the most effective methods for the avoidance of unwanted pregnancies, and it is the only method that can be chosen by women alone.

 

References

1. Cohen M et al. Antiretroviral treatment to prevent the sexual transmission of HIV-1: results from the HPTN 052 multinational randomized controlled ART. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome, Italy. Abstract MOAX0102, 2011.
2. Rohan LC et al. In vitro and ex vivo testing of Tenofovir shows it is effective as an HIV-1 microbicide. PLoS One 2010;5(2):e9310.
3. Abdool Karim Q et al; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329(5996):1168-74.
4. VOICE (MTN-003). Available from: http://www.mtnstopshiv.org/news/studies/mtn003. Last accessed November 2011.
5. García-Lerma JG et al. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med 2008;5(2):e28.
6. Tsai C-C et al. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl) adenine. Science1995;270(5239):1197-99.
7. Shih C-C et al. Postexposure prophylaxis with zidovudine suppresses human immunodeficiency virus type 1 infection in SCID-hu mice in a time-dependent manner. J Infect Dis 1991;163(3):625-27.
8. Van Rompay KK et al. Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: oral 3'-azido-3'-deoxythymidine prevents SIV infection. Antimicrob Agents Chemother 1992;36(11):2381-86.
9. Cardo DM et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med 1997;337(21):1485-90.
10. Panlilio AL et al. Updated US public health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. Morb Mortal Wkly Rep 2005;54:1-17.
11. Smith DK et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the US department of health and human services. MMWR Recomm Rep 2005;54:1-20.
12. Peterson L et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a Phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin. Trials 2007;2(5):e27.
13. NIAID: The FEM-PrEP HIV prevention study and its implications for NIAID research (2011) www.niaid.nih.gov/news/newsreleases/2011/Pages/FEMPrEP.aspx. Last accessed November 2011.
14. FHI. FHI to initiate orderly closure of FEM-PrEP www.fhi.org/en/Research/Projects/FEM-PrEP.htm. Last accessed November 2011.
15. Baeten J & Celum C. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study. Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome, Italy. Abstract MOAX0106.
16. Thigpen MC et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome, Italy. Abstract WELBC01.
17. Heffron R et al; for the Partners in Prevention HSV/HIV Transmission Study Team. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis 2011 [Epub ahead of print].

Women for Positive Action discuss the impact of recent research on the sexual transmission of HIV in women
To mark World AIDS Day (December 1, 2011), Women for Positive Action has released a commentary which discusses recent and ongoing research on prevention strategies for the sexual transmission of HIV. With expert opinion from Teresa Branco, Margaret Johnson, Karine Lacombe, Anne-Mette Lebech, Mona Loutfy, Angelina Namiba, Maria Jesús Pérez Elías and Sharon Walmsley, the article is focused on the potential clinical relevance of these studies. Women for Positive Action is led by a coalition of healthcare professionals, women living with HIV and community representatives from across Europe, Canada and Latin America. The group is committed to exploring the issues that face women with HIV and those involved in their care. The full article can be accessed at http://www.womenforpositiveaction.org/prevention-strategies-for-the-sexual-transmission-of-HIV/

“Women are one of the fastest growing population groups at risk for HIV infection but research among this group is limited. Recent research has focussed on reducing sexual transmission of HIV; these studies are of particular interest for those involved in the care of women at risk of HIV e.g. women with an HIV-positive partner. It is important that we highlight this research and encourage additional studies to address the many challenges facing women at risk of HIV” said Dr Mona Loutfy, Associate Professor at the University of Toronto, and Infectious Diseases Specialist and Clinician Scientist at Women’s College Hospital, Toronto, Canada.

Women for Positive Action is committed to raising awareness of the need to bridge the existing research gaps with the ultimate goal of improving the lives of women living with HIV.

---- ENDS ----

Note to Editors
Globally an estimated 33 million people are living with HIV. Women make up about 50% of HIV cases and a higher proportion of new diagnoses compared with men. This means that the share of HIV infection among women is increasing in several countries. Young women, in sub-Saharan Africa, aged 15-24 are three to four times more likely to become infected than young men (UNAIDS, 2009). The most common mode of infection is by heterosexual transmission and most women with HIV are of childbearing potential. Furthermore, women with HIV are more likely to present at a later stage of HIV infection than men.

Although women represent 50% of people living with HIV globally and are one of the fastest growing population groups at risk for HIV infection, relatively little research has looked at women-specific issues, and women only account for about 20% of participants in clinical trials of HIV to date. As part of its mission Women for Positive Action aims to raise awareness around recent and ongoing studies that focus on women. Visit the multilingual website http://www.womenforpositiveaction.org for further information about Women for Positive Action and ongoing projects. Women for Positive Action is supported by a grant from Abbott.

References
UNAIDS 2009, http://www.unaids.org/en/default.asp

For further information please contact the Women for Positive Action secretariat:

Email: WFPA@litmus-mme.com
Tel: +44 (0)20 7632 1969
Address: Women for Positive Action, Program Secretariat, Litmus MME, 151 Shaftesbury Avenue, London WC2H 8AL, United Kingdom

Women for Positive Action at the 13th European AIDS Conference, Belgrade, October 12-15, 2011

Women for Positive Action was invited to participate in a mini-lecture at the European AIDS Conference in Belgrade as part of the session ‘When people living with HIV grow up to become adults or want children’. Speaking on behalf of the faculty, Dr Teresa Branco (Portugal) and Dr Mariana Mărdărescu (Romania) presented an overview of the challenges facing women living with HIV who wish to start a family, specifically focussing on differences across Europe.

The epidemiology across the European region was discussed, highlighting that while the number of new diagnoses in western and central Europe is stabilising, it is still rising in eastern Europe. Dr Branco confirmed that in Portugal approximately 26% of the 40,235 people living with HIV are women and 1,156 of these were diagnosed during pregnancy. The principal modes of transmission in Portugal are heterosexual intercourse and intravenous drug use. Dr Mărdărescu highlighted that in Romania those children who contracted HIV during the late 1980s are now in early adulthood, many of whom are in stable relationships, often with an HIV-negative partner and now wish to start a family. In Romania, the main mode of HIV transmission is also through heterosexual intercourse and in 2010 there were a total of 10,405 people living with HIV/AIDS.

For those living with HIV who wish to start a family the key assisted fertility techniques available include intrauterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) following sperm washing. Availability of these assisted fertility services varies largely across Europe irrespective of east, west, north and south, and access to these services mainly depends on whether they are privately or publically funded. The information on the access to these services is limited and is included in few regional or national guidelines. Furthermore, adoption is either not available for couples where one partner is HIV-positive or can be very challenging. The importance of reproductive discussions for the care of women with HIV as well as involving both partners in discussions and providing information and education was identified as a priority in the care of those with HIV who are wishing to start a family.

Dr Mărdărescu also presented a UK-based case study ‘From pregnancy to baby and beyond’ as an example of a strategy that could be implemented in other countries to help support those who want to start a family, who are pregnant or who have already given birth. Based on a programme previously run in sub-Saharan Africa, the programme is based on training “Mentor Mothers” to offer peer support to women living with HIV to provide education, information and emotional support in all aspects of conception, antenatal and postnatal care. Please visit the Positively UK website for further information on ‘From pregnancy to baby and beyond’.

Other aspects of the care for women living with HIV, such as the management of complications during pregnancy and mother-to-child-transmission were also explored in this session.

Please click here to download the Women for Positive Action mini-lecture presentation.

Women for Positive Action was delighted to participate in activities at the XVIII International AIDS Conference, Vienna, 18–23 July, 2010

Building the leadership capacity of positive women through networks
ICW women's network symposium
Women for Positive Action collaborated with women's networks from across the globe as part of a symposium held by the International Community of Women Living with HIV/AIDS (ICW). The symposium aimed to highlight the importance of women's networks working together to enhance the lives of women living with HIV.

Speaking alongside representatives from Latin America, USA, Asia-Pacific and Africa, Angelina Namiba spoke about her personal experiences as part of European networks, including Women for Positive Action and WECARe+. 'Each Women's Network requires a clear vision and goals to enable them to evolve and work towards a common goal' highlighted Angelina 'For example, Women for Positive Action, which is led by a faculty of women living with HIV, healthcare professionals, and community representatives from Europe, Canada and Latin America aims to support both healthcare professionals and women living with HIV through the provision of resources.'

All groups who participated in the symposium are committed to ensuring that women living with HIV are meaningfully involved in the formation, implementation, monitoring and evaluation of programs that impact their lives. This symposium offered an opportunity to raise awareness of the importance of ongoing support and work in this arena.

Women's Networking Zone reception
Women for Positive Action sponsored the Women's Networking Zone (WNZ) reception which was attended by over 150 people. During the reception Angelina Namiba and Ulrike Sonnenberg-Schwan thanked the organisers, on behalf of Women for Positive Action, for providing such an informative area for attendees.

The WNZ was a community built forum within the International AIDS Conference open to the public - providing a place where community members, advocates, researchers, service providers, and decision-makers could meet, share, and learn together.

Please visit the resource centre to download educational slide resources, available in English and Spanish. To access information about ongoing projects please visit the initiative page.

News article
In some countries, criminal laws have been put in place to prosecute those who transmit or expose others to HIV infection. While these laws have been developed primarily for protection, there are concerns that they may in fact be counterproductive and undermine public health and human rights, particularly for women.
A publication by the International Planned Parenthood Foundation, 'Verdict on a Virus', concludes that laws criminalizing HIV transmission may do more harm than good, especially for women and result in disproportionate number of women being prosecuted for HIV transmission or exposure.
It is often the woman in a relationship who is first to find out about her HIV-status, and such laws would place the responsibility on her for disclosing her status to her partner. Such disclosure may put her at risk of violence and/or abandonment. Depending on the nature of her relationship, women may find it difficult to negotiate safer sex, making her more vulnerable to prosecution due to unintentional transmission. There are also fears that such broad criminal laws could result in women being prosecuted for transmitting HIV to a child during pregnancy or breastfeeding.
Organizations such as UNAIDS are urging governments to limit criminalization to cases of intentional transmission, i.e. where a person knows his or her HIV positive status, acts with the intention to transmit HIV, and does in fact transmit it.
Following an international consultation UNAIDS published a policy brief on the criminalization of HIV transmission in July 2008. They raised the concern that going beyond the 'intentional transmission' cases described above, may result in criminal sanctions being applied to people who are not deserve blame, which will further stigmatize people living with HIV and is likely to drive them further away from HIV prevention, treatment, care and support services.

References:
International Planned Parenthood Federation. Verdict on a Virus: Public Health, Human Rights and Criminal Law (November 2008) (http://www.ippf.org/en/Resources/Guides-toolkits/Verdict+on+a+virus.htm)
UNAIDS/UNDP Policy brief - Criminalization of HIV Transmission (August 2008) (http://www.unaids.org/en/PolicyAndPractice/HumanRights/humanrights_criminalization.asp).

News article
The United States Centers for Disease Control and Prevention (CDC) are considering recommendations for promoting routine circumcision for all baby boys born in the United States to reduce the spread of HIV. 
Clinical trials undertaken in some African countries, such as Uganda, Kenya and South Africa, have shown that adult heterosexual males who are circumcised have up to 60% reduced risk of contracting HIV from a HIV positive woman.
While every intervention that can potentially reduce HIV transmission should be investigated, in the case of male circumcision it has not been shown to offer women any protection from acquiring HIV. A study undertaken in Uganda investigated whether circumcision of HIV-infected men would reduce transmission of the virus to female sexual partners. Men were randomly assigned by to receive either immediate circumcision or circumcision delayed for 24 months (the control group). The HIV-negative female partners of the men were assessed at 6, 12, and 24 months to determine if they had contracted HIV. The trial was stopped early as it became apparent that circumcision of HIV-infected men was notable to reduce HIV transmission to their female partners.
If the proposals in the US go ahead, circumcision may be recommended for infant boys in addition to adult males whose sexual practices put them at high risk of HIV infection.  While circumcision appears to offer some level of protection to men in certain settings, it only reduces the risk of HIV infection, it does not prevent it. Most importantly it must be remembered that male circumcision has not been shown to provide protection to women and measures, such as using condoms, are essential to avoid HIV transmission to women and infection with other sexually transmitted diseases.

References:
Wawer MJ, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 2009;374(9685):229-37.
Centers for Disease Control and Prevention, 2008. Male circumcision and risk for HIV transmission and other health conditions: implications for the United States. http://www.cdc.gov/hiv/resources/factsheets/PDF/circumcision.pdf

More than 13 million children under the age of 15 have lost a parent due to HIV and AIDS. There are also many children who have HIV-positive parents or carers. These children are not only affected by the impact of HIV and AIDS on the people around them, but are also potentially vulnerable to HIV transmission themselves. These factors can have an impact on their emotional well-being compared with other children of the same age.
A number of strategies are generally adopted in clinical practice with the aim of improving the emotional well-being of children affected by HIV and AIDS – but how effective are they and what evidence exists to support their use?
To investigate this, a review was undertaken to look at published studies in order to assess the effectiveness of the various interventions. Surprisingly, the investigators found that no properly designed and controlled studies of interventions for improving the psychosocial well-being of children affected by HIV and AIDS had in fact been undertaken.
They concluded from this that current practice is based on anecdotal knowledge and on the results of studies that do not provide a strong evidence base for the effectiveness of these interventions. In the absence of rigorous intervention studies, the body of knowledge consists of ‘lessons learned’, child psychological theory, or is extrapolated from related research in the adult population.
This investigation highlighted the urgent need for high quality intervention studies in children. The investigators recommended that the quality and quantity of such studies could be improved by establishing a greater partnership between programme implementers and researchers.
However, it was recognized that such knowledge should not replace the urgent need for rigorous monitoring and evaluation of existing programmes and intervention studies to ensure that clinical practice and policy are truly evidence based. This will avoid the situation where children are subjected to interventions which show no benefit or interventions that could unintentionally lead to harm.

Reference
King E, De Silva M, Stein A, Patel V. Interventions for improving the psychosocial well-being of children affected by HIV and AIDS. Cochrane Database Syst Rev 2009; Apr 15;(2):CD006733.

The use of antiretroviral therapy during pregnancy and in the newborn baby has resulted in a decrease in mother-to-child transmission (MTCT) of HIV to less than 1% in areas that have adequate resources to provide these medications.
Despite these benefits, questions remain regarding their safety for the mother, the fetus, and the child.  Some studies have found associations between antiretrovirals and premature birth or other adverse pregnancy outcomes, but data are conflicting making it difficult to draw firm conclusions.
The Antiretroviral Pregnancy Registry (APR; www.apregistry.com) has been established to collect information on any major birth defects effect associated with a prenatal exposure to antiretroviral medication and the outcomes of pregnancy.
The APR’s most recent report, up to July 2008, provides the most comprehensive source of information on the safety of antiretrovirals in human pregnancies. The results are encouraging – they found 2.7 birth defects per 100 live births which does not differ from the rates usually found in the general population (US data).
There is also the question of whether highly active antiretroviral therapy (HAART) is necessary for all pregnant women. The effects of some antiretroviral medications on the body are altered significantly during pregnancy and placental transfer from the mother to the fetus is variable. Undoubtedly, the choice of which antiretroviral to use in a pregnant women must take into consideration the need for rapid control of viral suppression and both maternal and fetal safety. On balance, however, studies suggest that the well-documented benefits of HAART for preventing MTCT generally outweigh the potential risks to the fetus, infant, and mother.

However, it is clear that possible adverse effects of antiretroviral medications are of concern, and questions remain as to the best treatment strategy in this setting. More data on the effects of antiretrovirals during pregnancy are needed and this can only be provided by large randomized trials of antiretroviral treatment strategies used during pregnancy and the neonatal period.

Reference
Stek AM. Antiretroviral medications during pregnancy for therapy or prophylaxis. Curr HIV/AIDS Rep 2009;6(2):68-76.

Literature report
Italian investigators have discovered that HIV-positive women who are also infected with hepatitis B or C have lower bone density than HIV-positive women who do not have hepatitis co-infections. Importantly, this difference is not apparent in men.

It is known that people who are co-infected with HIV and also hepatitis B or C have higher rates of serious health complications, one of which can be low bone density. A decrease in bone density (also known as bone mass) is normal in both men and women as they age. In women, this decline is increased during menopause; in fact, a woman can lose up to 20% of her total bone mass in the 3–6 years after her menopause. Low bone density can result in the development of osteoporosis and lead to an increased risk of fracture.
The Italian study assessed the risk factors for reduced bone density at the hip and spine, over and above what would normally be expected, in a group of men and women with HIV, some of whom were also infected with hepatitis B or C. They found that both HIV/hepatitis co-infection and being female were associated with low bone density measurements.
Women co-infected with hepatitis C had significantly lower bone density in their spine than women infected with HIV only – this difference was not seen in men. In addition twice as many women as men were found to have low bone density measurements in this body region.
The same pattern was seen when hip bone density was investigated, even after taking into account factors such as use of antiretroviral therapy, smoking, and levels of physical activity that might influence the results.
The investigators concluded that viral hepatitis was associated with a higher risk of low bone density among HIV-infected women but not amongst HIV-infected men, but the reason for this difference is currently unclear.

Reference
Lo Re V et al. Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men. AIDS 23: 2191-98, 2009.

News article
The United Nations (UN, www.un.org) has created a ‘Women’s Agency’ to promote the rights and well-being of women worldwide and to work towards gender equality.
This initiative will result from the merger of four existing departments – the UN Development Fund for Women (UNIFEM), the Division for the Advancement of Women, the Office of the Special Adviser on Gender Issues and the UN International Research and Training Institute for the Advancement of Women (UN-INSTRAW).
UNAIDS – the joint United Nations programme on HIV/AIDS (www.unaids.org) – has welcomed this advance and aims to work closely with the new agency to promote women’s access to health and development.
It is well known that women are disproportionately affected by the AIDS epidemic. More than 60% of people living with HIV in sub-Saharan Africa are women and three out of four young people living with HIV are female. Gender inequalities, sexual abuse, violence, conflict and poverty often increase women’s vulnerability to HIV.
UNAIDS believes that protecting women from becoming infected with HIV and treating women living with HIV can help stem the epidemic. In addition, preventing women from becoming infected in the first place and increasing their access to treatment also directly contributes to reducing the number of children being born with HIV and becoming orphans.
Working alongside the new agency, UNAIDS hopes to strengthen the capacity of women’s organizations to deliver critical maternal and child health services to women and girls at a grassroots level.

Women for Positive Action: an International Partnership Dedicated to Enhancing the Lives of Women Living with HIV

To mark International Women’s Day (March 8, 2010) Women for Positive Action are launching a series of tools to raise awareness of the challenges facing women living with HIV/AIDS today. Women for Positive Action (WFPA) is led by a broad coalition of healthcare professionals, women living with HIV and community representatives from Europe, Canada and Latin America. This global initiative aims to support health care professionals and women living with HIV through the provision of resources, which are available for download, in English and Spanish, at www.womenforpositiveaction.org.

To view the multimedia news release, please click on:
http://multivu.prnewswire.com/mnr/prne/wfpa/40788

"Women living with HIV face many challenges as a consequence of their disease and its treatment including depression, guilt, isolation, discrimination and body image concerns" said Sharon Walmsley, Director of HIV Clinical Research, University of Toronto, Canada, “The new WFPA resources will encourage education and stimulate communication between women with HIV and those who care for them”. The educational resources include information on current best practices and research, in addition to informative case studies.

WFPA brings together a unique combination of those involved in the care of women living with HIV with the first-hand perspectives of those living with HIV themselves. Ophelia Haanyama Ørum, Senior Advisor, Global Partnerships on HIV and AIDS, Noah’s Ark Foundation, Stockholm, Sweden added “The women living with HIV represented in the WFPA initiative welcome the opportunity to incorporate our experiences and expertise into health and social care solutions for women everywhere who are affected by HIV.” The group aims to empower, educate and support the needs of women living with HIV, their healthcare professionals and community advocates involved in their care.

The theme for International Women’s Day this year is ‘Equal rights, equal opportunities: Progress for all’, and provides the ideal opportunity to consider the unique impact of HIV on women. Understanding the effect of the disease is a key step in improving the lives of women and working towards bridging gender inequalities in HIV.

Globally an estimated 33 million people are living with HIV. Women make up about 50% of HIV cases and a higher proportion of new diagnoses compared with men. This means that the share of HIV infection among women is increasing in several countries. Young women, in sub-Saharan Africa, aged 15–24 are three to four times more likely to become infected than young men (UNAIDS, 2009). The most common mode of infection is by heterosexual transmission and most women with HIV are of childbearing potential. Furthermore, women with HIV are more likely to present at a later stage of HIV infection than men. Visit www.womenforpositiveaction.org for further information about WFPA and ongoing projects. WFPA is supported by a grant from Abbott.

Reference:
UNAIDS 2009, http://www.unaids.org/en/default.asp

For further information please contact:
Women for Positive Action
Program Secretariat
Litmus MME
151 Shaftesbury Avenue
London WC2H 8AL
United Kingdom
Tel: +44 (0)20 7632 1815
WFPA@litmus-mme.com

Literature report
The VOICE Study (Vagina and Oral Interventions to Control the Epidemic) is a large clinical trial that has recently commenced to investigate whether antiretroviral (ARV) drugs normally used to treat HIV infection can also be used to prevent it. The study will investigate whether applying a vaginal microbicide gel containing an ARV every day or taking an oral ARV tablet once a day can reduce a woman's risk of acquiring HIV.
The main aim of VOICE is to evaluate the safety and effectiveness of the two regimens, however it will also aim to find out which of the two options – the tablet or the gel – the women in the study prefer to use.
Up to 5,000 women will be enrolled in VOICE at clinical trial sites in Uganda, South Africa, Zambia and Zimbabwe.  VOICE is being conducted under the leadership of the US National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), which is based at the University of Pittsburgh and Magee-Women’s Research Institute.
Although correct and consistent use of male condoms has been shown to prevent HIV infection, women often cannot control if or when condoms are used by their male partners. Women are also twice as likely as their male partners to acquire HIV during unprotected sex, due in part to biological factors that make them more susceptible to infection.
VOICE Study co-chair Jeanne Marrazzo, Associate Professor of Medicine in the Division of Allergy and Infectious Diseases at the University of Washington in Seattle, USA, commented that “Women need safe and effective methods for preventing HIV that they can control themselves, and need methods that they are willing and able to use.”
Researchers at the Uganda and Zimbabwe sites are also conducting a companion study called VOICE B, or the Bone Mineral Density Sub-study. VOICE B will involve about 300 women who have been randomized to the oral tablet groups to determine the potential effects, if any, that the oral ARVs may have on bone health in HIV-negative women.

Further information about the study can be found at: http://www3.niaid.nih.gov/news/QA/VOICEqa.htm

Literature report
Almost one in four HIV-positive women in the USA does not opt to undergo an annual Papanicolaou (Pap) test for cervical cancer even though they are at an increased risk for the disease, according to a study reported in the Journal of Acquired Immune Deficiency Syndromes. Due to the increased risk of cervical abnormalities, HIV treatment guidelines recommend annual Pap tests for HIV-infected women.
Dr Alexandra Oster and colleagues from the Centers for Disease Control and Prevention assessed screening prevalence and associated factors among HIV-infected women using data collected during 2000–2004 in an interview study of HIV-infected persons in 18 US states. Of the 2,417 women interviewed, 556 (23.0%) did not report receiving a Pap test during the past year. Not choosing to have a Pap test was associated with increasing age and most recent CD4 count of <200 cells/mL. Odds of a missed Pap test increased for women whose most recent pelvic examination was not performed at their usual place of HIV care.
The investigators concluded that HIV care providers should ensure that HIV-infected women receive annual Pap tests, recognizing that missed Pap tests are more likely among older women and those with low CD4 cell counts. They also suggested that there should be greater integration of HIV and gynecologic care, and clinicians should be made aware about the recommendations for screening in HIV-positive women
They commented that, "The risk of cervical cancer has not decreased since the introduction of highly active antiretroviral therapy, highlighting the continued importance of cervical cancer screening in this population. Cervical cancer screening should be a high priority for HIV-positive women”.


Reference:
Oster AM, Sullivan PS, Blair JM. Prevalence of cervical cancer screening of HIV-infected women in the United States. J Acquir Immune Defic Syndr 2009;51(4):430–6.

Literature report
Researchers in Chicago, USA, have highlighted the fact that the level of cognitive impairment – a decline in mental functioning and the ability to carry out tasks that require thinking, planning, and memory – among HIV-positive women is higher than that in non-infected individuals.
The investigators also noted that to date women have been under-represented in neuropsychological studies of HIV infection. However a small number of studies have reported significantly higher levels of cognitive impairment among HIV-positive women compared with HIV-negative subjects, regardless of their symptom status and whether they have an AIDS diagnosis. This impairment was most evident on psychomotor tasks – those that require a degree of physical movement. Notably, the risk of such impairment was found to increase among HIV-positive women who were not taking antiretroviral therapy. Age and depressive symptoms were also risk factors for poorer mental functioning.
The researchers concluded that the potential female-specific aspects of HIV-associated cognitive disorders required further investigation and that new studies were needed to asses the impact of other relevant factors, such as female hormones, post-traumatic stress disorder and other mental health conditions.

Reference:
Maki PM, Martin-Thormeyer E. HIV, cognition and women. Neuropsychol Rev 2009;19(2):204–14.

News article
Considerable advances have been made in the reduction of mother-to-child transmission (MTCT) in developing countries.
In many industrialized countries, treatment with antiretroviral drugs (ARVs), often with Caesarean section delivery and always combined with breastfeeding avoidance, have significantly reduced MTCT from 25% to 1–5%.
However, breastfeeding by HIV-positive women in poorer communities within developing countries is often unavoidable – in fact avoidance of breastfeeding places infants at greater risk of illness or of dying if formula milk is prepared without using clean water. Commonly, these communities have inadequate health care resources to help HIV-positive pregnant women and mothers, and this has contributed to the lack of success in reducing MTCT.
So the question remains – how can we reduce breastfeeding transmission of HIV while improving survival of infants born to HIV-infected mothers in developing countries? Data are now available that strongly suggest that breastfeeding transmission has been substantially decreased in regions that have adopted a preventative treatment strategy targeted at both infants and mothers.
The advances identified in the recent study have been achieved primarily by the use of ARVs in breastfeeding infants, with the aim of preventing them acquiring the virus, coupled with the treatment of HIV-infected lactating mothers – allowing them to continue to breastfeed while minimizing the risk of MTCT.
However to achieve the ultimate goal of elimination of MTCT, these measures need to be part of a comprehensive approach to the problem and include the prevention of unwanted pregnancies in all women living in areas with high levels of HIV infection, primary prevention of HIV infection in women of child-bearing age, and an improvement in the health service facilities for these women.
Current World Health Organization recommendations suggest individualized counselling to determine the best feeding method for each woman.

References:
Coovadia H. Current issues in prevention of mother-to-child transmission of HIV-1. Curr Opin HIV AIDS 2009;4(4):319–24.
Horvath T, Madi BC, Iuppa IM, Kennedy GE, Rutherford G, Read JS. Interventions for preventing late postnatal mother-to-child transmission of HIV. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006734.
Jackson DJ, Goga AE, Doherty T, Chopra M. An update on HIV and infant feeding issues in developed and developing countries.  J Obstet Gynecol Neonatal Nurs 2009;38(2):219–29.