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Preventing HIV infection in Women – a Global Health Imperative!


Women account for about half of all HIV infections globally. Sexual transmission is the dominant mode of HIV transmission to women and there is a concomitant, associated epidemic of transmission to infants. The majority of HIV infections in women are in sub-Saharan Africa with a disproportionate burden in young women under 25 years old. HIV acquisition and prevention in women is complex and influenced by biological, behavioral and structural factors. Efforts to reduce HIV infection in women in sub-Saharan African could play a substantial role in altering global HIV trajectories. Increasing access to sexual and reproductive health services, addressing gender based violence and social instability , reducing poverty and sex for survival, and encouraging greater male responsibility are critical short-to medium term interventions. Efforts to find a microbicide and HIV vaccine need to be matched with efforts to deepen understanding of HIV acquisition in the female genital tract to inform development of targeted molecules for HIV prevention.

1. Epidemiology

In contrast to the first two decades of the HIV pandemic, today women comprise about half of all adults living with HIV/AIDS globally [1]. H eterosexual transmission accounts for more than 80% of all new HIV infections in women. The majority of HIV-infected women live in sub-Saharan Africa where there is a substantial associated, concomitant epidemic of vertical transmission of HIV. Women acquire HIV infection at least 5-7 years earlier than men. HIV infection is 3-7 fold higher in adolescent women compared to adolescent boys in sub-Saharan Africa (Figure 1). This age and sex differential in HIV distribution is considered to be a key driver of the generalized, hyperendemic epidemics described in this region.

Figure 1
Age and sex distribution of HIV infection in Africa (Attachment 1)

Some indication of the unfolding catastrophe for women can be gleaned from temporal trends in age-specific HIV prevalence in pregnant women in South Africa [2]. While peak prevalence of HIV infection is observed in women aged between 20–24 years, the magnitude of that risk has grown about 8-10 fold over 15 years. The real picture of the devastation is illustrated by analyzing the experience of birth cohorts of 1972 who were 20 to 24 years old in 1992 when HIV infection was rare in southern Africa to how it has increased exponentially over almost two decades to a point where about a third of pregnant women are infected with HIV [3]

While the exact contribution of HIV/AIDS to maternal mortality rates is unknown, there is growing evidence which shows that HIV/AIDS is a leading cause of pregnancy-related death [4] and is also an important cause of death in populations with a high prevalence of HIV [5].

Notwithstanding, the estimated eight fold higher transmission efficiency from males-to-females compared to females-to-males [6, 7], and magnitude of the burden of HIV infection, HIV acquisition in women is complex, multi-factorial and not well understood. The relative contributions of age, anatomy, concurrent relationships, condom use, sexual networks, poverty, education, economic autonomy, power imbalances between men and women, gender based violence, access to sexual and reproductive health services, political and socio-cultural issues require elucidation.

2. Biology and HIV Risk

Age of sexual debut [8], viral load [9, 10], stage of infection [11], route of transmission [12], anatomy, epithelial integrity, and presence of curable sexually transmitted infections [6, 9, 11] are some biological factors associated with excess risk of HIV infection in women. The younger age of HIV acquisition in women is associated with sex with older men who are more likely to be in concurrent relationships with multiple partners and more likely to have a higher viral load [13].

Whilst there is a growing body of knowledge on HIV acquisition in the genital tract, it is insufficient to fully understand the biologic mechanisms responsible for driving the vulnerability in women. HIV infection occurs through cell-associated and cell free virus and infection can occur across an intact epithelium, however, mechanism of viral entry and passage across the mucosa remains incompletely understood.

Cervical explant studies demonstrate that thickness of the mucosal layer could play a protective role from HIV invasion [14] and other studies have shown that any factor that undermines the thickness of this barrier increases the probability of HIV transmission across the mucosa. Progesterone containing contraceptives have specifically been shown to lead to thinning of the epithelium with subsequent increased incidence of SIV infection in macaques [15]. Epithelial thinning has also been demonstrated in humans [16, 17] however; the subsequent translation into enhanced risk of HIV infection remains to be demonstrated [18]. Given the widespread use of progesterone containing contraceptives in Sub-Saharan Africa over intra-uterine devices (IUDs), implants and/or sterilization [19] this gap in our understanding requires urgent attention.

Studies investigating likely causes of breeches in the natural defense mechanisms in the female genital tract such as that due to breaks in the epithelial lining [20] following douching [21]; sexual intercourse [22], cervical ectopy with combined oral contraceptive use [23], and cytological changes from Human Papilloma Virus (HPV) infection [6, 20] have been inadequate and equivocal in explaining the excess burden of HIV in women and demand more attention.

An estimated 340 million new cases of curable sexually transmitted infections (STIs) occur globally in the 15-49 year age group [24] and could play a contributory role in HIV acquisition [25-27]. Whilst the promising 42% reduction in HIV incidence rates observed in Tanzania [28] following treatment of STIs, these results have not been reproduced in other randomized controlled trials (RCTs) in Uganda [29, 30] and Zimbabwe [31]. Notwithstanding , the inconsistent findings from these RCTs, the significant sexual and reproductive health challenge posed by the high burden of curable STIs needs to be addressed in any HIV prevention effort.

The cervix is thought to be an efficient primary site for viral transmission. The negative findings from the recently completed MIRA (Methods for Improving Reproductive Health in Africa) trial that tested the efficacy of a diaphragm for HIV prevention has been a setback in testing this hypothesis [32]. More recent studies suggest that HIV is transmitted more efficiently across the uterine lining compared to the ectocervix [33, 34] and that multiple mechanisms of transmission are used across the female reproductive tract [33, 34].

A deeper understanding of the female genital tract and mucosal immunity is key to guiding the development of strategic and targeted products most suitable for combating HIV infection in women. Two critical gaps in preventing HIV infection in women relate to firstly, our understanding of what underlies transmission efficiency between males to females compared to females to males and secondly, the viral-host events that occur immediately preceding and following exposure to HIV. Specifically we need to understand: (i) the sequence of events required to establish mucosal infection, (ii) the role of mucosal immunity in preventing HIV infection, (iii) characteristics of protective mucosal immune responses, and (iv) the role of innate immunity in early HIV infection and (v) the interface between innate and adaptive immunity to HIV infection [35].

3. Behavior and HIV Risk

Abstinence, being faithful, male and female condoms, voluntary counseling and HIV testing, and medical male circumcision are widely promulgated as the cornerstone of HIV prevention efforts. However, partnership characteristics, patterns of sexual networking and the age differences between partners impact on their relevance and adequacy for HIV prevention in women.

3.1. Abstinence

Abstinence is a HIV prevention strategy promoted for adolescents, especially women. In practice, abstinence often entails either delaying sexual initiation for a limited period of time or practicing “secondary abstinence”, that is, a prolonged period without sexual activity amongst those who have previously been sexually active [36, 37]. Evidence for the success of this approach remains sparse despite the widespread implementation of abstinence messages, particularly through life-skills education in schools and faith-based HIV risk-reduction interventions. In settings where the epidemic is generalized and probability of infection is high because of high disease burden, postponement of sexual initiation in women simply delays the age of infection, but does not in itself reduce rates of infection [38, 39]. Promotion of abstinence in young people and young women is a key intervention for several reasons: i. to enable young women to complete school and increase their economic opportunities, ii. Enable more informed decision-making about when to have sex, with who and how, iii. Acquire the skills to communicate their desires about preventing HIV infection, unwanted pregnancies and other issues to protect their rights as autonomous being and to life.

3.2. Be faithful

The practice of inter-generational sexual coupling between young women and older men, a common pattern of sexual networking in sub-Saharan Africa [40, 41], has been shown to increase women's risk of HIV infection almost seven fold where the age difference is about 5-7 years [13, 42]. The reasons for this is because older male partners are most likely to already be HIV-infected, or may engage in concurrent or multiple partnership patterns that increase their own and partners' HIV risk. Such sexual partnering is an important contributing factor to a HIV prevalence of 24.5% among young adult women [39].

Young people with multiple or concurrent partners also face increased HIV risk [43], although gender and other factors strongly influence this association [39, 44]. Concurrent relationships are more common in sub-Saharan Africa than one-time casual encounters, and the average duration of relationships is relatively long, resulting in tightly linked, overlapping sexual networks [45]. This link between age difference and concurrent relationships and HIV risk appears to be restricted to younger women and older men. Young men report concurrent relationships about three times more frequently compared to young women (23% vs 8.8%), but HIV infection in young men remains lower than in young women [46, 47]. Interventions targeted at reducing HIV risk in women require more targeted efforts directed at young boys and men. Greater male responsibility for actions and for HIV risk is critical for men and their sexual partner(s). The HIV risk associated with concurrent partner relationships and/or sexual relationships that involve frequent partner change needs to be more directly addressed.

3.3. Condoms

Numerous studies conducted over the past decade have demonstrated the steady increase in acceptability and use of male condoms by young people [36, 48], particularly in settings where consistent messages are promoted and support for continued use is provided through access to free condoms [39, 49].

Significantly, very high levels of consistent condom use are required to reduce HIV incidence rates. A review of HIV risk studies [50] estimate that only about 20% of adolescents use male condoms consistently. While 70% of youth report having ever used a condom, about 50% report use of a condom at last coital encounter [39, 51-53].

Among women, partnership type strongly influences condom use, with condoms generally viewed as less acceptable or desirable within long-term partnerships based on issues of love and trust [54-56], but acceptable in casual relationships. Various obstacles to condom use include negative beliefs about and attitudes toward condoms, often grounded in traditional gender constructions [46, 57]. Some studies have found that young people may also associate condom use with promiscuity and sexually transmitted infections including HIV/AIDS [58-60]. Further, peer pressure or stigma about condom use inhibits actual use [61-63]

Despite comparable efficacy rates between male and female condoms [64] and high acceptability levels [65], limited access to female condoms and substantially higher costs have limited uptake and use of female condoms and thus an opportunity to reduce HIV infection in women through a women initiated method.

3.4. Counseling and testing

Voluntary counseling and testing (VCT) has been shown to be both efficacious in reducing risky sexual behaviors [66] and cost-effective as a prevention intervention [67]. Knowledge of HIV status is an important gateway to access prevention or treatment services, including reducing vertical transmission of HIV in generalized epidemic settings. However, large numbers of people remain ignorant of their HIV status especially in sub-Saharan Africa [68]. Despite recognition of HIV risk, fear of stigma and discrimination and/or experience of violence remains a major obstacle to HIV testing particularly for women in low VCT uptake rates in prevention of mother-to-child transmission (PMTCT) programs in sub-Saharan Africa [69]. Given that the primary users of antenatal services in sub-Saharan Africa are young women under the age of 30 years, transforming delivery of PMTCT programs with greater emphasis on couple counseling, preventing unwanted pregnancies, keeping HIV negative mothers uninfected, early initiation of HIV infected mothers on antiretroviral treatment and ensuring safe infant feeding practices could make a substantial difference to current maternal and infant mortality rates and life expectancy patterns in women in these settings.

3.5. Medical Male Circumcision

Three, independent randomized controlled trials conducted in Africa have consistently demonstrated a 50%-60% protective effect of medical male circumcision [70-72]. Mathematical modeling has demonstrated the substantial prevention impact of medical male circumcision in generalized HIV epidemics with low male circumcision rates [73]. Significantly, reducing the number of HIV infected males is likely to reduce HIV risk for young women in these settings where marriage is rare, concurrent relationships common, condom use low and sexual coupling with young women is the norm. However, despite compelling scientific evidence, most countries in sub-Saharan Africa have been slow in developing national policies on circumcision or programmatically providing access to medical male circumcision. This provides another missed opportunity for reducing HIV risk in young women and implementing a highly efficacious HIV prevention intervention.

3.6. Microbicides

Microbicides represent a HIV prevention strategy that women can initiate and was first proposed almost two decades ago. Currently there are more than 50 candidate microbicide products in preclinical development and 11 products are being tested in 21 ongoing trials. A further 16 clinical trials are planned [74]. PRO 2000 gel and tenofovir gel are the in the most advanced stages of effectiveness testing. Thus far, only PRO 2000 gel, has demonstrated a moderate reduction in HIV infection [75]. While promising, further evidence of PRO 2000's effectiveness is still required. VivaGel and Dapivirine, are likely to enter last phase efficacy trials in the near future and research has started on combination microbicides of multiple active ingredients and/or target different points of viral entry. Despite numerous scientific, ethical and methodological challenges, microbicides provide real potential to influence the course of the HIV epidemic and are likely to be available and accessible sooner than HIV vaccines and will fill an important gap for women-initiated prevention methods. As such investments and research for an efficacious microbicide needs to continue to be a priority in the global HIV prevention agenda.

4. Structural factors and HIV risk – gender, poverty, power and migration

There has been slow but growing recognition and appreciation of the critical importance of how structural factors influence HIV risk. Particularly the role of gender and how it impacts HIV acquisition in women as well as how it affects access to services and social support when infected or affected by HIV/AIDS and single-handedly compounds the effects of biological and behaviorial risk.

With the social and economic constraints that limit women's access to resources in so many developing countries, sex becomes a commodity to ensure survival. In such a context, the definition of sex work is complex as there are many transactions that it can encompass in a scale extending from serial monogamous relationships, sporadic or occasional exchange of sex for transport, school uniforms and fees, food, accommodation, all the way through to more conventionally identified formal occupation as a sex worker [76-78].

Where marriage is rare, women enter into a series of monogamous relationships to ensure their and their children's survival [79]. Often these women have a child to ensure continued financial support from the father, and in the course of a lifetime may end up having several children with different biological fathers. Pre-occupied with survival, and with limited access to information and health services, the risk of infection and options to reduce risk are not immediate priorities for these women.

Poverty and lack of economic opportunities are more pronounced in rural and geographically isolated areas and influence both men and women to migrate in search of employment and income [80]. Where men and women are away from home for prolonged periods or seasonally, conjugal stability and social cohesion are disrupted and this increases the risk of HIV and other sexually transmitted infections [81] as they are likely to establish new sexual networks that present a greater risk of HIV acquisition. On their return home, gendered role expectations and dominant ideologies around marriage and procreation make it unlikely they will use HIV prevention methods such as male condoms [77].

The intersection of gender with age is an important determinant in the distribution of power in any society, with younger members of society typically having less power than older members and younger women having less power than younger boys. Gender based violence is perhaps the grossest manifestation of the power imbalance between men and women [82]. In the context of the HIV pandemic it renders young women even more vulnerable to HIV infection and further limits their ability to protect themselves. The overall power imbalances between men and women, at both societal and individual relationship levels, have their roots in adolescence [77, 83].

Notwithstanding context-specific differences, there is consistency in role differences between men and women, particularly in access to resources and in decision-making authority, which create and sustain an unequal balance of power. Typically men are expected to be breadwinners and to generate income through economic activities outside the home, while women are expected to be responsible for maintaining the home through nurturing and rearing. Almost uniformly across the world, women have less access to and control of productive resources outside the home. Evidence for this imbalance in power includes the gender gaps in literacy levels, employment patterns, access to credit, land ownership and school enrolment rates. This imbalance in access to, and control of, productive forces and resources translates into an unequal balance in sexual relations in favor of men.

While at a global level the economic divides between North and South have grown substantially in the past decade, the challenges in terms of unemployment, wage gaps, literacy levels and occupational segregation are greatest for poor, indigenous women. In South Africa, an important factor contributing to the high prevalence of HIV among women is the wide-spread ‘circular migration’ of men who work in the cities where they have ‘town wives’ while maintaining their spouses and children in rural areas [84]. These circumstances place young women in rural areas in a uniquely vulnerable situation for acquiring HIV. In one rural survey the prevalence of HIV infection in women who saw their partners less than ten days a months was 15% compared with 0% in women who saw their partners more frequently. HIV infection in mobile couples is two to three times higher than that of more stable couples [85].

Significantly these structural factors render both men and women vulnerable to HIV infection. An exclusive focus on behaviorial and biological factors to reduce HIV infection will have little impact. There is growing evidence of the positive impact of conditional cash transfers on catalyzing adherence in substance use programs, anti-smoking efforts, weight reduction, school attendance and human development outcomes [86-88] and importantly intrinsically sustained impact of benefits. Thus far the impact of providing financial incentives for reducing HIV risk remains to be established. Government HIV prevention efforts need to be matched by the private sector where the nature of occupation fosters conjugal instability such as mining and trucking industries to creating conditions that reduce HIV risk. New economic initiatives need to be cognizant of potential source of labor in deciding location. Short-term gains from a more urban and central location may be off-set by medium-to long-term goals resulting from premature loss of lives and expertise from AIDS.

5. Conclusion

This paper has highlighted the complexity of HIV acquisition in women as well as the biological, behaviorial and structural challenges in reducing this risk. Our failure to curb the HIV pandemic is a reflection on our failure to reduce HIV in young women especially in sub-Saharan Africa. HIV/AIDS is making a substantial impact in reducing life expectancy in women, and increasing maternal and infant mortality rates especially in sub-Saharan Africa and undermining the region's efforts to meet the Millennium Development Goals (MDGs). Despite the many challenges in reducing HIV infection in women, there are numerous opportunities to effectively act on now, even as we continue our efforts for longer term solutions for preventing HIV infection..


CAPRISA was established with support from the the National Institutes of Health (grant# AI069469 and AI51794). In addition, Quarraisha Abdool Karim is funded by the Fogarty International Center (grant # TW00231) and the HIV Prevention Trials Network (grant # AI068619).


Quarraisha Abdool Karim: No conflicts to declare

Sengeziwe Sibeko: No conflicts to declare

Cheryl Baxter: No conflicts to declare


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