Secondary Logo

Journal Logo

Article

Vulnerability of women in southern Africa to infection with HIV: biological determinants and priority health sector interventions

Chersich, Matthew F; Rees, Helen V

Author Information
doi: 10.1097/01.aids.0000341775.94123.75
  • Free

Abstract

Introduction

A disproportionate number of women in southern Africa are infected with HIV, with levels of infection far exceeding those of men in the region, and several orders of magnitude higher than that of women in other settings [1]. The extent of women's vulnerability to HIV infection in southern Africa is well described, but the precise short and long-range determinants of this vulnerability, and the interaction between these determinants still requires further elucidation. Unravelling these complexities is vital though, and key to designing prevention programmes that target the actual causes of vulnerability, tailored to the particular interplay of biosocial factors in each setting.

The extraordinary levels of HIV among women in southern Africa reflect and perpetuate deep-rooted social and gender inequities, although specific biological co-factors further fuel these epidemic dynamics. The risk of transmission is strongly influenced by the type of sexual activity and innate biological defences of uninfected women. Co-infection with sexually transmitted infections (STI) or the presence of genital lesions in either partner amplifies baseline risks. Also, too often women still have low levels of knowledge about HIV, inaccurate perceptions of their risk of infection and do not know their own or their partner's HIV status. All of these factors increase a woman's vulnerability to HIV.

A systematic analysis of biomedical and contextual factors would assist in defining a coordinated HIV prevention response, with improved prevention programming and results. This would enhance previous prevention efforts in southern Africa. Here, interventions have, thus far, been scattered and ill-defined, or focused narrowly on individual behaviours and weighted heavily towards a biological approach.

Within each country in the region, different epidemic scenarios exist and have evolved over time. This resulted in considerable variation in HIV prevalence among population groups within countries. Certain groups have markedly higher risks of HIV exposure, especially female sex workers (FSW) and communities affected by migration. Specific factors exacerbate the vulnerability of these groups, who require more intense or different interventions to address their heightened vulnerability. In southern Africa, as in other settings, groups such as FSW make a considerable impact on the transmission dynamics of the epidemic [2,3]. Mitigation of risk for HIV infection in such groups is vital also for preventing HIV within the general population (all social groups are interconnected). Another clear example of especially vulnerable women is those left with little financial support while their partners are away working, and who often rely on transactional sex for economic survival [4]. As these examples show, keeping up to date with the priority sources of new infections is key to meeting often-changing prevention needs.

From a biomedical perspective, this paper summarizes knowledge of the causes of women's vulnerability to HIV. It also outlines available interventions to counter biological risk factors. Intersections between these factors, and women's sexual behaviour and practices, are also briefly discussed. The use of condoms and alcohol directly affects the safety of sexual relationships in this setting; when relevant, their influence is outlined here. More distal factors such as economic vulnerability, societal norms, and gender-based inequality and violence are inseparable from women's sexual behaviour and, at least partly, determine women's sexuality and wellbeing. These later factors are not covered here in detail, but are discussed in other papers in this supplement.

Vulnerability of women to HIV acquisition: biomedical factors

Although addressing the more distal underlying determinants of vulnerability is critical, defining the key factors that directly affect the risk of HIV transmission and those that amplify this risk serves to identify important targets for HIV prevention within the biomedical and behavioural realm. Below, biomedical factors that affect the risk of HIV infection are dealt with first and then their interactions with sexual behaviours are considered.

Biomedical factors and risk of HIV

Key factors affecting HIV spread are the efficiency of transmission during a specific sexual encounter and the number of exposures, if any. Efficiency of transmission is generally believed to differ between sexes, with women at higher risk of HIV acquisition per sex act [5–7]; however, not all studies have found this [8]. Different types of sexual activity also have varying efficiency, well illustrated by relative rates of transmission via vaginal and anal intercourse. A study of heterosexual couples in the United States found that for women the odds of HIV transmission during receptive anal intercourse was approximately 10 times that of vaginal sex [9]. The remainder of this section predominately covers aspects of penile–vaginal sex, with further discussion of HIV transmission with anal or oral sex in the section on sexual behaviour and biomedical risks that follows.

Stage of HIV disease

HIV viral load is strongly correlated with the risk of transmission [10]. The stage of HIV infection is thus a critical predictor of infectivity [11] as viral load in all fluids and tissues, including semen, peaks approximately 4 weeks after infection and remains at high levels for a few months [12,13]. In a Ugandan study, nearly half of HIV infections could be ascribed to a sex partner with newly acquired HIV [8]. With this exceptionally higher risk of transmission and as they often are unaware they are infected, people with acute HIV make a marked contribution to HIV spread [14]. There are, however, many practical challenges, at a clinical and laboratory level, to diagnosing early HIV infection. Also, interventions to reduce infectivity at this time require further investigation. For now, recognition of the role of acute HIV in its transmission dynamics provides rationale for prevention strategies such as repeating HIV testing at prespecified intervals, or after a high-risk exposure, and interventions to reduce concurrent partners.

Concurrent partnerships create a most conducive environment for HIV transmission during acute infection [15,16]. When one person in a network of concurrent partners acquires HIV, others in the network, which can connect as many as half the sexually active members of a community [17], are at considerable risk. Serial relationships are likely to trap HIV within a single relationship during the acute infection stage.

Although the efficiency of HIV transmission per sexual exposure is lower during the chronic asymptomatic phase of HIV infection, that this period extends over several years means a large proportion of HIV transmissions still occur at this time. The risk of sexual transmission again begins to increase during the later stages of HIV disease, when viral load rises with advancing immune degradation [8,18].

Sexually transmitted infections facilitate HIV transmission

Evidence over the past two decades points to a strong link between STI, especially genital ulcer diseases, and an increased risk of the sexual transmission of HIV [19–21]. Lesions of the genital tract facilitate the transfer of HIV, thereby enhancing the baseline risk predicted by a factor such as semen viral load. Several mechanisms underlie this increased risk for women, including: increased contact with a larger volume of HIV-containing blood or secretions if male sexual partners have penile ulcers; raised HIV viral load in semen of men with STI such as herpes simplex virus type 2 (HSV-2); and disruptions of a woman's mucosal barriers to infection, which undermines innate defences of the vagina or cervix. The presence of STI in women also increases the risk of HIV infection by recruiting HIV-susceptible inflammatory cells to the genital tract.

In recent years, the prevalence of certain major STI (e.g. chancroid, syphilis and gonorrhoea) has fallen in many parts of the world. Simultaneously, however, there has been an absolute increase in the incidence of HSV-2 infection, which has become the predominant aetiology of genital ulcer disease. The prevalence of HSV-2 is as high as 80% in some groups of women in Africa [22,23]. Unfortunately, of all genital ulcer diseases, HSV-2 interacts most strongly with HIV, both through immune activation and disruption of the genital mucosa. In both cohort and cross-sectional studies, genital herpes has been associated with a doubling or tripling in the risk of HIV acquisition and with up to a fivefold increase in HIV transmission per sexual act. As much as 50% of new HIV infections in populations with a high prevalence of HSV-2 could be attributed to HSV-2 enhancement of susceptibility [24–27]. An increase in the risk of HIV infection has also been noted in those who have asymptomatic HSV-2 infection, suggesting that the biological mechanism of increased risk is not only through macroscopic impairments of the integrity of genital mucosa [24]. Thus far, antiviral prophylaxis directed against HSV-2 has not been demonstrated to reduce HIV acquisition [28,29]. Other research has, however, shown that treatment of HSV-2 infection lowers HIV plasma and genital viral load by an amount that is likely to have a beneficial impact on the course of HIV infection, and possibly on HIV infectivity [30–33]. Unlike bacterial or parasitic STI, genital herpes is not curable, but can still be treated. An HSV-2 vaccine, a major research priority, could make a marked contribution to HIV prevention, in addition to the control of HSV-2, an important pathogen in itself.

Bacterial vaginosis, a very common infection in women in southern Africa, has also been identified as a risk factor for HIV transmission in several studies [34]. Prospective studies also indicate that intermediate vaginal flora and other disturbances in vaginal microbes also increase the risk of HIV acquisition [35–38]. Although much uncertainty remains about the pathophysiology of bacterial vaginosis, its accompanying inflammatory milieu, characterized by pro-inflammatory cytokines and immune cell changes, could possibly enhance HIV transmission [39]. A better understanding of the risk factors for bacterial vaginosis and its optimal management will facilitate further investigation of the potential for bacterial vaginosis treatment to prevent HIV acquisition or transmission. More recently, Trichomonas vaginalis has also been implicated as a co-factor in HIV transmission [40–46]. As both these conditions are common, even small increases in risk at an individual level may have a marked impact on overall HIV levels in the population. An association between candida infection and the risk of HIV has been noted in some studies [47–49], but not in others [37,41,45].

There are immense challenges in increasing the proportion of people who recognize STI and seek appropriate treatment. The majority of men and women with almost every STI are asymptomatic. Furthermore, even if STI symptoms exist, findings from Demographic and Health Surveys indicate that a variable proportion of men seek care from trained personnel (91% in Botswana; 30% in Malawi; 69% in Mozambique; 78% in Zambia; and 25% in Zimbabwe) [50]. Corresponding figures for women, who are even more often asymptomatic than men, are: 93% in Botswana; 27% in Malawi; 64% in Mozambique; 77% in Zambia; and 22% in Zimbabwe. Women in these countries also have little knowledge of STI symptoms. In the African countries surveyed, less than half of ever-married women could name even one STI symptom in either a woman or man. Low levels of STI knowledge and of seeking prompt care for STI markedly undermine STI control efforts.

Vaginal practices and HIV acquisition

Vaginal practices and products are used by large numbers of women in southern Africa to tighten, dry, warm or clean their vaginas [51–54]. Women's efforts to change their genital environment, formerly known as ‘dry sex’, could potentially undermine each component of innate defences against pathogens [51]. In particular, vaginal practices have been linked with the loss of lactobacilli and disruption of the vaginal epithelium [55,56]. In past decades, both cross-sectional and longitudinal studies have found an association between intravaginal cleansing and adverse reproductive outcomes, including pelvic inflammatory disease, ectopic pregnancy and bacterial vaginosis [57,58]. Bacterial vaginosis is potentially an intermediary factor between vaginal practices and the risk of HIV infection.

Evidence as to whether intravaginal cleansing or the insertion of substances increases the risk of HIV acquisition is conflicting. From the spermicide nonoxynol-9 trials, it is clear that some apparently harmless substances inserted into the vagina can cause epithelial disruption and are likely to facilitate HIV acquisition [59]. The effects of cellulose sulphate, another candidate microbicide, provides further evidence for this mechanism. This substance disturbs junctions between vaginal cells and may thus enhance HIV passage across the epithelium and raise transmission risks. It is possible that many commercial and traditional products have similar effects. Limited prospective evidence is available, however, with two studies finding an increased risk of HIV infection with the practice of using fingers to clean inside the vagina [60,61], whereas a study in Zimbabwe and Uganda did not [36]. Given a plausible biological rationale and limitations of available evidence, further prospective evaluation of the effects of vaginal practices is needed.

In addition to biological mechanisms, perceptions of desired vaginal states and vaginal practices themselves can undermine condom use. For example, in some parts of southern Africa, a preference for dry sex and the mixing of bodily fluids is at odds with the use of condoms [53].

Associations between HIV acquisition and reproductive hormones and anatomy

Several sources of evidence indicate that the risk of HIV acquisition may be related to levels of the reproductive hormones oestrogen and progesterone. Perhaps most compelling is the finding, in a few studies, that the risk of HIV acquisition is higher for pregnant women than lactating or other women. A prospective study in Rakai Uganda, found HIV incidence rates were 2.3 per 100 person-years during pregnancy, 1.3 per 100 person-years during breastfeeding, and 1.1 per 100 person-years in non-pregnant and non-lactating women [62]. This finding appears more likely to be a result of physiological changes during gestation than to social and behavioural changes during pregnancy [35,62]. Previously, investigators in Rwanda and Zimbabwe also found an increased risk of HIV infection among pregnant and postpartum women [63,64], although this finding was not seen in another study in Uganda and Zimbabwe [65]. An important potential public health implication of existing evidence suggesting that pregnancy and lactation heightens the risk of HIV acquisition in women is that measures to reduce unintended pregnancies could potentially lower the risk of HIV infection in women, in addition to other inherent benefits.

Hormonal contraception has also been postulated to influence HIV transmission by the same mechanisms as pregnancy. The increased risk of HIV acquisition among women using hormonal contraception has been noted in some [66,67], but not all [68–71] studies. High levels of oestrogen and progesterone during pregnancy or from exogenous sources could, in theory, affect vulnerability to HIV by inducing structural changes in the genital mucosa [72,73] or by immunological effects [74,75]. Limited evidence suggests that potential immunological pathways include the hormone-induced overexpression of co-receptors associated with HIV infection [76] or increased mucosal lymphoid aggregates [77]. Raised oestrogen levels are also associated with cervical ectopy, which exposes the more susceptible columnar epithelium to pathogens, and has previously been associated with approximately a two to threefold increased susceptibility to HIV infection [7,72,75,78]. In addition to these potential biological mechanisms, the use of condoms generally decreases whenever prevention of pregnancy is no longer a motivation, such as in women receiving hormonal contraception, or among pregnant and postpartum women [79–81]. Substantial gaps in evidence remain, however, particularly in delineating these putative causal pathways.

Some authors believe that changes that occur with age in hormones and anatomy affect HIV transmission. Younger women, in earlier stages of physical development and more likely to have cervical ectopy, are possibly more biologically susceptible to HIV infection [82]. A study in South Africa found the per-partnership probability of HIV transmission from men to women aged 15–24 years was very high [83]. Women in that study reported a mean of 2.3 lifetime partners. A significant increase in HIV prevalence was observed with an increasing number of lifetime partners. The estimated per-partnership transmission probability varied from 0.74 to 1.00 (95% confidence interval 0.56–1.00). This may partly explain why age-discordant sex (often when older men provide gifts in exchange for sex from girls or young women) is a key driver of HIV in sub-Saharan Africa. Although additional information is required to elucidate the biological mechanisms that enhance the vulnerability of girls, delaying sexual debut and avoiding exposure to HIV during this especially vulnerable period is a key HIV prevention strategy.

Women at the other end of the age spectrum are also possibly at higher risk per sexual act [6]. Other biological factors that may affect HIV transmission efficiency include the larger surface area of the female genital tract compared with men, and a higher semen viral load and volume compared with vaginal fluids. Topical microbicides would clearly be an especially important method of prevention for women, who otherwise are mostly dependent on male-controlled modalities of protection. Much research is currently investigating this critical approach as well as the development of an HIV vaccine.

Immune activation

Aberrant immune activation, especially after infection with helminths, tuberculosis and malaria, may raise susceptibility to HIV infection. For example, a study showed that filariasis, an extracellular parasitic disease, increases the susceptibility of human peripheral blood mononuclear cells to HIV infection in vitro[84]. Many of these infections are highly prevalent in hyperendemic HIV areas, and increasingly evidence has implicated these infections in the risk of HIV infection [85–90]. Strengthened health services, with improved control of such infections, could also potentially have important benefits for HIV prevention, aside from inherent gains from reducing the burden of these major pathogens.

Male circumcision

The efficacy of male circumcision in preventing female-to-male HIV transmission at the level of individual men has been well demonstrated in trials (a reduction in risk by more than half) [91–93]. Also, a substantial body of observational evidence indicates that male circumcision among newborns or adolescents is effective in reducing HIV acquisition in men. Thus far, there is no evidence of effectiveness at a population-level of implementing specific programmes for male circumcision to prevent HIV.

Modelling data suggest that, over time, women would gain protection from HIV as male HIV prevalence decreases (via ‘herd immunity’) [94]. There is, however, little information available about the effect of male circumcision on male-to-female transmission at an individual level. Limited available data suggest that the risk of male-to-female transmission could even possibly increase when circumcision occurs in HIV-infected men [95]. It has been postulated that this increase may be as a result of having sex shortly after circumcision, before wound healing has taken place. Also, there are concerns that male behavioural disinhibition may occur post-circumcision, as men may believe the procedure fully protects them from HIV.

The potential for harms, such as behavioural disinhibition, to occur after male circumcision reinforces the need for high quality counselling and prevention support within these services. The responsibility for ensuring postoperative abstinence among men should not fall on women, who may have even less power to negotiate condom use after their male partner has been circumcised. Although male circumcision is a valuable prevention strategy, averting potential harms in these programmes is a priority, as yet largely unexplored.

Male circumcision is common in many African countries, and is almost universal in north Africa and most of west Africa. By contrast, it is less common in southern Africa, where self-reported prevalence is approximately 15% in several countries (Botswana, Namibia, Swaziland, Zambia, Zimbabwe) although higher in others (Malawi 21%, South Africa 35%, Lesotho 48%, Mozambique 60%, and Angola and Madagascar >80%) [96]. Circumcision has a long and complex traditional and cultural history in the region. Additional research is needed to investigate local attitudes towards male circumcision and their amenability to change. It remains to be seen whether cultural and political leaders in southern Africa will play their role in bringing about changes in perspectives towards male circumcision.

Sexual behaviours and biomedical vulnerability

Low abstinence, fidelity and condom use

Safe sex is defined as practices that limit contact between bodily fluids of sexual partners, particularly blood and semen. Increased condom use and the promotion of abstinence and fidelity remain critical for HIV prevention. Progressively increasing delays in sexual debut has been a prominent feature of most African countries in which HIV prevention successes have occurred [97,98]. Also, young women in a survey in South Africa, who reported an early age at first sex, were more likely to have experienced factors that may place them at risk of HIV infection (Pettifor A, O'Brien K, Miller WC, Macphail C, Rees H, 2008, in preparation). This supports efforts of prevention campaigns to delay coital debut and make first sexual experiences safer.

Similarly, a reduction in concurrent partners has been associated with population-level declines in HIV. The increased use of male condoms has played a decisive role in HIV prevention efforts in countries such as Uganda, Thailand, Cambodia and Brazil [99]. When used consistently and correctly, male and female condoms offer high degrees of protection. Gaps remain, however, in consistent condom use with long-term partners and to a lesser extent with casual partners. Persistent low acceptability of condoms within cohabiting couples is particularly concerning, as women in such relationships are often at elevated risk of HIV [1].

Many sources of evidence suggest that, on average, African women and men do not have a higher number of lifetime sexual partners than people elsewhere. In particular, adults in Africa report approximately similar, if not fewer, lifetime partners than heterosexual individuals in western countries [100–103]. Of much importance, however, is evidence that African men and women often have more than one concurrent partnership that can overlap for months or years [15,104]. Entrenched patterns of migrant labour drive this concurrency [105,106].

Despite high levels of HIV morbidity and mortality in southern Africa, a large proportion of people still do not believe they are at risk of acquiring HIV. For example, half the respondents in a national household survey in South Africa who were HIV infected, had reported that they felt they were at no risk of acquiring the infection [107]. Women may thus unwittingly engage in risky behaviour because they lack complete information about the level of risk they face. Accurate assessment of HIV risk has been shown to predict condom use among women and is a major determinant of behaviour change [108,109].

Anal and oral sex

Besides the number of partners and concurrency, the type of sexual activity is also a major determinant of transmission efficiency. With anal sex, the fragile epithelium raises HIV transmission risks. Few data are, however, available in southern Africa on heterosexual anal sex. In a household survey of South African youth (15–24 years), approximately 5% of sexually active women reported having anal intercourse [110]. A study among women of a similar age in Cape Town found 12% previously had unprotected anal intercourse [111]. Levels of almost 40% have been reported among FSW in this region [112]. Ethnographic findings here suggest that women often view anal sex as a form of sexual coercion, but also as sexual pleasure [113]. By contrast, in a rural study, anal sex was conceptualized as occurring within socially marginalized groups and as outside of traditional practices [114].

Sexual intercourse during menstruation or other genital bleeding is also believed to increase HIV transmission, both male-to-female and female-to-male [6,9,115,116]. Exposure to blood during sex, mostly attributed to menstruation, is reportedly common in southern Africa [115,117]. Estimating the precise risks for each HIV transmission route is complicated as individuals may engage in several sexual behaviours, making it difficult to establish whether the HIV pathway was oral, vaginal or anal. Nevertheless, it appears that the risk of HIV transmission via oral sexual practices is very low [118]. In a 10-year study of 135 discordant couples whose only exposure was oral–genital contact without a condom, no HIV transmissions occurred [119]. Cases of HIV transmission ascribed to oral–genital contact have, however, been reported, and were associated mostly with the presence of oral or genital ulcers, gingival inflammation and other infections of the oral cavity [120].

Control of alcohol use, within the scope of HIV prevention

Rapidly accruing evidence indicates that alcohol has independent effects on decision-making concerning sex, and on skills for condom negotiation and their correct use. The effects of alcohol depend on the way it is used; not only on the frequency or cumulative volume consumed. Stated otherwise, the effects of alcohol are determined by three factors: lifetime volume of alcohol consumed, patterns of drinking and drinking contexts [121,122]. The overall volume consumed is linked with chronic social problems (such as unemployment) and chronic alcohol diseases such as liver cirrhosis. By contrast, patterns of drinking, in particular frequent episodes of intoxication, are a powerful mediator for acute problems such as accidents, interpersonal violence and high-risk sexual behaviour [122,123].

As opposed to low-risk drinking patterns (low volume per drinking occasion, classically southern European patterns of drinking with meals), drinking patterns in much of Africa are characterized by sporadic heavy episodes of drinking, often in the form of weekend binge drinking [123,124]. This is also true of southern Africa, in both rural and urban areas, where patterns of intermittent episodes of intoxication predominate.

Given this pattern of drinking, acute problems associated with intoxication episodes typically occur, including interpersonal violence and unsafe sex. Many studies have shown that women with heavy episodic drinking patterns (defined as more than five drinks on one occasion) are more likely to use condoms inconsistently and incorrectly, to experience sexual violence, and to acquire a STI, including HIV [125–127].

Substantiating a causal link between alcohol and acute or social problems is ridden with epidemiological nuance [122] and, adopting similar strategies to those previously used by the tobacco industry, is likely to be contested by the alcohol industry. Nonetheless, arguments used to substantiate the widely accepted causal link between alcohol and road traffic accidents form a useful basis for defining the causal pathway between acute intoxication, unsafe sex and HIV. First, a biological explanation exists for the relationship [128,129]; alcohol affects serotonin and gamma-aminobutyric acid brain receptors in a similar way to some benzodiazepines. The subjective experience of this can be reduced anxiety about the consequences of one's actions, resulting in increased risk-taking, be it while driving or during sex. During acute intoxication episodes this reduction in cognitive restraint is especially pronounced, and can manifest as drunken driving or drunken risky sex [128,129].

Alcohol also causes disinhibition and impairs decision-making, decreasing awareness of social norms of acceptable behaviour [130]. Also, there appears to be a dose–response relationship: heavy-drinking occasions with intoxication are associated with higher sexual risks than non-binge drinking. Causality is also supported by results of event-level condom use (reduction of condom use coinciding with heavy-drinking events). Some initial reports have suggested that the adoption of safer drinking behaviour may reduce unsafe sex [131]. Overall, based on existing evidence, a strong argument can be made that alcohol has independent effects on decision-making and verbal skills. Not surprisingly, this also applies to decisions about sexual behaviour, and skills for condom negotiation and their correct use.

Despite large volumes of research demonstrating the effectiveness of alcohol-control measures [132], few interventions have been implemented thus far in African countries. Further research is, however, needed to document whether changes in alcohol use among women reduces unprotected sex, the incidence of sexual violence, and HIV and other STI. In particular, it is possible that women who are assisted to adopt safer patterns of alcohol use will have concomitant safer sexual behaviours and reduced STI burden. By applying similar strategies used to control tobacco, the health sector has an important role to play in mitigating alcohol-related harm. This was given high priority at the latest World Health Assembly [133]. For communities and individuals, interventions are needed to change the way alcohol is consumed, to shift hazardous drinking patterns to safer patterns.

Campaigns against alcohol may require time to take effect, but are equally essential as more direct measures such as condom promotion. More far-reaching structural measures create the conditions necessary for achieving sustained HIV prevention results. Such efforts will also have marked health and social benefits beyond a reduction in the burden of HIV and sexual violence.

Health sector interventions to prevent HIV among women in southern Africa

HIV incidence has decreased in African countries such as Kenya, Uganda and Zimbabwe, as well as within certain parts of other African countries. These examples have demonstrated that with adequate political and cultural leadership, fundamental society-wide changes in sexual norms can take place in Africa, as has occurred in other areas heavily affected by HIV. Even some of the poorest countries in the world have expanded access to HIV prevention. This shows that barriers to scale-up can be overcome through concerted, evidence-informed action, driven by political and cultural will. The dearth of such leadership remains a major barrier to the delivery of HIV prevention information and services in southern Africa.

Reaching girls and young adult women in the general population is a top priority. More effective outreach and innovation beyond formal health services is also needed to access the most at-risk populations and to reduce their vulnerability to HIV. Achieving universal access requires that the health sector develop models of service delivery that reach these populations, including through outreach visits and peer educators. Specific prevention initiatives are required for groups such as sex workers, which are coordinated at a national and regional level, such as 100% condom use programmes.

Sexual and reproductive health services can synergize with HIV prevention. Improved sexual and reproductive health services would intensify HIV prevention by strengthening health systems, preventing unintended pregnancies and STI, and addressing sex-based violence. Brief interventions for alcohol should be more systematically incorporated within STI services, antenatal care and other primary health settings as well as through outreach services. These are cost effective and recommended for wide use [132,134], although they have not yet been broadly disseminated or utilized in southern Africa.

Antiretroviral post-exposure prophylaxis (PEP) soon after possible sexual exposure to HIV is recommended in some countries, although additional evidence is needed to support its use outside the context of sexual violence. PEP is, however, an integral part of the management of sexual assault and should be available for all HIV-negative women who may have been exposed to HIV through sexual assault. Non-occupational post-exposure services also include counselling, assessing the status of the source when possible, emergency contraception, presumptive treatment of STI, and follow-up counselling [135].

Trials are assessing the efficacy of a daily dose of antiretroviral prophylaxis for individuals at risk of HIV infection. This ‘pre-exposure’ approach is a well-established tool for preventing other infectious diseases such as malaria. A more detailed description of other priority health sector interventions for reducing the biomedical vulnerability of women follows below and in Table 1.

Table 1
Table 1:
Priority biomedical interventions for reducing HIV acquisition in women in southern Africa.

Sexual counselling and condom promotion

Patient–provider interface at sexual and reproductive health services provides a key opportunity to disseminate information on HIV and, at a minimum, to explore women's risk perceptions. Providing focused messaging is critical, tailored to local circumstances. Repeated counselling may be necessary, with some evidence suggesting this is beneficial [136,137]. Perhaps best is to provide this counselling together with an HIV test. For HIV-negative pregnant or breastfeeding women, particular efforts are needed to provide tailored counselling and to promote male and female condoms. Additional information is needed on which types of counselling, components of counselling sessions, cadre of counsellor and counselling setting are most effective in promoting sexual behaviour change and altering HIV risk perception [138].

Female condoms remain an under-exploited prevention commodity. It is the only currently available technology that women control, although it still requires male cooperation. Acceptability studies indicate that were the female condom widely available and at low cost, many more women would be able to protect themselves from HIV and other STI [139–141]. A newer FC2 female condom, made of synthetic nitrile, was designed to improve affordability, while maintaining the high quality standards of the original female condom. The FC2 is being made increasing available through international campaigns.

In settings with unequal sexual power and economic disparities, women will, however, continue to have limited ability to negotiate protected sex and few alternatives to adopting practices that explicitly aim to satisfy men's sexual desires (often at great cost to their own health and wellbeing). Counselling and condom promotion cannot thus focus on sexual behaviour alone, because a woman does not make sexual decisions in isolation, but rather within her life context. Particularly as the implementation of male circumcision programmes take place, it is necessary to increase women's education and condom negotiation skills to ensure continued condom use among circumcised men who may perceive themselves to be fully protected against HIV.

In sum, women within southern Africa require contextualized counselling, which encompasses: frank discussion of the dangers of having more than one long-term sexual partner at a time; talking through locally appropriate strategies that women can use to avoid transactional sex, because in this cultural milieu the receipt of gifts often signals sexual acquiescence, mostly without a condom; female and male condom promotion, advice about their correct use and the dual benefits condoms offer for women who do not wish to become pregnant; informing women, including those who are married, that they should consider themselves at risk of acquiring HIV; and counselling women during pregnancy and lactation about the potential increased risk of HIV at this time and that the need for safe sex remains important.

Such messages must be piloted, evaluated and continuously improved.

HIV testing and counselling

Universal access to provider-initiated testing and counselling is required for women and men seen in all health facilities in southern Africa. HIV testing is a cornerstone of HIV prevention and prerequisite for the provision of more nuanced serostatus-specific interventions for HIV prevention. This acknowledges that prevention needs vary with HIV status [142,143]. Moreover, the high rates of transmission that occur during acute HIV infection, when the majority of people do not know they are infected, supports the need for more concerted efforts to provide HIV testing, repeated at pre-specified intervals. Better methods are, however, needed for identifying people during the early stages of HIV infection, accompanied by intensive prevention interventions in this critical time.

Increasing awareness of HIV status would reduce women's exposure to HIV by prompting behaviour change in men who become aware they are infected. Once diagnosed, the majority of men adopt safer behaviours, reducing risk for uninfected partners. Positive-prevention initiatives may also give men knowledge and skills to reduce their high-risk behaviours.

Prevention for negatives after HIV testing requires further refining, as little evidence supports the effectiveness of typical post-test counselling for changing behaviour in those who test negative. More evidence is available that intensive client-centered counselling in this group can alter sexual behaviour and reduce the incidence of STI [144]. Hierarchical admonishments from health workers and didactic messaging to use condoms during sex, or not to have too many partners are likely to have limited effect. Conversely, counselling well situated within a woman's reality may play a more conducive role. This counselling opportunity could also be used to link women to local prevention initiatives such as women and church groups.

Task-shifting, in concert with the optimal use of community service organizations and lay or peer counsellors, provides an important opportunity to shore up the quality of counselling. The question of which cadre in the health system is best placed to provide counselling must be explored, aiming to shift tasks to less specialized health workers, when appropriate [145]. In some respects, non-clinicians may be a better match for counselling than their clinical counterparts, who may be too busy, poorly suited or inexperienced in behavioural counselling.

Detection and treatment of sexually transmitted infections

STI services are critical for controlling the HIV epidemic, especially among populations with a high prevalence of curable STI and at substantial risk of exposure to HIV. Prompt and appropriate treatment of STI reduces an individual's risk of HIV acquisition. Several trials have evaluated the impact of STI control on the incidence of HIV at a population level [146–150]. Mostly they showed disappointing results. Evidence from those trials indicates that the effects of STI control at a population level depend on the phase of the HIV epidemic, the prevalence and type of STI, and the behavioural risk factors in a setting. Although STI treatment in low-level or concentrated HIV epidemics has a larger impact on HIV transmission at a population level, in generalized epidemics the population impact of STI treatment is nevertheless important. In southern Africa, STI control among groups such as sex workers, men who have sex with men and HIV-positive individuals is especially important; however, even among the general population, improved STI management will avert a large number of HIV infections [151].

STI interventions must, however, target those pathogens that contribute most to the expansion of the HIV epidemic in specific settings. Variability in the prevalence of individual STI thus affects the types of infection control strategies that should be emphasized in a specific target group or setting. This requires better STI surveillance data of different population groups in the region.

STI services also contribute to the achievement of universal access to HIV prevention by promoting condom use, behavioural change and the empowerment of vulnerable populations. It is also necessary to improve STI screening and education for symptom recognition in HIV services. Seeking treatment for STI symptoms remains stigmatizing for women, and it can destabilize their relationships [152]. With improved knowledge and support, women and men who suspect an STI would promptly seek care, reducing their individual risk of HIV infection.

Experience in various settings has demonstrated the impact that strengthened STI services can have on rates of STI, especially among populations at increased risk of acquiring these infections. In Botswana, for example, the prevalences of gonorrhoea, syphilis and chlamydia among family planning clients in 1993, before intensified treatment interventions for STI were introduced, were 6.9%, 18.0% and 19.6%, respectively. In 2002, after enhanced national treatment interventions for STI, but possibly influenced by other factors, the corresponding prevalences were 2.6%, 1.5%, and 12.3% [153].

Intersection between biomedical and contextual factors

Much focus of programming and research thus far has been on biomedical and behavioural risk factors, with inadequate recognition that these are determined by an equally complex set of cultural, social and economic factors. In essence, the biomedical vulnerability that most interventions seek to target is an outward manifestation of an underlying gendered social and economic vulnerability, which takes expression in behavioural risks.

Prevention approaches have largely ignored social contexts thus far, presuming a degree of individual control in decision-making that is dissonant with the reality of life for girls and women in southern Africa [154]. There are critical characteristics of the risk environment that condition and constrain the behavioural ‘choices’ available to girls and women in this setting. For example, women may be forced to enter sexual relationships to obtain food, clothing or school fees. Such transactions of material goods or money further skew existing power imbalances within relationships, and often portend an acquiescence to engage in sexual acts on the man's terms [155–157]. Furthermore, fidelity is undermined in certain occupational conditions, such as those of mining companies that involve single-sex hostels, or sell subsidized alcohol supplies. Intensive HIV prevention services are especially important for women exposed to migration themselves or indirectly through migration of their partner. Health workers also need also to advocate for the removal of work-place policies that prevent migrant workers from bringing spouses and families during periods away from home.

Overall, there is a need to mobilize entire communities to change the social, cultural and economic conditions that support unsafe sexual behaviours. Women still report having to ask their male partner for permission to test for HIV or to access health services; permission to protect themselves. Unless accompanied by broader structural interventions in both the political and occupational realm, people's ability to make changes in behaviour will continue to be severely constrained by prevailing social conditions. Not surprisingly, success in HIV prevention in other settings followed on society-wide changes, rather than stemming from interventions in the formal health sector.

In conclusion, understanding the principles of HIV infectivity and factors that modify vulnerability does provide an opportunity to identify local strategies to reduce HIV transmission. There are underutilized opportunities to address biological risks for HIV infection during contact between health workers and patients. Making better use of opportunities when women bring their children for immunization and other child health services is one such important example [79,158]. Also, more vigorous control of alcohol use in southern Africa is a long overdue example of matching prevention measures to local determinants of unsafe sex. Risk factors identified thus far are unlikely to be an exhaustive list, and the risk of transmission may be greatly influenced by interactions between the variables themselves.

In a number of settings, women's disproportionate vulnerability to HIV has been substantially reduced, altering the course of the HIV epidemic. Multisectoral interventions could have similar effects in southern Africa, especially by improving sexual and reproductive health services (such as condom promotion and provision, sexual health counselling and STI control), together with overarching structural interventions that transform sexual relations and reduce women's overall vulnerability. Thus far, however, the vigorous cultural and political leadership that would be required to alter sexual norms or to implement programmes such as male circumcision has been absent in southern Africa. This is consistent with the long-standing unwillingness of almost all leaders in this setting to spend political capital in addressing HIV. So thus it remains that the health sector's success in reducing the biomedical vulnerability of women is limited by a deep-rooted lack of women's social capital, income equality and sexual justice, in themselves highly important predictors of HIV [159,160].

Acknowledgements

Publication of this article was funded by UNAIDS.

Conflicts of interest: None.

References

1. UNAIDS, WHO. AIDS epidemic update: December 2007. Available at: http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdf. Accessed: August 2008.
2. Chen L, Jha P, Stirling B, Sgaier SK, Daid T, Kaul R, Nagelkerke N. Sexual risk factors for HIV infection in early and advanced HIV epidemics in sub-Saharan Africa: systematic overview of 68 epidemiological studies. PLoS ONE 2007; 2:e1001.
3. Steen R, Dallabetta G. Sexually transmitted infection control with sex workers: regular screening and presumptive treatment augment efforts to reduce risk and vulnerability. Reprod Health Matters 2003; 11:74–90.
4. Lurie MN, Williams BG, Zuma K, Mkaya-Mwamburi D, Garnett GP, Sweat MD, et al. Who infects whom? HIV-1 concordance and discordance among migrant and non-migrant couples in South Africa. AIDS 2003; 17:2245–2252.
5. O'Brien TR, Busch MP, Donegan E, Ward JW, Wong L, Samson SM, et al. Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners. J Acquir Immune Defic Syndr 1994; 7:705–710.
6. European Study Group on Heterosexual Transmission of HIV. Comparison of female to male and male to female transmission of HIV in 563 stable couples. BMJ 1992; 304:809–813.
7. Nicolosi A, Correa Leite ML, Musicco M, Arici C, Gavazzeni G, Lazzarin A. The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Italian Study Group on HIV Heterosexual Transmission. Epidemiology 1994; 5:570–575.
8. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191:1403–1409.
9. Seidlin M, Vogler M, Lee E, Lee YS, Dubin N. Heterosexual transmission of HIV in a cohort of couples in New York City. AIDS 1993; 7:1247–1254.
10. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000; 342:921–929.
11. Pilcher CD, Joaki G, Hoffman IF, Martinson FE, Mapanje C, Stewart PW, et al. Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS 2007; 21:1723–1730.
12. Cohen MS, Pilcher CD. Amplified HIV transmission and new approaches to HIV prevention. J Infect Dis 2005; 191:1391–1393.
13. Pilcher CD, Tien HC, Eron JJ Jr, Vernazza PL, Leu SY, Stewart PW, et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004; 189:1785–1792.
14. Motloung T, Myers M, Venter F, Delany S, Rees H, Stevens W. Identifying acute HIV infection – a major new public health challenge. S Afr Med J 2004; 94:531.
15. Halperin DT, Epstein H. Concurrent sexual partnerships help to explain Africa's high HIV prevalence: implications for prevention. Lancet 2004; 364:4–6.
16. Morris M, Kretzschmar M. Concurrent partnerships and the spread of HIV. AIDS 1997; 11:641–648.
17. Helleringer S, Kohler HP. Sexual network structure and the spread of HIV in Africa: evidence from Likoma Island, Malawi. AIDS 2007; 21:2323–2332.
18. de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med 1994; 331:341–346.
19. Reynolds SJ, Risbud AR, Shepherd ME, Rompalo AM, Ghate MV, Godbole SV, et al. High rates of syphilis among STI patients are contributing to the spread of HIV-1 in India. Sex Transm Infect 2006; 82:121–126.
20. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999; 75:3–17.
21. WHO, UNAIDS. Consultation on STI interventions for preventing HIV: appraisal of the evidence. Geneva: World Health Organization; 2007.
22. Global HIV Prevention Working Group. Bringing HIV prevention to scale: an urgent global priority. 2007. Available at: www.GlobalHIVPrevention.org.
23. Watson-Jones D, Weiss HA, Rusizoka M, Baisley K, Mugeye K, Changalucha J, et al. Risk factors for herpes simplex virus type 2 and HIV among women at high risk in northwestern Tanzania: preparing for an HSV-2 intervention trial. J Acquir Immune Defic Syndr 2007; 46:631–642.
24. Reynolds SJ, Risbud AR, Shepherd ME, Zenilman JM, Brookmeyer RS, Paranjape RS, et al. Recent herpes simplex virus type 2 infection and the risk of human immunodeficiency virus type 1 acquisition in India. J Infect Dis 2003; 187:1513–1521.
25. Shepherd ME, Gangakhedkar RR, Sahay S, Reynolds SJ, Ghate MV, Risbud AR, et al. Incident HIV infection among men attending STD clinics in Pune, India: pathways to disparity and interventions to enhance equity. J Health Popul Nutr 2003; 21:251–263.
26. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006; 20:73–83.
27. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis 2002; 185:45–52.
28. Celum C, Wald A, Hughes J, Sanchez J, Reid S, Delany-Moretlwe S, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 371:2109–2119.
29. Watson-Jones D, Weiss HA, Rusizoka M, Changalucha J, Baisley K, Mugeye K, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med 2008; 358:1560–1571.
30. Delany S, Mayaud P, Clayton T, Mlaba N, Akpomiemie G, Hira K, et al. Impact of HSV-2 suppressive therapy on genital and plasma HIV-1 RNA in HIV-1 and HSV-2 seropositive women not taking ART: a randomized placebo-controlled trial in Johannesburg, South Africa. Presented at the 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles, CA, USA, 25-28 February 2007 [Abstract 154LB].
31. Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med 2007; 356:790–799.
32. Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Zuniga R, et al. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis 2007; 196:1500–1508.
33. Baeten JM, Strick LB, Lucchetti A, Whittington WJH, Sanchez J, Coombs RM, et al. Herpes simplex virus suppressive treatment decreases plasma HIV-1 viral load in HSV-2/HIV-1 co-infected women: a randomised, placebo-controlled, cross-over trial. Presented at the 17th International Society for Sexually Transmitted Diseases Research Meeting. Seattle, WA, USA, 29 July–1 August 2007 [Abstract 96].
34. Atashili J, Poole C, Ndumbe PM, Adimora AA, Smith JS. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS 2008; 22:1493–1501.
35. Taha TE, Dallabetta GA, Hoover DR, Chiphangwi JD, Mtimavalye LA, Liomba GN, et al. Trends of HIV-1 and sexually transmitted diseases among pregnant and postpartum women in urban Malawi. AIDS 1998; 12:197–203.
36. van de Wijgert JH, Morrison CS, Cornelisse PG, Munjoma M, Moncada J, Awio P, et al. Bacterial vaginosis and vaginal yeast, but not vaginal cleansing, increase HIV-1 acquisition in African women. J Acquir Immune Defic Syndr 2008; 48:203–210.
37. Martin HL, Richardson BA, Nyange PM, Lavreys L, Hillier SL, Chohan B, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 1999; 180:1863–1868.
38. Myer L, Denny L, Telerant R, Souza M, Wright TC Jr, Kuhn L. Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case–control study. J Infect Dis 2005; 192:1372–1380.
39. St John E, Mares D, Spear GT. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4:22–28.
40. Ghys PD, Diallo MO, Ettiegne-Traore V, Satten GA, Anoma CK, Maurice C, et al. Effect of interventions to control sexually transmitted disease on the incidence of HIV infection in female sex workers. AIDS 2001; 15:1421–1431.
41. Kapiga SH, Sam NE, Bang H, Ni Q, Ao TTH, Kiwelu I, et al. The role of herpes simplex virus type 2 and other genital infections in the acquisition of HIV-1 among high-risk women in northern Tanzania. J Infect Dis 2007; 195:1260–1269.
42. Kleinschmidt I, Rees H, Delany S, Smith D, Dinat N, Nkala B, McIntyre JA. Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort. Contraception 2007; 75:461–467.
43. McClelland RS, Sangare L, Hassan WM, Lavreys L, Mandaliya K, Kiarie J, et al. Infection with trichomonas vaginalis increases the risk of HIV-1 acquisition. J Infect Dis 2007; 195:698–702.
44. Myer L, Denny L, de Souza M, Wright TC Jr, Kuhn L. Distinguishing the temporal association between women's intravaginal practices and risk of human immunodeficiency virus infection: a prospective study of South African women. Am J Epidemiol 2006; 163:552–560.
45. Taha TE, Hoover DR, Dallabetta GA, Kumwenda NI, Mtimavalye LA, Yang LP, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998; 12:1699–1706.
46. Van Der Pol B, Kwok C, Pierre-Louis B, Rinaldi A, Salata RA, Chen PL, et al. Trichomonas vaginalis infection and human immunodeficiency virus acquisition in African women. J Infect Dis 2008; 197:548–554.
47. Martin HL Jr, Nyange PM, Richardson BA, Lavreys L, Mandaliya K, Jackson DJ, et al. Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1. J Infect Dis 1998; 178:1053–1059.
48. Hester RA, Kennedy SB. Candida infection as a risk factor for HIV transmission. J Womens Health (Larchmt) 2003; 12:487–494.
49. van de Wijgert J, Morrison C, Cornelisse P, Munjoma M, Moncada J, Kaewvichit R, et al. Bacterial vaginosis and vaginal yeast, but not vaginal cleansing, increase HIV-1 acquisition in African women. J Acquir Immune Defic Syndr 2008; 48:203–210.
50. Measure DHS. Demographic and health surveys. Available at: http://www.measuredhs.com/accesssurveys/. Accessed: August 2008.
51. Hilber AM, Chersich MF, van de Wijgert JH, Rees H, Temmerman M. Vaginal practices, microbicides and HIV: what do we need to know? Sex Transm Infect 2007; 83:505–508.
52. Kunene B, Manzini N, Scorgie F, Chersich MF, Smit J. Prevalence of vaginal practices in KwaZulu–Natal, South Africa: results of a household survey. In: Microbicides 2008 Conference. New Delhi, India, 24–27 February 2008 [Abstract TC 591].
53. Beksinska ME, Rees HV, Kleinschmidt I, McIntyre J. The practice and prevalence of dry sex among men and women in South Africa: a risk factor for sexually transmitted infections? Sex Transm Infect 1999; 75:178–180.
54. van De Wijgert JH, Mason PR, Gwanzura L, Mbizvo MT, Chirenje ZM, Iliff V, et al. Intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in Zimbabwean women. J Infect Dis 2000; 181:587–594.
55. Kilmarx PH, Limpakarnjanarat K, Supawitkul S, Korattana S, Young NL, Parekh BS, et al. Mucosal disruption due to use of a widely-distributed commercial vaginal product: potential to facilitate HIV transmission. AIDS 1998; 12:767–773.
56. McClelland RS, Ndinya-Achola JO, Baeten JM. ‘Is vaginal washing associated with increased risk of HIV-1 acquisition?’ [Correspondence]. AIDS 2006; 20:1347–1348.
57. Hassan WM, Lavreys L, Chohan V, Richardson BA, Mandaliya K, Ndinya-Achola JO, et al. Associations between intravaginal practices and bacterial vaginosis in Kenyan female sex workers without symptoms of vaginal infections. Sex Transm Dis 2007; 34:384–388.
58. Simpson T, Merchant J, Grimley DM, Oh MK. Vaginal douching among adolescent and young women: more challenges than progress. J Pediatr Adolesc Gynecol 2004; 17:249–255.
59. Wilkinson D, Ramjee G, Tholandi M, Rutherford G. Nonoxynol-9 for preventing vaginal acquisition of sexually transmitted infections by women from men. Cochrane Database Syst Rev 2002; CD003939.
60. McClelland RS, Lavreys L, Hassan WM, Mandaliya K, Ndinya-Achola JO, Baeten JM. Vaginal washing and increased risk of HIV-1 acquisition among African women: a 10-year prospective study. AIDS 2006; 20:269–273.
61. Myer L, Denny L, de Souza M, Wright TC Jr, Kuhn L. Distinguishing the temporal association between women's intravaginal practices and risk of human immunodeficiency virus infection: a prospective study of South African women. Am J Epidemiol 2006; 163:552–560.
62. Gray RH, Li X, Kigozi G, Serwadda D, Brahmbhatt H, Wabwire-Mangen F, et al. Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study. Lancet 2005; 366:1182–1188.
63. Leroy V, Van de Perre P, Lepage P, Saba J, Nsengumuremyi F, Simonon A, et al. Seroincidence of HIV-1 infection in African women of reproductive age: a prospective cohort study in Kigali, Rwanda, 1988–1992. AIDS 1994; 8:983–986.
64. Mbizvo MT, Kasule J, Mahomed K, Nathoo K. HIV-1 seroconversion incidence following pregnancy and delivery among women seronegative at recruitment in Harare, Zimbabwe. Cent Afr J Med 2001; 47:115–118.
65. Morrison CS, Wang J, Van Der Pol B, Padian N, Salata RA, Richardson BA. Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe. AIDS 2007; 21:1027–1034.
66. Baeten JM, Benki S, Chohan V, Lavreys L, McClelland RS, Mandaliya K, et al. Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women. AIDS 2007; 21:1771–1777.
67. Wang CC, Reilly M, Kreiss JK. Risk of HIV infection in oral contraceptive pill users: a meta-analysis. J Acquir Immune Defic Syndr 1999; 21:51–58.
68. Morrison CS, Richardson BA, Mmiro F, Chipato T, Celentano DD, Luoto J, et al. Hormonal contraception and the risk of HIV acquisition. AIDS 2007; 21:85–95.
69. Kleinschmidt I, Rees H, Delany S, Smith D, Dinat N, Nkala B, McIntyre JA. Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort. Contraception 2007; 75:461–467.
70. Myer L, Denny L, Wright TC, Kuhn L. Prospective study of hormonal contraception and women's risk of HIV infection in South Africa. Int J Epidemiol 2007; 36:166–174.
71. Kiddugavu M, Makumbi F, Wawer MJ, Serwadda D, Sewankambo NK, Wabwire-Mangen F, et al. Hormonal contraceptive use and HIV-1 infection in a population-based cohort in Rakai, Uganda. AIDS 2003; 17:233–240.
72. Jacobson DL, Peralta L, Farmer M, Graham NM, Gaydos C, Zenilman J. Relationship of hormonal contraception and cervical ectopy as measured by computerized planimetry to chlamydial infection in adolescents. Sex Transm Dis 2000; 27:313–319.
73. Michael CW, Esfahani FM. Pregnancy-related changes: a retrospective review of 278 cervical smears. Diagn Cytopathol 1997; 17:99–107.
74. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003; 38:13–22.
75. Brabin L. Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression. AIDS Patient Care STDS 2002; 16:211–221.
76. Prakash M, Patterson S, Gotch F, Kapembwa MS. Ex vivo analysis of HIV-1 co-receptors at the endocervical mucosa of women using oral contraceptives. Br J Obstet Gynaecol 2004; 111:1468–1470.
77. Yeaman GR, Guyre PM, Fanger MW, Collins JE, White HD, Rathbun W, et al. Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium. J Leukoc Biol 1997; 61:427–435.
78. Myer L, Wright TC Jr, Denny L, Kuhn L. Nested case–control study of cervical mucosal lesions, ectopy, and incident HIV infection among women in Cape Town, South Africa. Sex Transm Dis 2006; 33:683–687.
79. Chersich MF, Luchters SM, Yard E, Othigo JM, Kley N, Temmerman M. Morbidity in the first year postpartum among HIV-infected women in Kenya. Int J Gynaecol Obstet 2008; 100:45–51.
80. Myer L, Mathews C, Little F. Condom use and sexual behaviors among individuals procuring free male condoms in South Africa: a prospective study. Sex Transm Dis 2002; 29:239–241.
81. Aklilu M, Messele T, Tsegaye A, Biru T, Mariam DH, van Benthem B, et al. Factors associated with HIV-1 infection among sex workers of Addis Ababa, Ethiopia. AIDS 2001; 15:87–96.
82. Sarkar K, Bal B, Mukherjee R, Saha MK, Chakraborty S, Niyogi SK, Bhattacharya SK. Young age is a risk factor for HIV among female sex workers–-an experience from India. J Infect 2006; 53:255–259.
83. Pettifor AE, Hudgens MG, Levandowski BA, Rees HV, Cohen MS. Highly efficient HIV transmission to young women in South Africa. AIDS 2007; 21:861–865.
84. Gopinath R, Ostrowski M, Justement SJ, Fauci AS, Nutman TB. Filarial infections increase susceptibility to human immunodeficiency virus infection in peripheral blood mononuclear cells in vitro. J Infect Dis 2000; 182:1804–1808.
85. Bentwich Z, Maartens G, Torten D, Lal AA, Lal RB. Concurrent infections and HIV pathogenesis. AIDS 2000; 14:2071–2081.
86. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 2006; 367:1521–1532.
87. Borkow G, Bentwich Z. HIV and helminth co-infection: is deworming necessary? Parasite Immunol 2006; 28:605–612.
88. Fauci AS. Pathogenesis of HIV disease: opportunities for new prevention interventions. Clin Infect Dis 2007; 45(Suppl. 4):S206–S212.
89. Hotez P, Stoever K, Fenwick A, Molyneux D, Savioli L. The Lancet's chronic diseases series. Lancet 2006; 367:563–564, author reply 564–565.
90. Hotez PJ, Molyneux DH, Stillwaggon E, Bentwich Z, Kumaresan J. Neglected tropical diseases and HIV/AIDS. Lancet 2006; 368:1865–1866.
91. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med 2005; 2:e298.
92. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369:643–656.
93. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369:657–666.
94. Williams BG, Lloyd-Smith JO, Gouws E, Hankins C, Getz WM, Hargrove J, et al. The potential impact of male circumcision on HIV in Sub-Saharan Africa. PLoS Med 2006; 3:e262.
95. WHO, UNAIDS. New data on male circumcision and HIV prevention: policy and programme implications. 2007. Available at: http://www.who.int/hiv/mediacentre/MCrecommendations_en.pdf. Accessed: August 2008.
96. UNAIDS. Male circumcision: global trends and determinants of prevalence, safety and acceptability. 2007. Available at: http://www.who.int/hiv/topics/malecircumcision/JC1320_MaleCircumcision_Final_UNAIDS.pdf. Accessed: August 2008.
97. UNAIDS. HIV prevention needs and successes: a tale of three countries – an update on HIV prevention success in Senegal, Thailand and Uganda. Geneva: UNAIDS; 2001.
98. UNAIDS. Evidence for HIV decline in Zimbabwe: a comprehensive review of the epidemiological data. Geneva: UNAIDS; 2005.
99. WHO, UNAIDS, UNFPA. Position statement on condoms and HIV prevention. 2004. Available at: http://www.who.int/reproductive-health/stis/docs/condom_statement04.pdf. Accessed: August 2008.
100. Balaji A, Lowry R, Brener N, Kann L, Romero R, Wechsler H. Trends in HIV- and STD-related risk behaviors among high school students – United States, 1991–2007. MMWR Morb Mortal Wkly Rep 2008; 57:817–822.
101. Johnson AM, Mercer CH, Erens B, Copas AJ, McManus S, Wellings K, et al. Sexual behaviour in Britain: partnerships, practices, and HIV risk behaviours. Lancet 2001; 358:1835–1842.
102. Pettifor AE, Rees HV, Kleinschmidt I, Steffenson AE, MacPhail C, Hlongwa-Madikizela L, et al. Young people's sexual health in South Africa: HIV prevalence and sexual behaviors from a nationally representative household survey. AIDS 2005; 19:1525–1534.
103. Snelling D, Rasugu Omariba DW, Hong S, Georgiades K, Racine Y, Boyle MH. HIV/AIDS knowledge, women's education, epidemic severity and protective sexual behaviour in low- and middle-income countries. J Biosoc Sci 2007; 39:421–442.
104. Mah TL, Halperin DT. Concurrent sexual partnerships and the HIV epidemics in Africa: evidence to move forward. AIDS Behav 2008; [Epub ahead of print].
105. Mabey D, Mayaud P. Sexually transmitted diseases in mobile populations. Genitourin Med 1997; 73:18–22.
106. Mbizvo MT, Machekano R, McFarland W, Ray S, Bassett M, Latif A, Katzenstein D. HIV seroincidence and correlates of seroconversion in a cohort of male factory workers in Harare, Zimbabwe. AIDS 1996; 10:895–901.
107. Shisana O, Rehle T, Simbayi L, Parker W, Zuma K, Bhana A, et al.South African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey. Cape Town: HSRC Press; 2005. Available at: http://www.hsrcpress.ac.za/product.php?productid=2134&freedownload=1
108. Maharaj P, Cleland J. Risk perception and condom use among married or cohabiting couples in KwaZulu–Natal, South Africa. Int Fam Plan Perspect 2005; 31:24–29.
109. Prata N, Morris L, Mazive E, Vahidnia F, Stehr M. Relationship between HIV risk perception and condom use: evidence from a population-based survey in Mozambique. Int Fam Plan Perspect 2006; 32:192–200.
110. Lane T, Pettifor A, Pascoe S, Fiamma A, Rees H. Heterosexual anal intercourse increases risk of HIV infection among young South African men. AIDS 2006; 20:123–125.
111. Simbayi LC, Kalichman SC, Jooste S, Cherry C, Mfecane S, Cain D. Risk factors for HIV–AIDS among youth in Cape Town, South Africa. AIDS Behav 2005; 9:53–61.
112. Karim SS, Ramjee G. Anal sex and HIV transmission in women. Am J Public Health 1998; 88:1265–1266.
113. Stadler JJ, Delany S, Mntambo M. Sexual coercion and sexual desire: ambivalent meanings of heterosexual anal sex in Soweto, South Africa. AIDS Care 2007; 19:1189–1193.
114. Ndinda C, Chimbwete C, McGrath N, Pool R. Perceptions of anal sex in rural South Africa. Cult Health Sex 2008; 10:205–212.
115. Kalichman SC, Simbayi LC, Cain D, Cherry C, Jooste S. Coital bleeding and HIV risks among men and women in Cape Town, South Africa. Sex Transm Dis 2006; 33:551–557.
116. Tanfer K, Aral SO. Sexual intercourse during menstruation and self-reported sexually transmitted disease history among women. Sex Transm Dis 1996; 23:395–401.
117. Kalichman SC, Simbayi LC. Sexual exposure to blood and increased risks for heterosexual HIV transmission in Cape Town, South Africa. Afr J Reprod Health 2004; 8:55–58.
118. Campo J, Perea MA, del Romero J, Cano J, Hernando V, Bascones A. Oral transmission of HIV, reality or fiction? An update. Oral Dis 2006; 12:219–228.
119. del Romero J, Marincovich B, Castilla J, Garcia S, Campo J, Hernando V, Rodriguez C. Evaluating the risk of HIV transmission through unprotected orogenital sex. AIDS 2002; 16:1296–1297.
120. Scully C, Porter S. HIV topic update: oro-genital transmission of HIV. Oral Dis 2000; 6:92–98.
121. Rehm J, Gmel G, Room R, Frick U. Average volume of alcohol consumption, drinking patterns and related burden of mortality in young people in established market economies of Europe. Eur Addict Res 2001; 7:148–151.
122. Rehm J, Room R, Graham K, Monteiro M, Gmel G, Sempos CT. The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease: an overview. Addiction 2003; 98:1209–1228.
123. World Health Organization. Surveys of drinking patterns and problems in seven developing countries. WHO monograph on alcohol epidemiology in developing countries. Geneva: WHO; 2000.
124. Rehm J, Rehn N, Room R, Monteiro M, Gmel G, Jernigan D, Frick U. The global distribution of average volume of alcohol consumption and patterns of drinking. Eur Addict Res 2003; 9:147–156.
125. Fisher JC, Bang H, Kapiga SH. The association between HIV infection and alcohol use: a systematic review and meta-analysis of African studies. Sex Transm Dis 2007; 34:856–863.
126. Fisher JC, Cook PA, Sam NE, Kapiga SH. Patterns of alcohol use, problem drinking, and HIV infection among high-risk African women. Sex Transm Dis 2008; 35:537–544.
127. Chersich MF, Luchters SMF, Malonza IM, Mwarogo P, King'ola N, Temmerman M. Heavy episodic drinking among Kenyan female sex workers is associated with unsafe sex, sexual violence and sexually transmitted infections. Int J STD AIDS 2007; 18:764–769.
128. Graham K, West P, Wells S. Evaluating theories of alcohol-related aggression using observations of young adults in bars. Addiction 2000; 95:847–863.
129. Pihl RO, Peterson JB, Lau MA. A biosocial model of the alcohol–aggression relationship. J Stud Alcohol Suppl 1993; 11:128–139.
130. Parsons JT, Vicioso K, Kutnick A, Punzalan JC, Halkitis PN, Velasquez MM. Alcohol use and stigmatized sexual practices of HIV seropositive gay and bisexual men. Addict Behav 2004; 29:1045–1051.
131. Lugalla J, Emmelin M, Mutembei A, Sima M, Kwesigabo G, Killewo J, Dahlgren L. Social, cultural and sexual behavioral determinants of observed decline in HIV infection trends: lessons from the Kagera Region, Tanzania. Soc Sci Med 2004; 59:185–198.
132. Chisholm D, Rehm J, Van Ommeren M, Monteiro M. Reducing the global burden of hazardous alcohol use: a comparative cost-effectiveness analysis. J Stud Alcohol 2004; 65:782–793.
133. 61st World Health Assembly. Strategies to reduce the harmful use of alcohol: report by the Secretariat. 2008. Available at: http://www.who.int/gb/ebwha/pdf_files/A61/A61_13-en.pdf. Accessed: August 2008.
134. World Health Organization. Brief intervention for hazardous and harmful drinking. A manual for use in primary care. Geneva: WHO; 2001.
135. WHO, ILO. Joint WHO/ILO guidelines on post-exposure prophylaxis (PEP) to prevent HIV infection. 2007. Available at: http://whqlibdoc.who.int/publications/2007/9789241596374_eng.pdf. Accessed: August 2008.
136. Chesson HW. Cost effectiveness of one to one STI prevention interventions. Sex Transm Infect 2007; 83:423–424.
137. Kamb ML, Fishbein M, Douglas JM Jr, Rhodes F, Rogers J, Bolan G, et al. Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted diseases: a randomized controlled trial. Project RESPECT Study Group. JAMA 1998; 280:1161–1167.
138. Chersich M, Temmerman M. Increasing access to HIV testing for women by simplifying pre- and post-test counselling. Curr Women's Health Rev 2008; in press.
139. World Health Organization. Reproductive health matters for the World Health Organisation. Beyond acceptability: users' perspectives on contraception. Geneva: WHO; 1997.
140. Thomsen SC, Ombidi W, Toroitich-Ruto C, Wong EL, Tucker HO, Homan R, et al. A prospective study assessing the effects of introducing the female condom in a sex worker population in Mombasa, Kenya. Sex Transm Infect 2006; 82:397–402.
141. Vijayakumar G, Mabude Z, Smit J, Beksinska M, Lurie M. A review of female-condom effectiveness: patterns of use and impact on protected sex acts and STI incidence. Int J STD AIDS 2006; 17:652–659.
142. De Cock KM, Marum E, Mbori-Ngacha D. A serostatus-based approach to HIV/AIDS prevention and care in Africa. Lancet 2003; 362:1847–1849.
143. Janssen RS, Holtgrave DR, Valdiserri RO, Shepherd M, Gayle HD, De Cock KM. The serostatus approach to fighting the HIV epidemic: prevention strategies for infected individuals. Am J Public Health 2001; 91:1019–1024.
144. Koblin B, Chesney M, Coates T. Effects of a behavioural intervention to reduce acquisition of HIV infection among men who have sex with men: the EXPLORE randomised controlled study. Lancet 2004; 364:41–50.
145. WHO, PEPFAR, UNAIDS. Task shifting: rational redistribution of tasks among health workforce teams. Global recommendations and guidelines. Geneva: WHO; 2008.
146. Gregson S, Adamson S, Papaya S, Mundondo J, Nyamukapa CA, Mason PR, et al. Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe. PLoS Med 2007; 4:e102.
147. Grosskurth H, Mosha F, Todd J, Senkoro K, Newell J, Klokke A, et al. A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 2. Baseline survey results. AIDS 1995; 9:927–934.
148. Kamali A, Quigley M, Nakiyingi J, Kinsman J, Kengeya-Kayondo J, Gopal R, et al. Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial. Lancet 2003; 361:645–652.
149. Kaul R, Kimani J, Nagelkerke NJ, Fonck K, Ngugi EN, Keli F, et al. Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. JAMA 2004; 291:2555–2562.
150. Wawer MJ, Sewankambo NK, Serwadda D, Quinn TC, Paxton LA, Kiwanuka N, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 1999; 353:525–535.
151. Orroth KK, White RG, Korenromp EL, Bakker R, Changalucha J, Habbema JD, Hayes RJ. Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: simulation results. Sex Transm Dis 2006; 33:536–544.
152. Voeten HA, O'Hara HB, Kusimba J, Otido JM, Ndinya-Achola JO, Bwayo JJ, et al. Gender differences in health care-seeking behavior for sexually transmitted diseases: a population-based study in Nairobi, Kenya. Sex Transm Dis 2004; 31:265–272.
153. Paz-Bailey G, Rahman M, Chen C, Ballard R, Moffat HJ, Kenyon T, et al. Changes in the etiology of sexually transmitted diseases in Botswana between 1993 and 2002: implications for the clinical management of genital ulcer disease. Clin Infect Dis 2005; 41:1304–1312.
154. Krishnan S, Dunbar MS, Minnis AM, Medlin CA, Gerdts CE, Padian NS. Poverty, gender inequities and women's risk of HIV/AIDS. Ann NY Acad Sci 2008; 1136:101–110.
155. Dunkle KL, Jewkes R, Nduna M, Jama N, Levin J, Sikweyiya Y, Koss MP. Transactional sex with casual and main partners among young South African men in the rural Eastern Cape: prevalence, predictors, and associations with gender-based violence. Soc Sci Med 2007; 65:1235–1248.
156. Dunkle KL, Jewkes RK, Brown HC, Gray GE, McIntryre JA, Harlow SD. Transactional sex among women in Soweto, South Africa: prevalence, risk factors and association with HIV infection. Soc Sci Med 2004; 59:1581–1592.
157. Wojcicki JM. She drank his money”: survival sex and the problem of violence in taverns in Gauteng province, South Africa. Med Anthropol Q 2002; 16:267–293.
158. Chersich MF, Luchters SM, Othigo MJ, Yard E, Mandaliya K, Temmerman M. HIV testing and counselling for women attending child health clinics: an opportunity for entry to prevent mother-to-child transmission and HIV treatment. Int J STD AIDS 2008; 19:42–46.
159. Crosby RA, Holtgrave DR. The protective value of social capital against teen pregnancy: a state-level analysis. J Adolesc Health 2006; 38:556–559.
160. Holtgrave DR, Crosby RA. Social capital, poverty, and income inequality as predictors of gonorrhoea, syphilis, chlamydia and AIDS case rates in the United States. Sex Transm Infect 2003; 79:62–64.
Keywords:

biological factors; HIV prevention; primary prevention; safe sex; sexual behaviour; women's health

© 2008 Lippincott Williams & Wilkins, Inc.