The Global Plan towards eliminating HIV infections among children by 2015 and keeping their mothers alive (Global Plan) revolved around 4 prongs: (1) prevent HIV among women of reproductive age; (2) prevent unintended pregnancies among women living with HIV; (3) prevent HIV transmission through the use of antiretroviral medicines during pregnancy and breastfeeding; and (4) provide treatment, care, and support for mothers living with HIV, their children, partners, and families.1 Since the launch of the Global Plan, coverage of services to prevent mother-to-child transmission of HIV increased dramatically, reaching 77% in 2015. As a result, new HIV infections among children aged 0–14 years have declined by 51% since 2010. In addition, the number of children aged 0–14 years on antiretroviral therapy globally has increased from 452,000 children in 2010 to 910,000 children by 2016, reducing AIDS-related deaths among children by 44%.2 The substantial reductions in new HIV infections among children and huge declines in AIDS-related deaths among infants were because of the early initiation of antiretroviral therapy for infants infected with HIV based on compelling scientific evidence and the implementation of prong 3 and prong 4. In contrast, progress made in keeping mothers alive has been limited primarily because of challenges in preventing HIV infection in women and operational challenges in implementing prongs 1 and 2 (and facets of prong 4), most notably in relation to treatment, care, and support of mothers living with HIV, their partners, and families. These limitations have been most pronounced in the high HIV burden settings of eastern and southern Africa.
The rationale for prongs 1 and 2 is based on scientific evidence and is an effective strategy for indirectly preventing infants from acquiring HIV.1 It also is an important opportunity to engage and link women to essential HIV prevention, treatment, care, and sexual and reproductive health services. However, adolescent girls and young women—particularly unmarried pregnant teenagers and/or survivors of sexual abuse—are less likely than older women to use the appropriate and available prevention or treatment services.
Given that entry into prevention of mother-to-child transmission (PMTCT) programs is usually through antenatal services, adolescent girls and young women who do not access antenatal care services also will not access PMTCT services. Furthermore, a study in KwaZulu-Natal among 19,093 women found that even when adolescent girls do access antenatal care during pregnancy, they do not always receive the appropriate HIV treatment and prevention services. There was also an apparent age disparity, where the HIV transmission rate at 4–8 weeks of age was significantly higher among infants of adolescent mothers than among infants of older mothers (OR: 1.7, 95% CI: 1.2 to 2.4).3
Notably, there has been insufficient progress in HIV prevention options for adolescent girls. As we move into the post-Global Plan era, particular attention needs to turn to 3 groups of adolescents: (1) children infected at birth or in infancy who are now transitioning to adolescence; (2) those who are HIV-negative but at high risk of acquiring HIV because of social circumstances (eg, AIDS orphans and children of child-headed households); and (3) other adolescents who engage in high-risk behavior.
In this study, we draw attention to the complexities associated with adolescence, describe factors impacting the risk of acquiring HIV among adolescents, and discuss the progress made both in preventing HIV in adolescent girls and young women—with specific reflections on its implications for fully realizing the goal of eliminating HIV among infants and keeping their mothers alive—and in sustaining the gains and progress made to date.
EPIDEMIOLOGY OF HIV IN ADOLESCENT GIRLS AND YOUNG WOMEN
Although global HIV trends indicate a decline in the number of new cases of HIV infection (from 3.4 million in 2001 to 2.1 million in 2015), these trends mask the continued spread of HIV in certain regions, populations, and age groups.4 Of the 10 countries that contribute two-thirds of all HIV infections globally, 7 are in eastern and southern Africa.5 In these regions, women account for 59% of all people living with HIV, and adolescent girls and young women aged 15–24 years are particularly vulnerable (Table 1). Of the estimated 3.9 million young people aged 15–24 years living with HIV in 2014, 2.3 million (58%) were young women. Throughout sub-Saharan Africa, HIV prevalence among adolescent girls and young women exceeds that of their male peers, with HIV prevalence up to 6 times higher in South Africa (Box 1).18 Although the cause of this vulnerability has not been fully elucidated, it is compounded by structural, social, and biological factors.
Focus on KwaZulu-Natal, South Africa
South Africa accounts for 18% of the global burden of HIV infection, with about 1000 new infections each day.6 The province of KwaZulu-Natal is at the epicenter of the pandemic: 4 of its 11 districts have HIV prevalence among pregnant women of greater than 40%, and the remaining 7 districts having an HIV prevalence between 35.9% and 39.9%.7
IMPORTANCE OF AGE STRATIFICATION
HIV surveillance in pregnant women and repeated cross-sectional studies conducted over the past decade in the high burden KwaZulu-Natal subdistrict of uMgungundlovu show that, although HIV prevalence has remained stable over recent years, incidence rates remain unacceptably high in women below 30 years of age. In the uMgungundlovu subdistrict, by age 16, 1 in every 10 women coming to antenatal services are already infected with HIV. This increases to 1 in 3 by age 20 and 1 in 2 by age 24 (see table below).8 A survey conducted among high school students in this subdistrict found that HIV prevalence in girls was 6-fold higher than in boys. An age-specific breakdown from this survey indicates that by age 18, 7.1% of girls are infected with HIV; by age 25, this increases to 24%.9 Several other cohort and longitudinal studies in South Africa show high HIV incidence rates among young women.10–16 High HIV incidence rates also have been observed in postpartum women in periurban communities in KwaZulu-Natal.17
HIV in Pregnant Women in the uMgungundlovu Subdistrict, KwaZulu-Natal, South Africa (2001–2013)
FACTORS CONTRIBUTING TO THE INCREASED VULNERABILITY OF YOUNG WOMEN IN ACQUIRING HIV
Adolescence and the Complexities of the Transition to Adulthood
Adolescence is a development phase characterized by increased risk-taking, instant gratification, and greater peer influence in decision-making. During this time, new boundaries are explored, and parental and societal rules and norms that were unchallenged during childhood are reexamined, questioned, and/or defied in preparation for adulthood and autonomy.19 The period of adolescence is associated with complex emotional, physical, and cognitive changes.20
Vulnerabilities in youth often are exacerbated by the interaction of the effects of social disparities and the realities of everyday life. Sexual risk-taking in settings where HIV infection is rare has a different impact and implication when compared to communities with a high prevalence of HIV, where the probability of acquiring HIV is substantially higher. In addition, where social disparities exist—for example in relation to access to health services—the outcomes from exposure to HIV or being infected also are different.21,22
Although adolescents comprise about 25% of the global population, sub-Saharan Africa is the only region in the world where more than one-third of the population is between 10 and 24 years of age, creating what is referred to as the “youth bulge” in the population pyramid.23 The implications of a high burden of HIV in adolescent girls and young women, together with increased HIV-related morbidity and mortality rates, have profound social implications in this setting given the central and critical social and economic role of women in society. This situation is exacerbated by an emerging trend of convergence between communicable and noncommunicable diseases.22 Concerted effort and investment are needed to ensure that equal numbers of young boys and girls in sub-Saharan Africa are able to enter adulthood healthy and realize their full potential. The age–sex disparities in HIV infection and survival being experienced, notably in eastern and southern Africa, pose a significant threat to social cohesion and economic development in the region, both immediately and in the long term, and they require urgent attention.
The “youth bulge,” in combination with the delayed rollout of treatment with antiretroviral medicines that led to the loss of several hundreds of thousands of parents from AIDS-related causes, contributed to a significant increase in child-headed households in sub-Saharan Africa.24 The implications of this situation are manifold, and they include poverty, concerns about livelihood, precocious familial responsibilities, and isolation and marginalization because of social stigma and discrimination. All of these implications impact the sexual decisions of adolescent girls and young women differently compared with boys. In some instances, this can lead to sex for survival or increased exposure to gender-based violence, which in turn has consequences that include sexually transmitted infections (STIs) and pregnancy.25 Young women in child-headed and poor households are especially vulnerable to acquiring HIV.
Sexual Coupling Patterns
In sub-Saharan Africa, adolescent girls and young women tend to acquire HIV infection at a much earlier age than their male peers.26,27 This age–sex disparity in infection rates is a consequence of young girls partnering with men who are about 5–10 years older than them, and who may have recently acquired HIV or who are already living with HIV but are not on treatment with antiretroviral medicines.28–31 Adolescent girls and young women engage in sexual relationships with older men for multiple reasons. Although some relationships are based on love or sexual curiosity, in some instances, particularly for those from impoverished backgrounds, young women may engage in transactional sex and form relationships with older men for financial and social security.32–34 Understanding the drivers of this partnering pattern and learning more about these male partners is critical for addressing the prevention needs of adolescent girls and young women.35
In addition to unknowingly choosing a sexual partner who may be already infected with HIV, early sexual debut, teen pregnancies, early school dropout, and sexual violence also increase the vulnerability of adolescent girls and young women to acquiring HIV infection and maintain them in vicious cycles of poverty and dependency.
Young people, on average, have their first sexual encounters during their teenage years: in sub-Saharan Africa, about 60% of young women are sexually active by the time they reach the age of 18 (Table 2). In this region, although unprotected sex between adolescent peers can result in pregnancy, HIV is rare. In contrast, sex with an older man is more likely to result in HIV acquisition and pregnancy. Data from South Africa show that women who have a young age of sexual debut are more likely to have an older first sexual partner and are more likely to have experienced sexual coercion.36 Early sexual debut has also been associated with subsequent sexual risk-taking, such as having multiple partners.28,37,38 Young people also are less likely to be experienced in discussing safe sex. Gender-power imbalances that exist in age-disparate relationships result in challenges for younger women in negotiating safer sex practices, including consistent condom use.
Adolescent girls and young women who engage in unprotected sex can become pregnant, which has the potential to adversely impact a young woman's opportunities for education, as it has been found that the majority of pregnant teenagers rarely return to school after childbirth.39 The vulnerability of teenage girls who drop out of school is further perpetuated as they transition to adulthood because of the limited economic options available or accessible to those who do not complete high school.
In addition to the economic disadvantages, pregnant adolescent girls below the age of 15 face a particularly high risk of maternal mortality. According to the United Nations Population Fund (UNFPA), girls below the age of 15 are 5 times as likely—and those aged 15–19 years are 2 times as likely—to die from complications of childbirth than women in their 20 seconds. A systematic analysis of population health data shows that complications in pregnancy and childbirth are one of the leading causes of death among adolescent girls in developing countries.40 Young women also are more likely than older women to seek abortions, particularly if the pregnancy is unintended. The estimated unintended pregnancy rate in Africa in 2008 was 86 per 1000 women, one-third of which were terminated through abortions, often under unsafe conditions.41 Globally, unsafe abortions are estimated to cause 70,000 maternal deaths each year.41 About 13% of the unsafe abortions that occur annually in the developing world (2.5 million of the approximately 19 million) are among adolescents.41
Provision of family planning and the prevention of unintended pregnancies is important for all women but especially for adolescent girls, who are at greater risk for pregnancy-related complications (such as obstetric hemorrhage and hypertension). Eliminating the unmet need for family planning among all women (including women living with HIV) is one prong of the Global Plan; however, the most recent population-based surveys show that most countries in eastern and southern Africa do not meet the need for family planning among at least 25% of all sexually active unmarried women (Table 2).
There is a bidirectional relationship between gender-based violence and HIV infection. Women who have been subjected to intimate partner violence or gender-based violence face an increased risk for acquiring HIV30,31,42,43 because they often adopt risky behaviors.44 A study in South Africa among 1099 women found an HIV incidence rate of 9.6 per 100 women-years of follow-up among women who reported more than 1 episode of intimate partner violence; this was compared with 5.2 per 100 women-years of follow-up among those who reported 1 or no episode (IRR: 1.51, 1.04–2.21, P = 0.032).42 In Rwanda, women who were HIV-positive were more likely to report a history of violent relationships (46% versus 29%) and sexual coercion by their partners (43% versus 29%) than those who were HIV-negative.45 A Tanzanian study found that women younger than 30 who were living with HIV were 10 times more likely to report at least 1 event of physical or sexual violence than HIV-negative women of similar age (OR: 9.99; 95% CI: 2.67 to 37.37).46
Biological Risk Factors
The high HIV incidence rates observed among adolescent girls and young women in sub-Saharan Africa suggest that factors beyond behavior may be contributing to the heightened vulnerability in this group. Women are biologically more vulnerable to HIV and are, on average, twice as likely as men to become infected after a single sexual encounter.47 The biological mechanisms that make women more vulnerable than men in acquiring HIV are in the process of being established, although one contributing factor could be that the large exposed mucosal surface of the vagina may facilitate HIV acquisition. Furthermore, the high levels of immune cell activation (which is the viral target for infection) in the female genital tract and the increased expression of HIV coreceptors in cervical cells (compared with foreskin cells) may explain why women have a higher per-act risk of HIV acquisition then men.48,49 Genital trauma experienced as a result of forced or unwanted sexual intercourse can facilitate HIV transmission.50
Inflammation in the female genital tract also may be an important risk factor: analysis of female genital tract samples from a recent microbicide trial that assessed tenofovir gel for HIV prevention showed that genital inflammation, defined by combinations of elevated proinflammatory cytokines, was associated with a 3-fold increase in the risk of HIV acquisition.51 The cause of this inflammation is still unclear, and a better understanding of the immunological basis of correlates of HIV transmission in young women could yield useful clues to future HIV prevention technologies and strategies.
Sexual debut also marks the initial exposure to a number of sexually transmitted pathogens, including viruses such as herpes simplex type-2 virus (HSV-2) and human papillomavirus (HPV), which have been associated with a 2-fold to 3-fold increased risk of HIV transmission.52,53
The use of injectable hormonal contraception, particularly depot-medroxyprogesterone acetate (DMPA), has recently emerged as a potential mediator of HIV risk. Although uncertainty remains about the association between DMPA use and HIV risk in young women, DMPA remains the most common choice of contraceptive in sub-Saharan Africa. A meta-analysis that included 18 studies has suggested that DMPA is associated with a moderate increase in the risk of HIV acquisition.54 Although we wait for definitive evidence of the association between DMPA and HIV risk from an ongoing randomized controlled trial, women at high risk of HIV using this method should be strongly advised to also use condoms (male or female). The United States Agency for International Development (USAID) has developed a strategic communication framework to guide country‐level activities to communicate the risks and benefits of hormonal contraception among women at risk of, or living with, HIV through the use of an easy-to-understand and comprehensive format.55
Limitations of Current HIV Prevention Options for Adolescent Girls and Young Women
Although the number of HIV prevention options has expanded, the number of strategies that empower women to directly control their risk of HIV remains quite limited. Numerous social and behavioral change interventions aimed at preventing HIV—including peer education, mass media communication, school-based sex education programs, and behavioral counseling—have been assessed.56 Although many of the studies result in slight improvements in behavioral outcomes (increased HIV knowledge, increased condom use, and a reduction in high-risk sexual behavior), few show a significant impact on biological outcomes (such as HIV incidence).
Campaigns promoting abstinence, mutual faithfulness, condom use, and circumcision also have had a limited impact on HIV incidence in young women. A systematic review that included 13 trials and 15,940 youths found that abstinence programs had no impact reducing unprotected vaginal sex, reducing the number of partners, increasing condom use, or delaying sexual initiation.57 Data from South Africa show that rates of reported early sexual debut (ie, before the age of 15 years) have remained almost stable at 10% since 2002.27
Male and female condoms are an essential component of HIV prevention programs. They are inexpensive and, when used correctly and consistently, provide protection against acquisition and transmission of HIV and a variety of other STIs, and against pregnancy.58 However, gender inequality and the threat of intimate partner violence also limit a women's ability to successfully negotiate condom use with male partners, to insist on mutual monogamy, or to convince partners to have an HIV test. Furthermore, medical male circumcision, which is widely promoted for HIV prevention in high HIV burden countries, primarily benefits the male partner. Any protective benefits for women are likely to be realized only 5 or more years later.59
Progress on Women-Initiated HIV Prevention Technologies
The development of HIV prevention strategies that can be directly controlled by women remains an important global goal. One promising HIV prevention option that could directly empower women to limit their HIV risk is the topical (microbicides) or oral use of antiretroviral-containing agents by HIV-uninfected persons, also referred to as preexposure prophylaxis (PrEP).
Although no topical microbicides are yet licensed or available, results from the CAPRISA 004 tenofovir gel trial provided proof-of-concept that topical antiretroviral microbicides, when used before and after sex, can reduce sexual transmission of HIV and HSV-2 in women.16 However, the 2 confirmatory trials—the FACTS 001 trial of pericoital gel use and the VOICE trial of daily tenofovir gel—were unable to confirm the CAPRISA 004 trial results.60,61 This may have been primarily because of suboptimal adherence: measurement of tenofovir concentrations in blood found that only 25% of women assigned to the tenofovir gel group in the VOICE trial and about half of the women in the FACTS 001 trial had detectable drug levels, meaning that most women in the trials did not take the study drug as prescribed.60,61
Given the adherence challenges, the field has shifted its focus to developing products that are long-acting and less user-dependent. Data from 2 efficacy trials evaluating the long-acting antiretroviral dapivirine intravaginal ring are encouraging and show that high levels of adherence are achievable (82% in ASPIRE and 73% in the IPM Ring study).62,63 The monthly dapivirine vaginal ring reduced HIV incidence rates by 27% in the MTN ASPIRE trial and 31% in the IPM Ring study.62,63 However, adherence (based on drug levels in plasma samples) was shown to be 2-fold to 4-fold lower in young women (<21 years) than older women; as a result, no protection was observed in young women.62 An open-label, posttrial access study is planned to further investigate this finding. If licensed, the product could become available as an HIV prevention option for women in about 4–5 years.
New formulations and delivery devices, such as PrEP injections lasting 2–3 months and implants lasting 6–12 months, are being evaluated. Furthermore, passive immunization studies using broadly neutralizing antibodies for HIV prevention are in development. Successful outcome of these trials could expand the prevention options for women and pave the way for multipurpose technologies that are being developed to simultaneously address HIV prevention, fertility control, and STI prevention for women.64
Several randomized double-blind, placebo-controlled trials in a range of settings and populations have demonstrated that oral PrEP, when used correctly and consistently, can prevent sexual transmission of HIV.65–70 Oral PrEP is an important HIV prevention option for women, and it is one of the few strategies that a woman can directly control. Oral PrEP is therefore a potentially promising strategy for reducing HIV among adolescent girls and young women. However, the evidence of efficacy in women is inconsistent.61,71 Although 2 trials (Partners PrEP68 and Botswana TDF269) have demonstrated a protective effect of oral PrEP ranging from 66% to 75% in women, 2 other trials (the FEMPrEP and VOICE trials) showed no protective effect of PrEP in this group.61,71 An analysis of drug concentrations revealed that less than 30% of the women in these trials were able to adhere to the prescribed intervention.71 The ADAPT Study (HPTN 067), conducted among women in Cape Town, has shown that young, single black women in South Africa can take and adhere to a daily regimen of PrEP.72 Nevertheless, consistent use is essential for the intervention to be effective. Notably, none of these trials included women under age 18 years. Data from the ongoing CHAMPS (“Pluspills”) study, which is the first adolescent PrEP study to be conducted in adolescent females globally, therefore will provide valuable information on the feasibility, acceptability, and use of oral PrEP in this vulnerable age group.73
Notwithstanding these challenges, the World Health Organization (WHO) released guidelines in 2015 on the use of oral PrEP containing tenofovir for HIV prevention to all populations at high risk of acquiring HIV and as part of combination prevention interventions.74 Several countries—including France, Kenya, South Africa, and the United States—have approved the use of oral tenofovir in combination with emtricitabine PrEP formulations for HIV prevention. The challenges are now to determine how best to implement PrEP services in populations that would benefit most and support high levels of adherence. Several combination HIV prevention and demonstration projects of oral PrEP have been initiated throughout the world to inform scale-up of PrEP in populations such as young women.
HIV Prevention Interventions to Address Structural Drivers of HIV
The use of microfinance, cash transfers, contingency management, and behavioral economics is a novel strategy being evaluated in several settings to incentivize safer HIV risk behaviors, particularly in settings where poverty, gender inequality, high school dropout rates, and other human rights violations are key drivers in HIV risk-taking.75 The use of contingency management has been successful in smoking cessation, adherence in substitution therapy, keeping girls in school, improving reproductive health outcomes, and enhancing childhood immunization coverage.76–80 The impact of cash transfers on reducing risky sexual behavior and HIV infection is mixed: some studies report reductions in risky sexual behavior among adolescents, such as delaying sexual debut, increasing condom use, and increasing retention in school.81 In South Africa, an assessment of a publically funded social grant program found that cash transfers were associated with a 51% decrease in transactional sex and a 71% reduction in age-disparate sex among girls, but that they had no impact among boys.82 A cluster randomized controlled trial in Malawi of cash incentives for school attendance resulted in lower HIV prevalence at 18 months in the intervention communities.83
However, 2 randomized controlled trials that assessed the impact of cash transfers on HIV incidence showed no impact. The HPTN 068 Swa Koteka study (n = 2448), which provided cash incentives for school attendance, found that there was no difference in HIV acquisition rates between the young women who received the cash transfer and those who did not.84 The CAPRISA 007 cluster randomized controlled trial, which involved 3217 consenting male (n = 1517) and female (n = 1700) students in grades 9/10 in 14 schools in rural KwaZulu-Natal, showed that conditional cash incentives for meeting any combination of 4 conditionalities (annual HIV testing, school performance, participation in an HIV prevention program, and participation in a community project) was associated with a 30% reduction in HSV-2 incidence, but the trial did not have sufficient statistical power to demonstrate an impact on HIV incidence rates.85
The use of contingency management for HIV prevention would need to carefully consider the desired behaviors that need to be changed and the feasibility and desirability thereof in relation to the outcome. Regardless of age, risk factors and context, HIV prevention is challenging, with no quick fixes or one-size-fits-all solutions.
Integrating HIV Prevention Efforts With Sexual and Reproductive Health Services
Early sexual debut, high teenage pregnancy rates, and high school dropout rates are more common among adolescent girls and young women from poorer socioeconomic settings than they are among those from wealthier settings. Not only is a woman's risk of acquiring HIV increased in high HIV burden settings, but there also is a high probability of transmission to infants, particularly if there are delays in seeking care and treatment. Information on sexual and reproductive health that includes information about HIV prevention is crucial from a young age. Schools are an important venue for information dissemination and support for young girls to complete high school and remain free from HIV, STIs, and pregnancy.
In addition, access to adolescent-friendly sexual and reproductive health services—including contraceptive choice, safe abortions, and antenatal care—is particularly important for the prevention of unintended pregnancies and maternal deaths.35 Integration of these services with HIV prevention efforts is an opportunity to reduce the obstacles between adolescent girls and young women and the information, support, and services they require. The Family Planning Association in Malawi for example has successfully introduced mobile clinics offering services for sexual and reproductive health and HIV testing in rural areas. These mobile education services can vastly increase the number of adolescent girls and young women who can obtain sexual health knowledge and services.86
Societal norms that place a high value on young women and men assuming more responsibility for their sexual behavior and that do not tolerate gender-based violence or older men having sex with teenagers are equally important to ensuring adolescent girls and young women are able to grow up in a safe environment and reach their full potential without bearing children as children or acquiring HIV and other STIs. Lessons from the PMTCT program in Malawi have shown that, when the male partner is involved in the process—from initial testing, to PMTCT, and through to the confirmation of HIV status—adherence and uptake rates are significantly higher.87 Greater male involvement increases uptake of PMTCT, acceptance of HIV-positive status, use of fertility control, and adherence to antiretroviral therapy (if infected); it also results in a gradual positive attitude shift toward prevention and reduces the rate of pediatric infections.88 In contrast, unsupportive male partners have been associated with poor communication between partners and higher rates of intimate partner violence, abandonment, and discrimination once a woman reveals her positive HIV status.89
NEW HOPE IN PREVENTING HIV IN ADOLESCENT GIRLS AND YOUNG WOMEN
UNAIDS estimates that the number of new HIV infections in the overall population in sub-Saharan Africa declined by about 46% between 2000 and 2015, and by 37% in young people.6 Although promising, these declines are too small and too slow to alter the vulnerability of adolescent girls and young women. After years of neglect, a global convergence is emerging around the urgency to address the multiple factors driving the HIV epidemic in adolescent girls and young women.90
PEPFAR's DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe) initiative, which was launched on World AIDS Day in 2014, brings new hope for meeting the prevention needs of adolescent girls and young women and for creating an environment that supports them. DREAMS is a public–private partnership that aims to reduce HIV infections among adolescent girls and young women in the 10 countries in sub-Saharan Africa that account for nearly half of all new HIV infections. This is the first time in the history of the HIV epidemic that a concerted advocacy and programmatic effort is being made with substantial funding to address the problem through a multipronged approach that includes national campaigns, access to combination prevention, the engagement of men (eg, linkage to HIV testing and counseling, treatment and voluntary medical male circumcision), integration of HIV services into sexual and reproductive services, and efforts to keep girls in school.
The goal of DREAMS is to ensure that adolescent girls and young women have access to prevention technologies and strategies, and the opportunity to complete high school and graduate HIV-negative, STI-free, and without pregnancies. This will be accomplished using a combination of available evidence and best practices (Fig. 1). It addresses gender-based violence, young women's rights, and the creation of supportive communities that address the structural drivers that directly and indirectly increase HIV risk among girls (including poverty, gender inequality, sexual violence, abbreviated schooling, and poor access to treatment for those already infected with HIV). The inclusion of oral PrEP in the DREAMS prevention package enhances access to a novel HIV prevention option for young women. Together, these efforts could help sustain the gains made to date and address some of the key gaps and challenges that persist after the end of the Global Plan by focusing on the most vulnerable group.
Although focusing on adolescent girls and young women is an important strategy to reduce the number of new infections, unplanned pregnancies, and premature maternal deaths; given the gender power disparities that underlie the vulnerability of adolescent girls and young women, inclusion of their male sexual partners in sexual and reproductive health information sessions and access to HIV prevention and treatment services could substantially enhance the effectiveness of these initiatives. The role of community and supportive environments to keep young girls in schools and reduce teenage pregnancies and HIV is equally important. The inclusion of both these aspects in the DREAMS initiative makes the intervention even more powerful.
To date, there have been limited concerted efforts to focus on or address the health needs of adolescents and young people, as they are assumed to be healthy and not in need of preventive, promotive, or therapeutic services. The “youth bulge” in sub-Saharan Africa—and the notably disproportionate burden of HIV infection, premature loss of life, and unmet sexual and reproductive health needs among adolescent girls and young women—and the convergence of communicable and noncommunicable diseases highlight this important gap that requires urgent attention if we are to bridge and reduce gender disparities. The gender divergence in HIV acquisition and AIDS-related survival mirror where the foundations for gender disparities and outcomes have been laid. These age and sex differences in HIV infection place young women in developing countries at substantial disadvantage that widens with age and has ramifications beyond health. Preventing HIV infection in adolescent girls and young women not only benefits this vulnerable population, but it is critical to altering the current epidemic trajectories and enabling epidemic control in eastern and southern Africa, while sustaining the achievements of the Global Plan.
1. UNAIDS. Global Plan
Towards Eliminating HIV
Infections Among Children by 2015 and Keeping Their Mothers Alive. Geneva, Switzerland: UNAIDS; 2011.
2. UNAIDS. Fast Track. The Life-cycle Approach to HIV
—Finding Solutions for Everyone at Every Stage of Life. Geneva, Switzerland: UNAIDS; 2016.
3. Horwood C, Butler LM, Haskins L, et al. HIV
-infected adolescent mothers and their infants: low coverage of HIV
services and high risk of HIV
transmission in KwaZulu-Natal, South Africa. PLoS One. 2013;8:e74568.
4. UNAIDS. Global AIDS Update 2016. Geneva, Switzerland: UNAIDS; 2016.
5. UNAIDS. The Gap Report. Geneva, Switzerland: UNAIDS; 2014.
6. UNAIDS. How AIDS Changes Everything: MDG 6—15 Years, 15 Lessons of Hope From the AIDS Response. Geneva, Switzerland: UNAIDS; 2015.
7. South Africa Department of Health. The 2013 National Antenatal Sentinel HIV
Prevalence Survey South Africa. Pretoria, South Africa: Department of Health; 2015.
8. Kharsany AB, Frohlich JA, Yende-Zuma N, et al. Trends in HIV
prevalence in pregnant women in rural South Africa. J Acquir Immune Defic Syndr. 2015;70:289–295.
9. Kharsany AB, Mlotshwa M, Frohlich JA, et al. HIV
prevalence among high school learners— opportunities for schools-based HIV
testing programmes and sexual reproductive health services. BMC Public Health. 2012;12:231.
10. Ramjee G, Kapiga S, Weiss S, et al. The value of site preparedness studies for future implementation of phase 2/IIb/III HIV prevention
trials: experience from the HPTN 055 study. J Acquir Immune Defic Syndr. 2008;47:93–100.
11. Nel A, Louw C, Hellstrom E, et al. HIV
prevalence and incidence among sexually active females in two districts of South Africa to determine microbicide trial feasibility. PLoS One. 2011;6:e21528.
12. Nel A, Mabude Z, Smit J, et al. HIV
incidence remains high in KwaZulu-Natal, South Africa: evidence from three districts. PLoS One. 2012;7:e35278.
13. Feldblum PJ, Latka MH, Lombaard J, et al. HIV
incidence and prevalence among cohorts of women with higher risk behaviour in Bloemfontein and Rustenburg, South Africa: a prospective study. BMJ Open. 2012;2:e000626.
14. Ramjee G, Wand H, Whitaker C, et al. HIV
incidence among non-pregnant women living in selected rural, semi-rural and urban areas in KwaZulu-Natal, South Africa. AIDS Behav. 2012;16:2062–2071.
15. Abdool Karim Q, Kharsany AB, Frohlich JA, et al. Stabilizing HIV
prevalence masks high HIV
incidence rates amongst rural and urban women in KwaZulu-Natal, South Africa. Int J Epidemiol. 2011;40:922–930.
16. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention
infection in women. Science. 2010;329:1168–1174.
17. Moodley D, Esterhuizen T, Reddy L, et al. Incident HIV
infection in pregnant and lactating women and its effect on mother-to-child transmission in South Africa. J Infect Dis. 2011;203:1231–1234.
18. UNAIDS. Global Report: UNAIDS Report on the Global AIDS Epidemic. Geneva, Switzerland: UNAIDS; 2013.
19. Arnett JJ. Adolescence and Emerging Adulthood. Saddle River, NJ: Prentice Hall; 2014.
20. Yurgelun-Todd D. Emotional and cognitive changes during adolescence. Curr Opin Neurobiol. 2007;17:251–257.
21. Hardgrove A, Pells K, Boyden J, et al. Youth Vulnerabilities in Life Course Transitions. New York, NY: United Nations Development Programme Human Development Report Office; 2014.
22. Fatusi AO, Hindin MJ. Adolescents
and youth in developing countries: health and development issues in context. J Adolesc. 2010;33:499–508.
23. Hervish A, Clifton D. The Status Report on Adolescents
and Young People in Sub-Saharan Africa: Opportunities and Challenges. Washington, DC: Population Reference Bureau; 2012.
24. UNICEF. Orphans and Child-Headed Households. Dreams
to Reality Web Site. Available at: http://www.dreamstoreality.co.za/orphans-and-child-headed-households/
. Published September 10, 2014. Accessed November 3, 2016.
25. Dellar R, Abdool Karim Q. Understanding and responding to HIV
risk in young South African women: clinical perspectives. S Afr Med J. 2015;105:952.
26. Abdool Karim Q, Abdool Karim SS, Singh B, et al. Seroprevalence of HIV
infection in rural South Africa. AIDS. 1992;6:1535–1539.
27. Shisana O, Rehle T, Simbayi LC, et al. South African National HIV
Prevalence, Incidence, and Behaviour Survey 2012. Cape Town, South Africa: HSRC Press; 2014.
28. Gregson S, Nyamukapa CA, Garnett GP, et al. Sexual mixing patterns and sex-differentials in teenage exposure to HIV
infection in rural Zimbabwe. Lancet. 2002;359:1896–1903.
29. Kelly RJ, Gray RH, Sewankambo NK, et al. Age differences in sexual partners and risk of HIV
-1 infection in rural Uganda. J Acquir Immune Defic Syndr. 2003;32:446–451.
30. MacPhail C, Williams BG, Campbell C. Relative risk of HIV
infection among young men and women in a South African township. Int J STD AIDS. 2002;13:331–342.
31. Pettifor AE, Rees HV, Kleinschmidt I, 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.
32. Abdool Karim Q. Barriers to preventing human immunodeficiency virus in women: experiences from KwaZulu-Natal, South Africa. J Am Med Womens Assoc (1972). 2001;56:193–196.
33. Leclerc-Madlala S. Transactional sex and the pursuit of modernity. Social Dyn. 2003;29:1–21.
34. Dunkle KL, Jewkes RK, Brown HC, et al. Transactional sex among women in Soweto, South Africa: prevalence, risk factors and association with HIV
infection. Soc Sci Med. 2004;59:1581–1592.
35. Dellar RC, Dlamini S, Abdool Karim Q. Adolescent girls and young women
: key populations for HIV
epidemic control. J Int AIDS Soc. 2015;18(2 suppl 1):19408.
36. Pettifor A, O'Brien K, Macphail C, et al. Early coital debut and associated HIV
risk factors among young women
and men in South Africa. Int Perspect Sex Reprod Health. 2009;35:82–90.
37. Wand H, Ramjee G. The relationship between age of coital debut and HIV
seroprevalence among women in Durban, South Africa: a cohort study. BMJ Open. 2012;2:e000285.
38. Duncan ME, Peutherer JF, Simmonds P, et al. First coitus before menarche and risk of sexually transmitted disease. Lancet. 1990;335:338–340.
39. Kaufman CE, de Wet T, Stadler J. Adolescent pregnancy and parenthood in South Africa. Stud Fam Plann. 2001;32:147–160.
40. Patton GC, Coffey C, Sawyer SM, et al. Global patterns of mortality in young people: a systematic analysis of population health data. Lancet. 2009;374:881–892.
41. Singh S, Wulf R, Hussain R, et al. Abortion Worldwide: A Decade of Uneven Progress. New York, NY: The Guttmacher Institute; 2009.
42. Jewkes RK, Dunkle K, Nduna M, et al. Intimate partner violence, relationship power inequity, and incidence of HIV
infection in young women
in South Africa: a cohort study. Lancet. 2010;376:41–48.
43. Dunkle KL, Jewkes RK, Brown HC, et al. Gender-based violence, relationship power, and risk of HIV
infection in women attending antenatal clinics in South Africa. Lancet. 2004;363:1415–1421.
44. UNAIDS. Together We Will End AIDS. Geneva, Switzerland: UNAIDS; 2012.
45. van der Straten A, King R, Grinstead O, et al. Couple communication, sexual coercion and HIV
risk reduction in Kigali, Rwanda. AIDS. 1995;9:935–944.
46. Maman S, Mbwambo JK, Hogan NM, et al. HIV
-positive women report more lifetime partner violence: findings from a voluntary counseling and testing clinic in Dar es Salaam, Tanzania. Am J Public Health. 2002;92:1331–1337.
Risk Behaviors. Centers for Diseases Control and Prevention
Web Site. Available at: https://www.cdc.gov/hiv/risk/estimates/riskbehaviors.html
. December 4, 2015. Accessed December 15, 2016.
48. Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8:737–744.
49. Prodger JL, Gray R, Kigozi G, et al. Foreskin T-cell subsets differ substantially from blood with respect to HIV
co-receptor expression, inflammatory profile, and memory status. Mucosal Immunol. 2012;5:121–128.
50. Klot JF, Auerbach JD, Berry MR. Sexual violence and HIV
transmission: summary proceedings of a scientific research planning meeting. Am J Reprod Immunol. 2013;69(suppl 1):5–19.
51. Masson L, Passmore JA, Liebenberg LJ, et al. Genital inflammation and the risk of HIV
acquisition in women. Clin Infect Dis. 2015;61:260–269.
52. Glynn JR, Biraro S, Weiss HA. Herpes simplex virus type 2: a key role in HIV
incidence. AIDS. 2009;23:1595–1598.
53. Houlihan CF, Larke NL, Watson-Jones D, et al. Human papillomavirus infection and increased risk of HIV
acquisition. A systematic review and meta-analysis. AIDS. 2012;26:2211–2222.
54. Morrison CS, Chen PL, Kwok C, et al. Hormonal contraception and the risk of HIV
acquisition: an individual participant data meta-analysis. PLoS Med. 2015;12:e1001778.
55. United States Agency for International Development. Strategic Communication Framework for Hormonal Contraceptive Methods and Potential HIV
-Related Risks. Washington, DC: United States Agency for International Development; 2016.
56. Medley A, Kennedy C, O'Reilly K, et al. Effectiveness of peer education interventions for HIV prevention
in developing countries: a systematic review and meta-analysis. AIDS Educ Prev. 2009;21:181–206.
57. Underhill K, Montgomery P, Operario D. Sexual abstinence only programmes to prevent HIV
infection in high income countries: systematic review. BMJ. 2007;335. Available at: http://dx.doi.org/10.1136/bmj.39245.446586.BE
. Accessed December 15, 2016.
58. Holmes KK, Levine R, Weaver M. Effectiveness of condoms in preventing sexually transmitted infections. Bull World Health Organ. 2004;82:454–461.
59. Weiss HA, Hankins CA, Dickson K. Male circumcision and risk of HIV
infection in women: a systematic review and meta-analysis. Lancet Infect Dis. 2009;9:669–677.
60. Rees H, Delany-Moretlwe SA, Lombard C, et al. FACTS 001 Phase III Trial of Pericoital Tenofovir 1% Gel for HIV Prevention
in Women. Paper presented at: Conference on Retroviruses and Opportunistic Infections; February 23–26, 2015; Seattle, Washington. Abstract 26LB.
61. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV
infection among African women. N Eng J Med. 2015;372:509–518.
62. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV
in women. N Eng J Med. 2016;375:2121–2132.
63. Two large studies show IPM's monthly vaginal ring helps protect women against HIV
. International Partnership for Microbicides Web Site. Available at: http://www.ipmglobal.org/publications/two-large-studies-show-ipm%E2%80%99s-monthly-vaginal-ring-helps-protect-women-against-hiv
. Published February 22, 2016. Accessed May 4, 2016.
64. Abdool Karim Q, Baxter C, Abdool Karim S. Microbicides and their potential as a catalyst for multipurpose sexual and reproductive health technologies. BJOG. 2014;121(suppl 5):53–61.
65. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention
in men who have sex with men. N Engl J Med. 2010;363:2587–2599.
66. Molina JM, Capitant C, Spire B, et al. On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial. Paper presented at: Conference on Retroviruses and Opportunistic Infections; February 23–26, 2015; Seattle, Washington. Abstract 23LB.
67. McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV
-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387:53–60.
68. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention
in heterosexual men and women. N Engl J Med. 2012;367:399–410.
69. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV
transmission in Botswana. N Engl J Med. 2012;367:423–434.
70. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV
infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381:2083–2090.
71. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV
infection among African women. N Eng J Med. 2012;367:411–422.
72. Bekker LG, Hughes J, Amico R, et al. HPTN 067/ADAPT Cape Town: A Comparison of Daily and Nondaily PrEP Dosing in African Women. Paper presented at: Conference on Retroviruses and Opportunistic Infections; February 23–26, 2015; Seattle, Washington. Abstract Number: 978LB.
73. Evaluating the Acceptability, Safety, and Use of Daily Truvada Pre-exposure Prophylaxis in Healthy, HIV
. Available at: ClinicalTrials.gov
Web site. https://clinicaltrials.gov/ct2/show/NCT02213328
. Published August 7, 2014. Updated June 1, 2016. Accessed November 3, 2016.
74. World Health Organization. Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV
. 2015; Available at: http://apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf
. Accessed December 15, 2016.
75. Auerbach JD, Parkhurst JO, Caceres CF. Addressing social drivers of HIV
/AIDS for the long-term response: conceptual and methodological considerations. Glob Public Health. 2011;6(suppl 3):S293–S309.
76. Volpp KG, Troxel AB, Pauly MV, et al. A randomized, controlled trial of financial incentives for smoking cessation. N Engl J Med. 2009;360:699–709.
77. Petry NM, Bickel WK, Tzanis E, et al. A behavioural intervention for improving client behaviour in a substance abuse treatment clinic. J Appl Behav Anal. 1998;31:291–297.
78. Sindelar JL, Olmstead TA, Peirce JM. Cost-effectiveness of prize-based contingency management in methadone maintenance treatment programs. Addiction. 2007;102:1463–1471.
79. Barber SL, Gertler PJ. The impact of Mexico's conditional cash transfer programme, Oportunidades, on birthweight. Trop Med Int Health. 2008;13:1405–1414.
80. Fernald LC, Hou X, Gertler PJ. Oportunidades program participation and body mass index, blood pressure, and self-reported health in Mexican adults. Prev Chronic Dis. 2008;5:A81.
81. Pettifor A, MacPhail C, Nguyen N, et al. Can money prevent the spread of HIV
? A review of cash payments for HIV prevention
. AIDS Behav. 2012;16:1729–1738.
82. Cluver L, Boyes M, Orkin M, et al. Child-focused state cash transfers and adolescent risk of HIV
infection in South Africa: a propensity-score-matched case-control study. Lancet Glob Health. 2013;1:e362–e370.
83. Baird S, Chirwa E, McIntosh C, et al. The short-term impacts of a schooling conditional cash transfer program on the sexual behavior of young women
. Health Econ. 2010;19:55–68.
84. Pettifor A, MacPhail C, Selin A, et al. HPTN 068 Conditional Cash Transfer to Prevent HIV
Infection Among Young Women
in South Africa: Results of a Randomized Controlled Trial. Paper presented at: Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention
; July 19–22, 2015; Vancouver, Canada. Abstract TUAC0106LB.
85. Abdool Karim Q, Leask K, Kharsany A, et al. Impact of Conditional Cash Incentives on HSV-2 and HIV Prevention
in Rural South African High School Students: Results of the CAPRISA 007 Cluster Randomized Controlled Trial. Paper presented at: Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention
; July 19–22, 2015; Vancouver, Canada. Abstract TUAC0101LB.
86. Family Planning Association of Malawi. International Planned Parenthood Federation Web Site. Available at: http://www.ippfar.org/about-us/member-associations/family-planning-association-malawi
Accessed December 15, 2016.
87. Kalembo FW, Zgambo M, Mulaga AN, et al. Association between male partner involvement and the uptake of prevention
of mother-to-child transmission of HIV
(PMTCT) interventions in Mwanza district, Malawi: a retrospective cohort study. PLoS One. 2013;8:e66517.
88. Auvinen J, Suominen T, Valimaki M. Male participation and prevention
of human immunodeficiency virus (HIV
) mother-to-child transmission in Africa. Psychol Health Med. 2010;15:288–313.
89. Visser MJ, Neufeld S, de Villiers A, et al. To tell or not to tell: South African women's disclosure of HIV
status during pregnancy. AIDS Care. 2008;20:1138–1145.
90. Fleischman J, Peck K. Addressing HIV
Risk in Adolescent Girls and Young Women
. Washington, DC: Center for Strategic & International Studies; 2015.