Global HIV Epidemiology: A Guide for Strategies in Prevention and Care

Abstract

Global trends in HIV incidence are estimated typically by serial prevalence surveys in selected sentinel populations or less often in representative population samples. Incidence estimates are often modeled since cohorts are costly to maintain and are rarely representative of larger populations. From global trends, we can see reason for cautious optimism. Downward trends in generalized epidemics in Africa, concentrated epidemics in persons who inject drugs (PWID), some female sex worker cohorts, and among older men who have sex with men (MSM) have been noted. However, younger MSM and those from minority populations, as with black MSM in the United States, show continued transmission at high rates. Among the many HIV prevention strategies, current efforts to expand testing, linkage to effective care, and adherence to antiretroviral therapy are known as “treatment as prevention” (TasP). A concept first forged for the prevention of mother to child transmission, TasP generates high hopes that persons treated early will derive considerable clinical benefits and that lower infectiousness will reduce transmission in communities. With the global successes of risk reduction for PWID, we have learned that reducing marginalization of drug users, implementation of non-judgmental and pragmatic sterile needle and syringe exchange programs, and offering of opiate substitution therapy to help persons eschew needle use altogether can work to reduce the HIV epidemic. Never has the urgency of stigma reduction and guarantees of human rights been more urgent; a public health approach to at-risk populations requires that to avail themselves of prevention services, they must feel welcomed.

Introduction

This Current HIV/AIDS Reports issue brings timely, helpful updates on the global epidemiology of HIV/AIDS, within the limitations of currently available surveillance data. It is worth presenting these contributions in the context of successes and challenges in HIV prevention, limitations of global estimations, and present a few caveats about current HIV/AIDS trends.

GLOBAL TRENDS

There is little doubt that HIV prevalence is dropping worldwide, but declines are dramatic only where prevention strategies have been highly implemented and taken up by the target population. In Africa, we have concrete evidence of a decline in prevalence among young women, for example, but the reasons for this are not yet well understood [1••]. Despite salutary trends, the most highly prevalent nations of southern Africa (Angola, Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Zambia, Zimbabwe) remain the continental and global epicenter for the generalized epidemic. There is no indication of a transmission breakpoint, i.e., a basic reproduction rate for transmission that has dropped below the level that can sustain a cycle of transmission, in these highest prevalence nations [2].

An additional challenge in Africa is among the key populations that would be likely to continue transmission even if incidence in the general population were to continue to wane [3,4]. Among these are men who have sex with men (MSM), long neglected in Africa, persons who inject drugs (PWID) in certain regions such as Zanzibar, and more familiar groups like female sex workers (FSWs) and migrant men in the trucking and mining industries whose multiple and often concurrent partnerships may provide a disproportionate impact on local transmission network dynamics [5,6].

In Asia, tremendous progress has been noted in rolling out effective prevention programs among PWID with consequent reductions in prevalence in India, China, Thailand, and elsewhere, though hepatitis C rates have risen markedly [7••,8•]. Yet success in some venues is matched with failure in others, such as Pakistan, where policy has been indolent and programs underdeveloped [9]. FSWs have been engaged in highly successful prevention programs in Cambodia, Thailand, Vietnam, and elsewhere with promising HIV trends as a consequent [10]. Trends among MSM are not salutary and it is apparent that the epidemic is rising or stable at a high level in Asian MSM [11].

In South America and the Caribbean, key populations are drivers of transmission, and except for Haiti, general populations have been spared the extent of epidemic penetration seen elsewhere [12••, 13••]. Considerable sexual transmission continues among MSM and high risk heterosexuals; the dominant circulating B subtype is the same as the major subtype circulating in high income nations.

High and high middle income nations continue to vary in their background prevalences [14••,15]. Australia’s pragmatic approach has yielded benefits in every risk group [16]. Europe and North America continue to struggle to make progress among MSM but see marked declines in both incidence and prevalence among PWID. Eastern Europe and Central Asia have had spotty results with risk reduction among PWID, with the worst trends noted where opiate substitution therapy and sterile needle/syringe exchange programs are illegal and/or underfunded, as in Russia [17••]. With PWID overrepresenting prison populations, tuberculosis (and likely HIV, hepatitis B, and hepatitis C) spread remains common decades after this phenomenon was first reported [18].

Aspirational goals of an “AIDS-free generation”, “zero transmission” from mother-to-infant, and the like are inspirational rallying slogans within popular and political audiences. However, considerable innovation will be needed to change the surveillance-based realities. Innovation in programmatic efforts for women and children are proposed in this issue of Current HIV/AIDS Reports [19•,20•].

PREVENTION

Prevention strategies are more numerous and promising today than ever before. For example, there is now a wide array of biomedical approaches using agents or devices that block virus spread either physically, chemically, or immunologically. These may focus on protecting the uninfected (acquisition) or reducing infectiousness (transmission). The advent of more and more products and strategies has emerged from a prevention developmental pathway epitomized by research networks that promulgate developmental science, clinical trials, and combination prevention strategies (Figure).

Figure 1.

Developmental pathway for HIV prevention science: discovery to trials to combination interventions that control the pandemic

Barriers to reduce acquisition

Barriers to acquisition of HIV include physical blocks such as condoms, both male and female. Their major challenges are five “A’s”: awareness, availability, acceptability, affordability, and adherence [21]. Male condoms have made a huge impact on the Thai epidemic, alongside policy changes in brothels and in the national consciousness. Low HIV prevalence among FSWs and clients in such nations as Japan may be due to very high condom use. Australian MSM use condoms more than counterparts elsewhere and also have lower prevalence rates. Female condoms have had niche utilities but do not seem to have made a major global impact. Chemical barriers include topic and systemic antiretroviral drugs to kill virus near the time of exposure or early infection [22]. Pre-exposure prophylaxis (PrEP) has been shown to work both systemically (most notably, tenofovir/emtricitabine) and topically (tenofovir vaginal gel). However, large efficacy trials suggest that adherence is very challenging and that low utilization dooms the approach to ineffectivity [23]. Current efforts seek to overcome challenges of poor adherence to oral and topical PrEP by testing depot long-acting injections for systemic administration and antiretroviral microbicide via a dapivirine vaginal ring (monthly changes) to the target cervicovaginal tissues. Immediate post-exposure treatment of infants born to infected mothers with high viral loads shows promise to block transmission, even when pre- and intrapartum prophylaxis opportunities have been missed [24,25].

Immunological barriers are in development and may be available in the future. These include HIV vaccines and passive immune barriers such as monoclonal antibodies [26]. We do not know the extent to which they will be protective against circulating strains, applicable across diverse sub-types, or will generate durable protective immunity. In any case, they will not be commercially available until 2025 or later.

Barriers to reduce transmission

One can think about barriers in the seropositive person analogous to how they are presented to avoid acquisition. Condoms interrupt transmission from condom wearer to uninfected sexual partner. Therapeutic vaccines could reduce infectiousness someday, if they could be engineered successfully to enhance human immune responses beyond what natural infection provides. But the principal innovation in recent years has been the documentation that treatment can reduce viral load and serve to protect others from infection. Treatment as prevention has been proposed since studies in the late 1990s demonstrated that lower viral loads were associated with lower transmission rates to sexual partners [27,28]. The observational and clinical trials evidence was even more dramatic than had been hoped, suggesting massive protective benefit of a seropositive partner taking combination antiretroviral therapy (cART) assiduously [29]. Of course, the implementation challenges of rolling out universal testing and near-universal treatment are daunting [30-32], and are the topic of intensive pragmatic investigation [33-40].

Male circumcision to reduce the vulnerability of male genital tissues to HIV infection has proven to be hugely successful in generalized heterosexual contexts [41-43]. There is even promise that male circumcision will help reduce MSM risk [44]. Lessons of how to bring circumcision programs to the large scale needed to truly impact the HIV pandemic are being applied in real field conditions [45,46].

Prevention of mother to child transmission programs are well established, but continuing health systems constraints and, in many venues, continued stigma and fear inhibit full program implementation and success [19,20,47,48]. Quality improvement programs are needed for the further reduction of pediatric HIV infections, as well as for the improved therapy of already infected children, elusive goals to date [49,50].

Behavioral change

The prospects of widespread behavior change to reduce sexual risk exposure are not promising [23,51,52]. Since the HIV pandemic began in the 1970s, changes in sexual behaviors have been dramatic following catastrophic viral spread in communities, as with reduced sexual risk taking among MSM in the USA in the mid 1980s, but so many men were infected by that point that the benefits of risk reduction were less dramatic [53]. In Thailand and Uganda, dramatic declines in HIV rates in the 1990s were noted, with commensurate behavioral data suggesting a decline in partner numbers and high risk partners [54,55]. Yet the global community has not yet seen a widespread effective replication of the dramatic Ugandan and Thai experiences.

PWID have had marked reductions in HIV incidence in venues where effective community outreach for needle and syringe exchange have increased clean needle usage [56,57]. Similarly, opiate substitution therapy has reduced injection behaviors altogether among subsets of PWID [58,59]. One example of many of a behavioral support strategy is the information, motivation, behavioral (IMB) skills model of care to improve uptake of biomedical interventions and reduce HIV risk behaviors, for example [60,61]. While behavior change must be a part of any successful combination prevention approach, it is not likely to be successful in isolation from biomedical approaches. However, all behavioral adherence strategies require client assent and adherence [62], even for user-friendly monthly changes of a microbicidal ring, a depot PrEP injection, or a vaccine series. For the decision to get circumcised, for daily adherence to antiretroviral drugs, or for coital compliance with condom use, it is obvious how essential behavioral intervention is to support complex or long-term decisions.

A combination of strategies is more likely to achieve success in global HIV control than single approaches, given the synergism of different approaches, the need for behavioral change just to implement biomedical tools, and the diversity of at-risk populations [63-70]. Historic initiatives to reduce HIV morbidity, to prevent transmission, and to stop deaths from AIDS have achieved unprecedented gains through the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria [71-73]. With resources never before marshalled for global disease control and prevention, millions of persons are on life-saving antiretroviral drugs and are less infectious to others [74,75].

We face daunting challenges in preserving the political will in donor countries to continue supporting these programs, nurturing indigenous support and expertise for long term program maintenance and expansion, and building health systems capacities to prevent stock-outs, to ensure respect for patients, and to maximize successful client empowerment [76,77]. We also have an opportunity to expand new HIV service infrastructures to provide care for other chronic diseases whose management has been neglected by poor medication supply chains, poor clinical infrastructures, or a lack of trained health workforce [78-82]. Adolescents and young adults continue to get infected and our tools for this population are limited [83]. Expanding HIV clinical services to others with chronic medical conditions like tuberculosis (as is being done now), diabetes, hypertension, malignancies, rheumatic and collagen vascular conditions, and sickle cell disease, to name but a few, can improve the political base of support to continue this historic global health initiative [84]. The Pink Ribbon Red Ribbon campaign to integrate HIV care with cervical and breast cancer screening for women is an example of such expansive inspiration [85,86]. While concerns are raised that changing the focus of HIV programs to more chronic disease conditions will compromise their effectiveness, one might also argue that such programs are doomed to shrinkage if they maintain their one-dimensional focus and fail to build wider constituencies [87•,88-92].