The HIV Epidemic in Southern Africa – Is an AIDS-Free Generation Possible?
Southern Africa, home to about 20 % of the global burden of infection continues to experience high rates of new HIV infection despite substantial programmatic scale-up of treatment and prevention interventions. While several countries in the region have had substantial reductions in HIV infection, almost half a million new infections occurred in this region in 2012. Sexual transmission remains the dominant mode of transmission. A recent national household survey in Swaziland revealed an HIV prevalence of 14.3 % among 18–19 year old girls, compared to 0.8 % among their male peers. Expanded ART programmes in Southern Africa have resulted in dramatically decreased HIV incidence and HIV mortality rates. In South Africa alone, it is estimated that more than 2.1 million of the 6.1 million HIV-positive people were receiving ART by the end of 2012, and that this resulted in more than 2.7 million life-years saved, and hundreds of thousands of HIV infections averted. Biological, behavioural and structural factors all contribute to the ongoing high rates of new HIV infection; however, as the epidemic matures and mortality is reduced from increased ART coverage, epidemiological trends become hard to quantify. What is clear is that a key driver of the Southern African epidemic is the high incidence rate of infection in young women, a vulnerable population with limited prevention options. Moreover, whilst ongoing trials of combination prevention, microbicides and behavioural economics hold promise for further epidemic control, an AIDS-free generation will not be realised unless incident infections in key populations are reduced.
KeywordsSouth AfricaAIDSGlobal epidemicSouthern AfricaAIDS-free generationInfectionMicrobicidesCombination preventionHIV-positiveARTReview
Scientific advances in the past three years, centred around the use of antiretrovirals (ARVs) to treat HIV infected persons and prevent onward transmission of HIV (HPTN 052) [4••] or prophylactically in HIV uninfected individuals to reduce HIV acquisition , have bought new hope and optimism to controlling HIV with combination prevention strategies . This is reflected in the discourse of an AIDS-free generation2 or UNAIDS’s “3 zeroes”: “zero new HIV infections, zero discrimination and zero AIDS-related deaths.” The challenge lies in implementation, and given limited resources this will need to be done smartly and efficiently. Large and sustained reductions in new HIV infections will be needed to reach the goal of zero new infections. In Southern Africa an AIDS-free generation will not be realized unless new infections in adolescent girls are eliminated. Notwithstanding the high burden of HIV infection in Southern Africa, there is a diversity of epidemics within the region. For instance, the HIV prevalence among 15 to 49 year old people in the South African province of KwaZulu-Natal (27.6 %) is three times higher than that in the Western Cape province (9.2 %)  and within KwaZulu-Natal there are three districts with the highest disease burden in the country – also referred to as “hotspots”. Targeting “hotspots” and key populations for more intensified responses is a novel way of responding to the epidemic. Modellers have already started to utilise this utilitarian approach and confirm that in a mature, hyper-endemic setting such as KwaZulu-Natal the goal of an AIDS-free generation may be feasible with a combination of antiretroviral (ARV) drugs to prevent onward transmission of HIV (TasP), voluntary medical male circumcision (VMMC) to prevent the sexual acquisition of HIV and the prophylactic use of ARVs to prevent HIV acquisition sexually pre-exposure prophylaxis (PrEP) and vertically through mother-to-child transmission (PMTCT) [8•].
Uncertainty about available future resources and healthcare capacity cast some doubt over model projections, and necessitate that priority regions and populations must be identified, engaged and preferentially targeted through better understanding of the biological, behavioural and structural drivers of the HIV epidemic and their interrelationships. Moreover, whether the large and sustained reductions in incidence rates required for an AIDS-free generation are achievable can only be assessed by more nuanced, contextualized models that account for the conditionality of this new prevention agenda on individual behaviours, community sexual networks, community viral loads and capacity to deliver interventions and guide efforts for optimal and efficient use of resources. For South Africa, the impact of intensified comprehensive programmatic scale-up in “hotspot” districts and focused directly or indirectly on eliminating HIV infection in adolescent girls has to be considered. What is needed to advance this agenda is a combination of understanding of the local epidemic, informed with local data and evidence on the feasibility of implementing advances in treatment and prevention, and interactive use of mathematical modelling to optimize a pragmatic approach for implementation.
Our review provides background to the key features of the HIV epidemics in Southern Africa, the population-level impact of ART scale-up, the recent HIV prevention advances, and the remaining challenges that must be overcome to assess the feasibility of, and perhaps ultimately achieve an AIDS-free generation.
Key Features of the HIV Epidemic in Southern Africa
The evolving HIV epidemics in Southern Africa have been well described . Heterosexual transmission is the dominant mode of spread. The epidemics are described as mature, generalized and hyper-endemic, capturing the unprecedented high HIV prevalence, continued high rates of new HIV infections and large numbers of patients living with AIDS. In 2012, the overall prevalence of HIV in South Africa was estimated at 17.9 % in 15 to 49 year old people, and an estimated 6.1 million people were living with HIV/AIDS .
The majority of these infections are caused by HIV-1 subtype C. Data from phylogenetic mapping of HIV strains isolated in South Africa indicate a relatively late introduction of HIV to the region compared to Eastern and Central Africa. Phylogenetic mapping of isolated viruses indicate that the epidemic was established through multiple sources of infection that coalesced around the mid-1990s .
Behavioural and Biological Drivers of HIV Transmission
Despite extensive research efforts, a consensus explanation for the unprecedented high prevalence and continued high rates of incident HIV infection in Southern Africa remains elusive, but unlikely to be attributable to a single factor. Important constituent factors may include, but are not limited to: (i) on a biological level, the extended high viraemia in people infected with HIV-1 subtype C , enhanced cervicovaginal inflammation, and the high burden of co-morbidities such as malaria and tuberculosis (TB); (ii) on a behavioural level, the high levels of concurrent relations and partner change, which might result partially from low levels of marriage; (iii) on a structural level, the migrant labour system and high levels of poverty.
Studies of transmission dynamics are beginning to define complex, synergistic interactions between the biological, behavioural and structural drivers of HIV infection. For example, a phase of high infectiousness resulting from high viraemia during acute HIV infection can only result in new HIV infections if recently infected individuals have sex with new partners; a high rate of partner change and/or concurrent relationships  can thus dramatically augment this risk factor. Recently, transmission potential data from theoretical modelling suggest that high viraemia during acute infection and high sexual activity actually correlate in a subpopulation of highly infectious but short-surviving individuals . Furthermore, recent empirical and modelling studies indicate that high set point viral load may be inherited by the newly infected individual [13, 14]. Thus, a high rate of partner turnover and concurrency in a critical fraction of the population in Southern Africa may have influenced the population distribution of HIV set point viral load and consequently the transmission dynamics of HIV. Together, these data imply that the HIV-positive people with high set point viral load are on average more sexually active at the time of HIV acquisition and transmission, and are part of high efficient transmission chains.
Confirmation of this recently defined correlation between high set point viral load and high-risk sexual behaviour and continuing explorations into the interrelationships between drivers may help to both explain the past HIV epidemic trajectories in Southern Africa and inform the impact of HIV prevention interventions alone and in combination. For example, behavioural interventions targeted at reducing sexual risk behaviours including relationship concurrency may avert more infections among the most sexually active than one would infer from models that do not take into account the heritability of set point viral load and assume independence between sexual activity level and HIV infectiousness.
This bio-behavioural nexus may also impact treatment as prevention interventions where people with high viral loads have immediate ART access regardless of disease staging or CD4 cell count; use of conventional mathematical models here could result in an under-estimate of intervention impact . Moreover, an enhanced understanding of the interrelationships between the biological, behavioural and structural drivers of the HIV epidemic is central to informing selection of interventions that impact transmission dynamics in Southern Africa and will result in more effective and efficient use of limited resources.
Incident Infections and Key Populations
Country-level analyses using the UNAIDS modes of transmission (MOT) model  indicate that most new HIV infections in Southern Africa occur in the general heterosexual population in people who have multiple sex partners and in those people’s regular partners; incident infections are also common in stable, mutually faithful but discordant relationships.
Substantial variation in the proportion of new infections among key populations of sex workers and their clients, men who have sex with men (MSM) and people who inject drug (PWID) has been established . For instance, MSM and their (female) partners were estimated to contribute only 1 % of all new infections in Zambia, but 10 % in South Africa, and sex work (the joint contribution of sex workers, their clients and the regular partners of clients) contributed an estimated 2 % of new infections in Lesotho and 20 % in Mozambique. However, given that collecting accurate and generalizable behavioural and epidemiological data on many of these key populations is a major challenge, it is unclear to what extent the MOT model output on key populations is a reflection of actual differences in the region or rather the result of large uncertainties and/or biases in input data. It is therefore of paramount importance that local and national surveillance programmes include components for systematic monitoring of indicators of HIV risk behaviours and HIV and ART status, not only among the general population, but also among key populations at increased risk of HIV acquisition. The paucity of data on the population fraction that engages in sex work, homosexual relationships and injecting drug use [18–20] stems from the fact that these populations at high risk of HIV infection are often hidden, marginalised and stigmatised, and their risk behaviours are criminalised in many countries. Stigmatisation and criminalisation of sex work, homosexual intercourse and injecting drug use should therefore be recognised, acknowledged and actively addressed [18–20], as these are major barriers to evidence-based HIV surveillance, as well as to HIV prevention and access to care [18, 20–22].
Young Women as a Key Population
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Indeed, the age-sex disparity in HIV prevalence and high incident rates in young women are driven by age-disparate and transactional sexual relationships between highly susceptible young women and older men with a high cumulative risk of HIV infection. Hence, HIV incidence and prevalence remain much higher in young women age 15–24 than in their male counterparts. The population-level consequences of the prevailing age-mixing pattern in Southern Africa are detrimental, as large age-asymmetries in sexual relationships and wide variation in age-gaps are essential for effective and sustainable HIV transmission, a finding supported by theoretical and applied mathematical models [28, 29].
Age-disparate and transactional sexual relationships are typically facilitated by unstable family and home environments , as well as age- and gender-gradients in material wealth and social status ; qualitative data also suggest that some young women may favour relationships with older men in an attempt to avoid physical and emotional abuse . Moreover, structural interventions to level the playing field of the relationship market and forge positive social environments in which safer relationship choices can be made, could lead to less HIV exposure among young women, and in the long run, to a fundamentally different epidemiological and socio-economic landscape [33, 34].
Data from a prospective cohort of young women in rural South Africa indicate high incidence rates of HIV and teenage pregnancies [35••] underscoring the importance of integrating HIV prevention efforts with broader sexual and reproductive health services. Data from high school learners in this community provide some indication of the care burden that already exists in young people and the importance of school based prevention interventions as well as keeping adolescent boys and girls in school .
The Impact of ART
Expanded ART programmes in Southern Africa have resulted in dramatically decreased HIV incidence and HIV mortality rates. In South Africa alone, it is estimated that more than 2.1 million of the 6.1 million HIV-positive people were receiving ART by the end of 2012, and that this has resulted in more than 2.7 million life-years saved  and hundreds of thousands of HIV infections averted. The net effect of this reduced “influx” and “outflux” on the size of the total pool of HIV-positive people, i.e. the national HIV prevalence, is comparatively small so far. Indeed, in a systematic comparison of mathematical models, all six models estimated that in the absence of the ART programme, HIV prevalence in South Africa in 2011 would not have been different by more than one percentage point .
A meaningful appreciation of the impact of the ART scale-up in Southern Africa cannot be obtained from merely observing time trends in national HIV prevalence estimates. Instead, it requires careful unpacking of the trends in ART coverage, HIV incidence and survival, as well as monitoring of sexual behaviours, which may be influenced by lower risk perceptions in the context of improved ART availability.
In a large population-based prospective cohort studies in rural KwaZulu-Natal, South Africa, sharp increases in ART coverage over the period 2004–2011 were associated with an increase in adult life expectancy, from 49.2 years in 2003 to 60.5 years in 2011 . Furthermore, a strong association was observed between an individual’s risk of HIV acquisition and the ART coverage in the surrounding local community: where 30-40 % of all HIV-positive people were receiving ART, risk of HIV infection was 38 % lower compared to communities where HIV treatment coverage was less than 10 % [40•]. The overall effect of decreased HIV incidence and increased survival among ART patients has caused an increase in HIV prevalence, especially in women aged 25–49, where ART coverage is highest . Indeed, ART protects HIV-positive people with advanced immune deficiency against opportunistic infections and other life-threatening comorbidities. However, unless linkage to care and ART coverage is also high among asymptomatic, sexually active people infected with HIV, the time window for onward HIV transmission is still wide enough to produce a steady stream of new HIV infections, and hence to drive HIV prevalence up.
As large as the survival and prevention benefits of the ART scale-up are to date, the future health benefits and economic return of investment are likely many times larger; indeed, there is a fast-growing body of demographic, health economic and epidemiological modelling literature on the potential benefits of HIV treatment as prevention in Southern Africa [37, 38, 42, 43•, 44–46]. While the broad qualitative consensus across models logically instils confidence in these modelling results, it is important to bear in mind that significant uncertainties around ART programme costs and outcomes may limit the accuracy and precision of projections of averted infections and deaths . Few patients in Southern Africa have been receiving ART for more than 10 years, in recent years the recommended first-line ART regimens have changed several times, and the cost of HIV care continues to shrink. In light of these evolving realities, one has to wonder about the predictability of long-term ART adherence and viral suppression, rates of progression to second and third line treatment and associated costs, ART programme retention, and the costs of chronic non-communicable comorbidities in an aging population of HIV-infected people on ART. Nevertheless, uncertainty about the potential long-term impact of ART should not be a reason for inaction . Not only is there a compelling case for the potential impact of ART on HIV incidence reduction , current understanding of the biological effects of HIV viral replication and ART suggests that the sooner treatment is initiated, the greater the reduction in morbidity and mortality in individuals living with HIV [50, 51].
Accordingly, the 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection stipulate that ART initiation is recommended in all individuals with a CD4+ cell count of 500 cells/microliter or less; and at any CD4+ cell count in those with active TB, hepatitis B infection and severe chronic liver disease, in HIV-positive partners in serodiscordant couples, and in pregnant and breastfeeding women . Some countries in Southern Africa are taking even bolder steps towards universal access to ART. South Africa, Zambia, Botswana and Swaziland are hosting numerous (community) randomized controlled trials and operational research projects aimed at establishing the feasibility, acceptability, population-level impact, affordability and generalizability of HIV treatment as prevention across different settings in Southern Africa [53–56].
Besides concerns over steep losses in the treatment and care cascades (i.e. lost prevention potential due to low testing uptake, linkage to care, ART adherence and retention in care), there is uncertainty about whether or not the move towards expanded, earlier access to ART is leading to risk compensation, in response to lower risk perceptions for HIV acquisition, transmission and disease progression. There is indeed evidence from other global regions that risk compensation in the context of increased availability of ART could jeopardize the prevention benefits of HIV treatment [ ]. In Southern Africa, the evidence has been mixed. Nationally representative household surveys from South Africa and Zimbabwe suggest a recent increase in the percentage of men and women aged 15 to 49 who have had sexual intercourse with more than one partner in the past year [3••]; however, a longitudinal study from rural KwaZulu-Natal dedicated to investigate risk compensation found no evidence of increased sexual risk taking following ART scale-up .
The Impact of Other HIV Prevention Interventions
In addition to estimating the past and potential future impact of ART, mathematical models have also been employed to estimate trends in HIV incidence at national and regional levels, based on HIV surveillance and surveys, programme statistics and epidemic patterns . For the whole of Southern Africa, the HIV prevalence among men and women aged 15–24 years (a crude yet robust indicator of HIV incidence among young adults) declined by about one third between 2001 and 2012. Data from Botswana, Malawi, Namibia and Zambia demonstrate a 50 % reduction in incident HIV infections between 2001 and 2012 [3••]. While declining incidence rates are anticipated as HIV epidemics mature and stabilise, even in the absence of any behaviour change and biomedical interventions, it only offers a partial explanation for the remarkable declines observed in these countries. Poor quality of routinely collected data on behaviours, routine surveillance data and intervention uptake and impact preclude definitive analyses of which fractions of the change in incidence can be attributable to which components of HIV prevention portfolios. Mathematical modelling studies have suggested that reductions in extramarital, commercial, and casual sexual relations, and associated reductions in partner concurrency are the main reasons for the sharp decline in new infections in Zimbabwe; in South Africa, condom use, and to a lesser extent ART scale-up, have been identified as key contributors [60–63].
Despite these notable HIV prevention successes, the incidence of HIV in Southern Africa remains higher than anywhere else in the world, especially among adolescent girls and young women.
A large number of biomedical, behavioural, structural and combination approaches to HIV prevention studies are underway. An exhaustive overview of recent, ongoing and planned HIV prevention studies in Southern Africa is beyond the scope of this paper; here we merely highlight some of the most promising findings for reducing HIV infection in adolescents.
In the past two years, very encouraging results have emerged from Southern African based evaluations of structural interventions that are not directly targeting safer sexual behaviours. In Malawi, a cluster randomised trial investigating the efficacy of a cash transfer programme to improve school attendance and thereby indirectly reduce the risk of HIV and other STIs in young women of school-going age (13–22 years old) demonstrated that girls in the intervention groups were less likely to drop out of school, and were also less likely to have had a sexual partner aged 25 years or older, compared to their counterparts in the control group . In South Africa, a case–control study assessing the effects of state-provided, child-focused cash transfers to primary caregivers of adolescent boys and girls (10–18 years old) from poor households demonstrated that receipt of a cash transfer was associated with reduced incidence and prevalence of transactional and age-disparate sex among adolescent girls . Taken together, these results suggest that structural interventions that successfully modify the age-mixing pattern may result in fewer new HIV infections among adolescent and young adult women.
While these studies offer hope for much-needed HIV prevention in adolescent girls in Southern Africa, they also trigger further questions about the population-level impact and health economics of cash transfer programmes for HIV prevention. Firstly, community-wide behavioural surveillance is required to understand the consequences of the altered relationship choices among cash transfer programme recipients for the wider sexual network. For instance, it is as yet unclear if or how (older) men in the study communities modified their sexual behaviour to compensate for the fewer opportunities to engage in transactional and/or age-disparate relationships with adolescent girls. Secondly, continued behavioural surveillance beyond the time window of the cash transfers is essential to establish sustainability of the impact of cash transfer programmes on risky sexual behaviours, relationship characteristics and HIV acquisition rates. Thirdly, if cash transfer programmes are able to make fundamental changes to the educational capital, social environment and future prospects of programme beneficiaries, their positive impact may reach far beyond HIV prevention benefits and may also include other health benefits and even accelerated socio-economic growth for the recipients of the cash transfers and the communities in which they grow up.
Notwithstanding the exclusion of adolescent girls in the biomedical and combination prevention trials underway, several combination prevention trials are underway that could indirectly impact HIV risk in this key population. These include (i) the Botswana Combination Prevention Project that seeks to identify individuals with high viral loads in the community and not accessing care for immediate ARV treatment initiation to reduce onward transmission of HIV , (ii) HPTN 071 (PopART) also a TasP intervention being undertaken in Zambia and South Africa [55, 64] and (iii) the ANRS 12249 TasP trial in rural South Africa . These studies underway could further enhance our understanding of the evolving epidemic in the region and the impact of implementation or programmatic scale-up of what we know works.
In 2010, the CAPRISA 004 trial demonstrated the efficacy and safety of coitally-linked 1 % tenofovir microbicidal gel; the gel was demonstrated to decrease HIV acquisition by 39 %, and HSV-2 acquisition by 51 % [65, 66]. The CAPRISA 004 confirmatory study, FACTS 001 is well underway and could lead to licensure of tenofovir gel to prevent HIV and HSV-2 infection and for the first time enable women the opportunity to control their risk of HIV acquisition. Several other structural interventions targeting adolescents are underway including CAPRISA 007, Choices for Adolescent Methods of Prevention in South Africa (CHAMPS) and HPTN 068. Further studies assessing the acceptability of oral and topical PrEP and testing novel delivery mechanisms or new drugs are also in implementation. The Women’s Health Research Initiative is evaluating the impact of injectable contraceptives on HIV acquisition in women and a trial of oral PrEP and/or early ART initiation in female sex workers.
Methodological Advances in HIV Surveillance
With increased survival of infected individuals using cART and strong PMTCT programmes, there is a need to expand current surveillance systems that are based on prevalence data to estimate the rate of incident HIV infections. A reliable proxy for HIV incidence trends is temporal trends in HIV prevalence in adolescent girls and young women. Various statistical and mathematical methods are in development to derive unbiased and precise estimates of HIV incidence and much of this work is being driven from Southern Africa. Some of the newly proposed methods require data from multiple (unlinked) age-structured HIV prevalence surveys [67, 68]. This approach is dependent on good estimates of “excess mortality” associated with HIV and requires transformation of mortality data from the form in which it is conveniently collected for prognostic models. Another dynamic and evolving method to estimate incidence uses biomarkers of recent HIV infection data on specimens collected from cross-sectional surveys [69•, 70]. However, while there are some tests that can already yield useful recent infection metrics applicable in very high incidence settings, this approach is still not routinely available, and requires some improvement of laboratory technology and adoption of consistent approaches in analysis. Additionally, measurement of incidence rates in cohorts in geographical hotspots or key populations such as adolescent girls and young women could complement country level surveillance.
Important lessons concerning health care delivery have been learned through the provision of cART and prevention of vertical transmission of HIV (PMTCT). The high rate of HIV acquisition in young women is a key barrier to an AIDS-free generation in this region. HIV prevention interventions targeting young women need to also meet their sexual and reproductive health needs. Cash based structural interventions that support school completion rates are very promising. Scale up of treatment as prevention efforts could indirectly reduce HIV acquisition rates in young women. Intensified combination prevention interventions including TasP in geographical hotspots and key populations provide an efficient use of limited resources for maximum impact. As studies on “treatment for prevention” proceed, the fraction of new HIV infections caused by those with acute HIV infection will increase. Innovative strategies for accurate and precise measurement of incident infection are not only key for identifying these individuals and linking them to care, but also for enhancing surveillance efforts. Ultimately, an AIDS-free generation in Southern Africa will require elimination of new HIV infections in an entire generation, for the duration of a lifetime. High rates of transmission to adolescent girls and among other key populations are arguably the most important barriers to reaching this target.
Swaziland, Lesotho, Botswana, South Africa, Zimbabwe, Namibia, Zambia, Mozambique, Angola and Malawi
According to the President’s Emergency Plan for AIDS Relief (PEPFAR), an AIDS-free generation entails that first, no one will be born with the virus; second, that as people get older, they will be at a far lower risk of becoming infected than they are today; and third, that if they do acquire HIV, they will get treatment that keeps them healthy and prevents them from transmitting the virus to others.
Compliance with Ethics Guidelines
Conflict of Interest
Wim Delva declares that he has no conflict of interest.
Quarraisha Abdool Karim has a patent PCT61/354.050 and PCT 61/357,892 (filed in 2011) for Tenofovir gel against HSV-1 and HSV-2 pending.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.