by Elliot Eton
The target is 2030. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has ambitiously set 2030 as the year by which we should achieve the end of the HIV/AIDS epidemic, which has claimed the lives of 39 million people globally since the first cases were reported in 1981.1 This past year, to help drive united progress and accountability towards the goal, UNAIDS articulated the 90-90-90 targets. If these goals are reached by 2020, UNAIDS predicts, then the AIDS epidemic could come to an end by 2030:
- Goal 1: “By 2020, 90% of all people living with HIV will know their HIV status.”
- Goal 2: “By 2020, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy.”
- Goal 3: “By 2020, 90% of all people receiving antiretroviral therapy will have viral suppression.”2
These new aims directly emphasize the importance of maintaining the HIV treatment cascade while scaling up treatment programs. In the past, programmatic success was measured by the number of those on treatment; the 2011 High-Level Meeting on AIDS, for example, set a goal of reaching 15 million people on treatment by 2015, which has since been reached.1,2 While the numbers certainly provide an essential indicator of progress, the new UNAIDS goals add an extra dimension: focusing on maintaining quality of treatment while expanding programs. Indeed, infectious disease specialist Dr. Edward Gardner and collaborators observed in 2011 that “to fully benefit from potent combination antiretroviral therapy, [infected individuals] need to know that they are HIV infected, be engaged in regular HIV care, and receive and adhere to effective antiretroviral therapy.”3
Approximately 36.9 million people are living with HIV, of which 25.8 million (~70%) live in sub-Saharan Africa.1 Though some countries are nearing 90-90-90 (e.g. Rwanda, Botswana), most of the region is lagging behind: 45% of those with HIV in sub-Saharan Africa know their status, 39% with diagnosed infection are receiving antiretroviral therapy (ART), and 29% of those on ART have suppressed viral load.2 A variety of obstacles hinder maximal treatment engagement (e.g. insufficient infrastructure). Furthermore, certain key populations, burdened by the persistence of stigma and discrimination, often institutionalized in national laws (e.g. criminalization of same-sex relations, sex work, and drug use), still experience inadequate access to care. The UNAIDS targets emphasize equity and speed: all communities must have equal access to comprehensive treatment, and infection must be recognized and treated early if the goals are to be met by 2030.3
To achieve 90-90-90, the HIV/AIDS community has rallied around the strategy “treatment as prevention” (TasP). In 2011, the 052 clinical trial conducted by the HIV Prevention Trials Network (HPTN) published breakthrough results, revealing that putting an HIV-infected individual on ART early reduced the risk of heterosexual viral transmission to the individual’s uninfected partner by 96%.5 Treatment hits two birds with one stone; it suppresses viral replication to “undetectable” levels, which thwarts disease progression and reduces the probability of viral transmission to a new host. As Professor Max Essex, Mary Woodward Lasker Professor of Health Sciences and head of the Harvard T.H. Chan School of Public Health AIDS Initiative, says, “People without high viral load don’t transmit.”4 The idea that treatment could stop heterosexual transmission was originally disparaged. A 2008 statement submitted by the Swiss Federal Commission for HIV/AIDS described it as “appalling,” “inconclusive,” and “dangerous.”5 The results of HPTN 052 are indeed revolutionary. As UNAIDS Executive Director Michel Sidibé commented in 2011, “This breakthrough is a serious game changer and will drive the prevention revolution forward. It makes HIV treatment a new priority prevention option.”6
Working to test the TasP strategy at the national level, Essex is working with partners from the Harvard T.H. Chan School of Public Health, the Botswana Ministry of Health, the Botswana-Harvard AIDS Institute Partnership, and the U.S. Centers for Disease Control and Prevention to lead an enormous trial in Botswana called the Botswana Combination Prevention Project (BCPP). Appropriately, in Setswana, the language of Botswana, the trial is called Ya Tsie, which means “Teamwork bears more fruit than individual efforts.” The study tests the effects of combining and strengthening traditional treatment strategies, such as inhome counseling and testing, mother-tochild interventions, and voluntary circumcision of infected men.
One major innovation in this trial is targeting interventions to individuals with high viral load but with CD4+ T-helper cell counts above the level for treatment eligibility. HIV destructively weakens the immune system by targeting and destroying the CD4+ cells, which are a type of white blood cell that coordinates the immune system response to foreign invaders. Thus, the CD4 count (cells per volume) is a strong indicator of disease stage, and the World Health Organization has long based its treatment eligibility criteria around this count. Yet there is a drawback: CD4 count does not directly indicate an individual’s infectivity. Indeed, individuals with relatively high CD4 counts may actually harbor high levels of virus.
Since decreasing infectivity is a key goal of TasP, and a high viral load may portend a more rapid progression to AIDS, BCPP is testing the use of viral load—not necessarily CD4 count—as the primary indicator of when to initiate treatment. Early initiation of treatment based on viral load levels will benefit the infected individual and prevent transmission.
Another central innovation is genetically evaluating transmission networks. HIV’s strongest—and most dangerous—asset is its ability to copy itself extraordinarily quickly. If replication is not controlled, the virus can mutate regularly, producing daughter viral progenies that vary slightly from their parents. As a result, the more closely two viral sequences match each other, the more likely is is that they share a recent common host.5 In addition, unrestricted replication means high viral load, which, in turn, increases the probability of transmission per sexual act. Hence, it is possible to track the spread of the virus—and use this information to design appropriate and effective strategies to block it—a technique called phylogenetic analysis.5
Phylogenetic analysis is centered around the concept of a “transmission cluster,” which is defined as a difference of less than 1.5% in HIV genomic sequences found in two or more individuals.7 While not necessarily proving that one person infected the other, one can conclude that the sequences are closely linked evolutionarily.5 Furthermore, researchers can estimate the time of transmission because of HIV’s constant mutation rate. Researchers can then create transmission maps that depict not only the direction of spread but also the speed.5
The Ya Tsie trial includes fifteen pairs of neighboring villages—one in a pair will receive the TasP intervention, while the other will continue receiving the standard of care (with improvements in medical logistics and equipment). Researchers hope to genetically track the virus to determine the transmission network: whether certain viral strains are circulating within communities or being transported across villages. Determining the direction and extent of transmission can hence be a key marker in evaluating whether the TasP intervention was successful or not.4
This comprehensive trial is the result of years of planning and refining statistical algorithms to aid in analysis. There are still challenges to overcome—especially in ensuring the sampling density (number of samples per community) is high enough to provide a representative depiction of the HIV transmission network. Indeed, certain key populations could be disproportionately represented.4
Results of the Ya Tsie trial will provide further evidence either in support of or against TasP as an effective treatment strategy to combat the HIV/AIDS pandemic. Approximately 2 million people were newly infected with HIV in 2014.1 We must end transmission and close the gaps in care— expanding treatment programs to reach certain key populations. As Michel Sidibé says, “Never has it been more important to focus on location and population—to be at the right place for the right people.”8 If TasP proves a valuable and cost-effective tool to combat the spread of HIV—and becomes included in national HIV/AIDS treatment programs—we may be one step closer to achieving the bold UNAIDS goals of ending the epidemic by 2030.
Elliot Eton ‘19 is a freshman in Apley Court.
- World Health Organization. HIV/AIDS Fact Sheet, 2015. http://www.who.int/mediacentre/factsheets/fs360/en/ (accessed Sep. 28, 2015).
- UNAIDS. 90-90-90: An ambitious treatment target to help end the AIDS epidemic. UNAIDS, 2014. http://www.unaids.org/sites/default/files/media_asset/90-90-90_en_0.pdf (accessed Sep. 28, 2015).
- Gardner, E. et al. Clin Infect Dis, 2011, 52, 793-800.
- Powell, A. Viral load as an anti-AIDS hammer. Harvard Gazette, Aug. 1, 2014. http://news.harvard.edu/gazette/story/2014/08/viral-load-as-an-antiaids-hammer/ (accessed Sep. 28, 2015).
- Cohen, J. Breakthrough of the Year: HIV Treatment as prevention, Dec. 23, 2011. http://www.sciencemag.org/content/334/6063/1628.full (accessed Oct. 10, 2015).
- UNAIDS. Groundbreaking trial results confirm HIV treatment prevents transmission of HIV. UNAIDS, 2011. http://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2011/may/20110512pstrialresults (accessed Oct. 10, 2015).
- Cohen, J. HIV family trees reveal viral spread: New studies could aid public health efforts, Jun. 12, 2015. https://www.sciencemag.org/content/348/6240/1188.short (accessed Sep. 28, 2015).
- UNAIDS. The Gap Report. UNAIDS, 2014. http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Gap_ report_en.pdf (accessed Oct. 10, 2015).