Fluent Essays

Capstone Project Topic Selection and Approval In collaboration with the approved course preceptor, students will identify a specific evidence-based topic for the capstone project change proposal. Students should consider the clinical environment in which they are currently employed or have recently worked. The capstone project topic can be a clinical practice problem, an organizational issue, a leadership or quality improvement initiative, or an unmet educational need specific to a patient population or community. The student may also choose to work with an interprofessional collaborative team. Students should select a topic that aligns to their area of interest as well as the clinical practice setting in which practice hours are completed. Write a 600 word description of your proposed capstone project topic. Include the following: The problem or issue, intervention, quality initiative, educational need, or collaborative interprofessional team project that will be the focus of the change proposal. The setting or context in which the problem or issue, intervention, quality initiative, educational need, or collaborative interprofessional team project can be observed. A description (providing a high level of detail) regarding the problem or issue, intervention, quality initiative, educational need, or collaborative interprofessional team project. Effect of the problem or issue, intervention, quality initiative, educational need, or collaborative interprofessional team project. Significance of the topic and its implications for nursing practice. A proposed solution to the identified project topic with an explanation of how it will affect nursing practice. You are required to cite to a minimum of eight peer-reviewed sources to complete this assignment. Sources must be published within the last 5 years, appropriate for the assignment criteria, and relevant to nursing practice. Plan your time accordingly to complete this assignment. Items to include: *What is HIV/AID *How is it transmited *At risk Population What is U=U and its goals Barriers to care, treatment and status disclosure: Stigma, culture, education, sexual orientation and or gender. My Capstone proposal: Using U=U 2020 initiative to Educate patients in risky sexual behaviors and or those that do not disclose HIV status prior to engaging in sexual activity. The Goal is to increase disclosure in HIV status by educating patients on U=U and finding comfortable ways to initiate/open a conversation and proper timing prior to partaking in consensual sexual activity. Data for the study will be limited due to the COVID epidemic and the number of clients willing to participate. But having a clear understanding of U=U can result in great outcomes, decreased new cases and change public perspective on HIV positive patients and safety. This is why compliance with IRT-Antiretroviral Therapy is important. https://www.oar.nih.gov/about/directors-corner/why-is-u-equals-u-game-changer https://www.niaid.nih.gov/diseases-conditions/treatment-prevention HIV Viral Load and Transmissibility of HIV Infection Undetectable Equals Untransmittable In 2016, the Prevention Access Campaign, a health eq- uity initiative with the goal of ending the HIV/AIDS pan- demic as well as HIV-related stigma, launched the Un- detectable = Untransmittable (U = U) initiative.1 U = U signifies that individuals with HIV who receive antiret- roviral therapy (ART) and have achieved and main- tained an undetectable viral load cannot sexually trans- mit the virus to others. This concept, based on strong scientific evidence, has broad implications for treat- ment of HIV infection from a scientific and public health standpoint, for the self-esteem of individuals by reduc- ing the stigma associated with HIV,2 and for certain le- gal aspects of HIV criminalization.3 In this Viewpoint, we examine the underlying science-based evidence sup- porting this important concept and the behavioral, so- cial, and legal implications associated with the accep- tance of the U = U concept. A major breakthrough in HIV/AIDS therapeutics came in 1996 with the advent of 3-drug combinations of antiretrovirals, including the newly developed prote- ase inhibitors. These therapeutic regimens resulted in substantial decreases in viral load in a high percentage of patients, usually below the level of detection in plasma and sustained for extended periods.2 Although not ap- preciated at the time, the accomplishment of a sus- tained, undetectable viral load was likely the definitive point when the U = U concept became a reality. Proof of that concept would await further clinical trials and co- hort studies. Based on a review of scientific data, a state- ment from Switzerland in 2008 indicated that individu- als with HIV who did not have any other sexually transmitted infection, and achieved and maintained an undetectable viral load for at least 6 months, did not transmit HIV sexually.4 This was the first declaration of the U = U concept, but it was not universally embraced because it lacked the rigor of randomized clinical trials. In 2011, the HIV Prevention Trials Network (HPTN) study 052 compared the effect of early with delayed ini- tiation of ART in the partner with HIV among 1763 HIV- discordant couples, of whom 98% were heterosexual. The finding of a 96.4% reduction in HIV transmission in the early-ART group, vs those in the delayed group, pro- vided the first evidence of treatment as prevention in a randomized clinical trial.5 At that point, the study could not address the durability of the finding or provide a pre- cise correlation of the lack of transmissibility with an un- detectable viral load. Importantly, after 5 additional years of follow-up, the durable, protective effect of early ART to maintain viral suppression and prevent HIV transmis- sion was validated. There were no linked transmissions when viral load was durably suppressed by ART.6 Subsequent studies confirmed and extended these findings. The PARTNER 1 study determined the risk of HIV transmission via condomless sexual intercourse in 1166 HIV-discordant couples in which the partner with HIV was receiving ART and had achieved and main- tained viral suppression (HIV-1 RNA viral load <200 cop- ies/mL). After approximately 58 000 condomless sexual acts, there were no linked HIV transmissions.3 Since a mi- nority of the HIV-discordant couples in PARTNER 1 were men who have sex with men (MSM), there was insuffi- cient statistical power to determine the effect of an un- detectable viral load on the transmission risk for recep- tive anal sex. In this regard, the Opposites Attract study evaluated transmissions involving 343 HIV-discordant MSM couples in Australia, Brazil, and Thailand. After 16 800 acts of condomless anal intercourse there were no linked HIV transmissions during 588.4 couple-years of follow-up during which time the partner with HIV had an undetectable viral load (<200 copies/mL).3 Building on these studies, the PARTNER 2 study con- clusively demonstrated that there were no cases of HIV transmission between HIV-discordant MSM partners de- spite approximately 77 000 condomless sexual acts if the partner with HIV had achieved viral suppression and the uninfected partner was not receiving preexposure prophylaxis or postexposure prophylaxis.7 The validity of the U = U concept depends on achiev- ing and maintaining an undetectable viral load in an indi- vidual with HIV. Because of the promise of U = U, achiev- ing and maintaining an undetectable viral load becomes an aspirational goal and offers hope for persons with HIV. The principles involved in achieving and maintaining an undetectable viral load are related to (1) taking ART as pre- scribed and the importance of adherence; (2) time to vi- ral suppression; (3) viral load testing recommendations; and (4) the risk of stopping ART (Box). Taking ART as prescribed is essential for achieving and maintaining an undetectable viral load. The Cen- ters for Disease Control and Prevention (CDC) reported that of the individuals with HIV in the United States in HIV clinical care in 2015, approximately 20% had not achieved viral suppression (<200 HIV-1 RNA copies/mL) at their last test. CDC also noted that 40% of the indi- viduals in HIV clinical care that same year did not main- tain viral suppression for more than 12 months.8 Lack of adherence with ART is associated with many factors, in- cluding the lack of accessibility of quality health care. The stability of health care provided by programs such as the Ryan White HIV/AIDS Program shows that high rates of viral suppression are possible in the context of quality care delivery. VIEWPOINT Robert W. Eisinger, PhD Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Carl W. Dieffenbach, PhD Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Anthony S. Fauci, MD Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Corresponding Author: Anthony S. Fauci, MD, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bldg 31, Room 7A03, Bethesda, MD 20892 ([email protected] niaid.nih.gov). Opinion jama.com (Reprinted) JAMA February 5, 2019 Volume 321, Number 5 451 © 2019 American Medical Association. All rights reserved.© 2019 American Medical Association. All rights reserved. Downloaded from jamanetwork.com by Jules Levin on 02/11/2019 mailto:[email protected] mailto:[email protected] http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2018.21167 The guidance that viral suppression measured at 6 months after starting therapy is required for U = U has several origins. First, Partners PrEP trial, a prospective cohort study conducted among 4747 heterosexual HIV-discordant couples in Kenya and Uganda, was designed to determine the risk of HIV transmission prior to and following achieving viral suppression (<80 HIV-1 RNA copies/mL). HIV incidence prior to initiation of ART was 2.08 per 100 person- years, 1.79 for 0 to 6 months after initiation of ART, and 0.00 with more than 6 months of ART, indicating that residual HIV transmis- sion risk persists during the first 6 months of ART, during which time there is incomplete suppression of HIV in blood and genital compartments.9 Second, a case of a linked transmission in Partners PrEP occurred when the treated partner had been taking ART for fewer than 4 months and prior to complete viral suppression.3 These findings support the requirement for 6 months of ART to achieve virologic suppression. The recommended schedule for viral load testing for individu- als with HIV in the United States, according to the Panel on Antiret- roviral Guidelines for Adults and Adolescents,2 includes testing (1) at entry into care; (2) on initiation of ART or at the time of treat- ment regimen modification; (3) 2 to 8 weeks after ART initiation or modification and repeated every 4 to 8 weeks until the HIV-1 RNA viral load is suppressed to less than 200 HIV-1 RNA copies/mL; and (4) repeated every 3 to 4 months. For individuals who are adherent to treatment with consistently suppressed viral load and stable im- munologic status for more than 2 years, the guidelines panel2 rec- ommends that monitoring can be extended to 6-month intervals. Stopping ART represents a significant challenge to successful implementation of U = U. When ART is stopped, viral rebound usu- ally occurs within 2 to 3 weeks. The SPARTAC and SMART clinical trials used stopping ART to determine if the same degree of protec- tion from progression to AIDS could be achieved by ART dosed for defined intervals or continuously delivered. In both studies, stop- ping ART resulted in viral rebound to levels that would have been associated with increased risk of HIV transmission.10 A systematic review of 12 recent clinical studies concluded that there is negligible risk (0.00 transmissions/100 person-years, 95% CI, 0.00-0.28) of HIV sexual transmission among HIV-discordant partners when the partner with HIV adheres to ART and maintains a suppressed viral load (<200 HIV-1 RNA copies/mL) measured routinely every 4 to 6 months.3 To enhance the overall success of the U = U concept, it is important to implement programs that help patients remain in care and address the challenges in their lives that result in their stopping therapy. In summary, even though the clinical data underpinning the concept of U = U have been accumulating for well over a decade, it is only recently that an overwhelming body of evidence has emerged to provide the firm basis to now accept this concept as scientifically sound. This has important implications in several areas. The U = U concept provides incentives for individuals with HIV to seek, initiate, and adhere to ART. In addition, it adds incen- tives to efforts to control and ultimately end the HIV/AIDS pan- demic because treatment as prevention is a critical tool in prevent- ing the spread of HIV infection.2 The U = U concept also bridges the best of biomedical science with current concepts in behavioral and social science by removing the sense of fear and guilt that a person may be harming someone else, as well as the feeling of self- imposed and external stigma that many people with HIV experi- ence. Finally, this concept has legal implications related to the criminalization of certain persons with HIV whereby criminal law is used to penalize alleged, perceived, or potential HIV exposure of one person to another. ARTICLE INFORMATION Published Online: January 10, 2019. doi:10.1001/jama.2018.21167 Conflict of Interest Disclosures: None reported. REFERENCES 1. Prevention Access Campaign. Undetectable=Untransmittable. https://www. preventionaccess.org/undetectable. Published July 2016. Updated August 23, 2018. Accessed October 18, 2018. 2. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. https://aidsinfo.nih.gov/guidelines/html/1/ adult-and-adolescent-arv/37/whats-new-in-the- guidelines-. October 25, 2018. Accessed January 4, 2019. 3. LeMessurier J, Traversy G, Varsaneux O, et al. Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review. CMAJ. 2018;190(46):E1350-E1360. doi:10. 1503/cmaj.180311 4. Vernazza P, Hirschel B, Bernasconi E, Flepp M. Les personnes seropositives ne souffrant d'aucune autre MST et suivant un traitement antiretroviral efficace ne transmettent pas le VIH voie sexuelle. Bulletin des medecins suisses. 2008;89(5):165-169. doi:10.4414/bms.2008.13252 5. Cohen MS, Chen YQ, McCauley M, et al; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365 (6):493-505. doi:10.1056/NEJMoa1105243 6. Cohen MS, Chen YQ, McCauley M, et al; HPTN 052 Study Team. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375(9):830-839. doi:10.1056/NEJMoa1600693 7. Rodger A, Cambiano V, Brunn T, et al. Risk of HIV transmission through condomless sex in MSM couples with suppressive ART: the Partners2 Study extended results in gay men. Presented at: 22nd International AIDS Conference; July 25, 2018; Amsterdam, the Netherlands. 8. Centers for Disease Control and Prevention. Evidence of HIV treatment and viral suppression in preventing the sexual transmission of HIV. https://www.cdc.gov/hiv/pdf/risk/art/cdc-hiv-art- viral-suppression.pdf. December 2018. 9. Mujugira A, Celum C, Coombs RW, et al; Partners PrEP Study Team. HIV transmission risk persists during the first 6 months of antiretroviral therapy. J Acquir Immune Defic Syndr. 2016;72(5):579-584. 10. Hamlyn E, Ewings FM, Porter K, et al; INSIGHT SMART and SPARTAC Investigators. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One. 2012;7(8):e43754. doi:10.1371/journal.pone.0043754 Box. Principles to Achieve and Maintain an Undetectable Viral Load • In order for antiretroviral therapy (ART) to provide maximum benefit, taking medication as prescribed is essential. • Achieving an undetectable viral load can take up to 6 months of ART. Once achieved, continued adherence is required. • According to guidelines from the Department of Health and Human Services, viral load testing should be performed every 3-4 months after the plasma HIV-1 RNA level reaches undetectable (<200 copies/mL). If viral suppression and stable immunologic status are maintained for >2 years, the viral load testing can be extended to every 6 months thereafter. • Stopping therapy negates the validity of assuming that U = U. Opinion Viewpoint 452 JAMA February 5, 2019 Volume 321, Number 5 (Reprinted) jama.com © 2019 American Medical Association. All rights reserved. Downloaded from jamanetwork.com by Jules Levin on 02/11/2019 https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2018.21167&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2018.21167 https://www.preventionaccess.org/undetectable https://www.preventionaccess.org/undetectable https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/37/whats-new-in-the-guidelines- https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/37/whats-new-in-the-guidelines- https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/37/whats-new-in-the-guidelines- https://dx.doi.org/10.1503/cmaj.180311 https://dx.doi.org/10.1503/cmaj.180311 https://dx.doi.org/10.4414/bms.2008.13252 https://dx.doi.org/10.1056/NEJMoa1105243 https://dx.doi.org/10.1056/NEJMoa1600693 https://www.cdc.gov/hiv/pdf/risk/art/cdc-hiv-art-viral-suppression.pdf https://www.cdc.gov/hiv/pdf/risk/art/cdc-hiv-art-viral-suppression.pdf https://www.ncbi.nlm.nih.gov/pubmed/27070123 https://dx.doi.org/10.1371/journal.pone.0043754 http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2018.21167 CAPSTONE FINAL REPORT UNDERSTANDING PERCEPTIONS OF HIV RISK AND PREVENTION PRACTICES ABSTRACT This report summarizes the results of my Capstone Project conducted at Miami-Dade County Health Department’s STD Department. My Capstone project was a continuation of my MPH field experience in which I assisted in collecting data for a study being conducted by the STD Department. This field project uses a subset of that data from the participants I personally interviewed to identify relationships between specific client characteristics and their preferences for HIV prevention strategies. The objective of this project was to better understand client needs in order to better design culturally acceptable interventions. The project considered four key independent variables: client gender, client ethnicity, and client sexual orientation. Client sexual orientation was defined as men who have sex with men (MSM), men who have sex with women only (MSW), women who have sex with men and/or women (WSM), and women who have sex with women only (WSW). The key dependent variable was the client’s preferred HIV prevention strategies, one of circumcision, female condom, male condom, Microbicides, or pre-exposure prophylaxis. The data collected was analyzed to determine whether client gender, partner gender, or race/ethnicity were related to HIV prevention strategy preferences. Of the four, only client gender showed a notable difference, with males strongly preferring male condoms, while females were approximately equally split among nearly all prevention strategies. The key limitation of the project was the very small sample size which precluded statistical hypothesis testing. Recommendations included both repeating the project with substantially larger sample in which statistically significant results for reasonable effect sizes would be more likely., . In the meantime, however, awareness than male and female clients may have significantly different HIV prevention strategy preferences is an important conclusion. TABLE OF CONTENTS SUMMARY STATEMENT ......................................................................................................... 5 PROJECT OBJECTIVES ........................................................................................................... 6 BACKGROUND LITERATURE ................................................................................................ 7 NEW STRATEGIES IN HIV PREVENTION .................................................................................... 7 ETHNIC ISSUES IN HIV PREVENTION STRATEGIES .................................................................... 9 GENDER ISSUES IN HIV PREVENTION STRATEGIES ................................................................. 10 SEXUAL ORIENTATION ISSUES IN HIV PREVENTION STRATEGIES .......................................... 10 SUMMARY OF LITERATURE REVIEW ....................................................................................... 12 METHODOLOGY AND PROJECT DESIGN ........................................................................ 12 MATERIALS AND METHODS .................................................................................................... 13 EVALUATION AND DATA ANALYSIS ....................................................................................... 14 RESULTS .................................................................................................................................... 15 PERSONAL PARTICIPATION ..................................................................................................... 15 FINDINGS FROM THE PROJECT ................................................................................................. 16 Gender and HIV Prevention Preferences .................................................................... 21 Ethnicity and HIV Prevention Preferences .................................................................. 21 Sexual Orientation and HIV Prevention Preferences .................................................. 21 Sexual Preference and HIV Prevention Preferences ................................................... 22 RECOMMENDATIONS AND CONCLUSIONS .................................................................... 22 DISCUSSION OF RESULTS ........................................................................................................ 22 LIMITATIONS AND RECOMMENDATIONS ................................................................................. 24 REFERENCES ............................................................................................................................ 25 APPENDIX A: RAW DATA FROM PROJECT ..................................................................... 28 UNDERSTANDING PERCEPTIONS OF HIV RISK AND PREVENTION PRACTICES Summary Statement The CDC estimates that as many as 50,000 new cases of HIV are diagnosed each year; 16,000 HIV cases died in 2008 alone (CDC, 2011). There are nearly 1.2 million individuals living with HIV in the U.S. at this time, and that number is continually growing each year (CDC 2011). HIV is also often found coincident with other sexually transmitted diseases (STDs). Statistics from 2010 compiled by the State of Florida (2011) found that there were nearly 400 cases of infectious syphilis in Miami Dade County, with nearly half of those also infected with HIV. Another 850 cases of syphilis in the county were identified as being in either early-latent or late-latent stages, again with between 25% and 50% of them co-infected with HIV (State of Florida, 2011). Several major population groups are at greater risk of HIV including MSM and bisexual men, as well African Americans and Hispanics or Latinos—the major ethnic groups in the Miami-Dade area (CDC, 2011). The Centers for Disease Control and Prevention (CDC) noted in 2011 that while gay and bisexual men (MSM, or Men who have Sex with Men) account for about 2% of the population in the U.S., they account for 61% of all new HIV infections (CDC 2011). Similarly, African Americans are about 14% of the U.S. population, but account for 44% of new HIV infections, with African American women being particularly at risk, with an infection rate 15 times higher than that of white women (CDC 2011). Hispanics are also at greater risk of HIV infections, accounting for 16% of the population, but having 20% of the total new HIV infections—a rate 3 times higher than in the white population (CDC 2011). Other at- risk groups include users of injected drugs, and transgender individuals, with males transitioning to females having approximately a 21% infection rate. A number of new prevention strategies have been developed to prevent HIV infections, including male circumcision, pre-exposure prophylaxis with antiretroviral (ARV) drugs for high- risk individuals, and Microbicides specifically aimed at HIV prevention. These strategies, discussed in more detail in the Literature Review that follows, are not always well known or understood in the community This project aimed to assess the level of understanding of the risk of HIV/AIDS and methods of prevention of HIV/AIDS, as well as to identify ways that public health information about HIV/AIDS can best be disseminated among people of different genders, sexual orientations, and ethnicities. This project should aid in better understanding how attitudes toward HIV prevention practices differ among various groups in the community based on gender, ethnicity, and sexual orientation. Project Objectives Two key objectives were associated with this project. First, the project had the objective of better understanding the attitudes toward HIV prevention strategies as a function of race/ethnicity gender, and partners’ gender. Second, the project was intended to provide a better understanding of how an inner city STD clinic operated, in terms of the its day-to-day operations and its relationship to its clients. These two objectives were intended to better understand how to educate clinic clients on effective means of HIV protection and to identify cultural, racial, gender, or sexual preference differences in how these clients may prefer to receive such education. These objectives are in line with the overall program objectives of understanding the social and behavioral factors that affect individual health choices and to apply that understanding to specific implementations of behavioral interventions. The intention behind the project is to be able to better serve the clients in a good cultural context. Background Literature This brief literature review addresses key themes in the research that address issues of HIV prevention strategies, with particular attention to the acceptability of those strategies to various groups differing by gender, sexual orientation, and ethnicity. New Strategies in HIV Prevention Several new strategies have been developed recently to address HIV prevention. Key among these are topical ARV-based microbicides, oral pre-exposure prophylaxis using ARV drugs, ARV drugs used in HIV-positive individuals to reduce transmission to non-infected persons. ARV therapy is demonstrated useful in treating individuals with HIV infections. It is now being used as a prophylactic therapy to prevent HIV in individuals exposed to others who carry the infection (El-Sadr et al., 2010). While mathematical models indicate that this therapy should be successful, evidentiary support is still thin (El-Sadr et al., 2010). Also, in the U.S. there are significant issues with using ARV therapies as prophylaxis. These barriers include the high number of those who most need the therapy who are also uninsured or underinsured; the demonstrated typical delays between HIV diagnosis and the beginning of HIV treatment, and problems with compliance with a long-term ARV therapy; and the potential for ARV therapy to grant “permission” for higher-risk behaviors more likely to spread the infection (El-Sadr et al. 2010). For this type of therapy to be effective, it will require social, policy, and insurance changes (El-Sadr et al. 2010). One example of the use of ARV drug therapies in HIV prevention campaigns is a pre- exposure prophylaxis method. This is when the ARV drug is used prior to sexual contact with a non-infected person to prevent transmission of the infection. Depending on how strictly the pre- exposure protocol is followed, studies have shown that the risk of infection is cut between 44% and 73% with this strategy (Hayden 2011). However, there is some concern that such a prevention approach may ultimately encourage riskier behavior, such as reduced use of condoms. Furthermore, pre-exposure prophylaxis requires ongoing and regular testing and intensive counseling, neither of which is easy to provide at the level of a population (Hayden 2011). Thus, the cost-effectiveness is uncertain for this particular approach to HIV prevention, an important factor for any strategic plan. Other biomedical approaches to HIV prevention are either in place, or are currently under study. These include a potential HIV vaccine, topical microbicides, male circumcision, and condom usage (Mayer, Skeer & Mimiaga 2010). Of these, topical microbicides are generally gels, sponges or rings applied to vaginal or rectal mucusal areas to prevent HIV infection transmission (Mayer et al. 2010). A large number of such products—at least 80—are either available or under development. Some work by reducing the pH of the mucusal tissues, some are detergents that break microbial membranes, some target the cell or virus receptors to prevent binding of virus to cells; and some inhibit the replication function of the HIV virus (Mayer et al. 2010). Male circumcision is another approach. Studies have shown that the risk of transmission of HIV is reduced by about half in MSM when the male is circumcised (Mayer et al. 2010). Unfortunately, this did not hold for women in contact with circumcised men; no reduction in infectiousness has been found in male-female interactions (Mayer et al. 2010)… [The body of this paper was cut to protect the content from copying and unregulated distribution] References Berkley-Patton, J., Goggin, K., Liston, R., Bradley-Ewing, A., Neville, S. (2009). Adapting effective narrative-based HIV –prevention interventions to increase minorities’ engagement In HIV/AIDS services. Health Communications, 24(3), 199-209. Centers for Disease Control and Prevention (CDC). (2011).High-impact HIV prevention. Centers for Disease Control and Prevention. Retrieved from: http://www.cdc.gov/hiv/strategy/dhap/pdf/nhas_booklet.pdf Centers for Disease Control and Prevention (CDC). (2013). Sexually transmitted diseases (STDs). Centers for Disease Control and Prevention. Retrieved from: http://www.cdc.gov/std/gonorrhea/default.htm Chirenje, Z. M., Marrazzo, J., Parikh, U. M. (2010). Antiretroviral-based HIV prevention strategies for women. Expert Review of Anti-Infective Therapy, 8(10), 1177-1186. Creative Research (2013). Sample size calculator. Creative Research Systems Retrieved from: http://www.surveysystem.com/sscalc.htm DuBois, S. N., Johnson, S. E., Mustanski, B. (2011). Examining racial and ethnic minority differences among YMSM during recruitment for an online HIV prevention intervention study. AIDS and Behavior, 16(6), 1430-1435. El-Sadr, W. M., Affrunti, M., Gambel, T., Zerbe, A. (2010). Antiretroviral therapy: A promising HIV prevention strategy? Journal of Acquired Immune Deficiency Syndromes, 55(Supplement 2), S116-S121. Gasiorowicz, M., Stodola, J. (2011). HIV prevalence estimates and alignment among recent diagnoses, targeted tests, and prevention services by demographic and racial/ethnic group in Wisconsin. AIDS Education and Prevention, 23(3 Supplement), 7-16. Harvey, S. M., Bird, S. T. (2001). Power in relationships and influencing strategies for condom use: Exploring cultural beliefs among African American men. International Quarterly of Community Health Education, 21, 147-162. Hayden, E. C. (2011). HIV drug-prevention strategy carries risks. Nature, 476(7360), 260-261. Hsu, J. ,Zinsou, C., Parkhurst, J., N’Dour, M., FOyet, L., Mueller, D. H. (2013). Comparative costs and cost-effectiveness of behaviorual interventions as part of HIV prevention strategies. Health Policy and Planning, 28(1), 20-29. Jarlais, D. C. D., Cooper, H.L. F., Bramson, H., Deren, S., Hatzakis, A., Hagan, H. (2012). Racial and ethnic disparities and implications for the prevention of HIV among persons who inject drugs. Current Opinion on HIV and AIDS, 7(4), 354-361. Lanier, Y., Sutton, M. Y. (2013). Reframing the context of preventative health care services and prevention of HIV an dother sexually transmitted infections for young men: New opportunities to reduce racial/ethnic sexual health disparities. American Journal of Public Health, 103(2), 262- Mayer, K H., Skeer, M., Mimiaga, M. J. (2010). Biomedical approaches to HIV prevention. Alcohol Research and Health, 33(3), 195- McIntosh, D. R. (2012). Cultural strategies for teaching HIV/AIDS prevention to American Indians. Journal of Adult Education, 41(2), 12- Miami-Dade (2013). Miami-Dade sexually transmitted disease (STD) control and prevention. Miam-Dade County Health Department. Retrieved from: http://www.dadehealth.org/std/STDintro.asp State of Florida. (2011). Reported cases of STDs and the number of those cases identified as co- infected with HIV. Florida Department of Health. Retrieved from: http://www.doh.state.fl.us/Disease_ctrl/std/trends/florida/STDs_HIV_10.pdf e632 www.thelancet.com/hiv Vol 6 September 2019 Viewpoint The disconnect between individual-level and population-level HIV prevention benefits of antiretroviral treatment Stefan Baral, Amrita Rao, Patrick Sullivan, Nancy Phaswana-Mafuya, Daouda Diouf, Greg Millett, Helgar Musyoki, Elvin Geng, Sharmistha Mishra In 2019, the HIV pandemic is growing and soon over 40 million people will be living with HIV. Effective population- based approaches to decrease HIV incidence are as relevant as ever given modest reductions observed over the past decade. Treatment as prevention is often heralded as the path to improve HIV outcomes and to reduce HIV incidence. Although treatment of an individual does eliminate onward transmission to serodifferent partners (unde tectable=untransmittable or U=U), population-level observational and experimental data have not shown a similar effect with scale-up of treatment on reducing HIV incidence. This disconnect might be the result of little attention given to heterogeneities of HIV acquisition and transmission risks that exist in people at risk for and living with HIV, even in the most broadly generalised epidemics. Available data suggest that HIV treatment is treatment, HIV prevention is prevention, and specificity of HIV treatment approaches towards people at highest risk of onward transmission drives the intersection between the two. All people living with HIV deserve HIV treatment, but both more accurately estimating and optimising the potential HIV prevention effects of universal treatment approaches necessitates understanding who is being supported with treatment rather than a focus on treatment targets such as 90-90-90 or 95-95-95. Introduction In 2019, we are at a pivotal time in the global HIV response in that many people believe that the HIV pandemic is over given the advances in HIV treatment.1 Yet the HIV pandemic continues to grow as defined by numbers of people living with HIV. Specifically, given the encouraging decreases in overall mortality among people living with HIV, in the context of universal treat ment as prevention, approximately 930 000 more people annually (1·7 million new infections minus 770 000 deaths of people living with HIV) require anti retroviral therapy (ART) and many more would need to change ART regimens. At the current rate of new infections, over 40 million people will be living with HIV by 2025.2 The global optimism about the HIV pandemic has not been matched by decreases in new HIV infections. New infections have declined by less than 2% per year since 2005, which means that between 1·8 and 2·5 million people acquired HIV in 2017.2,3 To date, just over 60% of the 37·9 million people living with HIV are on ART; of those 37·9 million, just over half (20·1 million) are estimated to have achieved viral sup­ pression.2 Taken together, these data suggest that an estimated 18 million people living with HIV require ART or improved ART regimens given increasing resistance and concerns about drug quality.2,4 Treatment as prevention for HIV was con ceptualised in response to both observational data5–7 and individually randomised controlled trials8–10 that showed risk of HIV transmission to one’s direct sexual partners were closely linked to the viral load among people living with HIV. If people with HIV had undetectable viral loads, then risk of HIV transmission is zero—referred to as undetectable=untransmittable (U=U).11 These trials were followed by observational studies reinforcing U=U, with no linked transmission events among heterosexual and same­sex male serodifferent couples who reported condomless sex in the absence of HIV pre­exposure prophylaxis.5–7,12 Given the consistent data supporting U=U, treatment as prevention at the population level was expected to reduce HIV incidence substantially through reductions in onward transmissions at the population level. Although the data on U=U at the individual level are clear, whether treatment has decreased HIV incidence at the population level in proportion to increases in coverage of effective treatment is far less clear. However, a linear or dose­ response effect between treatment and incidence re­ ductions would require all people living with HIV to have similar risks of onward transmission if they were not virally suppressed. Data on the heterogeneities that exist in every setting in onward HIV transmission risks in the context of different sexual networks challenge the dose­ response effects of treatment as prevention. These data are further contextualised by rich literature in disparities and inequities research showing that, often secondary to structural determinants, neither treatment nor viral suppression is equal among populations living with HIV. Three large­scale cluster randomised controlled trials did not show incidence declines attributable to universal access to ART. These experimental data complement observational data showing sustained HIV incidence despite increased HIV treatment across municipalities, regions, and nationally in countries across income levels. Here, we synthesise data supporting U=U for serodifferent couples, treatment as prevention at the population level, and potential reasons for the discon­ nect in observed effect between these two intervention strategies. Unequivocal data supporting benefits of U=U for individuals and serodifferent couples A series of randomised controlled trials showed that early ART initiation can have immediate and clinically meaningful individual­level benefits, including reductions in morbidity and mortality among people living with HIV and reductions in the rate of linked partner transmissions Lancet HIV 2019; 6: e632–38 Published Online July 19, 2019 http://dx.doi.org/10.1016/ S2352-3018(19)30226-7 Center for Public Health and Human Rights, Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA (S Baral MD, A Rao ScM); Department of Epidemiology, Laney Graduate School, Rollins School of Public Health, Emory University, Atlanta, GA, USA (P Sullivan PhD); Research and Innovation Office, North West University, Potchefstroom, South Africa (N Phaswana-Mafuya PhD); Enda Santé, Dakar, Senegal (D Diouf MS); amfAR, the Foundation for AIDS Research, Washington, DC, USA (G Millett MPH); National AIDS and Sexually Transmitted Infection Control Programme, Ministry of Health, Nairobi, Kenya (H Musyoki MPH); Department of Medicine, University of California, San Francisco, CA, USA (E Geng MD); and St Michael’s Hospital, Li Ka Shing Knowledge Institute, and Department of Medicine, Division of Infectious Disease, University of Toronto, Toronto, Canada (S Mishra PhD) Correspondence to: Dr Stefan Baral, Center for Public Health and Human Rights, Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA [email protected] For more on treatment as prevention see http://www.cfenet.ubc.ca/ http://crossmark.crossref.org/dialog/?doi=10.1016/S2352-3018(19)30226-7&domain=pdf www.thelancet.com/hiv Vol 6 September 2019 e633 Viewpoint (figure 1). The TEMPRANO ANRS 12136 trial,9 done at nine care centres in Abidjan, Côte d’Ivoire, between 2008 and 2012, found that among 2056 patients, early ART initiation compared with deferred initiation reduced the risk of death or severe HIV­related illness by nearly 50% (adjusted hazard ratio [HR] 0·56, 95% CI 0·41–0·76). Early ART initiation (ie, ART started immediately after randomisation) reduced HIV­related illness even among people with pre­ART CD4 counts of 500 cells per µL or more (0·56, 0·33–0·94).9 The START trial8 showed similar results. In this trial,8 4685 patients were recruited between 2009 and 2013 from 35 countries and followed up for a mean of 3·0 years. Adults living with HIV with a CD4 count of more than 500 cells per µL were randomly assigned to start ART immediately or to defer initiation until CD4 count decreased to 350 cells per µL, development of AIDS, or development of another condition that required the use of ART.8 Patients were followed up to ascertain the primary endpoint of any serious AIDS­related event, serious event not related to AIDS, or all­cause mortality.8 Early initiation again showed individual­level benefits over starting therapy after CD4 count had declined (eg, adjusted HR for morbidity or mortality 0·43, 95% CI 0·30–0·62).8 Between 2007 and 2010, the HPTN 052 trial10 randomly assigned 1763 index participants living with HIV from multiple low­income, middle­income, and high­income countries to early or deferred initiation to evaluate differences in genetically linked new HIV infections in previously HIV­negative partners.10 Compared with the delayed ART group, early ART was associated with a reduction in linked partner infection (HR 0·07, 95% CI 0·02–0·22).10 Of the 72 partner infections in which viral­ linkage was possible, 46 were linked and 26 were unlinked. Unlinked transmissions came from outside of the sero­ different partnership being evaluated, providing early insights into effectiveness challenges of this approach.10 Of these 26 unlinked partner infections, they were distributed relatively equally in both groups with 14 in the early­ART group and 12 in the delayed­ART group, foreshadowing limitations in HIV acquisition that happens outside primary partnerships. The HPTN 052 trial10 showed that 30% of partner infections could not be prevented by treatment as prevention. Only two­thirds of couples enrolled into the study were available for final analysis of effect, further reinforcing implementation challenges of a universal treatment approach. To complement these three experimental studies8–10 focused on leveraging HIV treatment to prevent trans­ mission within serodifferent partnerships and preventing HIV­related morbidity and mortality, three large obser­ vational studies evaluated HIV trans mission within serodifferent couples during periods of condomless sex and suppressed viral load of infected partners. Two studies5,7 have followed both heterosexual and same­ sex male HIV serodiff erent couples to track linked HIV transmissions. In the Oppo sites Attract observational cohort study,5 serodifferent gay male couples were recruited from Australia, Brazil, and Thailand. Between 2012 and 2016, 343 couples had at least one follow­up visit, with a total of 16 800 condomless anal intercourse acts and 258 (75%) HIV­positive partners having viral loads below 200 copies per mL. No linked transmissions were observed.5 In the prospective, observational PARTNER study,7 1166 sero different het erosexual and male homo sexual couples who reported condomless sexual activity between 2010 and 2014 were enrolled.7 Inclusion criteria included that the partner living with HIV was to be virally suppressed for the couple to be eligible.7 Male homosexual couples reported approxi­ mately 22 000 condomless sex acts and heterosexual couples reported about 36 000.7 Similarly, no phylo­ genetically linked new infections were observed.7 Results of the second phase of the PARTNER study were recently published.6 No linked trans missions were found between homosexual couples for nearly 77 000 condomless anal intercourse acts, in which the partner living with HIV was virally suppressed.6 Importantly, these prevention benefits will only be sustained in the context of programmes that address long­term treatment needs for people living with HIV. Recent data from the USA suggest that achieving sustained viral suppression, especially among the most marginalised communities living with HIV, might be a challenge yet to be overcome.18 Taken together, the observational data combined with the efficacy data from the HPTN 052 trial10 do reinforce the veracity of U=U and the efficacy for treatment to prevent HIV transmission in the context of serodifferent HIV partnerships. Figure 1: Experimental studies evaluating HIV treatment outcomes at the population level and individual level Details of studies and comparisons are given in the main text. Blue lines represent studies with population-level outcomes and red lines are studies with individual-level outcomes. aHR=adjusted hazard ratio. aRR=risk ratio. IRR=incidence rate ratio. ART=antiretroviral therapy. ANRS 12249 TasP13–15 Reduction in population-level incidence (aHR) SEARCH16 Reduction in 3-year cumulative population-level incidence (aRR) HPTN 071 (PopART)17 Reduction in population-level incidence (IRR) TEMPRANO9 Reduction in HIV morbidity or mortality (aHR) START8 Reduction in HIV morbidity or mortality (aHR) HPTN 05210 Reduction in linked-partner infection (HR) 0 0·2 0·4 0·6 0·8 1·0 1·2 1·4 1·6 M ea su re o f a ss oc ia ti on fo r t ria ls 1·01 0·95 0·93 0·56 0·43 0·07 e634 www.thelancet.com/hiv Vol 6 September 2019 Viewpoint Treatment as prevention as a population-based approach As of 2019, three fully powered cluster randomised trials have measured the effect of universal testing and treatment on population­level reductions in HIV incidence (figure 1). The ANRS 12249 TasP study13–15 was a cluster randomised trial designed to evaluate the effect of early ART, irrespective of CD4 count, on HIV incidence in specific clusters in northern KwaZulu­Natal, South Africa. Communities were randomly assigned either to immediate offer of ART or to standard of care in South Africa at the time (ART initiation at CD4 count ≤350 cells per µL or WHO stage 3 or 4 until December, 2014, then ≤500 cells per µL from January, 2015), and no differences were observed in population­level HIV incidence by group (adjusted HR 1·01, 95% CI 0·87–1·17).14,15 In the SEARCH study,16 32 communities in Kenya and Uganda were randomly assigned to receive universal ART with a multidisease model, which included patient­centred interventions related to hypertension, diabetes, tubercu­ losis, and HIV. The inter vention reduced annual tuberculosis incidence and improved population HIV viral suppression.16 Although HIV incidence declined across all observed communities, no difference was observed in 3­year cumulative HIV incidence between groups (adjusted risk ratio 0·95, 95% CI 0·77–1·17).16 Conclusions for non­significance associated with treat­ ment included that new infections were coming from outside the community, outbreaks of acute infection, and the small subset of the population living with HIV who were unsuppressed.16 Results from HPTN 071,17 also known as PopART, were presented at the Conference on Retroviruses and Opportunistic Infections 2019. The study17 was designed as a community­randomised trial among 21 urban com munities across Zambia and South Africa. Communities were randomly assigned to three groups between 2013 and 2018: group A (full PopART intervention, which was a combination prevention and treatment intervention, and included immediate ART for all individuals with HIV irrespective of CD4 count), group B (PopART prevention intervention with ART per local guidelines), and group C (standard of care).17 Incidence reductions were observed between the prevention only (group B) and standard of care (adjusted incidence rate ratio 0·70, 95% CI 0·55–0·88).17 However, similar to the SEARCH study and ANRS 12249, HPTN 071 showed no reduction in incidence when comparing the intervention group that included universal treatment (group A) with standard of care (0·93, 0·74–1·18).17 Low rates of linkage to care were seen across the study groups, adding to the evidence that treatment interventions are challenging to implement perfectly in trial settings; challenges that would be amplified in real­world programme settings with more restricted per person intervention budgets than those in trials. In 2016, the HIV Prevention Trials Network released a statement in response to null results released by the ANRS 12249 investigators at the International AIDS Conference in Durban in 2016.19 Specifically, HPTN 07117 was to differ from ANRS 12249 in three important ways: first, HPTN 071 would take place in urban communities in which the hypothesis was that treatment as prevention would be more effective than in the rural setting of northern KwaZulu­Natal; second, HPTN 071 would be able to assess the full effect of the combination HIV­ prevention package; and third, HPTN 071 would have a longer follow­up period in which to assess the intervention’s effect on incidence.19 That these differences did not change the outcome is now clear with the release of the HPTN 071 study17 results. The intervention did not have differential effect in urban communities compared with rural communities, and the longer follow­up period and larger sample size than in ANRS 12249 did not change HIV incidence outcomes. HPTN 07117 and Figure 2: Numbers of new HIV infections and HIV treatment coverage in Botswana, Rwanda, and Ethiopia 2010–17 ART=antiretroviral therapy. 2010 2011 2012 2013 2014 2015 2016 2017 0 0 5000 20 10 000 40 15 000 60 20 000 8025 000 30 000 100 N um be r o f n ew in fe ct io ns A RT coverage (% ) 0 0 5000 20 10 000 40 15 000 60 20 000 8025 000 30 000 100 N um be r o f n ew in fe ct io ns A RT coverage (% ) 0 0 5000 20 10 000 40 15 000 60 20 000 8025 000 30 000 Ethiopia Rwanda Botswana 100 N um be r o f n ew in fe ct io ns A RT coverage (% ) Year New HIV infections Coverage of people receiving ART www.thelancet.com/hiv Vol 6 September 2019 e635 Viewpoint SEARCH16 also provided insight into the potential for HIV prevention strategies to reduce HIV incidence. Group B of HPTN 07117 was the most effective, and overall incidence was reduced in SEARCH16 but not more so with universal access to ART. These data complement results of the Ya Tsie trial20 in Botswana released in 2018. Ya Tsie20 was a pair­matched community randomised trial of nearly 9000 individuals from communities covering about 10% of the population, and reported a significant reduction in HIV incidence of at least 30% (incidence ratio 0·65, 95% CI 0·46–0·90) associated with the delivery of a combi nation HIV prevention and treatment programme. The intervention included home­based and mobile testing and linkage­to­care support, with treatment guidelines changing in both groups of the trial over time, towards a treat all approach.20 Taken together, these studies reinforce the fundamental usefulness of HIV prevention in reducing population­level HIV incidence. Observational data from a range of settings provide consistent conclusions across epidemic and income settings. Estimates by UNAIDS for Botswana, Ethiopia, and Rwanda show a marked increase in HIV treatment coverage since 2010, but a plateau in new infections (figure 2). Botswana, for example, has made substantial improvements in treatment coverage, going from 45% of those living with HIV on treatment in 2010 to just over 80% as of 2017. During the same period, however, Botswana has seen a plateau, or even a small increase in annual new infections, from 12 000 to 14 000 (ie, 16% total increase or about 2·7% annual increase). Although these data focus on countries from across southern and eastern Africa where HIV epidemics are most broadly generalised, the same disconnect between treatment coverage and numbers of new infections and HIV incidence have been observed in high­income settings.21–24 In cities including Vancouver, Sydney, and London, and across the USA and the UK, the incidence rates have been sustained, especially among gay men and other men who have sex with men in the context of universal treatment policies.25–27 Where observed, encouraging declines in HIV incidence have been attributed to advances in HIV prevention including pre­exposure prophylaxis and novel testing approaches to address the most marginalised populations. Similar to the experimental data, these observational data highlight the underlying necessity of HIV prevention in decreasing population­level HIV incidence. Importance of understanding heterogeneity of risks Early modelling results projected the comparative benefits of scaling up universal and early ART for all people living with HIV.28,29 However, relying on foundational work of epidemic theory might be informative for estimating the potential effect of large­ scale HIV treatment pro grammes moving forward.30,31 Core­group theory posits that pre vention gaps among the relatively few who are most at risk of acquisition and transmission can sustain an epidemic.32,33 Implications of this epidemic theory are two fold when considering treatment as prevention. First, viral suppression within a serodifferent partnership can avert an infection in a direct partner, but also leads to indirect benefits to the partners’ partners (and any onward serial partners). These indirect benefits stem from the way prevention among a relatively few can protect many along a potential transmission chain—especially if those few are at the highest risk of acquisition and transmission.34,35 Intersecting individual and structural determinants underlie heterogeneity in the risks of acquisition and transmission, including through biology (eg, greater mucosal tearing for anal vs vaginal intercourse or differing cervical surface area exposure for younger vs older women) or structural determinants driving disparities in intervention uptake.36–40 This hetero­ geneity can create pockets of residual trans mission that might break a priori predictions of intervention effect. Acquisition risks (susceptibility) and onward transmission risks are intertwined but they are not synonymous, nor are they static: onward transmission risk, in particular, is dynamic over the sexual life course of individuals.41 Thus, for an onward prevention benefit associated with HIV treatment, the people living with HIV receiving treatment must still be at risk for onward HIV trans mission but can no longer transmit because they are virally suppressed. The intervention­specific corollary to duration of time experiencing high onward transmission risks is the person time of viraemia before viral suppression, often stemming from structural barriers to engagement in HIV testing and ART initiation.42,43 Historically, most HIV transmission models of universal test and treat in high­prevalence epidemics, such as that in South Africa, included some heterogeneity in risk between a few groups (usually high, medium, and low).28,44 However, these early models of high prevalence settings done before experimental treatment studies rarely included a focus on key populations because they are a smaller population and were assumed to be less relevant in generalised epidemic settings.28,44,45 Thus, heterogeneity has traditionally been collapsed within the number of risk strata incorporated into these models. Heterogeneity has been condensed further via assumptions about equal reach and access of interventions among populations with different transmission risks. For example, pre­trial modelling of the HPTN 071 study18 simulated heterosexual HIV transmission and anticipated over 60% reduction in HIV incidence in group A (home­based voluntary testing and counselling with universal ART) relative to group C (control group).44 The model included three levels of heterogeneity drawing on the available data at the time from demographic health surveys: low risk (on average one partner every 10 years), medium risk (on average one partner per year), and high risk (more than one partner per year). High­risk sexual prac tices were calibrated to overall HIV prevalence in the total population, e636 www.thelancet.com/hiv Vol 6 September 2019 Viewpoint leading to 1·8–2·0 partners per year among a high­risk group that comprised 18–23% of males and females. Thus, the high­risk group subsumed the subset of women engaged in sex work (whose number of partners in South Africa range between four and 19 per day) and who comprised 0·5–2·0% of the adult female population in South Africa.36,46,47 Importantly, the intervention was also assumed to reach each risk group equally. Although the pre­trial modelling did not include key populations, the sensitivity analyses gave prescient insight hinting at the importance of transmissions via sex with a subset of a population that did not receive the intervention. In this case, the anticipated effect of group A and group B was reduced when the proportion of sex acts with individuals outside the community went from 0% to 10%, and especially when the number of partners increased in the community as a whole after the intervention started. Given the empirical data of sexual practices, engagement in HIV prevention and treatment, and incidences of HIV infections collected in the PopART study,17 modelling after the trial of the HIV epidemic in the PopART study sites and its interventions might provide crucial insights into the role that heterogeneity has in explaining the absence of population­level effectiveness attributable to universal testing and treat ment alone. Conclusion The tools to end the HIV pandemic have existed for several years. But in 2019, the HIV pandemic is not over and, indeed, it is still growing and will likely do so for many years. The population­level treatment as prevention trials were well designed, well executed, and answered key questions regarding the population­level prevention benefits of universal HIV treatment. Their findings should not be discounted, but rather, they should be integrated into our understanding of the underlying HIV transmission dynamics powering the HIV pandemic. Successful application of tools to end the HIV pandemic necessitates a thorough understanding of HIV acquisition and onward transmission risks and effective implemen­ tation to support sustained viral suppression among people living with HIV and to prevent HIV acquisition among those people at risk of infection. The latter is crucial as treatment alone, as shown by both experimental and observational data, remains necessary but insufficient without primary prevention. The expectation of one to one reduction in onward HIV transmission is only applicable (or restricted) to fixed serodifferent partnerships that are mutually monogamous over time. Thus, U=U is additive across such partnerships over time. If considerable heterogeneity exists in onward transmission risks (eg, 30% of onward transmissions stem from the unmet prevention needs of 2% of the population) then equal distribution of treatment might actually reinforce disparities and continue to underserve those people at highest risk of onward HIV transmission. The assumption challenges the usefulness of targets such as 90­90­90 and 95­95­95, which were designed with a focus on coverage of all reproductive­age results, regardless of risk, in specific geographical areas. However, results from the previously mentioned trials are consistent with core epidemic theory in that, from an HIV prevention perspective, knowledge of for whom we are providing treatment is more relevant than for how many people.48 A model leveraging data from southern Africa supported this perspective by showing that if those people most likely to be left behind are also the same people who are most at risk of onward transmission, projections could underestimate the potential effect of achieving and surpassing UNAIDS treatment goals.49 Implementation strategies of HIV treatment focused on addressing those most marginalised will have key differences compared with programmes and resources focused only on treatment numbers. The HIV community often considers the implemen tation strategies for HIV treatment as treatment and HIV treatment as prevention to be the same. However, the disconnect between population­level improvements in treatment coverage and viral sup pression and HIV incidence suggests the need for a separate set of considerations for treatment as prevention. In this frame, we leverage the concept of patient­centred medicine to suggest that maximising the prevention effect of HIV treatment programmes to support HIV prevention outcomes necessitates understanding the individuals that we are trying to support in treatment in contrast to treating them as a general population. The three cluster randomised controlled trials evaluating treatment as prevention that we described in this Viewpoint are unlikely to be surpassed in size or comprehensiveness. Integrating these experimental data into a large body of observational data from around the world suggest that HIV treatment is treatment, HIV prevention is prevention, and specificity of HIV …