Epidemic modeling suggests that a major scale-up in HIV treatment could have a dramatic impact on HIV incidence. This has led both researchers and policymakers to set a goal of an “AIDS-Free Generation.” One of the greatest obstacles to achieving this objective is the number of people with undiagnosed HIV infection. Despite recent innovations, new research strategies are needed to identify, engage, and successfully treat people who are unaware of their infection.
Get full access to this article
View all access options for this article.
References
1.
SchwarczL, ChenM-J, VittinghoffE, et al.: Declining incidence of AIDS-defining opportunistic illnesses: Results from 16 years of population-based AIDS surveillance. AIDS, 2013; 27(4):597–605.
2.
UNAIDS: World AIDS Day Report 2012. www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/JC2434_WorldAIDSday_results_en.pdf. Accessed July15, 2013.
3.
WalenskyRP, PaltielAD, LosinaE, et al.: The survival benefits of AIDS treatment in the United States. J Infect Dis, 2006; 194(1):11–19.
4.
EatonJW, JohnsonLF, SalomonJA, et al.: HIV treatment as prevention: Systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa. PLoS Med, 2012; 9:e1001245.
5.
TanserF, BaernighausenT, GrapsaE, et al.: High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science, 2013; 339(6122):966–971.
6.
BoilyMC, MasseB, AlsallaqR, et al.: HIV treatment as prevention: Considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention. PLoS Med, 2012; 9(7):e1001250.
7.
SullivanPS, HamoudaO, DelpechV, et al.: Reemergence of the HIV epidemic among men who have sex with men in North America, Western Europe, and Australia, 1996–2005. Ann Epidemiol, 2009; 19(6):423–431.
8.
BezemerD, de WolfF, BoerlijstMC, et al.: A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy. AIDS, 2008; 22(9):1071–1077.
9.
PhillipsAN, CambianoV, NakagawaF, et al.: Increased HIV incidence in men who have sex with men despite high levels of ART-induced viral suppression: Analysis of an extensively documented epidemic. PLoS One, 2013; 8(2):e55312.
10.
HamersFF and PhillipsAN: Diagnosed and undiagnosed HIV-infected populations in Europe. HIV Med, 2008; 9(Suppl 2):6–12.
11.
ChenM, RhodesPH, HallIH, et al.: Prevalence of undiagnosed HIV infection among persons aged ≥13 years–National HIV Surveillance System, United States, 2005–2008. MMWR Morb Mortal Wkly Rep, 2012; 61(Suppl):57–64.
12.
AnandA, ShiraishiRW, BunnellRE, et al.: Knowledge of HIV status, sexual risk behaviors and contraceptive need among people living with HIV in Kenya and Malawi. AIDS, 2009; 23(12):1565–1573.
13.
UNAIDS: World AIDS Day Report 2011. www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/jc2216_worldaidsday_report_2011_en.pdf. Accessed June6, 2013.
14.
CherutichP, BunnellR, and MerminJ: HIV testing: Current practice and future directions. Curr HIV/AIDS Rep, 2013; 10(2):134–141.
15.
GouwsE and CuchiP: Focusing the HIV response through estimating the major modes of HIV transmission: A multi-country analysis. Sex Transm Infect, 2013; 88(Suppl 2):i76–i85.
16.
HallHI, HoltgraveDR, and MaulsbyC: HIV transmission rates from persons living with HIV who are aware and unaware of their infection. AIDS, 2012; 26(7):893–896.
17.
MarksG, CrepazN, and JanssenRS: Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA. AIDS, 2006; 20(10):1447–1450.
18.
WawerMJ, GrayRH, SewankamboNK, et al.: Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis, 2005; 191(9):1403–1409.
19.
PilcherCD, JoakiG, HoffmanIF, et al.: Amplified transmission of HIV-1: Comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS, 2007; 21(13):1723–1730.
20.
PowersKA, GhaniAC, MillerWC, et al.: The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: A modelling study. Lancet, 2011; 378(9787):256–268.
21.
MaZ-M, KeeleBF, QureshiH, et al.: SIVmac251 Is inefficiently transmitted to rhesus macaques by penile inoculation with a single SIVenv variant found in ramp-up phase plasma. AIDS Res Hum Retroviruses, 2011; 27(12):1259–1269.
22.
KimJH and KoopmanJS: HIV transmissions by stage in dynamic sexual partnerships. J Theor Biol, 2012; 298:147–153.
23.
AlamSJ, ZhangX, Romero-SeversonEO, et al.: Detectable signals of episodic risk effects on acute HIV transmission: Strategies for analyzing transmission systems using genetic data. Epidemics, 2013; 5(1):44–55.
24.
ErbeldingEJ, ChungSE, KambML, et al.: New sexually transmitted diseases in HIV-infected patients: Markers for ongoing HIV transmission behavior. J Acquir Immune Defic Syndr, 2003; 33:247–252.
25.
KalichmanSC, PellowskiJ, and TurnerC: Prevalence of sexually transmitted co-infections in people living with HIV/AIDS: Systematic review with implications for using HIV treatments for prevention. Sex Transm Infect, 2011; 87:183–190.
26.
PathelaP, BraunsteinS, ShepardC, et al.: Population-based HIV incidence among men diagnosed with infectious syphilis, 2000–2011. Paper presented at the 20th Meeting of the International Society for Sexually Transmitted Diseases Research, July 14–17, 2013, Vienna, Austria.
27.
CohenMS, ShawGM, McMichaelAJ, et al.: Acute HIV-1 infection. N Engl J Med, 2011; 364:1943–1954.
28.
CohenMS, DyeC, FraserC, et al.: HIV treatment as prevention: Debate and commentary—will early infection compromise treatment-as-prevention strategies?. PLoS Med, 2012; 9:e1001232.
29.
BirrellPJ, GillON, DelpechVC, et al.: HIV incidence in men who have sex with men in England and Wales 2001–2010: A nationwide population study. Lancet Infect Dis, 2013; 13(4):313–318.
30.
BlowerSM, GershengornHB, and GrantRM: A tale of two futures: HIV and antiretroviral therapy in San Francisco. Science, 2000; 287(5453):650–654.
31.
Velasco-HernandezJX, GershengornHB, and BlowerSM: Could widespread use of combination antiretroviral therapy eradicate HIV epidemics?. Lancet Infect Dis, 2002; 2(8):487–493.
32.
GranichRM, GilksCF, DyeC, et al.: Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: A mathematical model. Lancet, 2009; 373(9657):48–57.
33.
XiridouM, GeskusR, de WitJ, et al.: Primary HIV infection as source of HIV transmission within steady and casual partnerships among homosexual men. AIDS, 2004; 18(9):1311–1320.
34.
DelvaW, WilsonDP, Abu-RaddadL, et al.: HIV treatment as prevention: Principles of good HIV epidemiology modelling for public health decision-making in all modes of prevention and evaluation. PLoS Med, 2012; 9(7):e1001239.
35.
CohenMS, ChenYQ, McCauleyM, et al.: Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med, 2011; 365(6):493–505.
36.
JiaZ, MaoY, ZhangF, et al.: Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003–2011): A national observational cohort study. Lancet, 2013; 382(9899):1195–1203.
37.
HeN, DuanS, DingY, et al.: Antiretroviral therapy reduces HIV transmission in discordant couples in rural Yunnan, China. PloS One, 2013; 8(11):e77981.
38.
DonnellD, BaetenJM, KiarieJ, et al.: Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: A prospective cohort analysis. Lancet, 2010; 375(9731):2092–2098.
39.
WilsonDP: Evidence is still required for treatment as prevention for riskier routes of HIV transmission [letter]. AIDS, 2010; 24(18):2891–2892.
40.
MuessigKE, SmithMK, PowersKA, et al.: Does ART prevent HIV transmission among MSM?. AIDS, 2012; 26:2267–2273.
41.
Centers for Disease Control and Prevention: Today's HIV epidemic. www.cdc.gov/nchhstp/newsroom/docs/HIVFactSheets/TodaysEpidemic-508.pdf. Accessed July16, 2013.
42.
KranzerK, LawnSD, JohnsonLF, et al.: Community viral load and CD4 count distribution among people living with HIV in a South African township: Implications for treatment as prevention. J Acquir Immune Defic Syndr, 2013; 63:498–505.
43.
HallettTB and EatonJW: A side door into care cascade for HIV-infected patients?. J Acquir Immune Defic Syndr, 2013; 63(Suppl 2):S228–S232.
44.
MayRM and AndersonRM: Transmission dynamics of HIV infection. Nature, 1987; 326(6109):137–142.
45.
GarnettGP: The basic reproductive rate of infection and the course of HIV epidemics. AIDS Patient Care STDS, 1998; 12(6):435–449.
46.
KretzschmarM and CaraelM: Is concurrency driving HIV transmission in sub-Saharan African sexual networks? The significance of sexual partnership typology. AIDS Behav, 2012; 16(7):1746–1752.
47.
KretzschmarM, van der LoeffM, BirrellP, et al.: Prospects of elimination of HIV with test-and-treat strategy. Proc Natl Acad Sci USA, 2013; 110(39):15538–15543.
48.
HueS, ClewleyJP, CanePA, et al.: HIV-1 pol gene variation is sufficient for reconstruction of transmissions in the era of antiretroviral therapy. AIDS, 2004; 18:719–728.
49.
VolzEM, KoopmanJS, WardMJ, et al.: Simple epidemiological dynamics explain phylogenetic clustering of HIV from patients with recent infection. PLoS Comput Biol, 2012; 8(6):e1002552.
50.
AldousJL, PondSK, PoonA, et al.: Characterizing HIV transmission networks across the United States. Clin Infect Dis, 2012; 55(8):1135–1143.
51.
StadlerT and BonhoefferS: Uncovering epidemiological dynamics in heterogeneous host populations using phylogenetic methods. Philos Trans R Soc Lond B Biol Sci, 2013; 368:20120198.
52.
BrennerB, WainbergMA, and RogerM: Phylogenetic inferences on HIV-1 transmission: Implications for the design of prevention and treatment interventions. AIDS, 2013; 27(7):1045–1057.
53.
StadlerT, KouyosR, von WylV, et al.: Estimating the basic reproductive number from viral sequence data. Mol Biol Evol, 2012; 29(1):347–357.
Global Commission on HIV and the Law: Global Commission on HIV and the Law: Rights, Risk, Health. www.hivlawcommission.org/resources/report/FinalReport-Risks,Rights&Health-EN.pdf. Accessed July15, 2013.
56.
BernardE, AzadY, VandammeA, et al.: The use of phylogenetic analysis as evidence in criminal investigation of HIV transmission. www.nat.org.uk/Media%20library/Files/PDF%20Documents/HIV-Forensics.pdf. Accessed October21, 2013.
57.
SmithKP and ChristakisNA: Social networks and health. Annu Rev Sociol, 2008; 34:405–429.
58.
HelleringerS, MkandawireJ, Kalilani-PhiriL, et al.: Cohort profile: The Likoma Network Study (LNS). Int J Epidemiol, 2013; [Epub ahead of print]; DOI:10.1093/ije/dyt001.
59.
HootsBE, MacDonaldPDM, Hightow-WeidmanLB, et al.: Developing a predictive model to prioritize human immunodeficiency virus partner notification in North Carolina. Sex Transm Dis, 2012; 39(1):65–71.
60.
SalganikMJ and HeckathornDD: Sampling and estimation in hidden populations using respondent-driven sampling. Sociol Methodol, 2004; 34:193–239.
61.
KimbroughLW, FisherHE, JonesKT, et al.: Accessing social networks with high rates of undiagnosed HIV infection: The Social Networks Demonstration Project. Am J Public Health, 2009; 99(6):1093–1099.
62.
BengtssonL, LuX, NguyenQC, et al.: Implementation of web-based respondent-driven sampling among men who have sex with men in Vietnam. PLoS One, 2012; 7:e49417.
63.
McCoySI, ShiuK, MartzTE, et al.: Improving the efficiency of HIV testing with peer recruitment, financial incentives, and the involvement of persons living with HIV infection. J Acquir Immune Defic Syndr, 2013; 63(2):e56–e63.
64.
LuX, BengtssonL, BrittonT, et al.: The sensitivity of respondent-driven sampling. J R Stat Soc Ser A Stat Soc, 2012; 175:191–216.
65.
van SighemA, JansenI, BezemerD, et al.: Increasing sexual risk behaviour among Dutch men who have sex with men: Mathematical models versus prospective cohort data. AIDS, 2012; 26(14):1840–1843.
66.
FisherM, PaoD, BrownAE, et al.: Determinants of HIV-1 transmission in men who have sex with men: A combined clinical, epidemiological and phylogenetic approach. AIDS, 2010; 24(11):1739–1747.
67.
GrabowskiMK, LesslerJ, ReddAD, et al.: Frequent viral introductions sustain local HIV epidemics in rural Rakai, Uganda. Paper presented at the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, Georgia, 2013.
68.
RochaLE and BlondelVD: Bursts of vertex activation and epidemics in evolving networks. PLoS Comput Biol, 2013; 9:e1002974.
69.
Romero-SeversonE, AlamS, VolzE, et al.: Heterogeneity in number and type of sexual contacts in a gay urban cohort. Stat Commun Infect Dis, 2012; 4(4):1–18.
70.
GwadzM: Peer-driven intervention to seek, test and treat heterosexuals at high risk for HIV. www.cduhr.org/projects/description.aspx?projectID=72. Accessed June6, 2013.
71.
JennessSM, NeaigusA, MurrillCS, et al.: Estimated HIV incidence among high-risk heterosexuals in New York City, 2007. J Acquir Immune Defic Syndr, 2011; 56(2):193–197.
72.
TruongH: HIV transmission cluster analysis to inform prevention. http://projectreporter.nih.gov/project_info_description.cfm?aid=8263303&icde=16571418&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC. Accessed June6, 2013.
73.
RemienR: Structural intervention to increase screening and testing for acute HIV infection. http://projectreporter.nih.gov/project_info_description.cfm?aid=8434183&icde=16568781&ddparam=&ddvalue=&ddsub=&cr=3&csb=default&cs=ASC. Accessed June6, 2013.
74.
PilcherC, LouieB, FacenteS, et al.: Performance of rapid point-of-care and laboratory tests for acute and established HIV infection in San Francisco. PloS One, 2013; 8(12):e80629.
75.
ChristopoulosKA, ZetolaNM, KlausnerJD, et al.: Leveraging a rapid, round-the-clock HIV testing system to screen for acute HIV infection in a large urban public medical center. J Acquir Immune Defic Syndr, 2012; 62:e30–e38.
76.
Hightow-WeidmanLB, FowlerB, KibeJ, et al.: HealthMpowerment.org: Development of a theory-based HIV/STI website for young black MSM. AIDS Educ Prev, 2011; 23(1):1–12.
77.
Hightow-WeidmanLB, PikeE, FowlerB, et al.: HealthMpowerment.org: Feasibility and acceptability of delivering an Internet intervention to young black men who have sex with men. AIDS Care, 2012; 24(7):910–920.
78.
MuessigKE, PikeEC, LeGrandS, et al.: Mobile phone applications for the care and prevention of HIV and other sexually transmitted diseases: A review. J Med Internet Res, 2013; 15(1):19–40.
79.
CaseKK, GhysPD, GouwsE, et al.: Understanding the modes of transmission model of new HIV infection and its use in prevention planning. Bull World Health Organ, 2012; 90:831a–838a.
80.
LucasA and ArmbrusterB: The cost-effectiveness of expanded HIV screening in the United States. AIDS, 2012; 27:795–801.
81.
van RooyenH, BarnabasRV, BaetenJM, et al.: High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr, 2013; 64(1):e1–e8.
82.
JaniIV, SitoeNE, AlfaiER, et al.: Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: An observational cohort study. Lancet, 2011; 378(9802):1572–1579.
83.
JaniI, MeggiB, VubilA, et al.: Evaluation of point-of-care nucleic acid testing for HIV viral load and early infant diagnosis in primary health clinics: Mozambique. Paper presented at the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, Georgia, 2013.
84.
HeffronR, NgureK, MugoN, et al.: Willingness of Kenyan HIV-1 serodiscordant couples to use antiretroviral-based HIV-1 prevention strategies. J Acquir Immune Defic Syndr, 2012; 61(1):116–119.
85.
HannaDB, BuchaczK, GeboKA, et al.: Trends and disparities in antiretroviral therapy initiation and virologic suppression among newly treatment-eligible HIV-infected individuals in North America, 2001–2009. Clin Infect Dis, 2013; 56(8):1174–1182.
86.
WalkerBD and HirschMS: Antiretroviral therapy in early HIV infection. N Engl J Med, 2013; 368(3):279–281.
87.
DolanP, HallsworthM, HalpernD, et al.: Influencing behaviour: The mindspace way. J Econ Psychol, 2012; 33(1):264–277.
88.
GalarragaO, GenbergBL, MartinRA, et al.: Conditional economic incentives to improve HIV treatment adherence: Literature review and theoretical considerations. AIDS Behav, 2013; 17(7):2283–2292.
89.
MarteauTM, HollandsGJ, and FletcherPC: Changing human behavior to prevent disease: The importance of targeting automatic processes. Science, 2012; 337(6101):1492–1495.