Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

HIV infection

Nature Reviews Disease Primers volume 9, Article number: 42 (2023) Cite this article

Subjects

An Author Correction to this article was published on 11 September 2023

This article has been updated

Abstract

The AIDS epidemic has been a global public health issue for more than 40 years and has resulted in ~40 million deaths. AIDS is caused by the retrovirus, HIV-1, which is transmitted via body fluids and secretions. After infection, the virus invades host cells by attaching to CD4 receptors and thereafter one of two major chemokine coreceptors, CCR5 or CXCR4, destroying the host cell, most often a T lymphocyte, as it replicates. If unchecked this can lead to an immune-deficient state and demise over a period of ~2–10 years. The discovery and global roll-out of rapid diagnostics and effective antiretroviral therapy led to a large reduction in mortality and morbidity and to an expanding group of individuals requiring lifelong viral suppressive therapy. Viral suppression eliminates sexual transmission of the virus and greatly improves health outcomes. HIV infection, although still stigmatized, is now a chronic and manageable condition. Ultimate epidemic control will require prevention and treatment to be made available, affordable and accessible for all. Furthermore, the focus should be heavily oriented towards long-term well-being, care for multimorbidity and good quality of life. Intense research efforts continue for therapeutic and/or preventive vaccines, novel immunotherapies and a cure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The phylogenetic origins of HIV-1.
Fig. 2: The geographical spread of HIV-1 subtypes.
Fig. 3: New HIV infections by region 2015–2022.
Fig. 4: HIV infection and disease progression.
Fig. 5: Key features of cells in productive and latent HIV infection.
Fig. 6: The HIV life cycle and sites of action of the major classes of antiretroviral medication.

Similar content being viewed by others

Change history

References

  1. Djawe, K. et al. Mortality risk after AIDS-defining opportunistic illness among HIV-infected persons—San Francisco, 1981–2012. J. Infect. Dis. 212, 1366–1375 (2015).

    PubMed  Google Scholar 

  2. Violari, A. et al. Early antiretroviral therapy and mortality among HIV-infected infants. N. Engl. J. Med. 359, 2233–2244 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Garcia-Broncano, P. et al. Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile. Sci. Transl Med. 11, eaax7350 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Edwards, J. K. et al. Five-year mortality for adults entering human immunodeficiency virus care under universal early treatment compared with the general US population. Clin. Infect. Dis. 75, 867–874 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. UNAIDS. UNAIDS Epidemiological Estimates. UNAIDS https://www.unaids.org/en/resources/documents/2023/2022_unaids_data (2022).

  6. Ceccarelli, G. et al. Human immunodeficiency virus type 2: the neglected threat. Pathogens 10, 1377 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Cho, M., Min, X. & Son, H. S. Analysis of evolutionary and genetic patterns in structural genes of primate lentiviruses. Genes Genom. 44, 773–791 (2022).

    CAS  Google Scholar 

  8. Rambaut, A. et al. The causes and consequences of HIV evolution. Nat. Rev. Genet. 5, 52–61 (2004).

    CAS  PubMed  Google Scholar 

  9. Korber, B. et al. Timing the ancestor of the HIV-1 pandemic strains. Science 288, 1789–1796 (2000).

    CAS  PubMed  Google Scholar 

  10. Hahn, B. H., Shaw, G. M., De Cock, K. M. & Sharp, P. M. AIDS as a zoonosis: scientific and public health implications. Science 287, 607–614 (2000).

    CAS  PubMed  Google Scholar 

  11. Williams, K. C. & Burdo, T. H. HIV and SIV infection: the role of cellular restriction and immune responses in viral replication and pathogenesis. APMIS 117, 400–412 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Pepin, J., Plamondon, M., Alves, A. C., Beaudet, M. & Labbe, A. C. Parenteral transmission during excision and treatment of tuberculosis and trypanosomiasis may be responsible for the HIV-2 epidemic in Guinea-Bissau. AIDS 20, 1303–1311 (2006).

    PubMed  Google Scholar 

  13. Pepin, J. et al. Iatrogenic transmission of human T cell lymphotropic virus type 1 and hepatitis C virus through parenteral treatment and chemoprophylaxis of sleeping sickness in colonial Equatorial Africa. Clin. Infect. Dis. 51, 777–784 (2010).

    PubMed  Google Scholar 

  14. Pepin, J. & Labbe, A. C. Noble goals, unforeseen consequences: control of tropical diseases in colonial Central Africa and the iatrogenic transmission of blood-borne viruses. Trop. Med. Int. Health 13, 744–753 (2008).

    PubMed  Google Scholar 

  15. Chitnis, A., Rawls, D. & Moore, J. Origin of HIV type 1 in colonial French Equatorial Africa? AIDS Res. Hum. Retroviruses 16, 5–8 (2000).

    CAS  PubMed  Google Scholar 

  16. Worobey, M. et al. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960. Nature 455, 661–664 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. de Sousa, J. D., Muller, V., Lemey, P. & Vandamme, A. M. High GUD incidence in the early 20th century created a particularly permissive time window for the origin and initial spread of epidemic HIV strains. PLoS ONE 5, e9936 (2010).

    PubMed  PubMed Central  Google Scholar 

  18. Bennedbæk, M. et al. Phylogenetic analysis of HIV-1 shows frequent cross-country transmission and local population expansions. Virus Evol. 7, veab055 (2021).

    PubMed  PubMed Central  Google Scholar 

  19. Taylor, B. S., Sobieszczyk, M. E., McCutchan, F. E. & Hammer, S. M. The challenge of HIV-1 subtype diversity. N. Engl. J. Med. 358, 1590–1602 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gilbert, M. T. et al. The emergence of HIV/AIDS in the Americas and beyond. Proc. Natl Acad. Sci. USA 104, 18566–18570 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Sharp, P. M. & Hahn, B. H. Origins of HIV and the AIDS pandemic. Cold Spring Harb. Perspect. Med. 1, a006841 (2011).

    PubMed  PubMed Central  Google Scholar 

  22. Hladik, F. & McElrath, M. J. Setting the stage: host invasion by HIV. Nat. Rev. Immunol. 8, 447–457 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Cohen, M. S., Shaw, G. M., McMichael, A. J. & Haynes, B. F. Acute-HIV-1 infection: basic, clinical and public health perspectives. N. Engl. J. Med. 364, 1943–1954 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Humphrey, J. et al. Integration of HIV care into maternal and child health services in the global IeDEA consortium. Front. Glob. Women’s Health 4, 1066297 (2023).

    Google Scholar 

  25. Zuma, K. et al. The HIV epidemic in South Africa: key findings from 2017 national population-based survey. Int. J. Environ. Res. Public Health 19, 8125 (2022).

    PubMed  PubMed Central  Google Scholar 

  26. Roberts, D. A. et al. Predicting the risk of human immunodeficiency virus type 1 (HIV-1) acquisition in rural South Africa using geospatial data. Clin. Infect. Dis. 75, 1224–1231 (2022).

    PubMed  PubMed Central  Google Scholar 

  27. Gray, G. E. et al. Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120-MF59 in adults. N. Engl. J. Med. 384, 1089–1100 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. UNAIDS. In Danger: UNAIDS Global AIDS update. UNAIDS https://www.unaids.org/sites/default/files/media_asset/2022-global-aids-update-summary_en.pdf (2022).

  29. Farley, T. M. et al. Impact of male circumcision on risk of HIV infection in men in a changing epidemic context – systematic review and meta-analysis. J. Int. AIDS Soc. 23, e25490 (2020).

    PubMed  PubMed Central  Google Scholar 

  30. Lyons, C. E. et al. Associations between punitive policies and legal barriers to consensual same-sex sexual acts and HIV among gay men and other men who have sex with men in sub-Saharan Africa: a multicountry, respondent-driven sampling survey. Lancet HIV 10, e186–e194 (2023).

    CAS  PubMed  Google Scholar 

  31. Eleje, G. U. et al. Mother-to-child transmission of human immunodeficiency virus, hepatitis B virus and hepatitis C virus among pregnant women with single, dual or triplex infections of human immunodeficiency virus, hepatitis B virus and hepatitis C virus in Nigeria: a systematic review and meta-analysis. SAGE Open Med. 10, 20503121221095411 (2022).

    PubMed  PubMed Central  Google Scholar 

  32. UNAIDS. Anambra, Nigeria, commits to eliminating vertical transmission of HIV by end of 2022. UNAIDS https://www.unaids.org/en/resources/presscentre/featurestories/2021/september/20210906_nigeria-mother-child-transmission (2021).

  33. Beyrer, C. et al. Global epidemiology of HIV infection in men who have sex with men. Lancet 380, 367–377 (2012).

    PubMed  PubMed Central  Google Scholar 

  34. Sullivan, P. S. et al. Epidemiology of HIV in the USA: epidemic burden, inequities, contexts, and responses. Lancet 397, 1095–1106 (2021).

    PubMed  Google Scholar 

  35. SeyedAlinaghi, S. et al. HIV in Iran: onset, responses, and future directions. AIDS 35, 529–542 (2021).

    PubMed  Google Scholar 

  36. Khalid, H. & Fox, A. M. Political and governance challenges to achieving global HIV goals with injecting drug users: the case of Pakistan. Int. J. Health Policy Manag. 8, 261–271 (2019).

    PubMed  PubMed Central  Google Scholar 

  37. Govender, K. et al. Association of HIV intervention uptake with HIV prevalence in adolescent girls and young women in South Africa. JAMA Netw. Open 5, e228640 (2022).

    PubMed  PubMed Central  Google Scholar 

  38. Marinda, E. et al. Towards achieving the 90–90–90 HIV targets: results from the South African 2017 national HIV survey. BMC Public Health 20, 1375 (2020).

    PubMed  PubMed Central  Google Scholar 

  39. Marsh, K. et al. Global, regional and country-level 90-90-90 estimates for 2018: assessing progress towards the 2020 target. AIDS 33, S213–S226 (2019).

    PubMed  Google Scholar 

  40. Astawesegn, F. H. et al. Trends and effects of antiretroviral therapy coverage during pregnancy on mother-to-child transmission of HIV in sub-Saharan Africa: evidence from panel data analysis. BMC Infect. Dis. 22, 134 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Van de Perre, P. et al. HIV-1 reservoirs in breast milk and challenges to elimination of breast-feeding transmission of HIV-1. Sci. Transl Med. 4, 143sr3 (2012).

    PubMed  Google Scholar 

  42. Joseph Davey, D. L. et al. Early pre-exposure prophylaxis (PrEP) initiation and continuation among pregnant and postpartum women in antenatal care in Cape Town, South Africa. J. Int. AIDS Soc. 25, e25866 (2022).

    PubMed  PubMed Central  Google Scholar 

  43. Adimora, A. A. et al. Cohort profile: the Women’s Interagency HIV Study (WIHS). Int. J. Epidemiol. 47, 393–394i (2018).

    PubMed  PubMed Central  Google Scholar 

  44. Autenrieth, C. S. et al. Global and regional trends of people living with HIV aged 50 and over: estimates and projections for 2000–2020. PLoS ONE 13, e0207005 (2018).

    PubMed  PubMed Central  Google Scholar 

  45. Bigna, J. J. et al. Global burden of hypertension among people living with HIV in the era of increased life expectancy: a systematic review and meta-analysis. J. Hypertens. 38, 1659–1668 (2020).

    CAS  PubMed  Google Scholar 

  46. D’Souza, G. et al. Characteristics of the MACS/WIHS combined cohort study: opportunities for research on aging with HIV in the longest US observational study of HIV. Am. J. Epidemiol. 190, 1457–1475 (2021).

    PubMed  PubMed Central  Google Scholar 

  47. Davis, K. et al. Association between HIV infection and hypertension: a global systematic review and meta-analysis of cross-sectional studies. BMC Med. 19, 105 (2021).

    PubMed  PubMed Central  Google Scholar 

  48. Brennan, A. T. et al. Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa. EClinicalMedicine 57, 101836 (2023).

    PubMed  PubMed Central  Google Scholar 

  49. Rodés, B., Cadiñanos, J., Esteban-Cantos, A., Rodríguez-Centeno, J. & Arribas, J. R. Ageing with HIV: challenges and biomarkers. EBioMedicine 77, 103896 (2022).

    PubMed  PubMed Central  Google Scholar 

  50. Chiappini, E. et al. Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms. Aging 10, 3610–3625 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Des Jarlais, D. C., Kerr, T., Carrieri, P., Feelemyer, J. & Arasteh, K. HIV infection among persons who inject drugs: ending old epidemics and addressing new outbreaks. AIDS 30, 815–826 (2016).

    PubMed  Google Scholar 

  52. Baggaley, R. F. et al. National policies for delivering tuberculosis, HIV and hepatitis B and C virus infection services for migrants among member states of the WHO European Region. J. Travel Med. 30, taac136 (2022).

    PubMed Central  Google Scholar 

  53. Weiss, R. A., Dalgleish, A. G., Loveday, C., Pillay. D. in Principles and Practice of Clinical Virology (eds Zuckerman, A. J., Banatvala, J. E., Pattison, J. R., Griffiths, P. D. & Schoub, B. D.) 721–757 (John Wiley & Sons Ltd, 2004).

  54. Chan, D. C. & Kim, P. S. HIV entry and its inhibition. Cell 93, 681–684 (1998).

    CAS  PubMed  Google Scholar 

  55. Dragic, T. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381, 667–673 (1996).

    CAS  PubMed  Google Scholar 

  56. Bleul, C. C. et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382, 829–833 (1996).

    CAS  PubMed  Google Scholar 

  57. Checkley, M. A., Luttge, B. G. & Freed, E. O. HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J. Mol. Biol. 410, 582–608 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Koot, M. et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann. Intern. Med. 118, 681–688 (1993).

    CAS  PubMed  Google Scholar 

  59. Jekle, A. et al. In vivo evolution of human immunodeficiency virus type 1 toward increased pathogenicity through CXCR4-mediated killing of uninfected CD4 T cells. J. Virol. 77, 5846–5854 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367–377 (1996).

    CAS  PubMed  Google Scholar 

  61. Stephenson, K. E., Wagh, K., Korber, B. & Barouch, D. H. Vaccines and broadly neutralizing antibodies for HIV-1 prevention. Annu. Rev. Immunol. 38, 673–703 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Barré-Sinoussi, F. et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220, 868–871 (1983).

    PubMed  Google Scholar 

  63. Roberts, J. D., Bebenek, K. & Kunkel, T. A. The accuracy of reverse transcriptase from HIV-1. Science 242, 1171–1173 (1988).

    CAS  PubMed  Google Scholar 

  64. Bukrinsky, M. I. et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc. Natl Acad. Sci. USA 89, 6580–6584 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Preston, B. D., Poiesz, B. J. & Loeb, L. A. Fidelity of HIV-1 reverse transcriptase. Science 242, 1168–1171 (1988).

    CAS  PubMed  Google Scholar 

  66. Perelson, A. S., Neumann, A. U., Markowitz, M., Leonard, J. M. & Ho, D. D. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271, 1582–1586 (1996).

    CAS  PubMed  Google Scholar 

  67. Walker, B. D. et al. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 328, 345–348 (1987).

    CAS  PubMed  Google Scholar 

  68. Touloumi, G. et al. Impact of HIV-1 subtype on CD4 count at HIV seroconversion, rate of decline, and viral load set point in European seroconverter cohorts. Clin. Infect. Dis. 56, 888–897 (2013).

    CAS  PubMed  Google Scholar 

  69. Pantaleo, G. & Fauci, A. S. New concepts in the immunopathogenesis of HIV infection. Annu. Rev. Immunol. 13, 487–512 (1995).

    CAS  PubMed  Google Scholar 

  70. Biggs, B. A., Hewish, M., Kent, S., Hayes, K. & Crowe, S. M. HIV-1 infection of human macrophages impairs phagocytosis and killing of Toxoplasma gondii. J. Immunol. 154, 6132–6139 (1995).

    CAS  PubMed  Google Scholar 

  71. Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J. & Gusovsky, F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J. Biol. Chem. 274, 10689–10692 (1999).

    CAS  PubMed  Google Scholar 

  72. Brenchley, J. M. et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12, 1365–1371 (2006).

    CAS  PubMed  Google Scholar 

  73. Heil, F. et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526–1529 (2004).

    CAS  PubMed  Google Scholar 

  74. Zeng, M. et al. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J. Clin. Invest. 121, 998–1008 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Cooper, D. A. et al. Acute AIDS retrovirus infection. definition of a clinical illness associated with seroconversion. Lancet 1, 537–540 (1985).

    CAS  PubMed  Google Scholar 

  76. Brew, B. J. et al. The neurological features of early and ‘latent’ human immunodeficiency virus infection. Aust. N. Z. J. Med. 19, 700–705 (1989).

    CAS  PubMed  Google Scholar 

  77. Pantaleo, G. et al. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362, 355–358 (1993).

    CAS  PubMed  Google Scholar 

  78. Glushakova, S. et al. Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency. Nat. Med. 4, 346–349 (1998).

    CAS  PubMed  Google Scholar 

  79. El-Atrouni, W., Berbari, E. & Temesgenm, Z. HIV-associated opportunistic infections. bacterial infections. J. Med. Liban. 54, 80–83 (2006).

    PubMed  Google Scholar 

  80. Crowe, S. M., Carlin, J. B., Stewart, K. I., Lucas, C. R. & Hoy, J. F. Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons. J. Acquir. Immune Defic. Syndr. 4, 770–776 (1991).

    CAS  PubMed  Google Scholar 

  81. Zhang, L. et al. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J. Exp. Med. 190, 725–732 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Autran, B. et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 277, 112–116 (1997).

    CAS  PubMed  Google Scholar 

  83. Rajasuriar, R. et al. Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor α and microbial translocation. J. Infect. Dis. 202, 1254–1264 (2010).

    CAS  PubMed  Google Scholar 

  84. Rajasuriar, R., Wright, E. & Lewin, S. R. Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage. Curr. Opin. HIV AIDS 10, 35–42 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Hunt, P. W. et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J. Infect. Dis. 187, 1534–1543 (2003).

    CAS  PubMed  Google Scholar 

  86. Jain, V. et al. Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J. Infect. Dis. 208, 1202–1211 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N. Engl. J. Med 355, 2283–2296 (2006).

    Google Scholar 

  88. Chun, T. W. et al. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat. Med. 1, 1284–1290 (1995).

    CAS  PubMed  Google Scholar 

  89. Pitman, M. C., Lau, J. S. Y., McMahon, J. H. & Lewin, S. R. Barriers and strategies to achieve a cure for HIV. Lancet HIV 5, e317–e328 (2018).

    PubMed  PubMed Central  Google Scholar 

  90. Saleh, S. et al. CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood 110, 4161–4164 (2007).

    CAS  PubMed  Google Scholar 

  91. Shan, L. et al. Transcriptional reprogramming during effector-to-memory transition renders CD4+ T cells permissive for latent HIV-1 infection. Immunity 47, 766–775.e3 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Zhang, Z. et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286, 1353–1357 (1999).

    CAS  PubMed  Google Scholar 

  93. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295–1300 (1997).

    CAS  PubMed  Google Scholar 

  94. Abrahams, M. R. et al. The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation. Sci. Transl Med. 11, eaaw5589 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Peluso, M. J. et al. Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy. JCI Insight 5, e132997 (2020).

    PubMed  PubMed Central  Google Scholar 

  96. Finzi, D. et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat. Med. 5, 512–517 (1999).

    CAS  PubMed  Google Scholar 

  97. Maldarelli, F. et al. HIV latency. specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science 345, 179–183 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Simonetti, F. R. et al. Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo. Proc. Natl Acad. Sci. USA 113, 1883–1888 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. White, J. A. et al. Clonally expanded HIV-1 proviruses with 5′-leader defects can give rise to nonsuppressible residual viremia. J. Clin. Invest 133, e165245 (2023).

    PubMed  PubMed Central  Google Scholar 

  100. Sannier, G. et al. Combined single-cell transcriptional, translational, and genomic profiling reveals HIV-1 reservoir diversity. Cell Rep. 36, 109643 (2021).

    CAS  PubMed  Google Scholar 

  101. Li, J. Z. et al. The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. AIDS 30, 343–353 (2016).

    CAS  PubMed  Google Scholar 

  102. Einkauf, K. B. et al. Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses. Cell 185, 266–282.e15 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Chang, C. C. et al. Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1. AIDS 32, 2119–2128 (2018).

    CAS  PubMed  Google Scholar 

  104. Scully, E. P. et al. Sex-based differences in human immunodeficiency virus type 1 reservoir activity and residual immune activation. J. Infect. Dis. 219, 1084–1094 (2019).

    CAS  PubMed  Google Scholar 

  105. Sun, W. et al. Phenotypic signatures of immune selection in HIV-1 reservoir cells. Nature 614, 309–317 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Clark, I. C. et al. HIV silencing and cell survival signatures in infected T cell reservoirs. Nature 614, 318–325 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Ho, Y. C. et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155, 540–551 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Lewin, S. R. et al. Use of real-time PCR and molecular beacons to detect virus replication in human immunodeficiency virus type 1-infected individuals on prolonged effective antiretroviral therapy. J. Virol. 73, 6099–6103 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Hiener, B. et al. Identification of genetically intact HIV-1 proviruses in specific CD4+ T cells from effectively treated participants. Cell Rep. 21, 813–822 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Bruner, K. M. et al. A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 566, 120–125 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Turk, G. et al. A possible sterilizing cure of HIV-1 infection without stem cell transplantation. Ann. Intern. Med. 175, 95–100 (2022).

    PubMed  Google Scholar 

  112. Jiang, C. et al. Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Nature 585, 261–267 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Yang, O. O., Cumberland, W. G., Escobar, R., Liao, D. & Chew, K. W. Demographics and natural history of HIV-1-infected spontaneous controllers of viremia. AIDS 31, 1091–1098 (2017).

    CAS  PubMed  Google Scholar 

  114. Collins, D. R., Gaiha, G. D. & Walker, B. D. CD8+ T cells in HIV control, cure and prevention. Nat. Rev. Immunol. 20, 471–482 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Gaiha, G. D. et al. Structural topology defines protective CD8+ T cell epitopes in the HIV proteome. Science 364, 480–484 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Hocqueloux, L. et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS 24, 1598–1601 (2010).

    PubMed  Google Scholar 

  117. Li, J. Z. & Blankson, J. N. How elite controllers and posttreatment controllers inform our search for an HIV-1 cure. J. Clin. Invest. 131, e149414 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Namazi, G. et al. The control of HIV after antiretroviral medication pause (CHAMP) study: posttreatment controllers identified from 14 clinical studies. J. Infect. Dis. 218, 1954–1963 (2018).

    PubMed  PubMed Central  Google Scholar 

  119. Etemad, B. et al. HIV post-treatment controllers have distinct immunological and virological features. Proc. Natl Acad. Sci. USA 120, e2218960120 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Molinos-Albert, L. M. et al. Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers. Nat. Commun. 13, 1944 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Kahn, J. O. & Walker, B. D. Acute human immunodeficiency virus type 1 infection. N. Engl. J. Med. 339, 33–39 (1998).

    CAS  PubMed  Google Scholar 

  122. Moir, S., Chun, T. W. & Fauci, A. S. Pathogenic mechanisms of HIV disease. Annu. Rev. Pathol. 6, 223–248 (2011).

    CAS  PubMed  Google Scholar 

  123. Hurt, C. B., Nelson, J. A. E., Hightow-Weidman, L. B. & Miller, W. C. Selecting an HIV test: a narrative review for clinicians and researchers. Sex. Transm. Dis. 44, 739–746 (2017).

    PubMed  PubMed Central  Google Scholar 

  124. Fiebig, E. W. et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17, 1871–1879 (2003).

    PubMed  Google Scholar 

  125. Prakash, R., Yashaswini, M. K. in Future Opportunities and Tools for Emerging Challenges for HIV/AIDS Control (ed. Okware, S. I.) (IntechOpen, 2022).

  126. Alexander, T. S. Human immunodeficiency virus diagnostic testing: 30 years of evolution. Clin. Vaccin. Immunol. 23, 249–253 (2016).

    CAS  Google Scholar 

  127. World Health Organization. Consolidated Guidelines on HIV Testing Services. WHO https://www.who.int/publications/i/item/978-92-4-155058-1 (2019).

  128. Gökengin, D. et al. European guideline on HIV testing in genito-urinary medicine settings. J. Eur. Acad. Dermatol. Venereol. 35, 1043–1057 (2021).

    PubMed  Google Scholar 

  129. National Center for HIV/AIDS, Viral Hepatitis, and TB Prevention (U.S.), Division of HIV/AIDS Prevention, Association of Public Health Laboratories. 2018 Quick reference guide: Recommended laboratory HIV testing algorithm for serum or plasma specimens. CDC https://stacks.cdc.gov/view/cdc/50872 (2018).

  130. Drain, P. K. et al. Diagnostic point-of-care tests in resource-limited settings. Lancet Infect. Dis. 14, 239–249 (2014).

    PubMed  Google Scholar 

  131. Witzel, T. C. et al. Comparing the effects of HIV self-testing to standard HIV testing for key populations: a systematic review and meta-analysis. BMC Med. 18, 381 (2020).

    PubMed  PubMed Central  Google Scholar 

  132. World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. WHO https://www.who.int/publications/i/item/9789240031593 (2021).

  133. Branson, B. M. et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm. Rep. 55, 1–17 (2006).

    PubMed  Google Scholar 

  134. Wanyenze, R. K. et al. Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial. Lancet Glob. Health 1, e137–e145 (2013).

    PubMed  PubMed Central  Google Scholar 

  135. Eshleman, S. H. et al. Characterization of human immunodeficiency virus (HIV) infections in women who received injectable cabotegravir or tenofovir disoproxil fumarate/emtricitabine for HIV prevention: HPTN 084. J. Infect. Dis. 225, 1741–1749 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Cohan, D., Gomez, E., Greenberg, M., Washington, S. & Charlebois, E. D. Patient perspectives with abbreviated versus standard pre-test HIV counseling in the prenatal setting: a randomized-controlled, non-inferiority trial. PLoS ONE 4, e5166 (2009).

    PubMed  PubMed Central  Google Scholar 

  137. Eshleman, S. H. et al. HIV RNA screening reduces integrase strand transfer inhibitor resistance risk in persons receiving long-acting cabotegravir for HIV prevention. J. Infect. Dis. 226, 2170–2180 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Stover, J. et al. The case for investing in the male condom. PLoS ONE 12, e0177108 (2017).

    PubMed  PubMed Central  Google Scholar 

  139. Giannou, F. K. et al. Condom effectiveness in reducing heterosexual HIV transmission: a systematic review and meta-analysis of studies on HIV serodiscordant couples. Expert Rev. Pharmacoeconomics Outcomes Res. 16, 489–499 (2016).

    Google Scholar 

  140. Smith, D. K., Herbst, J. H., Zhang, X. & Rose, C. E. Condom effectiveness for HIV prevention by consistency of use among men who have sex with men in the United States. J. Acquir. Immune Defic. Syndr. 68, 337–344 (2015).

    PubMed  Google Scholar 

  141. Carey, R. F. et al. Effectiveness of latex condoms as a barrier to human immunodeficiency virus-sized particles under conditions of simulated use. Sex. Transm. Dis. 19, 230–234 (1992).

    CAS  PubMed  Google Scholar 

  142. Sanders, S. A. et al. Condom use errors and problems: a global view. Sex. Health 9, 81–95 (2012).

    PubMed  Google Scholar 

  143. Stover, J. & Teng, Y. The impact of condom use on the HIV epidemic. Gates Open Res. 5, 91 (2022).

    PubMed  PubMed Central  Google Scholar 

  144. Fasehun, L.-K., Lewinger, S., Fasehun, O. & Brooks, M. Barriers and facilitators to acceptability of the female condom in low- and middle-income countries: a systematic review. Ann. Glob. Health 88, 20 (2022).

    PubMed  PubMed Central  Google Scholar 

  145. Wiyeh, A. B., Mome, R. K. B., Mahasha, P. W., Kongnyuy, E. J. & Wiysonge, C. S. Effectiveness of the female condom in preventing HIV and sexually transmitted infections: a systematic review and meta-analysis. BMC Public Health 20, 319 (2020).

    PubMed  PubMed Central  Google Scholar 

  146. Prodger, J. L. et al. How does voluntary medical male circumcision reduce HIV risk. Curr. HIV/AIDS Rep. 19, 484–490 (2022).

    PubMed  PubMed Central  Google Scholar 

  147. Tobian, A. A. et al. Voluntary medical male circumcision in resource-constrained settings. Nat. Rev. Urol. 12, 661–670 (2015).

    PubMed  Google Scholar 

  148. Wawer, M. J. et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 374, 229–237 (2009).

    PubMed  PubMed Central  Google Scholar 

  149. Yuan, T. et al. Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data. Lancet Glob. Health 7, e436–e447 (2019).

    PubMed  PubMed Central  Google Scholar 

  150. Tobian, A. A., Kacker, S. & Quinn, T. C. Male circumcision: a globally relevant but under-utilized method for the prevention of HIV and other sexually transmitted infections. Annu. Rev. Med. 65, 293–306 (2014).

    CAS  PubMed  Google Scholar 

  151. Grund, J. M. et al. Association between male circumcision and women’s biomedical health outcomes: a systematic review. Lancet Glob. Health 5, e1113–e1122 (2017).

    PubMed  PubMed Central  Google Scholar 

  152. Morris, B. J. et al. Does male circumcision reduce women’s risk of sexually transmitted infections, cervical cancer, and associated conditions? Front. Public Health 7, 4 (2019).

    PubMed  PubMed Central  Google Scholar 

  153. Stegman, P. M. et al. Estimating male circumcision coverage in 15 priority countries in sub-Saharan Africa. J. Int. AIDS Soc. 24, e25789 (2021).

    PubMed  PubMed Central  Google Scholar 

  154. World Health Organization. Voluntary medical male circumcision: remarkable progress in the scale up of VMMC as an HIV prevention intervention in 15 ESA countries. WHO https://www.who.int/publications/i/item/voluntary-medical-male-circumcision-progress-brief-2019 (2019).

  155. Palmateer, N. et al. Interventions to prevent HIV and hepatitis C among people who inject drugs: latest evidence of effectiveness from a systematic review (2011 to 2020). Int. J. Drug. Policy 109, 103872 (2022).

    PubMed  Google Scholar 

  156. Larney, S. et al. Global, regional, and country-level coverage of interventions to prevent and manage HIV and hepatitis C among people who inject drugs: a systematic review. Lancet Glob. Health 5, e1208–e1220 (2017).

    PubMed  PubMed Central  Google Scholar 

  157. O’Keefe, D., Stoové, M., Doyle, J., Dietze, P. & Hellard, M. Injecting drug use in low and middle-income countries: opportunities to improve care and prevent harm. J. Viral Hepat. 24, 714–724 (2017).

    PubMed  Google Scholar 

  158. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. WHO https://www.who.int/publications/i/item/9789241509565 (2015).

  159. Fonner, V. A. et al. Effectiveness and safety of oral HIV preexposure prophylaxis for all populations. AIDS 30, 1973–1983 (2016).

    PubMed  Google Scholar 

  160. Hendrix, C. W. Exploring concentration response in HIV pre-exposure prophylaxis to optimize clinical care and trial design. Cell 155, 515–518 (2013).

    CAS  PubMed  Google Scholar 

  161. Chatterjee, A. et al. Chemokines and chemokine receptors in susceptibility to HIV-1 infection and progression to AIDS. Dis. Markers 32, 143–151 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. World Health Organization. Guidelines on long-acting injectable cabotegravir for HIV prevention. WHO https://www.who.int/publications/i/item/9789240054097 (2022).

  163. World Health Organization. What’s the 2+1+1? Event-driven oral pre-exposure prophylaxis to prevent HIV for men who have sex with men: update to WHO’s recommendation on oral PrEP. WHO https://www.who.int/publications/i/item/what-s-the-2-1-1-event-driven-oral-pre-exposure-prophylaxis-to-prevent-hiv-for-men-who-have-sex-with-men (2019).

  164. Molina, J. M. et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N. Engl. J. Med. 373, 2237–2246 (2015).

    CAS  PubMed  Google Scholar 

  165. Nel, A. et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N. Engl. J. Med. 375, 2133–2143 (2016).

    CAS  PubMed  Google Scholar 

  166. Baeten, J. M. et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N. Engl. J. Med. 375, 2121–2132 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Baeten, J. M., Brown, E. R. & Hillier, S. L. Dapivirine vaginal ring for HIV-1 prevention. N. Engl. J. Med. 376, 995–996 (2017).

    PubMed  Google Scholar 

  168. Marrazzo, J. M. et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N. Engl. J. Med. 372, 509–518 (2015).

    PubMed  PubMed Central  Google Scholar 

  169. Landovitz, R. J. et al. Cabotegravir for HIV prevention in cisgender men and transgender women. N. Engl. J. Med. 385, 595–608 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Delany-Moretlwe, S. et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet 399, 1779–1789 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. AVAC. The future of ARV-based prevention and more. AVAC https://www.avac.org/infographic/future-arv-based-prevention (2022).

  172. World Health Organization. Global PrEP Network: global state of PrEP. WHO https://www.who.int/groups/global-prep-network/global-state-of-prep (2022).

  173. Kuhar, D. T. et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect. Cont. Hosp. Epidemiol. 34, 875–892 (2013).

    Google Scholar 

  174. Dominguez, K. L. et al. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV—United States, 2016. Update May 23, 2018. CDC https://stacks.cdc.gov/view/cdc/38856 (2016).

  175. Otten, R. A. et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J. Virol. 74, 9771–9775 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Le Grand, R. et al. Post-exposure prophylaxis with highly active antiretroviral therapy could not protect macaques from infection with SIV/HIV chimera. AIDS 14, 1846–1866 (2000).

    Google Scholar 

  177. Sperling, R. S. et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N. Engl. J. Med. 335, 1621–1629 (1996).

    CAS  PubMed  Google Scholar 

  178. Wade, N. A. et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N. Engl. J. Med. 339, 1409–1414 (1998).

    CAS  PubMed  Google Scholar 

  179. Phillips, A. N. et al. Potential future impact of a partially effective HIV vaccine in a southern African setting. PLoS ONE 9, e107214 (2014).

    PubMed  PubMed Central  Google Scholar 

  180. Kim, J., Vasan, S., Kim, J. H. & Ake, J. A. Current approaches to HIV vaccine development: a narrative review. J. Int. AIDS Soc. 24, e25793 (2021).

    PubMed  PubMed Central  Google Scholar 

  181. Rerks-Ngarm, S. et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209–2220 (2009).

    CAS  PubMed  Google Scholar 

  182. Lu, S. Heterologous prime-boost vaccination. Curr. Opin. Immunol. 21, 346–351 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Zolla-Pazner, S., Michael, N. L. & Kim, J. H. A tale of four studies: HIV vaccine immunogenicity and efficacy in clinical trials. Lancet HIV 8, e449–e452 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  184. National Institutes of Health News Release. HIV vaccine candidate does not sufficiently protect women against HIV infection. NIH https://www.nih.gov/news-events/news-releases/hiv-vaccine-candidate-does-not-sufficiently-protect-women-against-hiv-infection (2021).

  185. HIV Vaccine Trials Network News Release. Phase 3 mosaic-based investigational hiv vaccine study discontinued following disappointing results of planned data review. HVTN https://www.hvtn.org/news/news-releases/2023/01/phase-3-mosaic-based-investigational-hiv-vaccine-study-discontinued-following-disappointing-results-planned-data-review.html?utm_source=AVAC+Email+Updates&utm_campaign=f35b021248-EMAIL_CAMPAIGN_2021_08_31_11_20_COPY_01&utm_medium=email&utm_term=0_6fd730be57-f35b021248-130140701 (2023).

  186. Corey, L. et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N. Engl. J. Med. 384, 1003–1014 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Haynes, B. F. et al. Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies. Nat. Rev. Immunol. 23, 142–158 (2023).

    CAS  PubMed  Google Scholar 

  188. Tseng, A., Seet, J. & Phillips, E. J. The evolution of three decades of antiretroviral therapy: challenges, triumphs and the promise of the future. Br. J. Clin. Pharmacol. 79, 182–194 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  189. Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV 4, e349–e356 (2017).

    Google Scholar 

  190. Group, T. A. S. et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N. Engl. J. Med. 373, 808–822 (2015).

    Google Scholar 

  191. Group, I. S. S. et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N. Engl. J. Med. 373, 795–807 (2015).

    Google Scholar 

  192. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf (2022).

  193. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. WHO https://www.who.int/publications/i/item/9789240031593 (2021).

  194. Ryom, L. et al. Major revision version 11.0 of the European AIDS clinical society guidelines 2021. HIV Med. 23, 849–858 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Saag, M. S. et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2020 recommendations of the international antiviral society-USA panel. JAMA 324, 1651–1669 (2020).

    CAS  PubMed  Google Scholar 

  196. Boulware, D. R. et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N. Engl. J. Med. 370, 2487–2498 (2014).

    PubMed  PubMed Central  Google Scholar 

  197. Devereux, H. L., Youle, M., Johnson, M. A. & Loveday, C. Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy. AIDS 13, F123–F127 (1999).

    CAS  PubMed  Google Scholar 

  198. Paton, N. I. et al. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. Lancet HIV 9, e381–e393 (2022).

    CAS  PubMed  Google Scholar 

  199. Mulenga, L. et al. Dolutegravir with recycled NRTIs is noninferior to PI-based ART: VISEND trial [abstract 135]. Conf. Retroviruses Opportunistic Infect. https://www.croiconference.org/abstract/dolutegravir-with-recycled-nrtis-is-noninferior-to-pi-based-art-visend-trial/ (2022).

  200. Emu, B. et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1. N. Engl. J. Med. 379, 645–654 (2018).

    CAS  PubMed  Google Scholar 

  201. Kozal, M. et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection. N. Engl. J. Med. 382, 1232–1243 (2020).

    CAS  PubMed  Google Scholar 

  202. Segal-Maurer, S. et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection. N. Engl. J. Med. 386, 1793–1803 (2022).

    CAS  PubMed  Google Scholar 

  203. Marzolini, C., Gibbons, S., Khoo, S. & Back, D. Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications. J. Antimicrob. Chemother. 71, 1755–1758 (2016).

    CAS  PubMed  Google Scholar 

  204. Clay, P. G. et al. A meta-analysis comparing 48-week treatment outcomes of single and multi-tablet antiretroviral regimens for the treatment of people living with HIV. AIDS Res. Ther. 15, 17 (2018).

    PubMed  PubMed Central  Google Scholar 

  205. Orkin, C. et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV 8, e185–e196 (2021).

    CAS  PubMed  Google Scholar 

  206. Overton, E. T. et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet 396, 1994–2005 (2021).

    PubMed  Google Scholar 

  207. Singh, K. P. et al. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. AIDS 31, 2035–2052 (2017).

    PubMed  Google Scholar 

  208. Zash, R., Makhema, J. & Shapiro, R. L. Neural-tube defects with dolutegravir treatment from the time of conception. N. Engl. J. Med. 379, 979–981 (2018).

    PubMed  PubMed Central  Google Scholar 

  209. Woodward, C. L. et al. Tenofovir-associated renal and bone toxicity. HIV Med. 10, 482–487 (2009).

    CAS  PubMed  Google Scholar 

  210. Grant, P. M. & Cotter, A. G. Tenofovir and bone health. Curr. Opin. HIV AIDS 11, 326–332 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  211. Ray, A. S., Fordyce, M. W. & Hitchcock, M. J. Tenofovir alafenamide: a novel prodrug of tenofovir for the treatment of human immunodeficiency virus. Antivir. Res. 125, 63–70 (2016).

    CAS  PubMed  Google Scholar 

  212. DeJesus, E. et al. Superior efficacy and improved renal and bone safety after switching from a tenofovir disoproxil fumarate- to a tenofovir alafenamide-based regimen through 96 weeks of treatment. AIDS Res. Hum. Retroviruses 34, 337–342 (2018).

    CAS  PubMed  Google Scholar 

  213. Hogg, R. S. Understanding the HIV care continuum. Lancet HIV 5, e269–e270 (2018).

    PubMed  Google Scholar 

  214. Deeks, S. G. HIV infection, inflammation, immunosenescence, and aging. Annu. Rev. Med. 62, 141–155 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  215. Brunet, L. et al. Switch from tenofovir disoproxil fumarate to tenofovir alafenamide in people living with HIV: lipid changes and statin underutilization. Clin. Drug Investig. 41, 955–965 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  216. Mallon, P. W. G. et al. Lipid changes after switch from TDF to TAF in the OPERA cohort: LDL cholesterol and triglycerides. Open Forum Infect. Dis. 9, ofab621 (2022).

    PubMed  Google Scholar 

  217. Arendt, G., de Nocker, D., von Giesen, H. J. & Nolting, T. Neuropsychiatric side effects of efavirenz therapy. Expert Opin. Drug Saf. 6, 147–154 (2007).

    CAS  PubMed  Google Scholar 

  218. Hoffmann, C. et al. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 18, 56–63 (2017).

    CAS  PubMed  Google Scholar 

  219. Hoffmann, C. & Llibre, J. M. Neuropsychiatric adverse events with dolutegravir and other integrase strand transfer inhibitors. AIDS Rev. 21, 4–10 (2019).

    PubMed  Google Scholar 

  220. O’Halloran, J. A. et al. Altered neuropsychological performance and reduced brain volumetrics in people living with HIV on integrase strand transfer inhibitors. AIDS 33, 1477–1483 (2019).

    PubMed  Google Scholar 

  221. Hill, A. M., Mitchell, N., Hughes, S. & Pozniak, A. L. Risks of cardiovascular or central nervous system adverse events and immune reconstitution inflammatory syndrome, for dolutegravir versus other antiretrovirals: meta-analysis of randomized trials. Curr. Opin. HIV AIDS 13, 102–111 (2018).

    CAS  PubMed  Google Scholar 

  222. D:A:D Study Group. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 22, F17–F24 (2008).

    Google Scholar 

  223. Elion, R. A. et al. Recent abacavir use increases risk of type 1 and type 2 myocardial infarctions among adults with HIV. J. Acquir. Immune Defic. Syndr. 78, 62–72 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  224. Ryom, L. et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV 5, e291–e300 (2018).

    PubMed  Google Scholar 

  225. Neesgaard, B. et al. Associations between integrase strand-transfer inhibitors and cardiovascular disease in people living with HIV: a multicentre prospective study from the RESPOND cohort consortium. Lancet HIV 9, e474–e485 (2022).

    CAS  PubMed  Google Scholar 

  226. Sax, P. E. et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin. Infect. Dis. 71, 1379–1389 (2019).

    PubMed Central  Google Scholar 

  227. Bourgi, K. et al. Greater weight gain in treatment naive persons starting dolutegravir-based antiretroviral therapy. Clin. Infect. Dis. 70, 1267–1274 (2019).

    PubMed Central  Google Scholar 

  228. Kerchberger, A. M. et al. Weight gain associated with integrase stand transfer inhibitor use in women. Clin. Infect. Dis. 71, 593–600 (2019).

    PubMed Central  Google Scholar 

  229. Norwood, J. et al. Brief report: weight gain in persons with HIV switched from efavirenz-based to integrase strand transfer inhibitor-based regimens. J. Acquir. Immune Defic. Syndr. 76, 527–531 (2017).

    PubMed  PubMed Central  Google Scholar 

  230. Eckard, A. R. & McComsey, G. A. Weight gain and integrase inhibitors. Curr. Opin. Infect. Dis. 33, 10–19 (2020).

    PubMed  PubMed Central  Google Scholar 

  231. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04636437 (2023).

  232. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04442737 (2023).

  233. Cohen, M. S. et al. Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 365, 493–505 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  234. Graham, S. M. et al. Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS 21, 501–507 (2007).

    PubMed  Google Scholar 

  235. Vernazza, P. L. et al. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV cohort study. AIDS 14, 117–121 (2000).

    CAS  PubMed  Google Scholar 

  236. Rodger, A. J. et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet 393, 2428–2438 (2019).

    PubMed  PubMed Central  Google Scholar 

  237. Marcelin, A. G. et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS 22, 1677–1679 (2008).

    PubMed  Google Scholar 

  238. Politch, J. A. et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS 26, 1535–1543 (2012).

    PubMed  Google Scholar 

  239. Bor, J. et al. Changing knowledge and attitudes towards HIV treatment-as-prevention and “undetectable = untransmittable”: a systematic review. AIDS Behav. 25, 4209–4224 (2021).

    PubMed  PubMed Central  Google Scholar 

  240. Davey, R. T. Jr. et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl Acad. Sci. USA 96, 15109–15114 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. Frescura, L. et al. Achieving the 95 95 95 targets for all: a pathway to ending AIDS. PLoS ONE 17, e0272405 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  242. World Health Organization. The role of HIV viral suppression in improving individual health and reducing transmission: policy brief. WHO https://apps.who.int/iris/bitstream/handle/10665/360860/9789240055179-eng.pdf (2023).

  243. Etemad, B., Esmaeilzadeh, E. & Li, J. Z. Learning from the exceptions: HIV remission in post-treatment controllers. Front. Immunol. 10, 1749 (2019).

    PubMed  PubMed Central  Google Scholar 

  244. Hutter, G. et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360, 692–698 (2009).

    PubMed  Google Scholar 

  245. Dybul, M. et al. The case for an HIV cure and how to get there. Lancet HIV 8, e51–e58 (2021).

    CAS  PubMed  Google Scholar 

  246. Deeks, S. G. et al. Research priorities for an HIV cure: international AIDS society global scientific strategy 2021. Nat. Med. 27, 2085–2098 (2021).

    CAS  PubMed  Google Scholar 

  247. International HIV/AIDS Alliance. Quality of life for people living with HIV: what is it, why does it matter, and how can we make it happen? International HIV/AIDS Alliance https://frontlineaids.org/wp-content/uploads/2019/02/quality_of_life_briefing_final_original.pdf (2018).

  248. Deeks, S. et al. HIV infection. Nat. Rev. Dis. Primers 1, 15035 (2015).

    PubMed  Google Scholar 

  249. Lazarus, J. V. et al. Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV. Nat. Commun. 12, 4450 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  250. Lazarus, J. V. et al. Beyond viral suppression of HIV - the new quality of life frontier. BMC Med. 14, 94 (2016).

    PubMed  PubMed Central  Google Scholar 

  251. Degroote, S., Vogelaers, D. & Vandijck, D. M. What determines health-related quality of life among people living with HIV: an updated review of the literature. Arch. Public Health 72, 40 (2014).

    PubMed  PubMed Central  Google Scholar 

  252. UNAIDS. Global partnership for action to eliminate all forms of HIV-related stigma and discrimination. UNAIDS https://investment-book.unaids.org/sites/default/files/Global%20Partnership%20for%20Action%20to%20Eliminate%20All%20Forms%20of%20HIV-related%20Stigma%20and%20Discrimination%20Proposal.pdf (2018).

  253. Andersson, G. Z. et al. Stigma reduction interventions in people living with HIV to improve health-related quality of life. Lancet HIV 7, e129–e140 (2020).

    PubMed  Google Scholar 

  254. Chapman Lambert, C. et al. HIV-related stigma, depression, and social support are associated with health-related quality of life among patients newly entering HIV care. AIDS Care 32, 681–688 (2019).

    PubMed  PubMed Central  Google Scholar 

  255. Pantelic, M., Boyes, M., Cluver, L. & Meinck, F. HIV, violence, blame and shame: pathways of risk to internalized HIV stigma among South African adolescents living with HIV: pathways. J. Int. AIDS Soc. 20, 21771 (2017).

    PubMed  PubMed Central  Google Scholar 

  256. Pantelic, M., Sprague, L. & Stangl, A. L. It’s not “all in your head”: critical knowledge gaps on internalized HIV stigma and a call for integrating social and structural conceptualizations. BMC Infect. Dis. 19, 210 (2019).

    PubMed  PubMed Central  Google Scholar 

  257. Katz, I. T. et al. Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis. J. Int. AIDS Soc. 16, 18640 (2013).

    PubMed  PubMed Central  Google Scholar 

  258. Ferguson, L. et al. Frameworks and measures for HIV-related internalized stigma, stigma and discrimination in healthcare and in laws and policies: a systematic review. J. Int. AIDS Soc. 25, e25915 (2022).

    PubMed  PubMed Central  Google Scholar 

  259. Rueda, S. et al. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses. BMJ Open 6, e011453 (2006).

    Google Scholar 

  260. Sabin, C. A. & Reiss, P. Epidemiology of ageing with HIV: what can we learn from cohorts? AIDS 31, S121–S128 (2017).

    PubMed  Google Scholar 

  261. Costagliola, D. Demographics of HIV and aging. Curr. Opin. HIV AIDS 9, 294–301 (2014).

    PubMed  Google Scholar 

  262. Guaraldi, G. et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin. Infect. Dis. 53, 1120–1126 (2011).

    PubMed  Google Scholar 

  263. Maciel, R. A., Klück, H. M., Durand, M. & Sprinz, E. Comorbidity is more common and occurs earlier in persons living with HIV than in HIV-uninfected matched controls, aged 50 years and older: a cross-sectional study. Int. J. Infect. Dis. 70, 30–35 (2018).

    PubMed  Google Scholar 

  264. Rodriguez-Penney, A. T. et al. Co-morbidities in persons infected with HIV: increased burden with older age and negative effects on health-related quality of life. AIDS Patient Care STDS 27, 5–16 (2013).

    PubMed  PubMed Central  Google Scholar 

  265. Sutton, S. S. et al. Chronic kidney disease, cardiovascular disease, and osteoporotic fractures in patients with and without HIV in the US veteran’s affairs administration system. Curr. Med. Res. Opin. 35, 117–125 (2019).

    CAS  PubMed  Google Scholar 

  266. Wang, Y. et al. Global prevalence and burden of HIV-associated neurocognitive disorder: a meta-analysis. Neurology 95, E2610–E2621 (2020).

    CAS  PubMed  Google Scholar 

  267. Maitre, T. et al. Increasing burden of noninfectious lung disease in persons living with HIV: a 7-year study using the French nationwide hospital administrative database. Eur. Respir. J. 52, 1800359 (2018).

    PubMed  Google Scholar 

  268. World Health Organization. Global health sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022–2030. WHO https://www.who.int/publications/i/item/9789240053779 (2022).

  269. UNAIDS. End Inequalities. End AIDS. Global AIDS strategy 2021–2026. UNAIDS https://www.unaids.org/sites/default/files/PCBSS_Global_AIDS_Strategy_2021--2026_EN.pdf (2021).

  270. Kall, M., Marcellin, F., Harding, R., Lazarus, J. V. & Carrieri, P. Patient-reported outcomes to enhance person-centred HIV care. Lancet HIV 7, e59–e68 (2020).

    PubMed  Google Scholar 

  271. Lazarus, J. V., Van Hout, M. C., Fuster-Ruizdeapodaca, M. J., Brown, G. & Guaraldi, G. A call for health systems to monitor the health-related quality of life of people living with HIV. HIV Med 24, 107–110 (2022).

    PubMed  Google Scholar 

  272. Burgui, C. et al. Patient satisfaction with HIV care service in Spain: results from a cross-sectional patient survey. AIDS Care 35, 892–898 (2022).

    PubMed  Google Scholar 

  273. Haute Autorité de Santé. Quality of care as perceived by patients – PROMs and PREMs indicators. Haute Autorité de Santé https://www.has-sante.fr/jcms/p_3324079/en/quality-of-care-as-perceived-by-patients-proms-and-prems-indicators (2022).

  274. Emuren, L. et al. Lower health-related quality of life predicts all-cause hospitalization among HIV-infected individuals. Health Qual. Life Outcomes 16, 107 (2018).

    PubMed  PubMed Central  Google Scholar 

  275. Matic, S., Lazarus, J. V. & Donoghoe, M. C. HIV/AIDS in Europe: moving from death sentence to chronic disease management. Cent. Eur. J. Public Health 14, 147 (2006).

    Google Scholar 

  276. Bekker, L. G. et al. Advancing global health and strengthening the HIV response in the era of the sustainable development goals: the International AIDS Society–Lancet Commission. Lancet 392, 312–358 (2018).

    PubMed  PubMed Central  Google Scholar 

  277. Bor, J., Herbst, A. J., Newell, M. L. & Bärnighausen, T. Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment. Science 339, 961–965 (2013).

    CAS  PubMed  Google Scholar 

  278. Alexander, S. Humanimmunodeficiency virus diagnostic testing: 30 years of evolution. Clin. Vaccin. Immunol. 23, 249–253 (2016).

    CAS  Google Scholar 

  279. Hemelaar et al. WHO–UNAIDS network for HIV isolation characterisation. global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis. Lancet Infect. Dis. 19, 143–155 (2019).

    PubMed  Google Scholar 

  280. Bertagnolio S. et al. Clinical characteristics and prognostic factors in people living with HIV hospitalized with COVID19: findings from the WHO Global Clinical Platform [abstract 2498]. IAS 2021 (2021).

  281. Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa. Risk factors for coronavirus disease 2019 (COVID-19) death in a population cohort study from the Western cape province, South Africa. Clin. Infect. Dis. 73, e2005–e2015 (2021).

    Google Scholar 

  282. Rinella, M. E. et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. https://doi.org/10.1016/j.jhep.2023.06.003 (2023).

Download references

Acknowledgements

J.V.L. acknowledges support to ISGlobal from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA programme. J.V.L. acknowledges input from G. Brown, D. Barger and P. Carrieri. R. L. Redondo and C. Reis Vieira developed Fig. 6. C. Williamson (University of Cape Town) reviewed the text. S.R.L. receives funding from the National Institutes for Allergy and Infectious Diseases. UM1 AI164560-01 Delaney AIDS Research Enterprise (DARE) Collaboratory and the National Health and Medical Research Council (NHMRC) of Australia including an NHMRC programme grant (to S.R.L.) and practitioner fellowship (to S.R.L.).

Author information

Authors and Affiliations

  1. The Desmond Tutu HIV Centre, University of Cape Town, RSA, Cape Town, South Africa

    Linda-Gail Bekker

  2. Duke Global Health Institute, Duke University, Durham, NC, USA

    Chris Beyrer

  3. University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe

    Nyaradzo Mgodi

  4. Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    Sharon R. Lewin

  5. Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    Sharon R. Lewin

  6. Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Victoria, Australia

    Sharon R. Lewin

  7. Wits RHI, University of the Witwatersrand, Johannesburg, South Africa

    Sinead Delany-Moretlwe

  8. Division of Infectious Diseases, Northwestern University, Chicago, IL, USA

    Babafemi Taiwo & Mary Clare Masters

  9. CUNY Graduate School of Public Health and Health Policy, New York, NY, USA

    Jeffrey V. Lazarus

  10. Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain

    Jeffrey V. Lazarus

Authors
  1. Linda-Gail Bekker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chris Beyrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nyaradzo Mgodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sharon R. Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sinead Delany-Moretlwe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Babafemi Taiwo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mary Clare Masters
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jeffrey V. Lazarus
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Introduction (L.-G.B.); Epidemiology (L.-G.B. and C.B.); Mechanisms/pathophysiology (L.-G.B., N.M. and S.R.L.); Diagnosis, screening and prevention (L.-G.B. and S.D.-M.); Management (L.-G.B., B.T. and M.C.M.); Quality of life (L.-G.B. and J.V.L.); Outlook (L.-G.B.); Overview of the Primer (L.-G.B.).

Corresponding author

Correspondence to Linda-Gail Bekker.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Disease Primers thanks P. Reiss and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bekker, LG., Beyrer, C., Mgodi, N. et al. HIV infection. Nat Rev Dis Primers 9, 42 (2023). https://doi.org/10.1038/s41572-023-00452-3

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-023-00452-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing