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  • Review Article
  • Published:

Paediatric HIV infection: the potential for cure

Key Points

  • Recent anecdotal reports of HIV remission in children following a discrete period of antiretroviral therapy (ART) have prompted the suggestion that HIV cure might be more readily achieved in children than in adults. This Review examines the evidence for such a claim and discusses the unique opportunities for immunotherapeutic interventions in children to maximize HIV cure potential.

  • ART can be initiated within minutes of birth following in utero infection with HIV. Early initiation of ART results in a substantially smaller viral reservoir. The decay half-life of the viral reservoir is shorter following ART initiation in children compared with adults, and the decrease in size of the reservoir seems to continue for longer in children.

  • The tolerogenic immune environment in utero and in early life increases the potential for HIV cure in infants. Other aspects of immune ontogeny, including the strong T helper 17 cell bias at birth, decrease cure potential in children. The overall balance between these opposing influences may depend crucially on the timing of initiation of ART.

  • Maternal factors — including maternal health (which influences child feeding, general care and ART provision), maternally transmitted infections (such as cytomegalovirus and tuberculosis) and genetic factors (such as the effect of HLA class I alleles on dendritic cell function through leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) binding avidity) — could all markedly affect the potential for HIV cure in children.

  • Paediatric infection presents particular opportunities for HIV cure through early interventions in addition to ART. Certain challenges are also posed by paediatric infection and the effects of immune ontogeny. The onset of puberty may limit the optimal window of opportunity for immunotherapeutic interventions in children to the ages of 3–9 years.

Abstract

Recent anecdotal reports of HIV-infected children who received early antiretroviral therapy (ART) and showed sustained control of viral replication even after ART discontinuation have raised the question of whether there is greater intrinsic potential for HIV remission, or even eradication ('cure'), in paediatric infection than in adult infection. This Review describes the influence of early initiation of ART, of immune ontogeny and of maternal factors on the potential for HIV cure in children and discusses the unique immunotherapeutic opportunities and obstacles that paediatric infection may present.

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Figure 1: Changes in viral load following HIV infection in paediatric and adult cases.
Figure 2: Risk of MTCT in utero and in early life.
Figure 3: Paediatric factors affecting immune activation and size of the HIV reservoir.
Figure 4: Principal opportunities for immunotherapeutic interventions to maximize the potential for HIV cure or remission in paediatric infection.

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References

  1. Newell, M. L. et al. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 364, 1236–1243 (2004).

    Article  PubMed  Google Scholar 

  2. Collaborative Group on AIDS Incubation & HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe. Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis. Lancet 355, 1131–1137 (2000).

  3. Kaslow, R. A. et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat. Med. 2, 405–411 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Pereyra, F. et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330, 1551–1557 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kiepiela, P. et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat. Med. 13, 46–53 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Shearer, W. T. et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J. Allergy Clin. Immunol. 112, 973–980 (2003).

    Article  PubMed  Google Scholar 

  7. Adland, E. et al. Mechanisms of non-pathogenicity in HIV: lessons from paediatric infection. IAS, 20th International AIDS Conference, Abstr. http://pag.aids2014.org/abstracts.aspx?aid=5075 (2014).

    Google Scholar 

  8. Adland, E. et al. Discordant impact of HLA on viral replicative capacity and disease progression in pediatric and adult HIV infection. PLoS Pathog. 11, e1004954 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ferrand, R. A. et al. HIV infection presenting in older children and adolescents: a case series from Harare, Zimbabwe. Clin. Infect. Dis. 44, 874–878 (2007).

    Article  PubMed  Google Scholar 

  10. Judd, A. et al. Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance. HIV Med. 10, 253–256 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Silvestri, G. et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18, 441–452 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Persaud, D. et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N. Engl. J. Med. 369, 1828–1835 (2013). This is the first paper to describe the Mississippi child.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Luzuriaga, K. et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N. Engl. J. Med. 372, 786–788 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Saez-Cirion, A. et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9, e1003211 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vigano, A. et al. Failure to eradicate HIV despite fully successful HAART initiated in the first days of life. J. Pediatr. 148, 389–391 (2006).

    Article  PubMed  Google Scholar 

  16. Butler, K. M. et al. Rapid viral rebound after 4 years of suppressive therapy in a seronegative HIV-1 infected infant treated from birth. Pediatr. Infect. Dis. J. 34, e48–e51 (2015).

    Article  PubMed  Google Scholar 

  17. Bitnun, A. et al. Early initiation of combination antiretroviral therapy in HIV-1-infected newborns can achieve sustained virologic suppression with low frequency of CD4+ T cells carrying HIV in peripheral blood. Clin. Infect. Dis. 59, 1012–1019 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Giacomet, V. et al. No cure of HIV infection in a child despite early treatment and apparent viral clearance. Lancet 384, 1320 (2014).

    Article  PubMed  Google Scholar 

  19. Cotton, M. F. et al. Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet 382, 1555–1563 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Prendergast, A. et al. Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. AIDS 22, 1333–1343 (2008).

    Article  PubMed  Google Scholar 

  21. Ndhlovu, Z. M. et al. Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impact viral set point. Immunity 43, 591–604 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schuetz, A. et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog. 10, e1004543 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Brossard, Y. et al. Frequency of early in utero HIV-1 infection: a blind DNA polymerase chain reaction study on 100 fetal thymuses. AIDS 9, 359–366 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Rouzioux, C. et al. Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission by use of a Markov model. The HIV Infection in Newborns French Collaborative Study Group. Am. J. Epidemiol. 142, 1330–1337 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. Jani, I. V. et al. Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test. J. Acquir. Immune Defic. Syndr. 67, e1–e4 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Whitney, J. B. et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature 512, 74–77 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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).

    Article  PubMed  Google Scholar 

  28. Frange, P. et al. HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report. Lancet HIV 3, e49–e54 (2016). This is the first paper to describe the VISCONTI child.

    Article  PubMed  Google Scholar 

  29. 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).

    Article  CAS  PubMed  Google Scholar 

  30. Siliciano, J. D. et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat. Med. 9, 727–728 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Crooks, A. M. et al. Precise quantitation of the latent HIV-1 reservoir: implications for eradication strategies. J. Infect. Dis. 212, 1361–1365 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang, L. et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N. Engl. J. Med. 340, 1605–1613 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. Chun, T. W. et al. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 24, 2803–2808 (2010).

    Article  PubMed  Google Scholar 

  34. Hocqueloux, L. et al. Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts. J. Antimicrob. Chemother. 68, 1169–1178 (2013).

    Article  CAS  PubMed  Google Scholar 

  35. Schmid, A. et al. Profound depletion of HIV-1 transcription in patients initiating antiretroviral therapy during acute infection. PLoS ONE 5, e13310 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Buzon, M. J. et al. Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. J. Virol. 88, 10056–10065 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Archin, N. M. et al. Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc. Natl Acad. Sci. USA 109, 9523–9528 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wightman, F. et al. Both CD31+ and CD31 naive CD4+ T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy. J. Infect. Dis. 202, 1738–1748 (2010).

    Article  PubMed  Google Scholar 

  39. Jaafoura, S. et al. Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4+ memory T Cells. Nat. Commun. 5, 5407 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. Persaud, D. et al. Dynamics of the resting CD4+ T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age. AIDS 26, 1483–1490 (2012).

    Article  CAS  PubMed  Google Scholar 

  41. Luzuriaga, K. et al. HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment. J. Infect. Dis. 210, 1529–1538 (2014). This paper indicates that decay of the viral reservoir not only occurs faster in early treated paediatric infection but also continues throughout childhood and possibly into adolescence.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ananworanich, J. et al. Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children. AIDS 28, 1015–1020 (2014).

    Article  CAS  PubMed  Google Scholar 

  43. van Zyl, G. U. et al. Early antiretroviral therapy in South African children reduces HIV-1-infected cells and cell-associated HIV-1 RNA in blood mononuclear cells. J. Infect. Dis. 212, 39–43 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. Martinez-Bonet, M. et al. Establishment and replenishment of the viral reservoir in perinatally HIV-1-infected children initiating very early antiretroviral therapy. Clin. Infect. Dis. 61, 1169–1178 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Besson, G. J. et al. HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy. Clin. Infect. Dis. 59, 1312–1321 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Uprety, P. et al. Cell-associated HIV-1 DNA and RNA decay dynamics during early combination antiretroviral therapy in HIV-1-infected infants. Clin. Infect. Dis. 61, 1862–1870 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Eriksson, S. et al. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 9, e1003174 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mold, J. E. et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322, 1562–1565 (2008). This paper describes the vigorous response of CD4+ T cells in utero to non-inherited maternal antigens; these T cells develop in the presence of TGFβ into long-lived T Reg cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Takahata, Y. et al. CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene. Exp. Hematol. 32, 622–629 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Kollmann, T. R. et al. Neonatal innate TLR-mediated responses are distinct from those of adults. J. Immunol. 183, 7150–7160 (2009). This study shows the marked differences between newborns and adults in terms of the cytokines produced by innate immune cells in response to a panel of TLR agonists.

    Article  CAS  PubMed  Google Scholar 

  51. Levy, O. et al. The adenosine system selectively inhibits TLR-mediated TNF-α production in the human newborn. J. Immunol. 177, 1956–1966 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Upham, J. W. et al. Development of interleukin-12-producing capacity throughout childhood. Infect. Immun. 70, 6583–6588 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Nowak, E. C. et al. IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med. 206, 1653–1660 (2009). This study highlights the striking contrast between the lack of target cells for HIV infection in the peripheral blood in utero and the high frequency of target cells in the fetal gut.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Elyaman, W. et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc. Natl Acad. Sci. USA 106, 12885–12890 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Doitsh, G. et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505, 509–514 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Munoz-Arias, I. et al. Blood-derived CD4 T Cells naturally resist pyroptosis during abortive HIV-1 infection. Cell Host Microbe 18, 463–470 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bunders, M. J. et al. Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1. Blood 120, 4383–4390 (2012).

    Article  CAS  PubMed  Google Scholar 

  58. Veazey, R. S. et al. Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4+ T cells are rapidly eliminated in early SIV infection in vivo. J. Virol. 74, 57–64 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bleul, C. C., Wu, L., Hoxie, J. A., Springer, T. A. & Mackay, C. R. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc. Natl Acad. Sci. USA 94, 1925–1930 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wu, L. et al. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J. Exp. Med. 185, 1681–1691 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Monteiro, P. et al. Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin β7. J. Immunol. 186, 4618–4630 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Gosselin, A. et al. Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J. Immunol. 184, 1604–1616 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Cameron, P. U. et al. Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton. Proc. Natl Acad. Sci. USA 107, 16934–16939 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Brenchley, J. M. et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 112, 2826–2835 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Alvarez, Y. et al. Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands. J. Virol. 87, 10843–10854 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gordon, S. N. et al. Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J. Immunol. 179, 3026–3034 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Pandrea, I. V. et al. Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J. Immunol. 179, 3035–3046 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Li, Q. et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434, 1148–1152 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Wang, X. et al. Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection. Blood 109, 1174–1181 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mattapallil, J. J. et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434, 1093–1097 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Favre, D. et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog. 5, e1000295 (2009). The central role of T H 17 cell maintenance in the non-pathogenicity of SIV infection is illustrated in African green monkeys compared with pig-tailed macaques.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. He, T. et al. Critical role for the adenosine pathway in controlling simian immunodeficiency virus-related immune activation and inflammation in gut mucosal tissues. J. Virol. 89, 9616–9630 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kourtis, A. P. et al. Role of intestinal mucosal integrity in HIV transmission to infants through breast-feeding: the BAN study. J. Infect. Dis. 208, 653–661 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Papasavvas, E. et al. Increased microbial translocation in ≤180 days old perinatally human immunodeficiency virus-positive infants as compared with human immunodeficiency virus-exposed uninfected infants of similar age. Pediatr. Infect. Dis. J. 30, 877–882 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Wallet, M. A. et al. Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. AIDS 24, 1281–1290 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Coovadia, H. M. et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 369, 1107–1116 (2007).

    Article  PubMed  Google Scholar 

  77. Iliff, P. J. et al. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 19, 699–708 (2005).

    Article  PubMed  Google Scholar 

  78. Tchakoute, C. T. et al. Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants. J. Infect. Dis. 211, 338–346 (2015).

    Article  CAS  PubMed  Google Scholar 

  79. Roy, A. et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ 349, g4643 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Aaby, P. et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J. Infect. Dis. 204, 245–252 (2011).

    Article  CAS  PubMed  Google Scholar 

  81. Miles, D. J. et al. Cytomegalovirus infection in Gambian infants leads to profound CD8 T-cell differentiation. J. Virol. 81, 5766–5776 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kovacs, A. et al. Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complication of Vertically Transmitted HIV Infection Study Group. N. Engl. J. Med. 341, 77–84 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chun, T. W. et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J. Infect. Dis. 197, 714–720 (2008).

    Article  CAS  PubMed  Google Scholar 

  84. Fletcher, C. V. et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc. Natl Acad. Sci. USA 111, 2307–2312 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Saksena, N. K. et al. HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites. HIV AIDS (Auckl.) 2, 103–122 (2010).

    CAS  Google Scholar 

  86. Couturier, J. et al. Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS 29, 667–674 (2015).

    Article  CAS  PubMed  Google Scholar 

  87. Damouche, A. et al. Adipose tissue is a neglected viral reservoir and an inflammatory site during chronic HIV and SIV infection. PLoS Pathog. 11, e1005153 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kandathil, A. J. et al. Liver macrophages and HIV-1 persistence. Conference on Retroviruses and Opportunistic Infections, Abstr. 281 http://www.croiconference.org/sites/default/files/uploads/croi2015-program-abstracts.pdf (2015).

    Google Scholar 

  89. Cribbs, S. K. et al. Metabolomics of bronchoalveolar lavage differentiate healthy HIV-1-infected subjects from controls. AIDS Res. Hum. Retroviruses 30, 579–585 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sturdevant, C. B. et al. Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. PLoS Pathog. 11, e1004720 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Churchill, M. J. et al. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann. Neurol. 66, 253–258 (2009).

    Article  PubMed  Google Scholar 

  92. Santangelo, P. J. et al. Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat. Methods 12, 427–432 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gorry, P. R., Francella, N., Lewin, S. R. & Collman, R. G. HIV-1 envelope-receptor interactions required for macrophage infection and implications for current HIV-1 cure strategies. J. Leukoc. Biol. 95, 71–81 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Gray, L. R. et al. CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies. Mol. Psychiatry http://dx.doi.org/10.1038/mp.2015.111 (2015).

  95. Josefsson, L. et al. The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time. Proc. Natl Acad. Sci. USA 110, E4987–E4996 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Luzuriaga, K. et al. HIV-1-specific cytotoxic T lymphocyte responses in the first year of life. J. Immunol. 154, 433–443 (1995).

    CAS  PubMed  Google Scholar 

  98. Thobakgale, C. F. et al. Human immunodeficiency virus-specific CD8+ T-cell activity is detectable from birth in the majority of in utero-infected infants. J. Virol. 81, 12775–12784 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Gray, G. E. et al. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study. Lancet Infect. Dis. 14, 388–396 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Leitman, E. M. et al. HLA-B*58:02-specific benefit of MRKAd5 Gag/Pol/Nef vaccine in an African population. J. Int. AIDS Soc. Abstr. 18 (5 Suppl. 4), 20479 (2015). This analysis of Phambili study participants who subsequently became HIV-infected shows the ability of a human T cell vaccine to switch the CD8+ T cell immunodominance pattern from an Env-dominated response associated with high viraemia to a broad Gag-specific response associated with a lower viral set point.

    Google Scholar 

  101. Ngumbela, K. C. et al. Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure. AIDS Res. Hum. Retroviruses 24, 72–82 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. Moodley, P., Parboosing, R. & Moodley, D. Reduction in perinatal HIV infections in KwaZulu-Natal, South Africa, in the era of more effective prevention of mother to child transmission interventions (2004-2012). J. Acquir. Immune Defic. Syndr. 63, 410–415 (2013).

    Article  PubMed  Google Scholar 

  103. Dickover, R. E. et al. Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load. JAMA 275, 599–605 (1996).

    Article  CAS  PubMed  Google Scholar 

  104. 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).

    Article  CAS  PubMed  Google Scholar 

  105. Goulder, P. J. & Walker, B. D. HIV and HLA class I: an evolving relationship. Immunity 37, 426–440 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kiepiela, P. et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432, 769–775 (2004).

    Article  CAS  PubMed  Google Scholar 

  107. Bashirova, A. A. et al. LILRB2 interaction with HLA class I correlates with control of HIV-1 infection. PLoS Genet. 10, e1004196 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Goonetilleke, N. et al. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J. Exp. Med. 206, 1253–1272 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Deng, K. et al. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517, 381–385 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Goulder, P. J. et al. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412, 334–338 (2001).

    Article  CAS  PubMed  Google Scholar 

  111. Matthews, P. C. et al. Central role of reverting mutations in HLA associations with human immunodeficiency virus set point. J. Virol. 82, 8548–8559 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Nsheha, A. H., Dow, D. E., Kapanda, G. E., Hamel, B. C. & Msuya, L. J. Adherence to antiretroviral therapy among HIV-infected children receiving care at Kilimanjaro Christian Medical Centre (KCMC), Northern Tanzania: a cross-sectional analytical study. Pan Afr. Med. J. 17, 238 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Biro, F. M. et al. Onset of breast development in a longitudinal cohort. Pediatrics 132, 1019–1027 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Herman-Giddens, M. E., Wang, L. & Koch, G. Secondary sexual characteristics in boys: estimates from the national health and nutrition examination survey III, 1988–1994. Arch. Pediatr. Adolesc. Med. 155, 1022–1028 (2001).

    Article  CAS  PubMed  Google Scholar 

  115. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307–312 (2003).

    Article  CAS  PubMed  Google Scholar 

  116. Moore, P. L. et al. Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape. Nat. Med. 18, 1688–1692 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Wu, X. et al. Neutralization escape variants of human immunodeficiency virus type 1 are transmitted from mother to infant. J. Virol. 80, 835–844 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Moldt, B. et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc. Natl Acad. Sci. USA 109, 18921–18925 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Mascola, J. R. et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat. Med. 6, 207–210 (2000).

    Article  CAS  PubMed  Google Scholar 

  120. Ng, C. T. et al. Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques. Nat. Med. 16, 1117–1119 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Barouch, D. H. et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 503, 224–228 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Caskey, M. et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature 522, 487–491 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Johnson, P. R. et al. Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys. Nat. Med. 15, 901–906 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Balazs, A. B. et al. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481, 81–84 (2012).

    Article  CAS  Google Scholar 

  125. Gardner, M. R. et al. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519, 87–91 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Baba, T. W. et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat. Med. 6, 200–206 (2000).

    Article  CAS  PubMed  Google Scholar 

  127. Hayden, E. C. Almighty antibodies? A new wave of antibody-based approaches aims to combat HIV. Nat. Med. 21, 657–659 (2015).

    Article  CAS  PubMed  Google Scholar 

  128. Kollmann, T. R., Levy, O., Montgomery, R. R. & Goriely, S. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37, 771–783 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Ahmed, R., Oldstone, M. B. & Palese, P. Protective immunity and susceptibility to infectious diseases: lessons from the 1918 influenza pandemic. Nat. Immunol. 8, 1188–1193 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Buchbinder, S. P. et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372, 1881–1893 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Borthwick, N. et al. Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1. Mol. Ther. 22, 464–475 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Frahm, N. et al. Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J. Clin. Invest. 122, 359–367 (2012).

    Article  CAS  PubMed  Google Scholar 

  133. Archin, N. M., Sung, J. M., Garrido, C., Soriano-Sarabia, N. & Margolis, D. M. Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nat. Rev. Microbiol. 12, 750–764 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Archin, N. M. et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487, 482–485 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Archin, N. M. et al. HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat. J. Infect. Dis. 210, 728–735 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Elliott, J. H. et al. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 10, e1004473 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Rasmussen, T. A. et al. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 1, e13–e21 (2014).

    Article  PubMed  Google Scholar 

  138. Sogaard, O. S. et al. The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLoS Pathog. 11, e1005142 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Elliott, J. H. et al. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2, e520–e529 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Henrich, T. J. et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann. Intern. Med. 161, 319–327 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Hurst, J. et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat. Commun. 6, 8495 (2015).

    Article  CAS  PubMed  Google Scholar 

  142. Klein, N. et al. Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission. Lancet Infect. Dis. 15, 1108–1114 (2015).

    Article  PubMed  Google Scholar 

  143. Mphatswe, W. et al. High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis. AIDS 21, 1253–1261 (2007).

    Article  PubMed  Google Scholar 

  144. Lisziewicz, J. et al. Control of HIV despite the discontinuation of antiretroviral therapy. N. Engl. J. Med. 340, 1683–1684 (1999).

    Article  CAS  PubMed  Google Scholar 

  145. Jessen, H., Allen, T. M. & Streeck, H. How a single patient influenced HIV research—15-year follow-up. N. Engl. J. Med. 370, 682–683 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Pereyra, F. et al. Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J. Infect. Dis. 197, 563–571 (2008).

    Article  PubMed  Google Scholar 

  147. Feeney, M. E., Tang, Y., Rathod, A., Kneut, C. & McIntosh, K. Absence of detectable viremia in a perinatally HIV-1-infected teenager after discontinuation of antiretroviral therapy. J. Allergy Clin. Immunol. 118, 324–330 (2006).

    Article  PubMed  Google Scholar 

  148. Day, C. L. et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350–354 (2006).

    Article  CAS  PubMed  Google Scholar 

  149. Kaufmann, D. E. et al. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat. Immunol. 8, 1246–1254 (2007).

    Article  CAS  PubMed  Google Scholar 

  150. Wightman, F. et al. Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma. AIDS 29, 504–506 (2015).

    Article  PubMed  Google Scholar 

  151. Schulze zur Wiesch, J. & van Lunzen, J. Hide and seek... can we eradicate HIV by treatment intensification? J. Infect. Dis. 203, 894–897 (2011).

    Article  PubMed  Google Scholar 

  152. Buzon, M. J. et al. The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates. AIDS 24, 17–25 (2010).

    Article  CAS  PubMed  Google Scholar 

  153. Hatano, H. et al. Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial. J. Infect. Dis. 208, 1436–1442 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01949116 (2016).

  155. US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01535235 (2015).

  156. US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT00000834 (2012).

  157. US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02272946 (2016).

  158. Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370, 901–910 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Hutter, G. et al. Long-term control of HIV by CCR5 Δ32/Δ32 stem-cell transplantation. N. Engl. J. Med. 360, 692–698 (2009).

    Article  PubMed  Google Scholar 

  160. Hutter, G. More on shift of HIV tropism in stem-cell transplantation with CCR5 Δ32/Δ32 mutation. N. Engl. J. Med. 371, 2437–2438 (2014).

    Article  PubMed  Google Scholar 

  161. Mori, M. et al. Sex differences in antiretroviral therapy initiation in pediatric HIV infection. PLoS ONE 10, e0131591 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Blanche, S. et al. Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 14, 442–450 (1997).

    Article  CAS  PubMed  Google Scholar 

  163. Paul, M. E. et al. Predictors of immunologic long-term nonprogression in HIV-infected children: implications for initiating therapy. J. Allergy Clin. Immunol. 115, 848–855 (2005).

    Article  PubMed  Google Scholar 

  164. Connor, E. M. et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N. Engl. J. Med. 331, 1173–1180 (1994).

    Article  CAS  PubMed  Google Scholar 

  165. De Cock, K. M. et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 283, 1175–1182 (2000).

    Article  CAS  PubMed  Google Scholar 

  166. Marinda, E. et al. Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr. Infect. Dis. J. 26, 519–526 (2007).

    Article  PubMed  Google Scholar 

  167. Taha, T. E. et al. Association of recent HIV infection and in utero HIV-1 transmission. AIDS 25, 1357–1364 (2011).

    Article  PubMed  Google Scholar 

  168. Mofenson, L. M. Prevention in neglected subpopulations: prevention of mother-to-child transmission of HIV infection. Clin. Infect. Dis. 50 (Suppl. 3), 130–148 (2010).

    Article  CAS  Google Scholar 

  169. Moodley, D. et al. Incident HIV infection in pregnant and lactating women and its effect on mother-to-child transmission in South Africa. J. Infect. Dis. 203, 1231–1234 (2011).

    Article  PubMed  Google Scholar 

  170. Drake, A. L., Wagner, A., Richardson, B. & John-Stewart, G. Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: a systematic review and meta-analysis. PLoS Med. 11, e1001608 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Humphrey, J. H. et al. Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study. BMJ 341, c6580 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

P.J.G. is funded by the Wellcome Trust (WT104748 MA). S.R.L. is supported by the National Institutes of Health Delaney AIDS Research Enterprise (Grant U19 AI096109) and a National Health and Medical Research Council (NHMRC) of Australia Practitioner Fellowship. E.M.L. is supported by the Clarendon Foundation.

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Glossary

Antiretroviral therapy

(ART). The combination of usually a minimum of three anti-HIV drugs that aim to suppress viral replication, slow disease progression and minimize the risk of transmission. Pre-exposure prophylactic ART has also been shown to protect against HIV infection.

CD4+ T cell counts

The number of T cells expressing the CD4 receptor on their surface in a microlitre of blood. These white blood cells 'help' the immune system to mount a response against pathogens and are the main target cells of HIV infection.

Elite controllers

A rare subset (less than 1%) of antiretroviral therapy (ART)-naive, HIV-infected individuals who have undetectable plasma viral load (by standard assays) and remain clinically healthy in the long term. HIV controllers is sometimes used synonymously with elite controllers.

VISCONTI cohort

(Viro-Immunologic Sustained Control after Treatment Interruption cohort). A French cohort of 14 adults in whom antiretroviral therapy (ART) was initiated during primary HIV infection and interrupted after a median of 36.5 months. For a median of 7.4 years after treatment interruption, the viral load remained at less than 400 copies per ml; these 14 individuals are therefore referred to as post-treatment controllers.

CHER study

(Children with HIV Early Antiretroviral Therapy study). A randomized Phase III study that enrolled 6–12-week-old HIV-positive infants in South Africa with a percentage of CD4+ lymphocytes of more than 25%, who were assigned either to receive immediate antiretroviral therapy (ART) for 40 or 96 weeks or to defer treatment until clinical criteria were met.

PEHSS study

(Paediatric Early HAART and Strategic Treatment Interruption study). A feasibility study of 63 perinatally infected infants in KwaZulu-Natal, South Africa, who were randomized to receive either immediate 12-month uninterrupted antiretroviral therapy (ART), immediate 18-month treatment with structured interruptions or deferred treatment.

Viral reservoir

Virus that persists in patients on antiretroviral therapy (ART) in the form of latent or productively infected cells. Latency is established in long-lived resting memory T cells as integrated virus that is replication competent but transcriptionally silent. Latently infected cells persist for decades and are more frequent in tissue compared with blood. Reactivation of virus in these cells (for example, upon ART interruption) is the major obstacle to HIV eradication.

Fiebig stages I–VI

Categorization of primary HIV infection in six stages based on the detection of different HIV markers. Staging begins with viral detection by PCR (stage I), then ELISA detection of Gag p24 (stage II) or HIV-specific antibody (stage III), and then sequential stages of HIV-specific antibody detection by western blot (stages IV–VI).

Cell-associated unspliced HIV RNA

Unspliced HIV RNA is detected in cells of individuals on antiretroviral therapy (ART) from the initial first step of long-terminal repeat-mediated HIV transcription before splicing, host promoter-initiated HIV transcription (or read-through transcription) or virus production. By contrast, plasma HIV RNA measures RNA in mature virus particles.

2-LTR circles

(2-long-terminal repeat circles). Circularized forms of unintegrated viral DNA that are by-products of HIV DNA integration into the host genome and exist only in the nucleus. The stability of 2-LTR circles is controversial, but they are generally thought to be short-lived.

Miliary tuberculosis

(Miliary TB). Dissemination of Mycobacterium tuberculosis most often throughout the body, including the brain.

Phambili trial

A trial that tested the efficacy of the MRKAd5 subtype B HIV-1 Gag/Pol/Nef vaccine in South Africa, where subtype C virus is dominant. The vaccine increased the risk of HIV acquisition and did not reduce early viraemia.

Escape mutants

Viral variants that reduce recognition by the immune system, typically arising in epitopes that are targeted by HIV-specific CD8+ T cells or neutralizing antibodies.

Broadly neutralizing antibodies

HIV-specific antibodies that arise during natural infection in 10–30% of individuals and can effectively neutralize diverse viral isolates.

Step trial

A trial that tested the efficacy of the MRKAd5 subtype B HIV-1 Gag/Pol/Nef vaccine in North and South Americas, Australia and the Caribbean, where subtype B virus is dominant. The vaccine increased the risk of HIV acquisition.

Treatment intensification

Introduction of additional antiretroviral drugs to a standard three-drug suppressive regimen.

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Goulder, P., Lewin, S. & Leitman, E. Paediatric HIV infection: the potential for cure. Nat Rev Immunol 16, 259–271 (2016). https://doi.org/10.1038/nri.2016.19

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