HIV disease progression rates: Wikis


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Following infection with HIV-1, the rate of clinical disease progression varies between individuals. Factors such as host susceptibility, genetics and immune function,[1] health care and co-infections[2] as well as viral genetic variability[3] may affect the rate of progression to AIDS.


Rapid progressors

A small percentage of HIV-infected individuals rapidly progress to AIDS within four years after primary HIV-infection and are termed Rapid Progressors (RP).[4] Indeed some individuals have been known to progress to AIDS and death within a year after primo-infection. Rapid progression was originally thought to be continent specific, as some studies reported that disease progression is more rapid in Africa,[4][5][6] but others have contested this view.[1][2][7][8]

Long term non-progressors

Another subset of individuals who are persistently infected with HIV-1, but show no signs of disease progression for over 12 years and remain asymptomatic are classified as Long Term Non-Progressors (LTNP). In these individuals, it seems that HIV-infection has been halted with regard to disease progression over an extended period of time.[9][10][11][12] However, the term LTNP is a misnomer, as it must be noted that progression towards AIDS can occur even after 15 years of stable infection.[13] LTNP are not a homogeneous group regarding both viral load and specific immune responses against HIV-1. Some LTNPs are infected with HIV that inefficiently replicates[14][15] whilst others are infected with HIV that is virally fit and replicates normally, but the infected individual has had a strong and broad set of HIV-specific humoral and cell-mediated responses that seems to delay the progression to AIDS. In some cohorts, individuals who experience signs of progression, but whose clinical and laboratory parameters remain stable over long periods of time, are classified as Long Term Survivors (LTS).[3]

Highly exposed persistently seronegative

There is another, smaller percentage of individuals who have been recently identified. These are called Highly Exposed Persistently Seronegative (HEPS). This is a small group of individuals and has been observed only in a group of uninfected HIV-negative prostitutes in Kenya and in The Gambia. When these individuals' PBMCs are stimulated with HIV-1 peptides, they have lymphoproliferative activity and have HIV-1 specific CD8+ CTL activity suggesting that transient infection may have occurred.[16][17][18][19] This does not occur in unexposed individuals. What is interesting, is that the CTL epitope specificity differs between HEPS and HIV positive individuals, and in HEPS, the maintenance of responses appears to be dependent upon persistent exposure to HIV.[20]

Prediction of progression rates

During the initial weeks after HIV infection, qualitative differences in the cell-mediated immune response are observed that correlate with different disease progression rates (i.e., rapid progression to WHO stage 4 and the rapid loss of CD4+ T cell levels versus normal to slow progression to WHO stage 4 and the maintenance of CD4+ T cell counts above 500/µl). The appearance of HIV-1-specific CD8+ cytotoxic T cells (CTLs) early after primo-infection has been correlated with the control of HIV-1 viremia.[21][22] The virus which escapes this CTL response have been found to have mutations in specific CTL epitopes.[23][24][25][26] Individuals with a broad expansion of the V-beta chain of the T cell receptor of CD8+ T cells during primo-infection appear seem to have low levels of virus six to twelve months later, which is predictive of relatively slow disease progression. In contrast, individuals with an expansion of only a single subset of the V-beta chain of the CD8+ T cells are not able to control HIV levels over time, and thus have high levels of virus six to twelve months later.[27] LTNP’s have also been shown to have a vigorous proliferation of circulating activated HIV-1-specific CD4+ T cell[28] and CTL response[29][30] against multiple epitopes with no detectable broadly cross-reactive neutralizing antibodies in the setting of an extremely low viral load.[13] However, a few reports have correlated the presence of antibodies against Tat in LTNP status.

HIV subtype variation and effect on progression rates

The HIV-1 subtype that an individual becomes infected with can be a major factor in the rate of progression from sero-conversion to AIDS. Individuals infected with subtypes C, D and G are 8 times more likely to develop AIDS than individuals infected with subtype A.[31] In Uganda, where subtypes A and D are most prevalent,[32] subtype D is associated with faster disease progression compared with subtype A.[33] Age has also been shown to be a major factor in determining survival and the rate of disease progression, with individuals over 40 years of age at sero-conversion being associated with rapid progression.[34][35][36][37]

Host genetic susceptibility

The Centers for Disease Control and Prevention (CDC) has released findings that genes influence susceptibility to HIV infection and progression to AIDS. HIV enters cells through an interaction with both CD4 and a chemokine receptor of the 7 transmembrane family. They first reviewed the role of genes in encoding chemokine receptors (CCR5 and CCR2) and chemokines (SDF-1). While CCR5 has multiple variants in its coding region, the deletion of a 32-bp segment results in a nonfunctional receptor, thus preventing HIV entry; two copies of this gene provide strong protection against HIV infection, although the protection is not absolute. This allele is found in around 10% of Europeans but is rare in Africans and Asians. Multiple studies of HIV-infected persons have shown that presence of one copy of this mutation, named CCR5-Δ32 (CCR5 delta 32) delays progression to the condition of AIDS by about 2 years.

The National Institute of Health (NIH) has funded research studies to learn more about this genetic mutation. In such research, NIH has found that there exist genetic tests that can determine if a person has this mutation. Implications of a genetic test may in the future allow clinicians to change treatment for the HIV infection according to the genetic makeup of an individual,[38] Currently there exist several at-home tests for the CCR5 mutation in individuals; however, they are not diagnostic tests.

A relatively new class of drugs for HIV treatment relies on the genetic makeup of the individual. Entry inhibitors bind to the CCR5 protein to block HIV from binding to the CD4 cell.

The effect of co-infections on progression rates

Coinfections or immunizations may enhance viral replication by inducing a response and activation of the immune system. This activation facilitates the three key stages of the viral life cycle: entry to the cell; reverse transcription and proviral transcription.[39] Chemokine receptors are vital for the entry of HIV into cells. The expression of these receptors is inducible by immune activation caused through infection or immunization, thus augmenting the number of cells that are able to be infected by HIV-1.[40][41] Both reverse transcription of the HIV-1 genome and the rate of transcription of proviral DNA rely upon the activation state of the cell and are less likely to be successful in quiescent cells. In activated cells there is an increase in the cytoplasmic concentrations of mediators required for reverse transcription of the HIV genome.[42][43] Activated cells also release IFN-alpha which acts on an autocrine and paracrine loop that up-regulates the levels of physiologically active NF-kappa B which activates host cell genes as well as the HIV-1 LTR.[44][45] The impact of co-infections by micro-organisms such as Mycobacterium tuberculosis can be important in disease progression, particularly for those who have a high prevalence of chronic and recurrent acute infections and poor access to medical care.[46] Often, survival depends upon the initial AIDS-defining illness.[37] Co-infection with DNA viruses such as HTLV-1, herpes simplex virus-2, varicella zoster virus and cytomegalovirus may enhance proviral DNA transcription and thus viral load as they may encode proteins that are able to trans-activate the expression of the HIV-1 pro-viral DNA.[47] Frequent exposure to helminth infections, which are endemic in Africa, activates individual immune systems, thereby shifting the cytokine balance away from an initial Th1 cell response against viruses and bacteria which would occur in the uninfected person to a less protective T helper 0/2-type response.[48] HIV-1 also promotes a Th1 to Th0 shift and replicates preferentially in Th2 and Th0 cells.[49] This makes the host more susceptible to and less able to cope with infection with HIV-1,viruses and some types of bacteria. Ironically, exposure to dengue virus seems to slow HIV progression rates temporarily.

See also


  1. ^ a b Morgan, D.; C. Mahe, B. Mayanja, J.M. Okongo, R. Lubega and J.A. Whitworth (2002). "HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries?". AIDS 16 (4): 597–603. doi:10.1097/00002030-200203080-00011. PMID 11873003.  
  2. ^ a b Morgan, D.; C. Mahe, B. Mayanja and J.A. Whitworth (2002). "Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study". BMJ 324 (7331): 193–196. ISSN 11809639.  
  3. ^ a b Campbell, G.R.; et al. (2004). "The glutamine-rich region of HIV-1 Tat protein involved in T cell apoptosis". Journal of Biological Chemistry 279 (46): 48197–48204. doi:10.1074/jbc.M406195200. PMID 15331610.  
  4. ^ a b Anzala, O.A.; N.J. Nagelkerke, J.J. Bwayo, D. Holton, S. Moses, E.N. Ngugi, J.O. Ndinya-Achola and F.A. Plummer (1995). "Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection". Journal of Infectious Disease 171 (3): 686–689. PMID 7876618.  
  5. ^ N'Galy, B.; R.W. Ryder, K. Bila, K. Mwandagalirwa, R.L. Colebunders, H. Francis, J.M. Mann T.C. and Quinn (1988). "Human immunodeficiency virus infection among employees in an African hospital". New England Journal of Medicine 319 (17): 1123–1127. PMID 3262826.  
  6. ^ Whittle, H.; A. Egboga, J. Todd, T. Corrah, A. Wilkins, E. Demba, G. Morgan, M. Rolfe, N. Berry and R. Tedder (1992). "Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-1 infection". AIDS 6 (7): 685–689. doi:10.1097/00002030-199207000-00011. PMID 1354448.  
  7. ^ French, N.; A. Mujugira, J. Nakiyingi, D. Mulder, E.N. Janoff and C.R. Gilks (1999). "Immunologic and clinical stages in HIV-1-infected Ugandan adults are comparable and provide no evidence of rapid progression but poor survival with advanced disease". Journal of Acquired Immune Deficiency Syntromes 22 (5): 509–516. PMID 10961614.  
  8. ^ Buchbinder, S.P.; M.H. Katz, N.A. Hessol, P.M. O'Malley and S.D. Holmberg (1994). "Long-term HIV-1 infection without immunologic progression". AIDS 8 (8): 1123–1128. doi:10.1097/00002030-199408000-00014. PMID 7986410.  
  9. ^ Cao, Y.; L. Qin, L. Zhang, J. Safrit and D.D. Ho (1995). "Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection". New England Journal of Medicine 332 (4): 201–208. doi:10.1056/NEJM199501263320401. PMID 7808485.  
  10. ^ Easterbrook, P.J. (1994). "Non-progression in HIV infection". AIDS 8 (8): 1179–1182. doi:10.1097/00002030-199408000-00023. PMID 7832923.  
  11. ^ Lévy, J.A. (1993). "HIV pathogenesis and long-term survival". AIDS 7 (11): 1401–1410. doi:10.1097/00002030-199311000-00001. PMID 8280406.  
  12. ^ a b Harrer, T.; et al. (1996). "Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection". Aids research and Human Retroviruses 12 (7): 585–592. doi:10.1089/aid.1996.12.585. PMID 8743084.  
  13. ^ Deacon, N.J.; et al. (1995). "Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients". Science 270 (5238): 988–991. doi:10.1126/science.270.5238.988. PMID 7481804.  
  14. ^ Kirchhoff, F.; T.C. Greenough, D.B. Brettler, J.L. Sullivan and R.C. Desrosiers (1995). "Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection". New England Journal of Medicine 332 (4): 228–232. doi:10.1056/NEJM199501263320405. PMID 7808489.  
  15. ^ Clerici, M.; J.M. Levin, H.A. Kessler, A. Harris, J.A. Berzofsky, A.L. Landay and G.M. Shearer (1994). "HIV-specific T- helper activity in seronegative health care workers exposed to contaminated blood". JAMA 271 (1): 42–46. doi:10.1001/jama.271.1.42. PMID 8258885.  
  16. ^ Pinto, L.A.; J. Sullivan, J.A. Berzofsky, M. Clerici, H.A. Kessler, A.L. Landay and G.M. Shearer (1995). "ENV-specific cytotoxic T cell responses in HIV seronegative health care workers occupationally exposed to HIV- contaminated body fluids". Journal of Clinical Investigation 96 (2): 867–876. doi:10.1172/JCI118133. PMID 7635981.  
  17. ^ Rowland-Jones, S.; et al. (1995). "HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women". Nature Medicine 1 (1): 59–64. doi:10.1038/nm0195-59. PMID 7584954.  
  18. ^ Fowke, K.R.; et al. (1996). "Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya". Lancet 348 (9038): 1347–1351. doi:10.1016/S0140-6736(95)12269-2. PMID 8918278.  
  19. ^ Kaul, R.; et al. (2001). "New insights into HIV-1 specific cytotoxic T cell responses in exposed, persistently seronegative Kenyan sex workers". Immunology Letters 79 (1-2): 3–13. doi:10.1016/S0165-2478(01)00260-7. PMID 11595284.  
  20. ^ Koup, R.A.; J.T. Safrit and Y.Z. Cao (1994). "Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome". Journal of Virology 68 (7): 4650–4655. PMID 8207839.  
  21. ^ Borrow, P.; H. Lewicki, B.H. Hahn, G.M. Shaw and M.B. Oldstone (1994). "Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection". Journal of Virology 68 (9): 6103–6110. PMID 8057491.  
  22. ^ Phillips, R.E.; et al. (1991). "Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition". Nature 354 (6353): 453–459. doi:10.1038/354453a0. PMID 1721107.  
  23. ^ Borrow, P.; et al. (1997). "Antiviral pressure exerted by HIV-1-specific cytotoxic T cells (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus". Nature Medicine 3 (2): 205–211. doi:10.1038/nm0297-205. PMID 9018240.  
  24. ^ Price, D.A.; P.J. Goulder, P. Klenerman, A.K. Sewell, P.J. Easterbrook, M. Troop, C.R. Bangham and R.E. Phillips (1997). "Positive selection of HIV-1 cytotoxic T cell escape variants during primary infection". PNAS 94 (5): 1890–1895. doi:10.1073/pnas.94.5.1890. PMID 9050875.  
  25. ^ Rowland-Jones, S.L.; et al. (1992). "Human immunodeficiency virus variants that escape cytotoxic T-cell recognition". AIDS Research and Human Retroviruses 8 (9): 1353–1354. PMID 1466955.  
  26. ^ Pantaleo, G.; et al. (1997). "The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia". PNAS 94 (1): 254–258. doi:10.1073/pnas.94.1.254. PMID 8990195.  
  27. ^ Rosenberg, E.S.; J.M. Billingsley, A.M. Caliendo, S.L. Boswell, P.E. Sax, S.A. Kalams and B.D. Walker (1997). "Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia". Science 278 (5342): 1447–1450. doi:10.1126/science.278.5342.1447. PMID 9367954.  
  28. ^ Rowland-Jones, S.L.; et al. (1999). "Broadly cross-reactive HIV-specific cytotoxic T-lymphocytes in highly exposed persistently seronegative donors". Immunology Letters 66 (1-3): 9–14. doi:10.1016/S0165-2478(98)00179-5. PMID 10203028.  
  29. ^ Dyer, W.B.; et al. (199). "Strong human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocytes activity in Sydney Blood Bank Cohort patients infected with nef-defective HIV-type 1". Journal of Virology 73 (1): 436–443. PMID 9847349.  
  30. ^ Kanki, P.J.; et al. (1999). "Human immunodeficiency virus type 1 subtypes differ in disease progression". Journal of Infectious Disease 179 (1): 68–73. doi:10.1086/314557. PMID 9841824.  
  31. ^ Kaleebu, P.; et al. (2000). "Molecular epidemiology of HIV type 1 in a rural community in southwest Uganda". AIDS Research and Human Retroviruses 16 (5): 393–401. doi:10.1089/088922200309052. PMID 10772525.  
  32. ^ Kaleebu, P.; et al. (2002). "Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda". Journal of Infectious Disease 185 (9): 1244–1250. doi:10.1086/340130. PMID 12001041.  
  33. ^ Koblin, B.A.; et al. (1999). "Long-term survival after infection with human immunodeficiency virus type 1 (HIV-1) among homosexual men in hepatitis B vaccine trial cohorts in Amsterdam, New York City, and San Francisco, 1978-1995". American Journal of Epidemiology 150 (10): 1026–1030. PMID 10568617.  
  34. ^ Pezzotti, P.; N. Galai, D. Vlahov, G. Rezza, C.M. Lyles and J. Astemborski (1999). "Direct comparison of time to AIDS and infectious disease death between HIV seroconverter injection drug users in Italy and the United States: results from the ALIVE and ISS studies. AIDS Link to Intravenous Experiences. Italian Seroconversion Study". Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 20 (3): 275–282. PMID 10077177.  
  35. ^ Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe (2000). "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. doi:10.1016/S0140-6736(00)02061-4.  
  36. ^ a b Morgan, D.; G.H. Maude, S.S. Malamba, M.J. Okongo, H.U. Wagner, D.W. Mulder and J.A. Whitworth (1997). "HIV-1 disease progression and AIDS-defining disorders in rural Uganda". Lancet 350 (9073): 245–250. doi:10.1016/S0140-6736(97)01474-8. PMID 9242801.  
  37. ^ Gonzalez, E.; et al. (2005). "The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility". Science 307 (5714): 1422–1424. doi:10.1126/science.1101160. PMID 15637236.  
  38. ^ Lawn, S.D.; S.T. Butera and T.M. Folks (2001). "Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection". Clinical Microbiology Reviews 14 (4): 753–777. doi:10.1128/CMR.14.4.753-777.2001. PMID 11585784.  
  39. ^ Wahl, S.M.; T. Greenwell-Wild, G. Peng, H. Hale-Donze, T.M. Doherty, D. Mizel and J.M. Orenstein (1998). "Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression". PNAS 95 (21): 12574–12579. doi:10.1073/pnas.95.21.12574. PMID 9770527.  
  40. ^ Juffermans, N.P.; P. Speelman, A. Verbon, J. Veenstra, C. Jie, S.J. van Deventer and T. van Der Poll (2001). "Patients with active tuberculosis have increased expression of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells.". Clinical Infectious Diseases 32 (4): 650–652. doi:10.1086/318701. PMID 11181132.  
  41. ^ Zack, J.A.; S.J. Arrigo, S.R. Weitsman, A.S. Go, A. Haislip and I.S. Chen (1990). "HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure". Cell 61 (2): 213–222. doi:10.1016/0092-8674(90)90802-L. PMID 2331748.  
  42. ^ Kinoshita, S.; B.K. Chen, H. Kaneshima and G.P. Nolan (1998). "Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells". Cell 95 (5): 595–604. doi:10.1016/S0092-8674(00)81630-X. PMID 9845362.  
  43. ^ Gaynor, R. (1992). "Cellular transcription factors involved in the regulation of HIV-1 gene expression". AIDS 6 (4): 347–363. doi:10.1097/00002030-199204000-00001. PMID 1616633.  
  44. ^ Baeuerle, P.A. (1991). "The inducible transcription activator NF-kappa B: regulation by distinct protein subunits". Biochimica et Biophysica Acta 1072 (1): 63–80. PMID 2018779.  
  45. ^ Blanchard, A.; L. Montagnier and M.L. Gougeon (1997). "Influence of microbial infections on the progression of HIV disease". Trends in Microbiology 5 (8): 326–331. doi:10.1016/S0966-842X(97)01089-5. PMID 9263412.  
  46. ^ Gendelman, H.E.; et al. (1986). "Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses". PNAS 83 (24): 9759–9763. doi:10.1073/pnas.83.24.9759. PMID 2432602.  
  47. ^ Bentwich, Z.; A. Kalinkovich and Z. Weisman (1995). "Immune activation is a dominant factor in the pathogenesis of African AIDS". Immunology Today 16 (4): 187–191. doi:10.1016/0167-5699(95)80119-7. PMID 7734046.  
  48. ^ Maggi, E.; et al. (1994). "Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells". Science 265 (5169): 244–248. doi:10.1126/science.8023142. PMID 8023142.  

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