HIV superinfection

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search

HIV superinfection (also called HIV reinfection) is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV, often of a different subtype.[1] The HIV superinfection strain appears when a person becomes simultaneously infected by two different strains. It is a recombinant strain, allowing the two viruses to exchange genetic material to produce a new unique strain that can possess the resistances of both previous strains. This new strain co-exists with the two prior strains and may cause more rapid disease progression or carry multiple resistances to certain HIV medications.

People with HIV risk superinfection by the same actions that would place a non-infected person at risk of acquiring HIV. These include sharing needles and forgoing condoms with HIV-positive sexual partners. For many years superinfection was thought to occur mainly in high-risk populations. Research from Uganda published in 2012 indicates that HIV superinfection among HIV-infected individuals within a general population remains unknown.[2] Further research from The Journal of Infectious Diseases indicates that there have been 16 documented cases of superinfection since 2002.[3]

Immunology[edit]

It is unknown what aspects of the natural immune response to HIV may protect someone from superinfection, but it has been shown that cytotoxic lymphocyte responses do not seem to be protective.[4] The effect of neutralizing antibodies (NAb) is also unknown, but it has been shown that individuals with HIV tend not to have a NAb response prior to superinfection.[5]

In addition, it has been demonstrated that superinfection can occur in individuals that demonstrate a robust anti-HIV antibody response. The anti-HIV antibody response broadens and strengthens in individuals post-superinfection.[6] The finding that superinfection occurs within and between HIV subtypes suggests that an immune response to initial HIV infection provide limited protection against infection by a new viral strain.[7] This means that HIV-vaccine strategies made to replicate the host's immune response to HIV infection may not prevent new infections.

Early studies of HIV superinfection analysed spikes in HIV viral load to diagnose cases of superinfection.[7] It is unclear whether superinfection causes a sustained increase in viral load.[7] The effect of superinfection on the progression of HIV infection is unclear because of its ambiguous effects on surrogate markers for the disease, such as an increase in viral load or a decrease in CD4 cell count.[8] The potential of superinfection to cause rapid disease progression depends on viral and host factors.[7]

Cases of superinfection are yet to be identified in sufficient numbers to conduct detailed studies on the effect of superinfection on the host immune response.[7]

Causes[edit]

HIV superinfection is distinct from HIV dual infection, where an individual is simultaneously infected with multiple distinct viral strains. HIV superinfection involves an individual with HIV being infected by a new, evolutionary distinct HIV strain.[9]

Studies have shown that a lack of neutralizing antibodies against HIV-1 infection predisposes patients to superinfection.[10]Additionally, the tendency of HIV-1 virions to recombine when two subtypes infect a single cell increases its susceptibility to HIV superinfection.[9]Further evidence of superinfection stems from the fact that nearly 10% of HIV-1 infections are associated with a transmittable recombinant strain.[9]HIV-1 virions are divided into nine subtypes, all of which are characterized by different rates of disease progression, viral load and sensitivity to assays used in detection.[9]When a single cell is infected by two HIV-1 subtypes, they recombine, forming a new, transmittable recombinant strain.[9]

Mechanism[edit]

Loss of immune control[edit]

Following initial acute HIV infection, CD8+ T-cellscontrol viral replication and maintain it at a viral set point.[11]Following superinfection, CD8+ T-cells lose control over replication and it deviates from the set point.[11]The mechanism responsible for this is unknown.[11]A weakened T-cell response against the initial virus enables the superinfecting strain to resist immune control, resulting in an increased replication and subsquent viremia.[11][12]Increased viral load and a declining T-cell response enables the superinfection strain to recombine rapidly, further decreasing immune control.[12]

Recombination[edit]

HIV virions each contain a double-stranded RNAgenome.[13]When superinfection occurs, cells contain 2 different HIV strains, which can exchange genetic material such that an RNA strand from each strain is contained in a single virion.[13]As this progeny virion infects new cells, the RNA template transcribed by viral reverse transcriptasechanges, resulting in a reverse transcript with genetic material from both parental viruses.[13]Recombination results in a rapid increase in HIV viral diversity, causing quicker adaptations to host immune response and resistance to ART.[13]

Recombination tends to produce two distinct recombinant forms, the presence of which are used as evidence of dual infection.[13]The high prevalence of interclade recombinants increases the likelihood of superinfection being more widespread than reported.[14]

Circulating recombinant forms (CRFs)[edit]

CRF's are mosaic viruses - recombinants with randomly assorted genetic material from phylogenetically distinct parental viruses - that spread geographically through human propagation.[13]CRF's account for 10% of HIV infections worldwide.[13]

Unique recombinant forms (URFs)[edit]

URF's are mosaic viruses that have not spread geographically.[13]

In 2004, a study by AIDS,an Official International AIDS Society Journal, on sex workers in Nairobi, Kenyareported URF generation in a women initially infected with cladeA, and then 9 years later acquired clade C, which recombined with the initial infecting virus to form a recombinant of clades A and C that fully replaced the parental clade A virions.[15]


HIV co-infection offset[edit]

A study in the New England Journal of Medicine titled "Inhibition of HIV-1 Disease Progression by Contemporaneous HIV-2 Infection" revealed that people who are HIV-positive with the two major subtypes have a slower progression towards AIDS than people with only HIV-1 or HIV-2. This challenges the notion of superinfection by illustrating that contemporaneous infection can offset itself.[16]

Diagnosis[edit]

Initial reports solely documented interclade superinfection, where patients are infected by a virus of a different clade from the initial virus.[17]This is because the viruses in initial cases were all subtypes of HIV-1, with at least a 30% difference in nucleotides in their envelope proteinsthat makes such superinfections easier to detect.[17]

Superinfection is identified by the detection of viral recombinants for phylogenetically distinct parent strains.[18]

Multiregion hybridisation assaysare used to identify interclade superinfection by detecting genetic differences between parental and progeny strains.[19]Heteroduplex mobility assayscan be used to sequence viral genetic material, allowing the detection of samples with a genetic difference exceeding 1.5%.[19]

Bulk sequencingis used to amplify viral RNA to enable the identification of new phylogenetic species in a patient over time.[19]However, this method is poor at detecting genetic differences at levels of 20% of lower.[19]

A third method, next-generation-sequencing assays, was developed in 2005.[20]It enables the rapid sequencing and screening of genomes, detecting genetic differences of 1% or less.[19]

There are no known methods to estimate the timing of superinfection.[19]

Prognosis[edit]

Studies on individuals with superinfection with 2 strains of HIV showed a poorer prognosis.[21]Superinfection is correlated with a faster progression of the HIV infection.[21]Patients in studies have displayed a shorter lag between seroconversionand experiencing an AIDS-defining clinical conditionor death.[21]However, it is unclear whether this rapid conversion is a direct effect of superinfection, or a result of a weaker immune response to the virus caused by superinfection.[21]


Epidemiology[edit]

HIV superinfection has been reported in the USA, Canada, Europe, Australia, Asia and Africa.[22]Data on the prevalence of superinfection has been gathered from case reports and observational studies, suggesting that it is underreported.[22]

Initial care reports and observational studies of superinfection were in men who have sex with men, intravenous drug usersand female sex workers.[22]Incidence in heterosexual populations was first reported in rural Africa.[22]

Incidence rates have been reported as 0% to 7.7% annually, although this varies across populations and depends on the frequency of antiretroviraldrug use, the length of the follow-up period, and the method used to detect superinfection.[22]However, a study in Uganda conducted using next-generation deep sequencing assays found that the rate of superinfection was large enough to be comparable to the primary HIV infection rate.[23]

Risk factors for superinfection are not clearly understood because of the small number of cases documented.[22]However, the risk factors for primary infection are considered to apply to superinfection, including:

  • high number of sexual partners
  • limited condom use
  • no anti-retroviral use
  • absence of male circumcision
  • non-martial relationships [22]

The results of studies modeling the effect of HIV superinfection on viral recombination have suggested that superinfection has been instrumental in spurring community recombination rates.[24]However, these studies were based on several epidemiological assumptions that are yet to be verified.[24]These include assumptions about the pattern of HIV-1transmission and that superinfection causes transmission to uninfected sexual partners.[22]

History[edit]

Evidence to suggest the possibility of superinfection was first observed in cases of co-infection with HIV-1 and HIV-2.[25]The two strains are phylogenetically different subtypes, sharing only 42% of the nucleotides in their genes.[25]

1987 - First evidence of superinfection reported in studies of chimpanzees.[26]

1999 - Studies on pig tailed macaquessuggest a "window of susceptibility" by showing that superinfection with a new viral strain was only possible 4 weeks after initial infection in macaques.[27]

2002 - First definitive study on superinfection published in the Journal of Virologyafter cases reported in IV drug users in Bangkok, Thailand.[28]Initial cases were all interclade superinfections.[28]

2003 - Study published by the AIDSjournal revealed the possibility of intraclade infection by illustrating that an immune response to one strain of HIV-1 cannot prevent superinfection with a second virus from the same clade.[29]

2005 - Study published in AIDSon the case of a man with HIV superinfection in San Diego who developed drug resistance indicated the ability of HIV superinfection to cause ART resistance.[30]

Implications for treatment and care[edit]

Drug resistance[edit]

Because of viral recombination, superinfection patients infected with at least one drug resistant strain are likely to develop a mosaic recombinant strain with multi-drug resistance.[31]This lowers the potential success of ART.[31]

Impact on vaccine development[edit]

Research on the development of a HIV-1 vaccine has sought to replicate virus-specific CD8+ T-cell responses, which play a role in the control of HIV-1 replication.[32]Observations in superinfection case reports have shown that superinfecting strains generally had different viral epitopesfrom the original infecting cell.[32]An immune response to the intial infection would therefore be ineffective against the super-infecting strain, leading to the proliferation of the superinfecting strain.[32]Additionally, a HIV-1 vaccine designed to recognize specific viral epitopes would be ineffective as it would not provide protection against HIV-1 viruses that do not share the same epitope.[32]A successful vaccine would therefore have to incorporate viral epitopes derived from several viral subtypes.[33]

Impact on clinical care[edit]

Increasing rates of antiretroviral therapy (ART) use have led to concerns about the development of drug-resistant strains which could be transmitted though superinfection.[34]Individuals with drug-resistant strains are vulnerable to superinfection with a susceptible strain of the virus, reversing the effect of ART's the clinical aspects of HIV infection.[34]Individuals with HIV found to have a sudden increase in viral load, or a decrease in CD4 count should be tested for a resistant viral strain to identify the resistance profile of the secondary strain.[34]


Sexual practices, such as serosorting, place individuals with HIV infection at a higher risk of superinfection and other sexually transmitted diseases(STDs).[35]HIV positive individuals engaging in unprotected sex with seroconcordantpartners require counseling on the risks of superinfection and STDs, both of which are expressed mroe virulently because of immunosuppression in HIV patients.[35]Counselling for HIV patients on the risk of HIV superinfection, and encouraging safe sexual and injection practices have shown an improvement in safer sexual practices, reducing the risk of superinfection.[34]

References[edit]

  1. ^ Smith DM, Richman DD, Little SJ (August 2005). "HIV superinfection". The Journal of Infectious Diseases. 192 (3): 438–44. doi:10.1086/431682. PMID 15995957.
  2. ^ Redd AD, Mullis CE, Serwadda D, Kong X, Martens C, Ricklefs SM, Tobian AA, Xiao C, Grabowski MK, Nalugoda F, Kigozi G, Laeyendecker O, Kagaayi J, Sewankambo N, Gray RH, Porcella SF, Wawer MJ, Quinn TC (July 2012). "The rates of HIV superinfection and primary HIV incidence in a general population in Rakai, Uganda". The Journal of Infectious Diseases. 206 (2): 267–74. doi:10.1093/infdis/jis325. PMC 3415936. PMID 22675216.
  3. ^ Smith DM, Richman DD, Little SJ (August 2005). "HIV superinfection". The Journal of Infectious Diseases. 192 (3): 438–44. doi:10.1086/431682. PMID 15995957.
  4. ^ Blish CA, Dogan OC, Jaoko W, McClelland RS, Mandaliya K, Odem-Davis KS, Richardsonb BA, Overbaugh J (March 2012). "Cellular immune responses and susceptibility to HIV-1 superinfection: a case-control study". Aids. 26 (5): 643–6. doi:10.1097/QAD.0b013e3283509a0b. PMC 3511787. PMID 22210637.
  5. ^ Smith DM, Strain MC, Frost SD, Pillai SK, Wong JK, Wrin T, Liu Y, Petropolous CJ, Daar ES, Little SJ, Richman DD (November 2006). "Lack of neutralizing antibody response to HIV-1 predisposes to superinfection". Virology. 355 (1): 1–5. doi:10.1016/j.virol.2006.08.009. PMID 16962152.
  6. ^ Cortez V, Odem-Davis K, McClelland RS, Jaoko W, Overbaugh J (2012). "HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response". PLoS Pathogens. 8 (3): e1002611. doi:10.1371/journal.ppat.1002611. PMC 3315492. PMID 22479183.
  7. ^ a b c d e Redd AD, Quinn TC, Tobian AA (July 2013). "Frequency and implications of HIV superinfection". The Lancet. Infectious Diseases. 13 (7): 622–8. doi:10.1016/s1473-3099(13)70066-5. PMC 3752600. PMID 23726798.
  8. ^ Smith DM, Strain MC, Frost SD, Pillai SK, Wong JK, Wrin T, Liu Y, Petropolous CJ, Daar ES, Little SJ, Richman DD (November 2006). "Lack of neutralizing antibody response to HIV-1 predisposes to superinfection". Virology. 355 (1): 1–5. doi:10.1016/j.virol.2006.08.009. PMID 16962152.
  9. ^ a b c d e Redd AD, Quinn TC, Tobian AA (July 2013). "Frequency and implications of HIV superinfection". The Lancet. Infectious Diseases. 13 (7): 622–8. doi:10.1016/s1473-3099(13)70066-5. PMC 3752600. PMID 23726798.
  10. ^ Smith DM, Strain MC, Frost SD, Pillai SK, Wong JK, Wrin T, Liu Y, Petropolous CJ, Daar ES, Little SJ, Richman DD (November 2006). "Lack of neutralizing antibody response to HIV-1 predisposes to superinfection". Virology. 355 (1): 1–5. doi:10.1016/j.virol.2006.08.009. PMID 16962152.
  11. ^ a b c d Streeck, Hendrik; Li, Bin; Poon, Art F. Y.; Schneidewind, Arne; Gladden, Adrianne D.; Power, Karen A.; Daskalakis, Demetre; Bazner, Suzane; Zuniga, Rosario (14 July 2008). "Immune-driven recombination and loss of control after HIV superinfection". Journal of Experimental Medicine. 205 (8): 1789–1796. doi:10.1084/jem.20080281. ISSN 0022-1007. PMC 2525594. PMID 18625749. Retrieved 27 October 2018.
  12. ^ a b Altfeld, Marcus; Allen, Todd M.; Yu, Xu G.; Johnston, Mary N.; Agrawal, Deepak; Korber, Bette T.; Montefiori, David C.; O'Connor, David H.; Davis, Ben T. (November 2002). "HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus". Nature. 420 (6914): 434–439. doi:10.1038/nature01200. ISSN 0028-0836. Retrieved 28 October 2018.
  13. ^ a b c d e f g h Smith, Davey M.; Richman, Douglas D.; Little, Susan J. (2005-08-01). "HIV Superinfection". Journal of Infectious Diseases. 192 (3): 438–444. doi:10.1086/431682. ISSN 0022-1899. PMID 15995957.
  14. ^ Smith, Davey M; Wong, Joseph K; Hightower, George K; Ignacio, Caroline C; Koelsch, Kersten K; Petropoulos, Christos J; Richman, Douglas D; Little, Susan J (August 2005). "HIV drug resistance acquired through superinfection". AIDS. 19 (12): 1251–1256. doi:10.1097/01.aids.0000180095.12276.ac. ISSN 0269-9370. Retrieved 28 October 2018.
  15. ^ Fang, Guowei; Weiser, Barbara; Kuiken, Carla; Philpott, Sean M; Rowland-Jones, Sarah; Plummer, Francise; Kimani, Joshua; Shi, Binshan; Kaul, Rupert (23 January 2004). "Recombination following superinfection by HIV-1". AIDS. 18 (2): 153–159. Retrieved 28 October 2018.
  16. ^ Esbjörnsson J, Månsson F, Kvist A, Isberg PE, Nowroozalizadeh S, Biague AJ, da Silva ZJ, Jansson M, Fenyö EM, Norrgren H, Medstrand P (July 2012). "Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection". The New England Journal of Medicine. 367 (3): 224–32. doi:10.1056/NEJMoa1113244. PMID 22808957.
  17. ^ a b Smith, Davey M.; Strain, Matthew C.; Frost, Simon D.W.; Pillai, Satish K.; Wong, Joseph K.; Wrin, Terri; Liu, Yang; Petropolous, Christos J.; Daar, Eric S. (November 2006). "Lack of neutralizing antibody response to HIV-1 predisposes to superinfection". Virology. 355 (1): 1–5. doi:10.1016/j.virol.2006.08.009. ISSN 0042-6822.
  18. ^ Redd, Andrew; et al. (June 2012). "The Rates of HIV Superinfection and Primary HIV Incidence in a General Population in Rakai, Uganda". Journal of Infectious Diseases. 206 (2): 267–274. doi:10.1093/infdis/jis325. PMC 3415936. PMID 22675216.
  19. ^ a b c d e f Redd, Andrew D; Quinn, Thomas C; Tobian, Aaron AR (June 2013). "Frequency and implications of HIV superinfection". The Lancet Infectious Diseases. 13 (7): 622–628. doi:10.1016/s1473-3099(13)70066-5. ISSN 1473-3099. PMC 3752600. PMID 23726798.
  20. ^ "Method of the Year". Nature Methods. 5 (1): 1–1. 2008-01. doi:10.1038/nmeth1153. ISSN 1548-7091. Retrieved 27 October 2018. Check date values in: |date= (help)
  21. ^ a b c d Michaels, Julia; Grant, Robert; McConnell, J. Jeff (November 2005). "HIV Superinfection vs Dual Initial Infection: What Clinicians and Patients Should Know". Research Gate. Retrieved 24 October 2018.
  22. ^ a b c d e f g h Redd, Andrew D; Quinn, Thomas C; Tobian, Aaron AR (June 2013). "Frequency and implications of HIV superinfection". The Lancet Infectious Diseases. 13 (7): 622–628. doi:10.1016/s1473-3099(13)70066-5. ISSN 1473-3099. PMC 3752600. PMID 23726798.
  23. ^ Redd, Andrew D.; Mullis, Caroline E.; Serwadda, David; Kong, Xiangrong; Martens, Craig; Ricklefs, Stacy M.; Tobian, Aaron A. R.; Xiao, Changchang; Grabowski, Mary K. (2012-06-06). "The Rates of HIV Superinfection and Primary HIV Incidence in a General Population in Rakai, Uganda". The Journal of Infectious Diseases. 206 (2): 267–274. doi:10.1093/infdis/jis325. ISSN 1537-6613. PMC 3415936. PMID 22675216.
  24. ^ a b TAYLOR, J; KORBER, B (January 2005). "HIV-1 intra-subtype superinfection rates: estimates using a structured coalescent with recombination". Infection, Genetics and Evolution. 5 (1): 85–95. doi:10.1016/j.meegid.2004.07.001. ISSN 1567-1348.
  25. ^ a b Redd, Andrew D; Quinn, Thomas C; Tobian, Aaron AR (June 2013). "Frequency and implications of HIV superinfection". The Lancet Infectious Diseases. 13 (7): 622–628. doi:10.1016/s1473-3099(13)70066-5. ISSN 1473-3099. PMC 3752600. PMID 23726798.
  26. ^ Fultz, PN; Srinivasan, A; Greene, CR; Butler, D; Swenson, RB; McClure, HM (1987). "Superinfection of a chimpanzee with a second strain of human immunodeficiency virus". Journal of Virology – via Medscape.
  27. ^ Otten, RA; Ellenberger, DL; Adams, DR; Fridlund, CA; Jackson, E; Pieniazek, D; Rayfield, MA (1999). "Identification of a window period for susceptibility to dual infection with two distinct human immunodeficiency virus type 2 isolates in a Macaca nemestrina (pig-tailed macaque) model". Journal of Infectious Diseases – via Medscape.
  28. ^ a b Ramos, Artur; Hu, Dale J.; Nguyen, Lily; Phan, Kim-Oanh; Vanichseni, Suphak; Promadej, Nattawan; Choopanya, Kachit; Callahan, Margaret; Young, Nancy L. (August 2002). "Intersubtype human immunodeficiency virus type 1 superinfection following seroconversion to primary infection in two injection drug users". Journal of Virology. 76 (15): 7444–7452. doi:10.1128/JVI.76.15.7444-7452.2002. ISSN 0022-538X. PMC 136380. PMID 12097556.
  29. ^ Koelsch, Kersten K; Smith, Davey M; Little, Susan J; Ignacio, Caroline C; Macaranas, Theresa R; Brown, Andrew J; Petropoulos, Christos J; Richman, Douglas D; Wong, Joseph K (2 May 2003). "Clade B HIV-1 superinfection with wild-type virus after primary infection with drug-resistant clade B virus". AIDS. 17 (7): F11–F16 – via Google Scholar.
  30. ^ Smith, Davey M; Wong, Joseph K; Hightower, George K; Ignacio, Caroline C; Koelsch, Kersten K; Petropoulos, Christos J; Richman, Douglas D; Little, Susan J (August 2005). "HIV drug resistance acquired through superinfection". AIDS. 19 (12): 1251–1256. doi:10.1097/01.aids.0000180095.12276.ac. ISSN 0269-9370. Retrieved 28 October 2018.
  31. ^ a b Smith, Davey M; Wong, Joseph K; Hightower, George K; Ignacio, Caroline C; Koelsch, Kersten K; Petropoulos, Christos J; Richman, Douglas D; Little, Susan J (August 2005). "HIV drug resistance acquired through superinfection". AIDS. 19 (12): 1251–1256. doi:10.1097/01.aids.0000180095.12276.ac. ISSN 0269-9370. Retrieved 28 October 2018.
  32. ^ a b c d Altfeld, Marcus; Allen, Todd M.; Yu, Xu G.; Johnston, Mary N.; Agrawal, Deepak; Korber, Bette T.; Montefiori, David C.; O'Connor, David H.; Davis, Ben T. (November 2002). "HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus". Nature. 420 (6914): 434–439. doi:10.1038/nature01200. ISSN 0028-0836. Retrieved 28 October 2018.
  33. ^ Ramos, Artur; Hu, Dale J.; Nguyen, Lily; Phan, Kim-Oanh; Vanichseni, Suphak; Promadej, Nattawan; Choopanya, Kachit; Callahan, Margaret; Young, Nancy L. (August 2002). "Intersubtype human immunodeficiency virus type 1 superinfection following seroconversion to primary infection in two injection drug users". Journal of Virology. 76 (15): 7444–7452. doi:10.1128/JVI.76.15.7444-7452.2002. ISSN 0022-538X. PMC 136380. PMID 12097556.
  34. ^ a b c d Redd, Andrew D; Quinn, Thomas C; Tobian, Aaron AR (June 2013). "Frequency and implications of HIV superinfection". The Lancet Infectious Diseases. 13 (7): 622–628. doi:10.1016/s1473-3099(13)70066-5. ISSN 1473-3099. PMC 3752600. PMID 23726798.
  35. ^ a b Michaels, Julia; Grant, Robert; McConnell, J. Jeff (November 2005). "HIV Superinfection vs Dual Initial Infection: What Clinicians and Patients Should Know". Research Gate. Retrieved 24 October 2018.