HIV drug resistance acquired through superinfection

Smith, Davey M.; Wong, Joseph K.; Hightower, George K.; Ignacio, Caroline; Koelsch, Kersten K.; Petropoulos, Christos J.; Richman, Douglas D.

doi:10.1097/01.aids.0000180095.12276.ac

Cited by 88 publications

(79 citation statements)

References 15 publications

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“…In theory, a more prolonged time of HIV infection could allow multiple rounds of transmission of different drug-resistant viruses, resulting in more extensive resistance patterns in drug-naive subjects tested at later stages of infection. However, findings pertaining to the relatively rare occurrence of HIV superinfection (9,25) do not seem to support this hypothesis. Multiple parallel testing of plasma and PBMCs at different time points could elucidate the kinetics of transmitted resistance over time.…”

Section: Discussionmentioning

confidence: 92%

Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients

et al. 2007

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Section: Discussionmentioning

confidence: 92%

Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients

et al. 2007

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“…The first documented cases of HIV superinfection were found in individuals with various modes of transmission and included inter-and intrasubtype cases (1,9,17). Subsequently, multiple studies have documented superinfection in small populations of high-risk individuals (2,3,7,8,11,13,17,20,22,23,26,29). The rate of HIV superinfection in these high-risk groups was relatively frequent and was comparable to the incidence rate in similar populations from the same regions, especially if multiple viral genes were examined (3,13,14,21,24).…”

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confidence: 99%

Identification of HIV Superinfection in Seroconcordant Couples in Rakai, Uganda, by Use of Next-Generation Deep Sequencing

Redd

Collinson-Streng

Martens³

et al. 2011

J Clin Microbiol

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HIV superinfection, which occurs when a previously infected individual acquires a new distinct HIV strain, has been described in a number of populations. Previous methods to detect superinfection have involved a combination of labor-intensive assays with various rates of success. We designed and tested a next-generation sequencing (NGS) protocol to identify HIV superinfection by targeting two regions of the HIV viral genome, p24 and gp41. The method was validated by mixing control samples infected with HIV subtype A or D at different ratios to determine the inter-and intrasubtype sensitivity by NGS. This amplicon-based NGS protocol was able to consistently identify distinct intersubtype strains at ratios of 1% and intrasubtype variants at ratios of 5%. By using stored samples from the Rakai Community Cohort Study (RCCS) in Uganda, 11 individuals who were HIV seroconcordant but virally unlinked from their spouses were then tested by this method to detect superinfection between 2002 and 2005. Two female cases of HIV intersubtype superinfection (18.2%) were identified. These results are consistent with other African studies and support the hypothesis that HIV superinfection occurs at a relatively high rate. Our results indicate that NGS can be used for detection of HIV superinfection within large cohorts, which could assist in determining the incidence and the epidemiologic, virologic, and immunological correlates of this phenomenon.

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“…There is accruing evidence for HIV-1 intra-and intersubtype superinfection in settings of intravenous drug use, structured treatment interruptions, and with strains that are resistant to antiretroviral drugs (2,4,6,22,26,28,32,39,42,43,52,60,66). Epidemiologic studies have suggested that the frequency of superinfection ranges from rare to as high as 5% per year in high-risk populations (9,10,15,20,24,27,31,40,41,51,59,65,67).…”

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confidence: 99%

Partial Protection of Simian Immunodeficiency Virus (SIV)-Infected Rhesus Monkeys against Superinfection with a Heterologous SIV Isolate

Yeh

Jaru-Ampornpan

Nevidomskyte

et al. 2009

J Virol

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Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4 ؉ T-cell count, CD4 ؉ memory T-cell subsets, cytokine production by virus-specific CD8 ؉ or CD4 ؉ cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4؉ T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.Superinfection with human immunodeficiency virus type 1 (HIV-1) is the infection of an HIV-seropositive individual with a second heterologous strain of the virus after infection with the first infecting strain is established. There is accruing evidence for HIV-1 intra-and intersubtype superinfection in settings of intravenous drug use, structured treatment interruptions, and with strains that are resistant to antiretroviral drugs (2,4,6,22,26,28,32,39,42,43,52,60,66). Epidemiologic studies have suggested that the frequency of superinfection ranges from rare to as high as 5% per year in high-risk populations (9,10,15,20,24,27,31,40,41,51,59,65,67). However, it remains unclear how readily superinfections occur after exposure of an infected individual to a heterologous strain of virus. Furthermore, the variables that may contribute to susceptibility or resistance to superinfection, such as the timing of exposure to a second virus or the immunologic status of the exposed individual, have not been well defined. It is also uncertain whether superinfection is invariably associated with the loss of HIV containment and clinical deterioration (8,17,21,23,26,27,30,60). Understanding the risks for and the biological consequences of HIV superinfection will not only clarify an important clinical problem, it may also provide important insig...

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HIV drug resistance acquired through superinfection

Abstract: HIV drug resistance acquired through superinfection significantly lowers the likelihood of successful antiretroviral therapy and undermines the clinical value of a patient's prior drug resistance testing and lack of prior antiretroviral use.

Cited by 88 publications

References 15 publications

Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients

Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients

Identification of HIV Superinfection in Seroconcordant Couples in Rakai, Uganda, by Use of Next-Generation Deep Sequencing

Partial Protection of Simian Immunodeficiency Virus (SIV)-Infected Rhesus Monkeys against Superinfection with a Heterologous SIV Isolate

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