The Experts below are selected from a list of 19899 Experts worldwide ranked by ideXlab platform
Andrew D Redd - One of the best experts on this subject based on the ideXlab platform.
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limited anti hiv neutralizing antibody breadth and potency before and after hiv Superinfection in danish men who have sex with men
Infectious diseases, 2019Co-Authors: Andrew D Redd, Craig Martens, Daniel Bruno, Marie Helleberg, Matthew Sievers, Stephen D Schmidt, Nicole A Doriarose, Shelby Traeger, Jannik Fonager, Gitte KronborgAbstract:Background: The role of the anti-HIV neutralizing antibody response in protecting against HIV Superinfection, and changes in neutralizing antibody potency and breadth after HIV Superinfection have ...
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HIV-1 Superinfection can occur in the presence of broadly neutralizing antibodies
Vaccine, 2018Co-Authors: Jennifer Serwanga, Andrew D Redd, Deogratius Ssemwanga, Michael Muganga, Ritah Nakiboneka, Susan Nakubulwa, Sylvia Kiwuwa-muyingo, Lynn Morris, Thomas C. Quinn, Pontiano KaleebuAbstract:Abstract Background Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to Superinfection. Methods Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-Superinfection (n = 6); one superinfected volunteer lacked pre-Superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before Superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after Superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after Superinfection; and were correlated with the volunteer HIV-1 Superinfection status, CD4 counts, and pseudovirus clade. Results Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after Superinfection. In one of the five subjects, HIV-1 Superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of Superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the Superinfection status. Conclusion These data demonstrate that HIV-1 Superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
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evaluation of postpartum hiv Superinfection and mother to child transmission
AIDS, 2015Co-Authors: Andrew D Redd, Daniel Bruno, Sarah K Wendel, Andrew F Longosz, Jessica M Fogel, Sufia Dadabhai, Newton Kumwenda, Jin Sun, Michael P Walker, Craig MartensAbstract:OBJECTIVE This study examined HIV Superinfection in HIV-infected women postpartum, and its association with mother-to-child transmission (MTCT). DESIGN Plasma samples were obtained from HIV-infected women who transmitted HIV to their infants after 6 weeks of age (transmitters, n = 91) and HIV-infected women who did not transmit HIV to their infants (nontransmitters, n = 91). These women were originally enrolled in a randomized trial for prevention of MTCT of HIV in Malawi (Post-Exposure Prophylaxis of Infants trial in Malawi). METHODS Two HIV genomic regions (p24 and gp41) were analyzed by next-generation sequencing for HIV Superinfection. HIV Superinfection was established if the follow-up sample contained a new, phylogenetically distinct viral population. HIV Superinfection and transmission risk were examined by multiple logistic regression, adjusted for Post-Exposure Prophylaxis of Infants study arm, baseline viral load, baseline CD4 cell count, time to resumption of sex, and breastfeeding duration. RESULTS Transmitters had lower baseline CD4 cell counts (P = 0.001) and higher viral loads (P < 0.0001) compared with nontransmitters. There were five cases of Superinfection among transmitters (rate of Superinfection = 4.7/100 person-years) compared with five cases among the nontransmitters (rate of Superinfection = 4.4/100 person-years; P = 0.78). HIV Superinfection was not associated with increased risk of postnatal MTCT of HIV after controlling for maternal age, baseline viral load, and CD4 cell count (adjusted odds ratio = 2.32, P = 0.30). Longer breastfeeding duration was independently associated with a lower risk of HIV Superinfection after controlling for study arm and baseline viral load (P = 0.05). CONCLUSION There was a significant level of HIV Superinfection in women postpartum, but this was not associated with an increased risk of MTCT via breastfeeding.
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Limited HIV-1 Superinfection in seroconverters from the CAPRISA 004 microbicide trial
Journal of Clinical Microbiology, 2013Co-Authors: Andrew D Redd, Caroline E Mullis, Craig Martens, Daniel Bruno, Sarah K Wendel, Daniel J. Sheward, Lise. Werner, Nigel Garrett, Quarraisha Abdool Karim, Carolyn WilliamsonAbstract:ABSTRACT HIV-1 Superinfection (SI) occurs when an infected individual acquires a distinct new viral strain. The rate of Superinfection may be reflective of the underlying HIV risk in a population. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 clinical trial demonstrated that women who used a tenofovir-containing microbicide gel had lower rates of HIV infection than women using a placebo gel. Women who contracted HIV-1 during the trial were screened for the occurrence of Superinfection by next-generation sequencing of the viral gag and env genes. There were two cases (one in each trial arm) of subtype C Superinfection identified from the 76 women with primary infection screened at two time points (rate of Superinfection, 1.5/100 person-years). Both women experienced a >0.5-log increase in viral load during the window when Superinfection occurred. The rate of Superinfection was significantly lower than the overall primary HIV incidence in the microbicide trial (incidence rate ratio [IRR], 0.20; P = 0.003). The women who seroconverted during the trial reported a significant increase in sexual contact with their stable partner 4 months after seroconversion (P
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Frequency and implications of HIV Superinfection
The Lancet Infectious Diseases, 2013Co-Authors: Andrew D Redd, Thomas C. Quinn, Aaron A R TobianAbstract:HIV Superinfection occurs when an individual with HIV is infected with a new distinct HIV viral strain. Superinfection has been reported throughout the world, and studies have recorded incidence rates of 0–7·7% per year. Use of next-generation sequencing has improved detection of Superinfection, which can be transmitted by injecting drug use and sexual intercourse. Superinfection might have incidence rates comparable to those of initial HIV infection. Clinicians should encourage safe sexual and injecting drug use practices for HIV-infected patients because Superinfection has detrimental effects on clinical outcomes and could pose a concern for large-scale antiretroviral treatment plans. The occurrence of Superinfection has implications for vaccine research, since it seems initial HIV infection is not fully protective against a subsequent infection. Additional collaborative research could benefit care of patients and inform future vaccine design.
Craig Martens - One of the best experts on this subject based on the ideXlab platform.
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limited anti hiv neutralizing antibody breadth and potency before and after hiv Superinfection in danish men who have sex with men
Infectious diseases, 2019Co-Authors: Andrew D Redd, Craig Martens, Daniel Bruno, Marie Helleberg, Matthew Sievers, Stephen D Schmidt, Nicole A Doriarose, Shelby Traeger, Jannik Fonager, Gitte KronborgAbstract:Background: The role of the anti-HIV neutralizing antibody response in protecting against HIV Superinfection, and changes in neutralizing antibody potency and breadth after HIV Superinfection have ...
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evaluation of postpartum hiv Superinfection and mother to child transmission
AIDS, 2015Co-Authors: Andrew D Redd, Daniel Bruno, Sarah K Wendel, Andrew F Longosz, Jessica M Fogel, Sufia Dadabhai, Newton Kumwenda, Jin Sun, Michael P Walker, Craig MartensAbstract:OBJECTIVE This study examined HIV Superinfection in HIV-infected women postpartum, and its association with mother-to-child transmission (MTCT). DESIGN Plasma samples were obtained from HIV-infected women who transmitted HIV to their infants after 6 weeks of age (transmitters, n = 91) and HIV-infected women who did not transmit HIV to their infants (nontransmitters, n = 91). These women were originally enrolled in a randomized trial for prevention of MTCT of HIV in Malawi (Post-Exposure Prophylaxis of Infants trial in Malawi). METHODS Two HIV genomic regions (p24 and gp41) were analyzed by next-generation sequencing for HIV Superinfection. HIV Superinfection was established if the follow-up sample contained a new, phylogenetically distinct viral population. HIV Superinfection and transmission risk were examined by multiple logistic regression, adjusted for Post-Exposure Prophylaxis of Infants study arm, baseline viral load, baseline CD4 cell count, time to resumption of sex, and breastfeeding duration. RESULTS Transmitters had lower baseline CD4 cell counts (P = 0.001) and higher viral loads (P < 0.0001) compared with nontransmitters. There were five cases of Superinfection among transmitters (rate of Superinfection = 4.7/100 person-years) compared with five cases among the nontransmitters (rate of Superinfection = 4.4/100 person-years; P = 0.78). HIV Superinfection was not associated with increased risk of postnatal MTCT of HIV after controlling for maternal age, baseline viral load, and CD4 cell count (adjusted odds ratio = 2.32, P = 0.30). Longer breastfeeding duration was independently associated with a lower risk of HIV Superinfection after controlling for study arm and baseline viral load (P = 0.05). CONCLUSION There was a significant level of HIV Superinfection in women postpartum, but this was not associated with an increased risk of MTCT via breastfeeding.
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Limited HIV-1 Superinfection in seroconverters from the CAPRISA 004 microbicide trial
Journal of Clinical Microbiology, 2013Co-Authors: Andrew D Redd, Caroline E Mullis, Craig Martens, Daniel Bruno, Sarah K Wendel, Daniel J. Sheward, Lise. Werner, Nigel Garrett, Quarraisha Abdool Karim, Carolyn WilliamsonAbstract:ABSTRACT HIV-1 Superinfection (SI) occurs when an infected individual acquires a distinct new viral strain. The rate of Superinfection may be reflective of the underlying HIV risk in a population. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 clinical trial demonstrated that women who used a tenofovir-containing microbicide gel had lower rates of HIV infection than women using a placebo gel. Women who contracted HIV-1 during the trial were screened for the occurrence of Superinfection by next-generation sequencing of the viral gag and env genes. There were two cases (one in each trial arm) of subtype C Superinfection identified from the 76 women with primary infection screened at two time points (rate of Superinfection, 1.5/100 person-years). Both women experienced a >0.5-log increase in viral load during the window when Superinfection occurred. The rate of Superinfection was significantly lower than the overall primary HIV incidence in the microbicide trial (incidence rate ratio [IRR], 0.20; P = 0.003). The women who seroconverted during the trial reported a significant increase in sexual contact with their stable partner 4 months after seroconversion (P
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the rates of hiv Superinfection and primary hiv incidence in a general population in rakai uganda
The Journal of Infectious Diseases, 2012Co-Authors: Andrew D Redd, Caroline E Mullis, David Serwadda, Xiangrong Kong, Craig Martens, Stacy M Ricklefs, Aaron A R Tobian, Changchang Xiao, Mary K Grabowski, Fred NalugodaAbstract:Background. Human immunodeficiency virus (HIV) Superinfection has been documented in high-risk individuals; however, the rate of Superinfection among HIV-infected individuals within a general population remains unknown. Methods. A novel next-generation ultra-deep sequencing technique was utilized to determine the rate of HIV Superinfection in a heterosexual population by examining two regions of the viral genome in longitudinal samples from recent HIV seroconverters (n = 149) in Rakai District, Uganda. Results. The rate of Superinfection was 1.44 per 100 person years (PYs) (95% confidence interval [CI], .4–2.5) and consisted of both inter- and intrasubtype Superinfections. This was compared to primary HIV incidence in 20 220 initially HIV-negative individuals in the general population in Rakai (1.15 per 100 PYs; 95% CI, 1.1–1.2; P= .26). Propensity score matching (PS) was used to control for differences in sociodemographic and behavioral characteristics between the HIV-positive individuals at risk for Superinfection and the HIV-negative population at baseline and follow-up. After PS matching, the estimated rate of primary incidence was 3.28 per 100 PYs (95% CI, 2.0–5.3; P= .07) controlling for baseline differences and 2.51 per 100 PYs (95% CI, 1.5–4.3; P= .24) controlling for follow-up differences. Conclusions. This suggests that the rate of HIV Superinfection in a general population is substantial, which could have a significant impact on future public health and HIV vaccine strategies.
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identification of hiv Superinfection in seroconcordant couples in rakai uganda by use of next generation deep sequencing
Journal of Clinical Microbiology, 2011Co-Authors: Andrew D Redd, Caroline E Mullis, Craig Martens, Stacy M Ricklefs, Aaron A R Tobian, Aleisha Collinsonstreng, Jordyn Manucci, Ethan J Selig, Oliver LaeyendeckerAbstract: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.
François Trottein - One of the best experts on this subject based on the ideXlab platform.
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Mechanisms of Bacterial Superinfection Post-influenza: A Role for Unconventional T Cells
Frontiers in Immunology, 2019Co-Authors: Christophe Paget, François TrotteinAbstract:Despite the widespread application of vaccination programs and antiviral drug treatments, influenza viruses are still among the most harmful human pathogens. Indeed, influenza results in significant seasonal and pandemic morbidity and mortality. Furthermore, severe bacterial infections can occur in the aftermath of influenza virus infection, and contribute substantially to the excess morbidity and mortality associated with influenza. Here, we review the main features of influenza viruses and current knowledge about the mechanical and immune mechanisms that underlie post-influenza secondary bacterial infections. We present the emerging literature describing the role of "innate-like" unconventional T cells in post-influenza bacterial Superinfection. Unconventional T cell populations span the border between the innate and adaptive arms of the immune system, and are prevalent in mucosal tissues (including the airways). They mainly comprise Natural Killer T cells, mucosal-associated invariant T cells and γδ T cells. We provide an overview of the principal functions that these cells play in pulmonary barrier functions and immunity, highlighting their unique ability to sense environmental factors and promote protection against respiratory bacterial infections. We focus on two major opportunistic pathogens involved in Superinfections, namely Streptococcus pneumoniae and Staphylococcus aureus. We discuss mechanisms through which influenza viruses alter the antibacterial activity of unconventional T cells. Lastly, we discuss recent fundamental advances and possible therapeutic approaches in which unconventional T cells would be targeted to prevent post-influenza bacterial Superinfections.
Oliver Laeyendecker - One of the best experts on this subject based on the ideXlab platform.
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identification of hiv Superinfection in seroconcordant couples in rakai uganda by use of next generation deep sequencing
Journal of Clinical Microbiology, 2011Co-Authors: Andrew D Redd, Caroline E Mullis, Craig Martens, Stacy M Ricklefs, Aaron A R Tobian, Aleisha Collinsonstreng, Jordyn Manucci, Ethan J Selig, Oliver LaeyendeckerAbstract: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.
Julie Overbaugh - One of the best experts on this subject based on the ideXlab platform.
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hiv 1 Superinfection is associated with an accelerated viral load increase but has a limited impact on disease progression
AIDS, 2014Co-Authors: Keshet Ronen, Barbra A Richardson, Susan M Graham, Walter Jaoko, Kishor Mandaliya, Scott R Mcclelland, Julie OverbaughAbstract:Objective: HIV-1 Superinfection occurs frequently in high-risk populations, but its clinical consequences remain poorly characterized. We undertook this study to determine the impact of HIV-1 Superinfection on disease progression. Design/methods: In the largest prospective cohort study of Superinfection to date, we compared measures of HIV-1 progression in women who acquired Superinfection with those who did not. Clinical and laboratory data were collected at quarterly intervals. Linearmixedeffectsmodelswereused tocomparepostacuteviralloadandCD4 þ T-cell counts over time in singly infected and superinfected women. Cox proportional hazards analysiswas usedtodeterminethe effectofSuperinfectionontimetoclinicalprogression [CD4 þ cell count <200cells/ml, antiretroviral therapy (ART) initiation or death]. Results: Among 144 women, 21 of whom acquired Superinfection during follow-up, the rate of viral load increase was higher in superinfected than in singly infected women (P ¼0.0008). In adjusted analysis, superinfected women had lower baseline viral load before Superinfection (P ¼0.05) and a trend for increased viral load at Superinfection acquisition (P ¼0.09). We also observed a borderline association of Superinfection with accelerated CD4 þ cell count decline (P ¼0.06). However, there was no significant difference in time to clinical progression events. Conclusion: These data suggest that Superinfection is associated with accelerated progression in laboratory measures of HIV-1 disease, but has a limited impact on the occurrence of clinical events. Our observation that superinfected individuals have lower baseline viral load prior to Superinfection suggests that there may be host or viral determinants of susceptibility to Superinfection.
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Hiv-1 Superinfection Is Associated With An Accelerated Viral Load Increase But Has A Limited Impact On Disease Progression.
AIDS, 2014Co-Authors: Keshet Ronen, Barbra A Richardson, Susan M Graham, Walter Jaoko, Kishor Mandaliya, R. Scott Mcclelland, Julie OverbaughAbstract:Objective: HIV-1 Superinfection occurs frequently in high-risk populations, but its clinical consequences remain poorly characterized. We undertook this study to determine the impact of HIV-1 Superinfection on disease progression. Design/methods: In the largest prospective cohort study of Superinfection to date, we compared measures of HIV-1 progression in women who acquired Superinfection with those who did not. Clinical and laboratory data were collected at quarterly intervals. Linearmixedeffectsmodelswereused tocomparepostacuteviralloadandCD4 þ T-cell counts over time in singly infected and superinfected women. Cox proportional hazards analysiswas usedtodeterminethe effectofSuperinfectionontimetoclinicalprogression [CD4 þ cell count
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Cellular immune responses and susceptibility to HIV-1 Superinfection: a case-control study.
AIDS, 2012Co-Authors: Catherine A. Blish, Walter Jaoko, Kishor Mandaliya, Ozge C. Dogan, Rs Mcclelland, Katherine Odem-davis, Ba Richardsonb, Julie OverbaughAbstract:A case control study was performed to determine the effects of HIV-1-specific cellular immune responses on the odds of acquiring a second HIV-1 infection (Superinfection). Changes in the frequency of cytokine-producing or cytolytic CD8+ or CD4+ T cells were not associated with significant alterations in the odds of Superinfection, suggesting that HIV-1 specific cellular immune responses at the level induced by chronic infection do not appear to significantly contribute to protection from HIV-1 Superinfection.
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HIV-1 Superinfection and its Implications for Vaccine Design
Current HIV Research, 2010Co-Authors: Bhavna Chohan, Anne Piantadosi, Julie OverbaughAbstract:HIV-1 Superinfection, which refers to a subsequent HIV-1 infection from a different source partner after the first HIV-1 infection is established, has now been well documented in multiple populations. Some studies suggest that the risk of Superinfection may be close to that of initial infection, suggesting that the immunity induced by chronic HIV-1 infection may not be adequate to confer protection from another HIV-1 strain. Detailed studies that examined immune responses in individuals who became superinfected generally support this hypothesis, but such studies have been limited. Indeed, Superinfection represents one of the few settings, apart from vaccine trials, where there is an opportunity to gain insights into the role of HIV-specific immunity in protection in humans, and this should be exploited. Likewise, studies of Superinfection in HIV-1 positive individuals on antiretroviral therapy who continue to be exposed to HIV could provide insight into the role of antiretroviral treatment in protecting from HIV-1 infection, a concept that is also being explored for its potential to prevent a first HIV-1 infection. To address these questions, larger population-based studies that define the incidence and timing of Superinfection and include collection of samples for immunological studies are needed.
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Examination of a second region of the HIV type 1 genome reveals additional cases of Superinfection.
AIDS Research and Human Retroviruses, 2008Co-Authors: Anne Piantadosi, Musa Otieno Ngayo, Bhavna Chohan, Julie OverbaughAbstract:Abstract HIV-1 Superinfection may occur at a rate similar to that of initial infection, raising concerns for HIV-1 vaccine strategies predicated on eliciting immune responses similar to those in natural infection. Because of the high rate of recombination during HIV-1 replication, studies examining only one region of the HIV-1 genome are likely to miss cases of HIV-1 Superinfection. We examined HIV-1 gag sequences from 14 high-risk Kenyan women in whom Superinfection was not detected in a previous study of env sequences. We detected two additional cases of HIV-1 Superinfection: one intersubtype Superinfection that occurred between 1046 and 1487 days postinfection (DPI) and one intrasubtype Superinfection that occurred between 341 and 440 DPI. Our results suggest that studies that examine only small genome regions may lead to underestimates of the risk of Superinfection, highlighting the need for more extensive studies examining multiple regions of the HIV-1 genome.
