Dataset Information

Identification of HIV superinfection in seroconcordant couples in Rakai, Uganda, by use of next-generation deep sequencing.

ABSTRACT: 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.

SUBMITTER: Redd AD

PROVIDER: S-EPMC3147722 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Identification of HIV superinfection in seroconcordant couples in Rakai, Uganda, by use of next-generation deep sequencing.

Redd Andrew D AD Collinson-Streng Aleisha A Martens Craig C Ricklefs Stacy S Mullis Caroline E CE Manucci Jordyn J Tobian Aaron A R AA Selig Ethan J EJ Laeyendecker Oliver O Sewankambo Nelson N Gray Ronald H RH Serwadda David D Wawer Maria J MJ Porcella Stephen F SF Quinn Thomas C TC

Journal of clinical microbiology 20110622 8

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 infect ...[more]

PMID: 21697329

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Project description:BACKGROUND:Acquisition of more than one strain of human immunodeficiency virus type 1 (HIV-1) has been reported to occur both during and after primary infection, but the risks and repercussions of dual and superinfection are incompletely understood. In this study, we evaluated a longitudinal cohort of chronically HIV-infected men who were sexual partners to determine if individuals acquired their partners' viral strains. METHODOLOGY:Our cohort of HIV-positive men consisted of 8 couples that identified themselves as long-term sexual partners. Viral sequences were isolated from each subject and analyzed using phylogenetic methods. In addition, strain-specific PCR allowed us to search for partners' viruses present at low levels. Finally, we used computational algorithms to evaluate for recombination between partners' viral strains. PRINCIPAL FINDINGS/CONCLUSIONS:All couples had at least one factor associated with increased risk for acquisition of new HIV strains during the study, including detectable plasma viral load, sexually transmitted infections, and unprotected sex. One subject was dually HIV-1 infected, but neither strain corresponded to that of his partner. Three couples' sequences formed monophyletic clusters at the entry visit, with phylogenetic analysis suggesting that one member of the couple had acquired an HIV strain from his identified partner or that both had acquired it from the same source outside their partnership. The 5 remaining couples initially displayed no evidence of dual infection, using phylogenetic analysis and strain-specific PCR. However, in 1 of these couples, further analysis revealed recombinant viral strains with segments of viral genomes in one subject that may have derived from the enrolled partner. Thus, chronically HIV-1 infected individuals may become superinfected with additional HIV strains from their seroconcordant sexual partners. In some cases, HIV-1 superinfection may become apparent when recombinant viral strains are detected.

Project description:BACKGROUND:The ability to understand another's emotions and act appropriately, empathy, is an important mediator of relationship function and health intervention fidelity. We adapted the Interpersonal Reactivity Index (IRI) - an empathy scale - among seroconcordant expectant couples with HIV in the Homens para Saúde Mais (HoPS+) trial - a cluster randomized controlled trial assessing couple-based versus individual treatment on viral suppression - in Zambézia Province, Mozambique. METHODS:Using baseline data from 1332 HoPS+ trial participants (666 couples), an exploratory factor analysis assessed culturally relevant questions from the IRI. Because empathy is interdependent among couples, we validated the results of the exploratory factor analysis using a dyadic confirmatory factor analysis (CFA) with dyadic measurement invariance testing. Finally, we assessed the relationship between scores on our final scale and basic demographic characteristics (sex, age, education, and depression) using t-tests. RESULTS:We found two subscales: 1) a seven-item cognitive empathy subscale (Cronbach's alpha 0.78) and 2) a six-item affective empathy subscale (Cronbach's alpha 0.73). The dyadic CFA found acceptable model fit and metric invariance across partners (Comparative Fit Index (CFI)?=?0.914, Tucker Lewis Index?=?0.904, Root Mean Squared Error of Approximation?=?0.056, ?CFI?=?0.011). We observed higher cognitive (p: 0.012) and affective (p: 0.049) empathy among males and higher cognitive (p: 0.031) and affective (p: 0.030) empathy among younger participants. More educated participants had higher affective empathy (p: 0.017) and depressed participants had higher cognitive empathy (p: <?0.001). This two-subscale, 13-item version of the IRI measures cognitive and affective empathy in HoPS+ trial participants and adults while accounting for the interdependent nature of empathy within partner dyads. CONCLUSIONS:This scale will allow us to assess the interplay between empathy and other psychometric constructs (stigma, social support, etc.) in the HoPS+ trial and how each relates to retention in HIV, adherence to treatment, and prevention of maternal to child HIV transmission. Furthermore, this scale can be adapted for other sub-Saharan African populations, which will allow researchers to better assess HIV-related intervention efficacy. TRIAL REGISTRATION:This study is within the context of the HoPS+ trial, registered at ClinicalTrials.gov as number NCT03149237 . Registered May 11, 2017.

Dataset Information

Identification of HIV superinfection in seroconcordant couples in Rakai, Uganda, by use of next-generation deep sequencing.

Publications

Identification of HIV superinfection in seroconcordant couples in Rakai, Uganda, by use of next-generation deep sequencing.

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