PubMed · 12219687
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H Bergstermann, K Häussinger. 2002. [Tuberculosis].. https://doi.org/10.1007/s00108-002-0640-7
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OBJECTIVE: To describe and evaluate a simple procedure to identify HIV-1 co- or super-infections based on a heteroduplex mobility assay (HMA). METHODS: To identify heteroduplexes corresponding to divergent viral populations in a the same individual, HMA was applied to single DNA samples from each subject in a prospective cohort of commercial sex workers (CSW) in Bobo-Dioulasso, Burkina Faso. After denaturation and renaturation of env DNA amplicons, hybridized DNA was separated by electrophoresis through polyacrylamide gel. HIV-1 co-infections were suspected by slow migration of heteroduplex, at a level comparable to that of mixed reference strains. Following electrophoresis, DNA in bands representing heteroduplex was extracted and cloned in a plasmid vector; identification of phylogenetically distinct clones was confirmed by sequencing divergent clones identified through a second HMA step of a pair of two mixed clones. RESULTS: Among 147 HIV-1 infected CSW, four had an autologous HMA profile comparable to low mobility of hybridized DNA from mixed reference strains representing most frequent HIV-1 clades and circulating recombinant forms (CRF) prevalent in Burkina Faso. In two of them, two phylogenetically distinct HIV-1 populations were coexisting. The first woman presented with a CRF02-AG and CRF06-cpx co-infection, and the second with a CRF02-AG and a divergent virus co-infection not significantly related to any other known subtypes. In both women, retrospective analyses of stored samples by the same HMA procedure showed acquisition of a second virus concomitent with an increasing plasma HIV RNA. CONCLUSIONS: Autologous HMA procedure followed by acrylamide extraction of heteroduplexes allowed identifying HIV-1 co- and super-infections in a large cohort study. HIV-1 super-infection is not an uncommon phenomenon.
OBJECTIVE: The authors previous studies documented persistence of multidrug resistance (MDR) acquired in five primary HIV-1 infection (PHI) cases for 1-2 years in the absence of antiretroviral treatment. This study characterizes the evolution of transmitted wild-type (WT) (n = 15), resistant (n = 10), and MDR (n = 6) infections. Long-term persistence of MDR infections (2-7 years), leading to one observed MDR superinfection is documented. METHODS: Genotypic changes in circulating viral quasi-species were evaluated over 1.5-7 years in patients (n = 31) enrolled in the PHI study. Sequencing of reverse transcriptase and protease regions identified nucleotide substitutions in the viral quasi-species and mutations at sites implicated in resistance to antiretroviral drugs. Phylogenetic and clonal analysis were performed to confirm one observed superinfection. RESULTS: Patients acquiring WT, drug-resistant and MDR infections showed little quasi-species evolution (> 99.6% homology) for more than 1.5 years, regardless of route of transmission. Transmitted resistance mutations (other than 184V) persisted for 2-7 years. MDR persistence in two PHI cases contrasted with the corresponding rapid reversion of MDR infections to WT in their partners following treatment interruption. One MDR transmission eliciting low-level viremia resulted in clearance of the original MDR infection followed by re-infection with a second heterologous MDR strain from a different partner. Phylogenetic and clonal analysis of source and index partner confirmed the superinfection. Both MDR species showed approximately 13-fold reductions in replication capacity relative to the homologous WT strain isolated from the source partner. CONCLUSIONS: Genotypic analysis in PHI may identify superinfection and MDR infections that represent important determinants of virological and treatment outcome.
Current guidelines recommend consideration of CD4 cell percentage as well as CD4 cell count in therapeutic decisions. The relative value of CD4 cell count compared with CD4 cell percentage in predicting risk of AIDS-defining illnesses (ADIs) in the post-HAART (highly active antiretroviral therapy) era is unknown. Data from an observational clinical cohort of adult HIV-infected patients were used to assess the risk of developing an ADI associated with specific absolute CD4 counts (CD4) and CD4%'s (CD4%) using all CD4-CD4% pairs obtained after January 1996. The incidence of developing an ADI was assessed over a maximum of 6 months after the CD4-CD4% pair was obtained. Using multivariable negative binomial regression, the incidence rate ratio (IRR) for developing an ADI by CD4 and CD4% categories was computed. A total of 15,736 CD4-CD4% pairs from 2185 patients who developed 608 ADIs was analyzed. The IRR for developing an ADI by absolute CD4 was 17.9 (95% CI: 13.2, 24.4) events/100 person-years for <50 cells/mm, 6.2 (95% CI: 4.4, 7.9) for 50-100 cells/mm, and 2.7 (95% CI: 1.9, 4.0) for 100-200 cells/mm, compared with the referent stratum of 200-350 cells/mm. Without adjustment for absolute CD4, the IRR was 14.4 (95% CI: 9.3,22.6) for CD4% <7%, 3.7 (95% CI: 2.4,5.9) for 7-14%, 1.9 (95% CI: 1.1, 3.1) for 15-21%, compared with the referent stratum of >21%. However, in a multivariable analysis adjusting for absolute CD4, CD4%, and other clinical and demographic variables, the absolute CD4 but not the CD4% was associated strongly with developing an ADI. The results suggest that CD4% adds little further predictive information after accounting for the absolute CD4 count for the short-term risk of developing an ADI. The absolute CD4 count is the more important measure of immune status and is preferred over the CD4% for making treatment decisions in HIV-infected adults.