IntroductionLong-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes.MethodsNewly HIV infected Ugandan and Zimbabwean women (N = 303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5 years.ResultsUgandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P < 0.001), a difference not associated with any other clinical parameters. Relative replicative fitness and entry efficiency of HIV-1 variants directly correlated with virulence in the patients, subtype D > A > C (P < 0.001, ANOVA).DiscussionHIV-1 subtype C was less virulent than either A or D in humans; the latter being the most virulent. Longer periods of asymptomatic HIV-1 subtype C could explain the continued expansion and dominance of subtype C in the global epidemic.
Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified lowfrequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drugresistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.
Many hypotheses suggest that pollinators act to maintain or change floral color morph frequencies in nature, although pollinator preferences do not always match color morph frequencies in the field. Therefore, non-pollinating agents may also be responsible for color morph frequencies. To test this hypothesis, we examined whether Raphanus sativus plants with white flowers received different amounts of florivory than plants with pink flowers, and whether florivores preferred one floral color over the other. We found that white-flowered plants received significantly more floral damage than pink-flowered plants in eight populations over 4 years in northern California. Both generalists and specialists on Brassicaceae preferred white petals in choice and short-term no choice tests. In performance tests, generalists gained more weight on white versus pink petals whereas specialists gained similar amounts of weight on pink and white morphs. Because our results suggest that florivores prefer and perform better on white versus pink flowers, these insects may have the opportunity to affect the frequency of color morphs in the field.
to address the emerging public health emergency in persons who inject drugs in Middlesex-London, with further details on strategy and resources to come to the Board of Health in September.Key Points Rates of HIV, Hepatitis C, Invasive Group A Streptococcal Disease, and infective endocarditis have all been increasing in persons who inject drugs in Middlesex-London. Rates are being driven by several intersecting factors, including underlying mental health and addictions issues, and changes in prescription opioid drug practices.
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