Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.
ObjectivesTo evaluate the feasibility of providing regular, live, text-based teaching to medical students and junior doctors in Somaliland using a dedicated case-based medical education website ().DesignReview of MedicineAfrica database for details of teaching sessions held in Somaliland from December 2008-October 2010 and evaluation of user experiences through focus groups.SettingKing's College Hospital, London, UK and Ahmoud University, Borama, Somaliland.ParticipantsFinal year medical students, newly graduated interns and second year interns at Ahmoud University, Borama, Somaliland.Main outcome measuresQualitative and quantitative user rating of online case-based tutorials in the context of pre-existing educational opportunities available to them.ResultsRegular online teaching sessions are received enthusiastically by students and junior doctors and are reported to improve their clinical practice.ConclusionsDespite technological limitations in Somaliland, a live text-based teaching service can be delivered effectively and streamlined with local curricula. This represents an alternative to traditional static teaching methodologies currently used in international medical education.
Objective
Since community viral load (CVL) measurements are associated with incidence of new HIV-1 infections in a population, we hypothesized that similarly measured community drug resistance (CDR) could predict prevalence of transmitted drug resistance (TDR).
Methods
Between 2001 and 2011, the prevalence of HIV-1 drug resistance for patients with established infection receiving HIV care (i.e. CDR) and TDR in recently infected patients was determined in San Diego. At each position in HIV-1 reverse transcriptase (RT) and protease (pro), drug resistance was evaluated both as the overall prevalence of resistance associated mutations and by weighting each resistance position to concurrent viral load of the patient and its proportion to the total viral load of the clinic (CVL). The weighting was the proportion of the CVL associated with patients identified with resistance at each residue. Spearman ranked correlation coefficients were used to determine associations between CDR and TDR.
Results
We analyzed 1,088 resistance tests from 971 clinic patients and baseline resistance tests for 542 recently infected patients. CDR at positions 30, 46, and 88 in pro was associated with TDR between 2001 and 2011. When CDR was weighted by viral load of patients, CDR was associated with TDR at position 103 in RT. Each of these associations was corroborated at least once using shorter measurement intervals.
Conclusions
Despite evaluation of a limited percentage of chronically infected patients in San Diego, CDR correlated with TDR at key resistance positions and therefore may be a useful tool to predict the prevalence of TDR.
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