Gazzard BG. British HIV Association Guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008

Chelsea and Westminster Hospital, Foundation Trust, London, UK.
HIV Medicine (Impact Factor: 3.99). 11/2008; 9(8):563-608. DOI: 10.1111/j.1468-1293.2008.00636.x
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    • "We measured the expression levels of CD11b, CD13, CD15, CD16, CD33, CD63, CD66b and arginase on NDGs from treatment naïve HIV+ patients with high (≥350 cells/µL, CD4high) and low (<350 cells/µL, CD4low) CD4+ T cell counts. The division of patients based on a CD4+ T cell count <350 cells/µL was chosen because 1) once the CD4+ T cell count falls below 350 cells/µL differences in clinical outcome increasingly appear [19] and 2) the initiation of antiretroviral therapy is recommended once CD4+ T cell count falls to <350 cells/µL [20]. Our results show that the MFIs of CD13 and arginase are statistically significantly lower (p = 0.0008 and p = 0.0048, respectively) and that of CD63 significantly higher (p = 0.0346) in the blood of CD4low HIV+ patients (Figure 1, Table 2) as compared to CD4high HIV+ patients. "
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    ABSTRACT: We have recently identified a novel population of activated low-density granulocytes (LDGs) in peripheral blood mononuclear cells of HIV seropositive patients. LDGs have a similar morphology to normal density granulocytes (NDGs), but are phenotypically different. Here we measured the expression levels of different phenotypic markers of granulocytes in the blood of HIV seropositive patients at different stages of HIV infection to determine whether the phenotype of NDGs and LDGs are affected by disease severity. Our results reveal that the phenotype of NDGs, but not that of LDGs, varies according to the severity of the disease.
    Full-text · Article · Sep 2013 · PLoS ONE
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    • "This has sometimes been combined with whether an individual presented with an AIDS-defining diagnosis [19,20]. However, current UK guidelines recommend initiation of antiretroviral therapy (ART) in all patients with a CD4 cell count of less than 350 cells/mm3[21] and the European consensus is now that late presentation for care refers to persons presenting with CD4 cell count below 350 cells/mm3 or those presenting with an AIDS-defining event regardless of CD4 count [20,22]. Two recent studies have reported on late presentation using this European consensus definition. "
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    ABSTRACT: Initiating therapy with a low CD4 cell count is associated with a substantially greater risk of disease progression and death than earlier initiation. We examined factors associated with late presentation of HIV using the new European consensus definition (CD4 cell count <350 cells/mm3) and mortality. Patients newly diagnosed with HIV infection at a UK clinic were recruited from January 1996 to May 2010. Factors associated with late presentation were assessed using logistic regression. Factors associated with mortality rates were analysed using Poisson regression. Of the 1536 included in the analysis, 86% were male and 10% were aged 50 years and older. Half the cohort (49%) had a CD4 cell count below 350 cells/mm3 at presentation (“late presentation”). The frequency of late presentation was highest in those aged 50 years or older and remained unchanged over time (64.3% in 1996-1998 and 65.4% in 2008-2010). In contrast, among those aged less than 50 years, the proportion with late presentation decreased over time (57.1% in 1996-1998 and 38.5% in 2008-2010). Other factors associated with late presentation were African ethnicity and being a male heterosexual. The mortality rate was 15.47/1000 person-years (pyrs) (95%-CI: 13.00-18.41). When compared with younger adults, older individuals had a higher mortality, after adjusting for confounders (rate ratio (RR) = 2.87; 95%-CI: 1.88-4.40). Older adults were more likely to present late and had a higher mortality. Initiatives to expand HIV testing in clinical and community setting should not neglect individuals aged over 50.
    Full-text · Article · Apr 2013 · BMC Public Health
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    • "Various factors underlie this failure to achieve viral suppression, but resistance to current medications has been increasingly recognized as an important factor. Rational choice of the NRTI component of second-line therapy should be based on patterns of resistance developed during first-line therapy [7]. "
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    ABSTRACT: In this study we report the prevalence of antiretroviral drug resistant HIV-1 genotypes of virus isolated from Djiboutian patients who failed first-line antiretroviral therapy (ART) and from ART naïve patients.A total of 35 blood samples from 16 patients who showed first-line ART failure (>1000 viral genome copies/ml) and 19 ART-naïve patients were collected in Djibouti from October 2009 to December 2009. Both the protease (PR) and reverse transcriptase (RT) genes were amplified and sequenced using National Agency for AIDS Research (ANRS) protocols. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping.Among the 16 patients with first-line ART failure, nine (56.2%) showed reverse transcriptase inhibitor-resistant HIV-1 strains: two (12.5%) were resistant to nucleoside (NRTI), one (6.25%) to non-nucleoside (NNRTI) reverse transcriptase inhibitors, and six (37.5%) to both. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38%) for NRTI and K103N (25%) for NNRTI. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naïve individuals. No protease inhibitor resistant strains were detected. In our study, we found no detectable resistance in ∼ 44% of all patients who experienced therapeutic failure which was explained by low compliance, co-infection with tuberculosis and malnutrition. Genotyping revealed that 65.7% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C.The results of this first study about drug resistance mutations in first-line ART failures show the importance of performing drug resistance mutation test which guides the choice of a second-line regimen. This will improve the management of HIV-infected Djiboutian patients.The virtual slide(s) for this article can be found here:
    Full-text · Article · Oct 2012 · Diagnostic Pathology
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