A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013–March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56–7.50]); risk group (OR, 5.65 [95% CI, 3.27–9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64–4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07–3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10–3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31–.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions Our findings suggest high levels of transmission and bridging between risk groups

Ramaria abietina: A rare Coral Fungus

Volume: 132Start Page: 176End Page: 17

Public health for the 21st Century: New perspectives on policy, participation and practice. Second edition.

Edisi ini memuat bab baru tentang pengkajian kebutuhan kesehatan. Tim ahli memberikan analisis tentang sikap saat ini terhadap kesehatan masyarakat, mulai dari kebijakan pemerintah hingga praktik yang sebenarnya.New Yorkxx, 401 hlm.: bibli., index; 25x18c

Infection of CD127(+) (Interleukin-7 Receptor(+)) CD4(+) Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection

We recently found that human immunodeficiency virus (HIV)-specific CD4(+) T cells express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1 infection (PHI) but then rapidly disappear from the circulation. This cell loss may be due to susceptibility to infection with HIV-1 but could also be due to inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of the circulation, or dysfunction. We purified CD38(+++)CD4(+) T cells from peripheral blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that about 10% of this population was infected. However, a small subset of HIV-specific CD4(+) T cells also expressed CD127, a marker of long-term memory cells. Purified CD127(+)CD4(+) lymphocytes contained fivefold more copies of HIV-1 DNA per cell than did CD127-negative CD4(+) cells, suggesting preferential infection of long-term memory cells. We observed no apoptosis of antigen-specific CD4(+) T cells in vitro and only a small increase in CD45RO(+)CD25(+)CD127dimCD4(+) T regulatory cells during PHI. However, 40% of CCR5(+)CD38(+++) CD4(+) T cells expressed gut-homing integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT). Furthermore, 80% of HIV-specific CD4(+) T cells expressed high levels of the negative regulator CTLA-4 in response to antigen stimulation in vitro, which was probably contributing to their inability to produce interleukin-2 and proliferate. Taken together, the loss of HIV-specific CD4(+) T cells is associated with a combination of an infection of CCR5(+) CD127(+) memory CD4(+) T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4

Time to virological failure, treatment change and interruption for individuals treated within 12 months of HIV seroconversion and in chronic infection.

BACKGROUND Estimates of treatment failure, change and interruption are lacking for individuals treated in early HIV infection. METHODS Using CASCADE data, we compared the effect of treatment in early infection (within 12 months of seroconversion) with that seen in chronic infection on risk of virological failure, change and interruption. Failure was defined as two subsequent measures of HIV RNA>1,000 copies/ml following suppression (500 copies/ml 6 months following initiation. Treatment change and interruption were defined as modification or interruption lasting >1 week. In multivariable competing risks proportional subdistribution hazards models, we adjusted for combination antiretroviral therapy (cART) class, sex, risk group, age, CD4(+) T-cell count, HIV RNA and calendar period at treatment initiation. RESULTS Of 1,627 individuals initiating cART early (median 1.8 months from seroconversion), 159, 395 and 692 failed, changed and interrupted therapy, respectively. For 2,710 individuals initiating cART in chronic infection (median 35.9 months from seroconversion), the corresponding values were 266, 569 and 597. Adjusted hazard ratios (HRs; 95% CIs) for treatment failure and change were similar between the two treatment groups (0.93 [0.72, 1.20] and 1.06 [0.91, 1.24], respectively). There was an increasing trend in rates of interruption over calendar time for those treated early, and a decreasing trend for those starting treatment in chronic infection. Consequently, compared with chronic infection, treatment interruption was similar for early starters in the early cART period, but the relative hazard increased over calendar time (1.54 [1.33, 1.79] in 2000). CONCLUSIONS Individuals initiating treatment in early HIV infection are more likely to interrupt treatment than those initiating later. However, rates of failure and treatment change were similar between the two groups