Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for>3 months. A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA>500 HIV-1 RNA copies/mL were included in the analysis: 2741 www.selleckchem.com/products/Rapamycin.html late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced
and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19–3.51; P=0.01]; by year 2, event rates were similar in all groups. Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal starters. Differences between late presenters
and late starters suggest that factors other see more than CD4 for cell count alone may be driving adverse treatment outcomes in late-presenting individuals. Despite the dramatic improvements in prognosis for HIV-infected individuals since the introduction of highly active antiretroviral therapy (HAART), some individuals continue to experience virological and immunological failure when they start treatment. A major risk factor for a poorer outcome on HAART is a low CD4 cell count at treatment initiation; those starting HAART with a CD4 cell
count<200 cells/μL have increased risks of opportunistic infections (OIs) and death [1,2], drug-related toxicity  and long-term complications such as neurocognitive impairment  as well as impaired CD4 recovery [5–7]. Despite several changes to treatment guidelines to recommend HAART initiation in all individuals with a CD4 count<350 cells/μL, late initiation of HAART remains common, with almost two-in-three patients in the United Kingdom who start HAART doing so at a CD4 count<200 cells/μL . A global cohort analysis of 42 countries revealed that, in the majority of developed countries world-wide, the average CD4 count at start of therapy is <200 cells/μL . One of the main reasons for late initiation of HAART is late diagnosis of HIV infection. In the United Kingdom, approximately one-in-three patients are diagnosed with a CD4 count<200 cells/μL , and between 24 and 43% of HIV-positive patients are reported to be diagnosed with CD4 counts<200 cells/μL in industrialized countries world-wide .