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Objectives: Subcutaneous administration of interleukin-2 (IL-2) has been shown to increase CD4 counts in HIV-infected patients. It remains unclear whether this effect is associated with a clinical benefit. Patients and methods: We conducted a long-term follow-up in the cohort of the UK-Vanguard study in which three groups of 12 antiretroviral-naive subjects with CD4 cell counts >350 cells/mm 3 received no treatment or IL-2 at either 4.5 or 7.5 MIU twice daily in 5 day cycles, respectively. Results: Mean follow-up was 376 weeks. IL-2 therapy was associated with a higher area under the curve of CD4 cell count change from baseline at week 48 but not thereafter. HIV-RNA levels were unaffected. Highly active antiretroviral therapy (HAART) was initiated after a mean of 172, 175 and 152 weeks in the control group, low-dose and high-dose IL-2 treatment group, respectively, a statistically non-significant difference. There was a tendency to start HAART soon after discontinuation of IL-2 therapy which may have been triggered by the steep decay of CD4 counts. There were two serious adverse events in the control group, seven in the low-dose IL-2 group and eight in the high-dose IL-2 group. No pattern of disease was detected, making an association with IL-2 therapy unlikely. Conclusions: We could detect neither a benefit of IL-2 therapy after week 48 nor delayed initiation of HAART. This is currently the longest follow-up data comparing IL-2 therapy with no therapy in antiretroviral-naive HIV-infected patients and does not show a persistent benefit of the intervention.

Objectives To determine prevalence and predictors of antiretroviral drug resistance in newly diagnosed individuals with HIV-1 infection, using a systematic approach to avoid selection bias. Methods Plasma samples from all persons diagnosed HIV-1 seropositive at a large London centre between April 2004 and February 2006 underwent sequencing of HIV-1 reverse transcriptase (RT) and protease genes. Subtype was assigned by phylogenetic analysis. Resistance was scored according to the IAS-USA list (2005) modified to include T215revertants and exclude isolated E44D or V118I and minor protease mutations. Recent seroconversion was identified by HIV antibody avidity testing. Results The cohort of 239 included 169 (70.7%) males, 126 (52.7%) homosexuals, 118 (49.5%) persons of white ethnicity and 144 (60.0%) persons born outside the UK. Subtypes included B 134 (56.1%), C 46 (19.2%), A 17 (7.1%), other non-B 42 (17.6%). The prevalence of resistance mutations was 17/239 (7.1%; 95% confidence interval 4.5-11.1%), comprising 10/239 (4.2%) nucleoside/nucleotide RT inhibitor (NRTI); 4/239 (1.7%) non-nucleoside RT inhibitor (NNRTI) and 4/239 (1.7%) protease inhibitor (PI) associated mutations. Dual-class (NRTI + PI) resistance mutations were detected in 1/239 (0.4%) person. The prevalence of resistance mutations was 7/85 (8.2%) and 10/154 (6.5%) in persons with recent and established infection, respectively. In multivariate analysis, having been born in the UK and high CD4 count, but not gender, age, risk group, ethnicity or subtype, were independent predictors of resistance. Conclusions In an unselected UK cohort, subtypes other than B accounted for 43.9% of new HIV-1 diagnoses. The prevalence of resistance mutations was 7.1% and highest in those born in the UK.

This study evaluated 1433 human immunodeficiency virus (HIV)–infected patients starting highly active antiretroviral therapy (HAART), 409 (28%) of whom had prior nucleoside experience and achieved an HIV load of !400 copies/mL by 24 weeks of therapy. Three hundred seven patients experienced virus rebound during a total of 2773.3 person-years of follow-up. There was a higher rate of virus rebound among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; 95% confidence interval, 2.22–3.84; ) and a P ! .0001 decreasing rate of virus rebound with increasing duration of virus suppression (i.e., time since achieving a virus load of !400 HIV RNA copies/mL) among both the nucleoside-experienced and naive patients ( ), but the difference between the groups persisted into the third P ! .0001 year of follow-up ( ). Even patients who had experienced !2 months of nucleoside P p .0007 therapy before beginning HAART had an increased risk of virus rebound (RH, 1.95; P p ). It appears that only a small period of pre-HAART nucleoside therapy is sufficient to .009 confer a disadvantage, in terms of risk of virus rebound, that persists for several years.

The efficacy and toxicity of oral azidothymidine has been studied in 145 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The median survival time of AIDS patients on azidothymidine was 4.5 times higher when compared to a historical AIDS group who had not received the drug. This result must be interpreted with caution because of changes in treatment of HIV infection and growing awareness of AIDS which may have led to earlier diagnosis in the group treated with azidothymidine. The mortality was significantly higher in those patients who received transfusions and was particularly high in those who were transfused before azidothymidine. There was a significant difference in the occurrence of opportunistic infections in the patients who received transfusions compared with those who did not. AIDS patients treated immediately after an episode of Pneumocystis carinii pneumonia survived significantly longer than those in whom treatment was delayed for three months or more, and longer than those who were treated with azidothymidine because of another opportunistic infection or Kaposi's sarcoma. The T4 cell median counts increased in patients treated with azidothymidine reaching a peak at the end of the fourth month of treatment in the ARC group and at the end of the first month in the AIDS group with a subsequent fall in both groups. Sixty per cent of patients were p24 viral antigen positive at the start of treatment and 19 per cent of these patients had a fall of more than 50 per cent in antigen level while 32 per cent became antigen negative following treatment with azidothymidine. The mortality in the patients where the antigen disappeared or in whom there was a major fall of more than 50 per cent in antigen level was significantly less than in those where there was no change in antigen level. Twenty-nine patients were treated with azidothymidine because of skin Kaposi's sarcoma and in 17 tumour regressed or was stable. Thirty-two per cent of patients treated with azidothymidine became anaemic. Neutropenia occurred in 3 per cent of patients. Platelets increased initially after treatment but subsequently fell to thrombocytopenic levels in eight patients. Nine of 12 patients with thrombocytopenia before azidothymidine was commenced responded with an increased platelet count.

One hundred and twenty-three patients with human immunodeficiency virus infection have been referred to rheumatologists at our hospitals between October 1985 and April 1989 because of musculoskeletal symptoms. Thirty-four homosexual men presented with acute, peripheral, non-erosive arthritis (mean number of four joints affected) with the knees being involved in 23. Other features developing concurrently with arthritis included psoriasis, keratoderma blenorrhagica, plantar fasciitis, urethritis, conjunctivitis and anterior uveitis. Four of five patients investigated were HLA-B27-positive; none of 15 patients tested had raised titres of rheumatoid or antinuclear factors. Various infections were associated with the onset of arthritis and two patients with a recent history of diarrhoea had serological evidence of yersinia infection. No micro-organisms were identified within the joint except for HIV itself. At the time of onset of arthritis four of these individuals had the acquired immunodeficiency syndrome (AIDS); 11 were not known to be HIV-positive before testing which was performed following referral for arthritis. Six patients have since developed AIDS and four have died. In 15 individuals, including those who progressed to AIDS, joint symptoms have been severe, persistent and poorly responsive to non-steroidal anti-inflammatory drugs. In only five patients has the arthritis been known to resolve. Synovitis has also been seen in two women: in one of these HIV infection was thought to have been acquired through intravenous drug abuse. Other rheumatic lesions included myalgia/myositis, non-inflammatory peripheral arthritis, spinal pain, soft tissue lesions, arthralgia or myalgia of unknown cause and infective lesions including septic arthritis and bony infection due to histoplasmosis and atypical mycobacterial infection. It appears likely that HIV infection is a risk factor for the development of seronegative arthritis and other rheumatic lesions.