nan Delpech

Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count.

Objective:To assess the absolute rate of AIDS and death in antiretroviral therapy (ART)-naive patients with a high CD4 cell count. Such information would be helpful in the design of a trial investigating early initiation of ART. Design:Analysis of data from an ongoing HIV cohort study. Methods:The rate of (severe) AIDS or death and death alone was evaluated in ART-naive patients according to the current CD4 cell count, focusing on CD4 cell counts ≥ 350 cells/μl among patients in the UK CHIC Study. Results:In a total of 30 313 person-years of follow-up, there were 1557 AIDS or death events. The rate of AIDS or death in persons with most recent CD4 cell count 350–499, 500–649 and > 650 cells/μl was 2.49, 1.54 and 0.96 per 100 person-years, respectively. The rate ratio for those with CD4 cell count 500–649 cells/μl compared with those with CD4 cell count ≥ 650 cells/μl was 1.55 [95% confidence interval (CI), 1.11–2.17; P = 0.01]. In a Poisson regression model based on person years with CD4 cell count ≥ 350 cells/μl, there was a strong effect of CD4 cell count on rate of AIDS or death (rate ratio, 0.84; 95% CI, 0.76–0.93; P = 0.001), independent of viral load and age. Conclusions:The trend of decreasing rate of AIDS and death with higher CD4 cell count is present throughout the CD4 cell count ≥ 350 cells/μl range in ART-naive people.

HIV testing in community settings in resource-rich countries: a systematic review of the evidence.

Community HIV testing represents an opportunity for diagnosing HIV infection among individuals who may not have contact with health services, especially in hard‐to‐reach groups. The aim of this review was to assess the evidence for feasibility, acceptability and effectiveness of HIV testing strategies in community settings in resource‐rich countries.

Late diagnosis in the HAART era: proposed common definitions and associations with mortality

Objective:To identify a definition of presentation after clinical or immunological disease progression that will reliably identify an individual at high risk of mortality over the first 3 months after HIV diagnosis and that can be adopted as a basis for comparing over time and regions. Design:An observational cohort study. Methods:Individuals seen for the first time at a UK Collaborative HIV Cohort study clinic from 1996 to 2006 were identified. Two immunological (CD4 cell count < 200 cells/μl and CD4 cell count <50 cells/μl) and two clinical (AIDS and severe/moderate AIDS) criteria for presentation with advanced HIV disease were compared, as well as combinations of them. The predictive ability of each diagnosis for identifying individuals who died in the first 3 months after HIV diagnosis was assessed. Results:Fifteen thousand seven hundred and seventy-four patients were included, of whom 1495 (9.5%), 4231 (26.8%), 1523 (9.7%) and 379 (2.4%) had a CD4 cell count below 50 cells/μl, CD4 cell count below 200 cells/μl, AIDS or severe/moderate AIDS at diagnosis; CD4 cell counts were unavailable for 2264 (14.4%) patients. Two hundred and six (1.3%) patients died within the first 3 months. Sensitivities of the individual criteria ranged from 18.0% (severe/moderate AIDS) to 50.5% (CD4 cell count < 200 cells/μl) with specificities ranging from 73.5% (CD4 < 200 cells/μl) to 97.8% (severe/moderate AIDS). Combinations of clinical and immunological criteria increased the sensitivity but decreased the specificity. Conclusion:We propose that presentation with ‘advanced HIV disease’ is presentation with a CD4 cell count below 200 cells/μl or AIDS, whereas ‘late’ presentation is defined as presentation when the CD4 cell count is below that when treatment should be initiated (currently CD4 cell count < 350 cells/μl or AIDS).

Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study.

Objective To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom. Design Multicentre observational study. Setting All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care. Participants 14 584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009. Main outcome measure Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization. Results 1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t)ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively). Conclusions The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.

Long-Term Probability of Detecting Drug-Resistant HIV in Treatment-Naive Patients Initiating Combination Antiretroviral Therapy

BACKGROUND Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. METHODS We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. RESULTS Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, > or =1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, > or =1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and > or =1 major PI IAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a PI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P=.98). CONCLUSIONS In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.

The associations between age and the development of laboratory abnormalities and treatment discontinuation for reasons other than virological failure in the first year of highly active antiretroviral therapy

The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time.

Evaluating the extent of potential resistance to pre-exposure prophylaxis within the UK HIV-1-infectious population of men who have sex with men

Recent studies have shown that pre‐exposure prophylaxis (PrEP) can substantially reduce the chance of acquiring HIV infection. However, PrEP efficacy has been found to be compromised in macaque studies if the challenge virus is antiretroviral therapy (ART)‐resistant. Our objective was to evaluate the likelihood that a UK man who has sex with men (MSM) would be exposed to PrEP‐resistant HIV in a homosexual encounter with an HIV‐infectious partner.

Responses to highly active antiretroviral therapy and clinical events in patients with a low CD4 cell count: late presenters vs. late starters

We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors.

Position statement on the use of antiretroviral therapy to reduce HIV transmission, January 2013: The British HIV Association (BHIVA) and the Expert Advisory Group on AIDS (EAGA)

S Fidler,1 J Anderson,2 Y Azad,3 V Delpech,4 C Evans,5 M Fisher,6 B Gazzard,5 N Gill,4 L Lazarus,4 R Lowbury,7 K Orton,8 B Osoro,9 K Radcliffe,10 B Smith,11 D Churchill,6 K Rogstad12 and G Cairns13 1Imperial College London, London, UK, 2Homerton University Hospital, London, UK, 3National AIDS Trust, London, UK, 4Health Protection Agency, London, UK, 5Chelsea and Westminster Hospital, London, UK, 6Royal Sussex County Hospital, Brighton, UK, 7Medical Foundation for HIV & Sexual Health (MEDFASH), London, UK, 8Department of Health, London, UK, 9Positively UK, London, UK, 10University Hospital Birmingham Foundation NHS Trust, Birmingham, UK, 11Terrence Higgins Trust, London, UK, 12Royal Hallamshire Hospital, Sheffield, UK and 13NAM Publications/Aidsmap.com, London, UK

Non-uptake of highly active antiretroviral therapy among patients with a CD4 count < 350 cells/μL in the UK

Current British HIV Association (BHIVA) guidelines recommend that all patients with a CD4 count <350 cells/μL are offered highly active antiretroviral therapy (HAART). We identified risk factors for delayed initiation of HAART following a CD4 count <350 cells/μL.