Comparison of the rate and size of HIV-1 viral load blips with Roche COBAS TaqMan HIV-1 versions 1.0 and 2.0 and implications for patient management.

BACKGROUND: The Roche COBAS TaqMan HIV-1 version 1.0 (v1.0) real-time PCR test detects more low level viral loads (VL) compared to the previous Roche Amplicor version 1.5 assay. Due to under-quantification issues, the Roche TaqMan HIV-1 version 2.0 (v2.0) was introduced in 2009. Controversy remains on differences at the low VL end, where clinical decisions regarding possible viral escape are based. OBJECTIVES: To compare the rate and size of VL blips with v1.0 and v2.0 in virologically suppressed patients and describe the impact of v2.0 on patient management. STUDY DESIGN: A cohort study of HIV-positive patients on antiretroviral therapy with a VL <50 copies/ml at the beginning and end of the study period (July 2008-February 2010). VL blips were compared during two consecutive 9-month periods, initially measured by v1.0, then v2.0. Genotypic resistance testing and treatment switches were described. RESULTS: 1037 of 2584 patients (73.1% male) with median age 43 years were included. 2465 VL samples were measured on v1.0 and 2206 on v2.0. 108 (10.4%) patients had blips on v1.0 (4.4% of samples) compared to 99 (9.5%) patients (4.5% of samples) on v2.0. Median log VL was 1.89 (78 copies/ml) for v1.0 and 2.06 (116 copies/ml) for v2.0 (p=0.002). Further characterisation of 11 samples detected no resistance and no treatment modifications were identified. CONCLUSIONS: TaqMan v1.0 and v2.0 have similar blip rates, while blips are higher with v2.0. This study supports the strategy to increase the threshold of concern for VL blips on v2.0.

The cost-effectiveness of early access to HIV services and starting cART in the UK 1996-2008.

AIM: To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3. METHODS: Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices). RESULTS: cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI(boosted) with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685-£12,937) compared with £10,478 (95%CI £10,376-£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960). CONCLUSION: PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK.

Successful treatment of acute hepatitis C virus in HIV positive patients using the European AIDS Treatment Network guidelines for treatment duration.

BACKGROUND: The incidence of acute hepatitis C virus (HCV) in HIV-positive patients is rising. Recent studies summarized by the European AIDS Treatment Network (NEAT)(1) show that pegylated interferon alpha (PEG-IFNα) and ribavirin can lead to a sustained virological response (SVR) in approximately 60-80% of patients. Controversy remains on when to start treatment and whether 24 or 48 weeks of treatment lead to better outcomes. OBJECTIVES: To assess the effectiveness of a treatment strategy for acute HCV infection in HIV-positive patients, in which patients with undetectable HCV RNA at 4 weeks (rapid virological response, RVR) receive 24 weeks, while those without receive 48 weeks of PEG-IFNα and ribavirin, as per the NEAT guidelines. STUDY DESIGN: A retrospective cohort study of HIV-positive patients diagnosed with acute HCV infection between December 2006 and May 2010. Those who received acute treatment with PEG-IFNα and ribavirin had HCV RNA levels monitored and outcomes evaluated. For patients who did not receive acute treatment, the reason for deferral and most recent available HCV RNA were recorded. RESULTS: Twenty-two patients received acute treatment with PEG-IFNα and ribavirin. Twelve patients achieved RVR and had 24 weeks treatment, 10 patients had no RVR and had 48 weeks treatment. Two patients discontinued treatment (due to adverse effects [AEs] and failure to suppress HCV RNA sufficiently at 12 weeks). All 20 patients who completed treatment had SVR. CONCLUSION: Our high SVR rate of 91% supports the new NEAT treatment duration recommendations.

Cost-effectiveness of early treatment with first-line NNRTI-based HAART regimens in the UK, 1996-2006.

AIM: Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996-2006. BACKGROUND: Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PI(boosted) regimens. METHODS: Times to first-line treatment failure and annual costs were calculated for first-line HAART regimens by CD4 count when starting HAART (2006 UK prices). Cost-effectiveness of 2NRTIs+NNRTI versus 2NRTIs+PI(boosted) regimens was calculated for four CD4 strata. RESULTS: 55% of 5,541 people living with HIV (PLHIV) started HAART with CD4 count ≤ 200 cells/mm3, many of whom were Black Africans. Annual treatment cost decreased as CD4 count increased; most marked differences were observed between starting HAART with CD4 ≤ 200 cells/mm3 compared with CD4 count >200 cells/mm3. 2NRTI+PI(boosted) and 2NRTI+NNRTI regimens were the most effective regimens across the four CD4 strata; 2NRTI + NNRTI was cost-saving or cost-effective compared with 2NRTI + PI(boosted) regimens. CONCLUSION: To ensure more effective and efficient provision of HIV services, 2NRTI+NNRTI should be started as first-line HAART regimen at CD4 counts ≤ 350 cell/mm3, unless specific contra-indications exist. This will increase the number of PLHIV receiving HAART and will initially increase population costs of providing HIV services. However, starting PLHIV earlier on cost-effective regimens will maintain them in better health and use fewer health or social services, thereby generating fewer treatment and care costs, enabling them to remain socially and economically active members of society. This does raise a number of ethical issues, which will have to be acknowledged and addressed, especially in countries with limited resources.

Rising population cost for treating people living with HIV in the UK, 1997-2013.

BACKGROUND: The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997-2006 and projected them 2007-2013. METHODS: Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997-2006 and projected 2007-2013. RESULTS: Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013. CONCLUSIONS: Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources.

Predictors of renal outcome in HIV-associated nephropathy.

BACKGROUND: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of end-stage renal disease among African American patients. This study was performed to study the epidemiology of HIVAN in a predominantly black African population and the impact of highly active antiretroviral therapy and other factors on the development of end-stage renal disease. METHODS: We retrospectively identified all patients with HIVAN, defined by biopsy or strict clinical criteria, in 8 clinics in the United Kingdom. Baseline renal function, HIV parameters, renal pathological index of chronic damage, and responses to highly active antiretroviral therapy were analyzed, and factors associated with adverse renal outcome were identified. RESULTS: From 1998 through 2004, we studied 16,834 patients, 61 of whom had HIVAN. HIVAN prevalence in black patients was 0.93%, and HIVAN incidence in those without renal disease at baseline was 0.61 per 1000 person-years. After a median of 4.2 years, 34 patients (56%) had developed end-stage renal disease. There were no significant differences in renal function and HIV parameters at baseline, time to initiation of highly active antiretroviral therapy, and rates of HIV RNA suppression between the 20 patients who developed end-stage renal disease >3 months after receiving the HIVAN diagnosis and the 23 patients who maintained stable renal function. However, the index of chronic damage score was significantly higher in those who developed end-stage renal disease (P < .001), and an index of chronic damage score >75 was associated with shorter renal survival (P < .001). CONCLUSIONS: Whereas overall patient survival suggested an important benefit of highly active antiretroviral therapy, no additional renal benefit of early initiation of highly active antiretroviral therapy or viral suppression could be demonstrated in this large cohort of patients with established HIVAN. Severity of chronic kidney damage, as quantified by biopsy, was the strongest predictor of renal outcome.

Symptomatic HIV viraemia during a drug holiday: an argument against treatment interruption?

An HIV-positive African woman developed severe constitutional symptoms associated with rebound viraemia during a planned antiretroviral treatment interruption, requiring reinitiation of highly active antiretroviral therapy.