Rebecca Lodwick

Projected life expectancy of people with HIV according to timing of diagnosis

Background and objectives:Effective antiretroviral therapy (ART) has contributed greatly toward survival for people with HIV, yet many remain undiagnosed until very late. Our aims were to estimate the life expectancy of an HIV-infected MSM living in a developed country with extensive access to ART and healthcare, and to assess the effect of late diagnosis on life expectancy. Methods:A stochastic computer simulation model of HIV infection and the effect of ART was used to estimate life expectancy and determine the distribution of potential lifetime outcomes of an MSM, aged 30 years, who becomes HIV positive in 2010. The effect of altering the diagnosis rate was investigated. Results:Assuming a high rate of HIV diagnosis (median CD4 cell count at diagnosis, 432 cells/&mgr;l), projected median age at death (life expectancy) was 75.0 years. This implies 7.0 years of life were lost on average due to HIV. Cumulative risks of death by 5 and 10 years after infection were 2.3 and 5.2%, respectively. The 95% uncertainty bound for life expectancy was (68.0,77.3) years. When a low diagnosis rate was assumed (diagnosis only when symptomatic, median CD4 cell count 140 cells/&mgr;l), life expectancy was 71.5 years, implying an average 10.5 years of life lost due to HIV. Conclusion:If low rates of virologic failure observed in treated patients continue, predicted life expectancy is relatively high in people with HIV who can access a wide range of antiretrovirals. The greatest risk of excess mortality is due to delays in HIV diagnosis.

Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population

Background:Due to the success of antiretroviral therapy (ART), it is relevant to ask whether death rates in optimally treated HIV are higher than the general population. The objective was to compare mortality rates in well controlled HIV-infected adults in the SMART and ESPRIT clinical trials with the general population. Methods:Non-IDUs aged 20–70 years from the continuous ART control arms of ESPRIT and SMART were included if the person had both low HIV plasma viral loads (⩽400 copies/ml SMART, ⩽500 copies/ml ESPRIT) and high CD4+ T-cell counts (≥350 cells/&mgr;l) at any time in the past 6 months. Standardized mortality ratios (SMRs) were calculated by comparing death rates with the Human Mortality Database. Results:Three thousand, two hundred and eighty individuals [665 (20%) women], median age 43 years, contributed 12 357 person-years of follow-up. Sixty-two deaths occurred during follow up. Commonest cause of death was cardiovascular disease (CVD) or sudden death (19, 31%), followed by non-AIDS malignancy (12, 19%). Only two deaths (3%) were AIDS-related. Mortality rate was increased compared with the general population with a CD4+ cell count between 350 and 499 cells/&mgr;l [SMR 1.77, 95% confidence interval (CI) 1.17–2.55]. No evidence for increased mortality was seen with CD4+ cell counts greater than 500 cells/&mgr;l (SMR 1.00, 95% CI 0.69–1.40). Conclusion:In HIV-infected individuals on ART, with a recent undetectable viral load, who maintained or had recovery of CD4+ cell counts to at least 500 cells/&mgr;l, we identified no evidence for a raised risk of death compared with the general population.

Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study.

BACKGROUND Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. METHODS We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per microL while ART naive. All pre-ART CD4 counts greater than 350 cells per microL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups--men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. FINDINGS Data were analysed for 40,830 patients contributing 80,682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1.30, 95% CI 1.06-1.58); 68 heterosexual people (2.94, 2.28-3.73); 203 injecting drug users (9.37, 8.13-10.75); and 30 in the other or unknown risk category (4.57, 3.09-6.53). Compared with CD4 counts of 350-499 cells per microL, death rate was lower in patients with counts of 500-699 cells per microL (adjusted rate ratio 0.77, 95% CI 0.61-0.95) and counts of 700 cells per microL (0.66, 0.52-0.85). INTERPRETATION In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. FUNDING European Commission, FP6. European AIDS Treatment Network (NEAT). Project number LSHP-CT-2006-037570.BACKGROUND Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. METHODS We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per microL while ART naive. All pre-ART CD4 counts greater than 350 cells per microL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups--men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. FINDINGS Data were analysed for 40,830 patients contributing 80,682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1.30, 95% CI 1.06-1.58); 68 heterosexual people (2.94, 2.28-3.73); 203 injecting drug users (9.37, 8.13-10.75); and 30 in the other or unknown risk category (4.57, 3.09-6.53). Compared with CD4 counts of 350-499 cells per microL, death rate was lower in patients with counts of 500-699 cells per microL (adjusted rate ratio 0.77, 95% CI 0.61-0.95) and counts of 700 cells per microL (0.66, 0.52-0.85). INTERPRETATION In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. FUNDING European Commission, FP6. European AIDS Treatment Network (NEAT). Project number LSHP-CT-2006-037570.Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries.

Long-term trends in adherence to antiretroviral therapy from start of HAART.

Objective:People on antiretroviral therapy are likely to be required to maintain good adherence throughout their lives. We aimed to investigate long-term trends in highly active antiretroviral therapy (HAART) adherence to identify the main predictors and to evaluate whether participants experience periods of low adherence (≤60%). Methods:Participants in the Royal Free Clinic Cohort were followed from the date of start of HAART until the end of the last recorded ART prescription or death. Follow-up was divided into 6-month periods, and for each period, a value of adherence, measured as the percentage of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs, was calculated. Results:Patients were assessed for drug coverage adherence for a median of 4.5 years [inter-quartile range (IQR) 2.4–7.2; maximum 9 years] covering a period up to 13 years from start of HAART. There was evidence of a slight increase in adherence over time [adjusted odds ratio (OR) of >95% adherence = 1.02 per year; 95% confidence interval (CI) 1.01–1.04; P = 0.0053]. Independent predictors of adherence were age, demographic group, calendar year period, drug regimen and previous virologic failures. The overall rate of at least one period of low adherence was 0.12 per person-year, but this rate decrease markedly over time to 0.01 in 2007/2008. Conclusion:Adherence, as measured by drug coverage, does not decrease on average over more than a decade from start of HAART. This is encouraging, because it shows that patients could potentially maintain viral suppression for many years.

Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

BACKGROUND Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades. METHODS We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed. RESULTS Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.

Stability of antiretroviral regimens in patients with viral suppression

Objective:To study the rate of treatment change due to toxicities in patients who achieved viral suppression within 6 months of starting antiretroviral therapy and who have never experienced virological failure. Methods:Included patients attended the Royal Free Hospital in London, started antiretroviral therapy in 2000–2005, and achieved viral suppression within 6 months. Included follow-up (censored at virological failure) was spent on a regimen of lamivudine or emtricitabine, with a second nucleoside/nucleotide reverse transcriptase inhibitor, and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Results:In 912 person-years, there were 140 treatment changes due to toxicities (rate = 15.4 per 100 person-years, confidence interval = 12.8–17.9). In the multivariable analysis, factors associated with a higher rate of treatment change due to toxicities included increased age (for every 10 years increase: incidence rate ratio = 1.28, confidence interval = 1.04–1.57), being on stavudine compared with zidovudine (incidence rate ratio = 2.04, confidence interval = 1.28–3.26), and being on lopinavir compared with efavirenz (incidence rate ratio = 1.55, confidence interval = 1.04–2.31), whereas factors associated with a lower rate were being on tenofovir compared with zidovudine (incidence rate ratio = 0.46, confidence interval = 0.29–0.73), and being on atazanavir compared with efavirenz (incidence rate ratio = 0.23, confidence interval = 0.06–0.91). Conclusions:In patients who have never experienced virological failure, the rate of treatment change due to toxicities is low, and certain regimens are associated with an even lower rate of change. If virological failure is avoided, some regimens are so far proving to be sufficiently stable to suggest that very long-term use is potentially feasible.

Use of a prescription-based measure of antiretroviral therapy adherence to predict viral rebound in HIV-infected individuals with viral suppression

The aim of the study was to assess whether a simple, routinely available measure of antiretroviral therapy (ART) adherence predicts viral rebound at the next HIV viral load (VL) measurement in virally suppressed patients.

Projected Lifetime Healthcare Costs Associated with HIV Infection.

Objective Estimates of healthcare costs associated with HIV infection would provide valuable insight for evaluating the cost-effectiveness of possible prevention interventions. We evaluate the additional lifetime healthcare cost incurred due to living with HIV. Methods We used a stochastic computer simulation model to project the distribution of lifetime outcomes and costs of men-who-have-sex-with-men (MSM) infected with HIV in 2013 aged 30, over 10,000 simulations. We assumed a resource-rich setting with no loss to follow-up, and that standards and costs of healthcare management remain as now. Results Based on a median (interquartile range) life expectancy of 71.5 (45.0–81.5) years for MSM in such a setting, the estimated mean lifetime cost of treating one person was £360,800 (

Ongoing changes in HIV RNA levels during untreated HIV infection: implications for CD4 cell count depletion

567,000 or €480,000). With 3.5% discounting, it was £185,200 (

Calendar Time Trends in the Incidence and Prevalence of Triple-Class Virologic Failure in Antiretroviral Drug-Experienced People With HIV in Europe

291,000 or €246,000). The largest proportion (68%) of these costs was attributed to antiretroviral drugs. If patented drugs are replaced by generic versions (at 20% cost of patented prices), estimated mean lifetime costs reduced to £179,000 (