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 ($567,000 or € 480,000). With 3.5% discounting, it was £ 185,200 ($291,000 or € 246,000). The largest proportion (68%) of these costs was attributed to antiretroviral drugs. If patented drugs are replaced by generic versions (at 20% cost of patented prices), estimated mean lifetime costs reduced to £ 179,000 ($ 281,000 or € 238,000) and £ 101,200 ($ 158,900 or € 134,600) discounted. CONCLUSIONS: If 3,000 MSM had been infected in 2013, then future lifetime costs relating to HIV care is likely to be in excess of £ 1 billion. It is imperative for investment into prevention programmes to be continued or scaled-up in settings with good access to HIV care services. Costs would be reduced considerably with use of generic antiretroviral drugs.

Use of surveillance data on HIV diagnoses with HIV-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy.

BACKGROUND: It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART). METHODS: The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method. RESULTS: For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150-199 cells/mm3, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150-199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29-100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum. CONCLUSIONS: The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count <200 cells/mm3 due to the low rate of developing HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART.

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/µl), 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/µl), 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.

Risk of triple-class virological failure in children with HIV: a retrospective cohort study.

BACKGROUND: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children. METHODS: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation. FINDINGS: Of 1007 children followed up for a median of 4·2 (IQR 2·4-6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4-14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6-3·0, p<0·0001]). INTERPRETATION: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression. FUNDING: UK Medical Research Council award G0700832.

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.

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

BACKGROUND: Understanding of the interplay between plasma HIV RNA level and CD4 cell count depletion in untreated infection remains incomplete. METHODS: We studied 1169 people with HIV seen for care at a major London clinic while naive to antiretroviral therapy. We considered pairs (n = 5940) of consecutive simultaneously measured CD4 cell count and plasma HIV RNA values from patients who had never started therapy. Baseline was the first date when both measures were known. RESULTS: HIV RNA levels increased variably and often substantially from baseline (60% experience an increase of over 50 000 copies/ml by 5 years of follow-up). The current HIV RNA level (i.e. first value of the pair) was strongly associated with the time-standardized change in CD4 cell count, with a mean 106 cells/microl per year greater rate of CD4 cell count decline per log-copy/ml higher current HIV RNA level (P < 0.0001). After adjustment for the current level, higher baseline HIV RNA was not associated with CD4 cell count decline. There was no average CD4 cell count decline with current HIV RNA level below 3.0 log-copies/ml, compared with a 159 cells/microl per year decline for those with HIV RNA at least 5.5 log-copies/ml (P < 0.0001). Further, the current CD4 cell count predicted subsequent changes in HIV RNA level (0.04 log-copies/year greater increases per 100 cells/microl lower CD4 cell count; P < 0.0001). CONCLUSION: The often substantial increases in HIV RNA level observed in untreated HIV infection appear fundamentally linked to CD4 cell count depletion. Research into mechanisms by which HIV RNA levels rise over time should yield insights into the causes of CD4 cell count depletion, as the two processes are intimately linked.

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 (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.

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.