Efficiency of the EmERGE Pathway of Care in Five European HIV Centres.

OBJECTIVE: We aimed to calculate the efficiency of the EmERGE Pathway of Care in five European HIV clinics, developed and implemented for medically stable people living with HIV. METHODS: Participants were followed up for 1 year before and after implementation of EmERGE, between April 2016 and October 2019. Micro-costing studies were performed in the outpatient services of the clinics. Unit costs for outpatient services were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices to enable between clinic comparisons in terms of outcomes and costs. Unit costs were linked to the mean use of services for medically stable people living with HIV,  before and after implementation of EmERGE. Primary outcome measures were CD4 count and viral load; secondary outcomes were patient activation (PAM13) and quality of life (PROQOL-HIV). Out-of-pocket expenditure data were collected. RESULTS: There were 2251 participants: 87-93% were male, mean age at entry was 41-47 years. Medically stable people living with HIV had outpatient visits in four sites which decreased by 9-31% and costs by 5-33%; visits and costs increased by 8% in one site, which had to revert back to face-to-face visits. Antiretroviral drugs comprised 83-91% of annual costs: the Portuguese site had the highest antiretroviral drug costs in US$ purchasing parity prices. Primary and secondary outcome measures of participants did not change during the study. CONCLUSIONS: EmERGE is acceptable and provided cost savings in different socio-economic settings. Antiretroviral drug costs remain the main cost drivers in medically stable people living with HIV. While antiretroviral drug prices in local currencies did not differ that much between countries, conversion to US$ purchasing parity prices revealed antiretroviral drugs were more expensive in the least wealthy countries. This needs to be taken into consideration when countries negotiate drug prices with pharmaceutical vendors. Greater efficiencies can be anticipated by extending the use of the EmERGE Pathway to people with complex HIV infection or other chronic diseases. Extending such use should be systematically monitored, implementation should be evaluated and funding should be provided to monitor and evaluate future changes in service provision.

FRAX assessment in people ageing with HIV.

OBJECTIVES: Current British HIV Association (BHIVA) guidelines recommend the use of FRAX for the routine assessment of bone fracture risk in people living with HIV over 50 years of age every 3 years. Bone mineral density measurement with dual-energy X-ray absorptiometry (DXA) scan is recommended for those with increased fracture risk (FRAX major > 10%). Our objectives were to estimate the prevalence of and risk factors for osteoporosis in a population of PLWH aged > 50 years and assess the utility of FRAX in predicting the presence of DXA-proven osteoporosis in this cohort. METHODS: This was a cross-sectional study of a cohort of PLWH aged > 50 years attending the Chelsea and Westminster Hospital and who had a DXA scan between January 2009 and December 2018. FRAX scores were calculated using the Sheffield algorithm. Multiple regression models and Cohen's kappa values were used to assess risk factors for osteoporosis and agreement between FRAX and DXA scan results, respectively. RESULTS: In all, 744 patients were included (92.9% male, mean age 56 ± 5 years). The prevalence rates of osteoporosis (at DXA scans) and osteopenia were 12.2% and 63.7%, respectively. FRAX major was > 10% in only two patients, while 90/91 (98.9%) patients with osteoporosis had a normal FRAX score. The presence of osteoporosis was significantly associated with low body mass index and estimated glomerular filtration rate (p < 0.05). CONCLUSION: Our results indicate that FRAX scores did not predict the presence of osteoporosis in our population of PLWH over 50 years of age and therefore FRAX scores may not be the appropriate tool to define eligibility to perform DXA scans in PLWH.

The cost of care for people living with stable HIV in Croatia and the efficiency of EmERGE.

AIM: To estimate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV (PLHIV) at the University Hospital for Infectious Diseases (UHID), Zagreb. The Pathway includes a mobile application enabling individuals to communicate with their caregivers. METHODS: This study involving 293 participants collected data on the use of HIV outpatient services one year before and after EmERGE implementation. In departments supporting HIV outpatients, a micro-costing exercise was performed to calculate unit costs. These were combined with mean use of HIV services per patient year (MPPY) to estimate average annual costs. Primary outcomes were CD4 count, viral load, and secondary outcomes were patient activation, PAM13; and quality of life, PROQOL-HIV. Information on out-of-pocket expenditures was also collected. RESULTS: Outpatient visits decreased by 17%, from 4.0 (95% CI 3.8-4.3) to 3.3 MPPY (95% CI 3.1-3.5). Tests, including CD4 count, decreased, all contributing to a 33% reduction of annual costs: 7139 HRK (95% CI 6766-7528) to 4781 HRK (95% CI 4504-5072). Annual costs including anti-retroviral drugs (ARVs) decreased by 5%: 43101 HRK (95% CI 42728-43,490) to 40 743 HRK (95% CI 40466-41,034). ARVs remain the main cost driver in stable PLHIV. Primary and secondary outcomes did not change substantially between periods. CONCLUSION: EmERGE Pathway was a cost-saving intervention associated with changes in management, and a reduction in outpatient visits, tests, and costs. ARV costs dominated costs. Future efficiencies are possible if EmERGE is introduced to other PLHIV across the UHID and if ARV prices are reduced.

Does the political will exist to bring quality-assured and affordable drugs to low- and middle-income countries?

BACKGROUND: Increased coverage with antiretroviral therapy for people living with HIV in low- and middle-income countries has increased their life expectancy associated with non-HIV comorbidities and the need for quality-assured and affordable non-communicable diseases drugs . Funders are leaving many middle-income countries that will have to pay and provide quality-assured and affordable HIV and non-HIV drugs, including for non-communicable diseases. OBJECTIVE: To estimate costs for originator and generic antiretroviral therapy as the number of people living with HIV are projected to increase between 2016 and 2026, and discuss country, regional and global factors associated with increased access to generic drugs. METHODS: Based on estimates of annual demand and prices, annual cost estimates were produced for generic and originator antiretroviral drug prices in low- and middle-income countries and projected for 2016-2026. RESULTS: Drug costs varied between US$1.5 billion and US$4.8 billion for generic drugs and US$ 8.2 billion and US$16.5 billion for originator drugs between 2016 and 2026. DISCUSSION: The global HIV response increased access to affordable generic drugs in low- and middle-income countries. Cheaper active pharmaceutical ingredients and market competition were responsible for reduced drug costs. The development and implementation of regulatory changes at country, regional and global levels, covering intellectual property rights and public health, and flexibilities in patent laws enabled prices to be reduced. These changes have not yet been applied in many low- and middle-income countries for HIV, nor for other infectious and non-communicable diseases, that lack the profile and political attention of HIV. Licensing backed up with Trade-Related Aspects of Intellectual Property Rights safeguards should become the norm to provide quality-assured and affordable drugs within competitive generic markets. CONCLUSION: Does the political will exist among policymakers and other stakeholders to develop and implement these country, regional and global frameworks for non-HIV drugs as they did for antiretroviral drugs?

Perceived need of, and interest in, HIV pre-exposure prophylaxis amongst men who have sex with men attending three sexual health clinics in London, UK.

HIV pre-exposure prophylaxis (PrEP) has proven efficacy in reducing the risk of HIV infection in men who have sex with men (MSM), but has not yet been commissioned in the UK. The aim of this study was to investigate perceived need and benefit (or experience of) PrEP among HIV-negative MSM attending sexual health clinics. HIV-negative MSM attending three sexual health centres in London, UK were opportunistically invited to complete a questionnaire. Data collected comprised demographic data and sexual and drug use behaviours as well as questions regarding perceptions of risk and need for PrEP. Logistic regression analysis was undertaken to identify variables predicting acceptability of, and intention to use, PrEP. In addition, data were gathered in respondents already taking PrEP. Eight hundred and thirty-nine questionnaires were analysed. The median age of respondents was 35 years (IQR 28-41, range 18-78), 650 (77%) were of white ethnicity and 649 (77%) had a university education. Four hundred and fifty-six (54%) reported at least one episode of condomless anal sex in the preceding three months, 437 (52%) reported recreational drug use in the preceding three months and 311 (37%) had been diagnosed with a sexually transmitted infection within the preceding six months. Four hundred and sixty-three (64%) of 726 strongly agreed with the statement 'I think I would benefit from PrEP'. Multivariate logistic regression analysis demonstrated that having receptive anal intercourse (RAI) without condoms, having an awareness of the risk of unprotected RAI and having belief in the effectiveness of PrEP were independent predictors for someone thinking they would benefit from taking PrEP. Eight percent of respondents (59/724) had already taken or were currently taking PrEP. The results suggest that individuals at risk are likely to perceive themselves as benefiting from PrEP. The majority perceived their risk of acquiring HIV and benefit from PrEP accurately. Overall they appeared to have little concern over the use of PrEP and generally positive attitudes. Further investigation is warranted to understand why those at risk do not perceive benefit from PrEP.

Expanded HIV testing in low-prevalence, high-income countries: a cost-effectiveness analysis for the United Kingdom.

OBJECTIVE: In many high-income countries with low HIV prevalence, significant numbers of persons living with HIV (PLHIV) remain undiagnosed. Identification of PLHIV via HIV testing offers timely access to lifesaving antiretroviral therapy (ART) and decreases HIV transmission. We estimated the effectiveness and cost-effectiveness of HIV testing in the United Kingdom (UK), where 25% of PLHIV are estimated to be undiagnosed. DESIGN: We developed a dynamic compartmental model to analyze strategies to expand HIV testing and treatment in the UK, with particular focus on men who have sex with men (MSM), people who inject drugs (PWID), and individuals from HIV-endemic countries. METHODS: We estimated HIV prevalence, incidence, quality-adjusted life years (QALYs), and health care costs over 10 years, and cost-effectiveness. RESULTS: Annual HIV testing of all adults could avert 5% of new infections, even with no behavior change following HIV diagnosis because of earlier ART initiation, or up to 18% if risky behavior is halved. This strategy costs £67,000-£106,000/QALY gained. Providing annual testing only to MSM, PWID, and people from HIV-endemic countries, and one-time testing for all other adults, prevents 4-15% of infections, requires one-fourth as many tests to diagnose each PLHIV, and costs £17,500/QALY gained. Augmenting this program with increased ART access could add 145,000 QALYs to the population over 10 years, at £26,800/QALY gained. CONCLUSIONS: Annual HIV testing of key populations in the UK is very cost-effective. Additional one-time testing of all other adults could identify the majority of undiagnosed PLHIV. These findings are potentially relevant to other low-prevalence, high-income countries.

Lower healthcare costs associated with the use of a single-pill ARV regimen in the UK, 2004-2008.

AIM: Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months. METHODS: Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996-2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses. Use and cost of hospital services were calculated at six and twelve months respectively. RESULTS: All regimens reduced viral load to below the limit of detection and CD4 counts increased to similar levels at six and twelve months for all treatment regimens. No statistically significant differences were observed for rate of treatment failure at six and twelve months. People on Atripla® generated lower healthcare costs for non-AIDS patients at £5,340 (£5,254 to £5,426) per patient-semester and £9,821 (£9,719 to £9,924) per patient-year that was £1,344 (95%CI £1,222 to £1,465) less per patient-semester and £1,954 (95%CI £1,801 to £2,107) less per patient-year compared with Truvada®+EFV; healthcare costs for AIDS patients were similar across all regimens. CONCLUSION: The single pill regimen is as effective as the two- and three-pill regimens of the same drugs, but if started as first-line induction therapy there would be a 20% savings on healthcare costs at six and 17% of costs at twelve months compared with Truvada®+EFV, that generated the next lowest costs.

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.

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.

Protecting HIV information in countries scaling up HIV services: a baseline study.

BACKGROUND: Individual-level data are needed to optimize clinical care and monitor and evaluate HIV services. Confidentiality and security of such data must be safeguarded to avoid stigmatization and discrimination of people living with HIV. We set out to assess the extent that countries scaling up HIV services have developed and implemented guidelines to protect the confidentiality and security of HIV information. METHODS: Questionnaires were sent to UNAIDS field staff in 98 middle- and lower-income countries, some reportedly with guidelines (G-countries) and others intending to develop them (NG-countries). Responses were scored, aggregated and weighted to produce standard scores for six categories: information governance, country policies, data collection, data storage, data transfer and data access. Responses were analyzed using regression analyses for associations with national HIV prevalence, gross national income per capita, OECD income, receiving US PEPFAR funding, and being a G- or NG-country. Differences between G- and NG-countries were investigated using non-parametric methods. RESULTS: Higher information governance scores were observed for G-countries compared with NG-countries; no differences were observed between country policies or data collection categories. However, for data storage, data transfer and data access, G-countries had lower scores compared with NG-countries. No significant associations were observed between country score and HIV prevalence, per capita gross national income, OECD economic category, and whether countries had received PEPFAR funding. CONCLUSIONS: Few countries, including G-countries, had developed comprehensive guidelines on protecting the confidentiality and security of HIV information. Countries must develop their own guidelines, using established frameworks to guide their efforts, and may require assistance in adapting, adopting and implementing them.

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.

Cost and cost-effectiveness of antiretroviral therapy for HIV infection in Singapore.

The objective of this study was to determine the cost and cost-effectiveness of antiretroviral therapy (ART) in Singapore. The use and cost of HIV services was calculated for patients managed at the national HIV referral centre in Singapore between 1996 and 2001 from a hospital perspective. Three groups of patients were compared by Centers for Disease Control and Prevention (CDC) stage of HIV infection: those who had never received ART; those who had received only dual therapy; and those who had only received highly active antiretroviral therapy (HAART). Hospital charges were used to estimate the average hospital inpatient and outpatient care costs. Life years gained (LYG) were calculated for different stages of HIV infection and the incremental costs per LYG were calculated comparing those on dual ART and HAART with those who did not receive ART. Patients on ART progressed less rapidly across all CDC stages. For CDC stage A, the incremental cost per LYG was 17,007 dollars (Singaporean dollar) (interquartile range [IQR] 7963-25,113 dollars ) and 22,511 dollars (IQR 11,299-33,724 dollars) for those on dual therapy and HAART, respectively. The incremental cost per LYG in stage B was 10,868 dollars (IQR 4506-17,239 dollars) and 21,094 dollars (IQR 7774-34,431 dollars) for patients on dual therapy and HAART, respectively, while the incremental cost per LYG for stage C patients was 9,848 dollars (IQR 5256-14,419 dollars ) and 16,513 dollars (IQR 8677-24,337 dollars) for dual therapy and HAART, respectively. Dual ART therapy and HAART were cost-effective interventions in Singapore. Cost-effectiveness is likely to improve if drug prices continue to decrease.

Cost-effectiveness of highly active antiretroviral therapy in South Africa.

BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19) for the HAART group versus 3.73 (95% CI: 3.55-3.97) for the No-ART group, and 8.71 (95% CI: 8.40-9.03) versus 4.35 (95% CI: 4.12-5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52) for the HAART versus 15.36 (95% CI: 13.97-16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49) compared with 6.60 (95% CI: 5.69-7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25%) and upper (75%) interquartile range survival percentiles, the incremental cost per LYG ranged from $1,557 to $1,772 for the group without AIDS and from cost saving to $111 for patients with AIDS. CONCLUSION: HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included.

The cost-effectiveness of highly active antiretroviral therapy, Canada 1991-2001.

AIM: To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada. DESIGN: A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection). METHODS: For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count. RESULTS: For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P < 0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P < 0.0001); incremental cost per LYG between periods was US$ 12 813. CONCLUSION: HAART appeared a cost-effective intervention in Canada.

Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors.

OBJECTIVE: To evaluate the prevalence, outcome and possible risk factors for hyperlactataemia and lactic acidosis in HIV-positive persons receiving antiretroviral therapy. METHODS: Cross-sectional and longitudinal data from a prospectively collected clinical database. Associations with antiretroviral regimen, clinical and laboratory parameters were assessed using univariate and multivariate Cox's proportional hazards model. RESULTS: Patients naive to therapy and patients on current therapy for a minimum of 4 months were assessed. Median lactate was 1.1 mol/l in 253 untreated individuals and 1.4 mmol/l in 1239 patients stable on therapy for at least 4 months. At least two on-therapy samples were available for 750 of the 1239 individuals, taken a median 92 days apart. Lactate measurement showed a low positive predictive value of 38.9% but a high negative predictive value (98%) for normal values. Lactate was elevated > or = 2.4 mmol/l in 102 individuals on at least one occasion. In the multivariate Cox's proportional hazards model, no demographic characteristics were associated with hyperlactataemia. Didanosine-containing regimens doubled the relative hazard of hyperlactataemia compared with those sparing didanosine. Abacavir-containing regimens reduced the hazard of hyperlactataemia. Choice of thymidine analogue did not influence risk. Hyperlactataemia was associated with acid-base disturbance. Use of didanosine and female sex were over-represented amongst nine patients with severe hyperlactataemia (> 5 mmol/l) or lactic acidosis. CONCLUSIONS: Screening of lactate is of limited use in asymptomatic individuals on antiretroviral therapy. Raised lactate represents part of a spectrum of lactate and acid-base disturbance that infrequently includes lactic acidosis. Didanosine appears associated with an increased risk of hyperlactataemia.