DESIGN: We estimated the cost-effectiveness ratios of three treatments for heroin dependence. We used a microcosting methodology to determine fixed, variable, and societal costs of each intervention. Cost data were collected from investigators, staff, and project records on the number and type of resources used and unit costs; societal costs for participants' time were estimated using Malaysia's minimum wage. Costs were estimated from a provider and societal perspective and reported in 2004 US dollars.

SETTING: Muar, Malaysia.

PARTICIPANTS: 126 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial in Malaysia (2003-2005) receiving counseling and buprenorphine, naltrexone, or placebo for treatment of heroin dependence.

MEASUREMENTS: Primary outcome measures included days in treatment, maximum consecutive days of heroin abstinence, days to first heroin use, and days to heroin relapse. Secondary outcome measures included treatment retention, injection drug use, illicit opiate use, AIDS Risk Inventory total score, and drug risk and sex risk subscores.

FINDINGS: Buprenorphine was more effective and more costly than naltrexone for all primary and most secondary outcomes. Incremental cost-effectiveness ratios were below $50 for primary outcomes, mostly below $350 for secondary outcomes. Naltrexone was dominated by placebo for all secondary outcomes at almost all endpoints. Incremental treatment costs were driven mainly by medication costs, especially the price of buprenorphine.

METHODS: A total of 1075 young adult respondents aged 15-24 years participated in this survey. The response rate was 82.2%.

RESULTS: The data indicated that HIV/AIDS knowledge among the respondents was moderate, with a mean knowledge score of 20.1 out of 32 points. The great majority had adequate knowledge of the major routes of HIV transmission, but fewer were aware of other modes of transmission, such as tattooing and piercing, sharing personal items, and breast-feeding from an infected mother. The great majority knew that HIV is not transmitted by mosquito bites, sharing meals, casual contact, and using public swimming pools and toilets.

METHODS: We used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 analytical framework to compute age-sex-specific HIV mortality, incidence, and prevalence estimates for 204 countries and territories (1990-2021). We aimed to analyse all available data sources, including data on the provision of HIV programmes reported to UNAIDS, published literature on mortality among people on antiretroviral therapy (ART) identified by a systematic review, household surveys, sentinel surveillance antenatal care clinic data, vital registration data, and country-level case report data. We calibrated a mechanistic simulation of HIV infection and natural history to available data to estimate HIV burden from 1990 to 2021 and generated forecasts to 2050 through projection of all simulation inputs into the future. Historical outcomes (1990-2021) were simulated at the 1000-draw level to support propagation of uncertainty and reporting of uncertainty intervals (UIs). Our approach to forecasting utilised the transmission rate as the basis for projection, along with new rate-of-change projections of ART coverage. Additionally, we introduced two new metrics to our reporting: prevalence of unsuppressed viraemia (PUV), which represents the proportion of the population without a suppressed level of HIV (viral load <1000 copies per mL), and period lifetime probability of HIV acquisition, which quantifies the hypothetical probability of acquiring HIV for a synthetic cohort, a simulated population that is aged from birth to death through the set of age-specific incidence rates of a given time period.

FINDINGS: Global new HIV infections decreased by 21·9% (95% UI 13·1-28·8) between 2010 and 2021, from 2·11 million (2·02-2·25) in 2010 to 1·65 million (1·48-1·82) in 2021. HIV-related deaths decreased by 39·7% (33·7-44·5), from 1·19 million (1·07-1·37) in 2010 to 718 000 (669 000-785 000) in 2021. The largest declines in both HIV incidence and mortality were in sub-Saharan Africa and south Asia. However, super-regions including central Europe, eastern Europe, and central Asia, and north Africa and the Middle East experienced increasing HIV incidence and mortality rates. The number of people living with HIV reached 40·0 million (38·0-42·4) in 2021, an increase from 29·5 million (28·1-31·0) in 2010. The lifetime probability of HIV acquisition remains highest in the sub-Saharan Africa super-region, where it declined from its 1995 peak of 21·8% (20·1-24·2) to 8·7% (7·5-10·7) in 2021. Four of the seven GBD super-regions had a lifetime probability of less than 1% in 2021. In 2021, sub-Saharan Africa had the highest PUV of 999·9 (857·4-1154·2) per 100 000 population, but this was a 64·5% (58·8-69·4) reduction in PUV from 2003 to 2021. In the same period, PUV increased in central Europe, eastern Europe, and central Asia by 116·1% (8·0-218·2). Our forecasts predict a continued global decline in HIV incidence and mortality, with the number of people living with HIV peaking at 44·4 million (40·7-49·8) by 2039, followed by a gradual decrease. In 2025, we projected 1·43 million (1·29-1·59) new HIV infections and 615 000 (567 000-680 000) HIV-related deaths, suggesting that the interim 2025 targets for reducing these figures are unlikely to be achieved. Furthermore, our forecasted results indicate that few countries will meet the 2030 target for reducing HIV incidence and HIV-related deaths by 90% from 2010 levels.

INTERPRETATION: Our forecasts indicate that continuation of current levels of HIV control are not likely to attain ambitious incidence and mortality reduction targets by 2030, and more than 40 million people globally will continue to require lifelong ART for decades into the future. The global community will need to show sustained and substantive efforts to make the progress needed to reach and sustain the end of AIDS as a public threat.