Care interruptions and mortality among adults in Europe and North America: a collaborative analysis of cohort studies.

OBJECTIVE: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART. DESIGN: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004-2019. METHODS: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/pre-interruption or post-interruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care. RESULTS: Of 89197 PWH, 83.4% were male and median age at ART start was 39 years (interquartile range [IQR]: 31-48). 8654 PWH (9.7%) had ≥1 care interruption; 10913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536,334 person-years, a crude mortality rate of 11.4 (95%CI: 11.1-11.7) per 1000 person-years. The adjusted mortality hazard ratio (HR) for the post-interruption group was 1.72 (95%CI: 1.57-1.88) compared with the no/pre-interruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95%CI: 1.40-1.60) and ≥545-day (HR 1.67, 95%CI: 1.48-1.88) interruptions. CONCLUSIONS: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care.

Investigating the Associations between Drought, Poverty, High-Risk Sexual Behaviours, and HIV Incidence in Sub-Saharan Africa: A Cross-Sectional Study.

Climate change is increasing the likelihood of drought in sub-Saharan Africa, where HIV prevalence is high. Drought could increase HIV transmission through various mediating mechanisms; we investigated these associations. We used data on people aged 15-59 from Population-Based HIV Impact Assessment surveys from 2016 in Eswatini, Lesotho, Tanzania, Uganda, and Zambia. Survey data were geospatially linked to precipitation data for 2014-2016, with local droughts defined as cumulative rainfall between 2014 and 2016 being in < 15th percentile of all 2-year periods over 1981-2016. Using multivariable logistic regression, stratified by sex and rural/urban residence, we examined associations between (a) drought and poverty, (b) wealth quintiles and sexual behaviours (transactional, high-risk, and intergenerational sex), (c) sexual behaviours and recently acquiring HIV, and (d) drought and recent HIV. Among 102,081 people, 31.5% resided in areas affected by drought during 2014-2016. Experiencing drought was positively associated with poverty for women and men in rural, but not urban, areas. For each group, increasing wealth was negatively associated with transactional sex. For rural women, intergenerational sex was positively associated with wealth. Women reporting each sexual behaviour had higher odds of recent HIV, with strong associations seen for high-risk sex, and, for urban women, intergenerational sex, with weaker associations among men. Women in rural areas who had been exposed to drought had higher odds of having recently acquired HIV (2.10 [95%CI: 1.17-3.77]), but not women in urban areas, or men. Droughts could potentially increase HIV transmission through increasing poverty and then sexual risk behaviours, particularly among women in rural areas.

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.

BACKGROUND: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. METHODS: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. FINDINGS: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99). INTERPRETATION: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Estimation of Improvements in Mortality in Spectrum Among Adults With HIV Receiving Antiretroviral Therapy in High-Income Countries.

INTRODUCTION: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates. METHODS: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts. RESULTS: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates. DISCUSSION: Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.

Associations Between Sexual Behavior Stigma and HIV Risk Behaviors, Testing, Treatment, and Infection Among Men Who have Sex with Men in Ukraine.

Stigma toward same-sex behaviors may be a structural driver of HIV epidemics among men who have sex with men (MSM) in Eastern Europe and has been linked to adverse HIV-outcomes elsewhere. We explored associations between sexual behavior stigma with HIV risk behaviors, testing, treatment, and infection. From November 2017 to February 2018, MSM across 27 Ukrainian cities were recruited to cross-sectional surveys using respondent driven sampling. Eligible participants were cisgender males aged ≥ 14 years residing in participating cities that reported ≥ 1 sexual contact with another man in the prior 6 months. Participants self-reported experience of stigma (ever) and various HIV-outcomes and were tested for HIV antibodies. Regression models were used to explore associations between three sexual behavior stigma variables with demographic and HIV-related variables. Of 5812 recruited cisgender MSM, 5544 (95.4%) were included. 1663 (30.0%) MSM reported having experienced stigma due to being MSM from family and friends, 698 (12.6%) reported anticipated healthcare stigma, and 1805 (32.6%) reported general public/social stigma due to being MSM (enacted). All forms of stigma were associated with heightened HIV risk behaviors; those experiencing stigma (vs not) had more anal sex partners in the prior month and were less likely to have used condoms during their last anal intercourse. Stigma was not associated with HIV infection, testing, or treatment variables. A sizeable proportion of Ukrainian MSM reported ever experiencing stigma due to being MSM. MSM that had experienced stigma had higher odds of HIV sexual risk behaviors. Further study using longitudinal designs is required to determine causality.

Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.

BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm3, viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66-0.98] per 10 percentile rainfall rank decrease). CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.

BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.

All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.

BACKGROUND: Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning. METHODS: Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year. FINDINGS: Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals. INTERPRETATION: Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support. FUNDING: Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.

Limited impact of contact tracing in a University setting for COVID-19 due to asymptomatic transmission and social distancing.

Contact tracing is an important tool for controlling the spread of infectious diseases, including COVID-19. Here, we investigate the spread of COVID-19 and the effectiveness of contact tracing in a university population, using a data-driven ego-centric network model constructed with social contact data collected during 2020 and similar data collected in 2010. We find that during 2020, university staff and students consistently reported fewer social contacts than in 2010, however those contacts occurred more frequently and were of longer duration. We find that contact tracing in the presence of social distancing is less impactful than without social distancing. By combining multiple data sources, we show that University-aged populations are likely to develop asymptomatic COVID-19 infections. We find that asymptomatic index cases cannot be reliably discovered through contact tracing and consequently transmission in their social network is not significantly reduced through contact tracing. In summary, social distancing restrictions had a large impact on limiting COVID-19 outbreaks in universities; to reduce transmission further contact tracing should be used in conjunction with alternative interventions.

Estimates of hepatitis B virus prevalence among general population and key risk groups in EU/EEA/UK countries: a systematic review.

BackgroundThe burden of chronic hepatitis B virus (HBV) varies across the European Union (EU) and European Economic Area (EEA).AimWe aimed to update the 2017 HBV prevalence estimates in EU/EEA countries and the United Kingdom for 2018 to 2021.MethodsWe undertook a systematic review, adding to HBV prevalence estimates from an existing (2005-2017) database. Databases were searched for original English-language research articles including HBV surface antigen prevalence estimates among the general population, pregnant women, first-time blood donors (FTB), men who have sex with men (MSM), migrants and people in prison. Country experts contributed grey literature data. Risk of bias was assessed using a quality assessment framework.FindingsThe update provided 147 new prevalence estimates across the region (updated total n = 579). Median HBV prevalence in the general population was 0.5% and the highest was 3.8% (Greece). Among FTB, the highest prevalence was 0.8% (Lithuania). Estimates among pregnant women were highest in Romania and Italy (5.1%). Among migrants, the highest estimate was 31.7% (Spain). Relative to 2017 estimates, median prevalence among pregnant women decreased by 0.5% (to 0.3%) and increased by 0.9% (to 5.8%) among migrants. Among MSM, the highest estimate was 3.4% (Croatia). Prevalence among people in prison was highest in Greece (8.3%) and the median prevalence increased by 0.6% (to 2.1%).ConclusionsThe HBV prevalence is low in the general population and confined to risk populations in most European countries with some exceptions. Screening and treatment should be targeted to people in prison and migrants.

Estimating hepatitis B virus prevalence among key population groups for European Union and European Economic Area countries and the United Kingdom: a modelling study.

BACKGROUND: Hepatitis B virus (HBV) epidemiology in Europe differs by region and population risk group, and data are often incomplete. We estimated chronic HBV prevalence as measured by surface antigen (HBsAg) among general and key population groups for each country in the European Union, European Economic Area and the United Kingdom (EU/EEA/UK), including where data are currently unavailable. METHODS: We combined data from a 2018 systematic review (updated in 2021), data gathered directly by the European Centre for Disease Control (ECDC) from EU/EEA countries and the UK and further country-level data. We included data on adults from the general population, pregnant women, first time blood donors (FTBD), men who have sex with men (MSM), prisoners, people who inject drugs (PWID), and migrants from 2001 to 2021, with three exceptions made for pre-2001 estimates. Finite Mixture Models (FMM) and Beta regression were used to predict country and population group HBsAg prevalence. A separate multiplier method was used to estimate HBsAg prevalence among the migrant populations within each country, due to biases in the data available. RESULTS: There were 595 included studies from 31 countries (N = 41,955,969 people): 66 were among the general population (mean prevalence ([Formula: see text]) 1.3% [range: 0.0-7.6%]), 52 among pregnant women ([Formula: see text]1.1% [0.1-5.3%]), 315 among FTBD ([Formula: see text]0.3% [0.0-6.2%]), 20 among MSM ([Formula: see text]1.7% [0.0-11.2%]), 34 among PWID ([Formula: see text]3.9% [0.0-16.9%]), 24 among prisoners ([Formula: see text]2.9% [0.0-10.7%]), and 84 among migrants ([Formula: see text]7.0% [0.2-37.3%]). The FMM grouped countries into 3 classes. We estimated HBsAg prevalence among the general population to be < 1% in 24/31 countries, although it was higher in 7 Eastern/Southern European countries. HBsAg prevalence among each population group was higher in most Eastern/Southern European than Western/Northern European countries, whilst prevalence among PWID and prisoners was estimated at > 1% for most countries. Portugal had the highest estimated prevalence of HBsAg among migrants (5.0%), with the other highest prevalences mostly seen in Southern Europe. CONCLUSIONS: We estimated HBV prevalence for each population group within each EU/EAA country and the UK, with general population HBV prevalence to be < 1% in most countries. Further evidence is required on the HBsAg prevalence of high-risk populations for future evidence synthesis.

Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.

Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.

Impact of hepatitis C cure on risk of mortality and morbidity in people with HIV after antiretroviral therapy initiation.

OBJECTIVE: Hepatitis C virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS nonliver (NANL) cancers between HCV-co-infected PWH who reached SVR and mono-infected PWH. DESIGN: Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at the time of ART initiation. METHODS: Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV-co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (hazard ratio) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. RESULTS: Among 62 495 PWH, 2756 acquired HCV, of whom 649 reached SVR. For 582 of these, at least one mono-infected PWH could be matched, producing a total of 5062 mono-infected PWH. The estimated hazard ratios comparing HCV-co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95% confidence interval (CI) 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. CONCLUSION: PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared with mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV-co-infected PWH who reached SVR after a DAA-based treatment compared with mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.

Modelling the impact and cost-effectiveness of non-governmental organizations on HIV and HCV transmission among people who inject drugs in Ukraine.

INTRODUCTION: People who inject drugs (PWID) in Ukraine have high prevalences of HIV and hepatitis C virus (HCV). Non-governmental organizations (NGOs) provide PWID with needles/syringes, condoms, HIV/HCV testing and linkage to opioid agonist treatment (OAT) and antiretroviral therapy (ART). We estimated their impact and cost-effectiveness among PWID. METHODS: A dynamic HIV and HCV transmission model among PWID was calibrated using data from four national PWID surveys (2011-2017). The model assumed 37-49% coverage of NGOs among community PWID, with NGO contact reducing injecting risk and increasing condom use and recruitment onto OAT and ART. We estimated the historic (1997-2021) and future (2022-2030, compared to no NGO activities from 2022) impact of NGOs in terms of the proportion of HIV/HCV infections averted and changes in HIV/HCV incidence. We estimated the future impact of scaling-up NGOs to 80% coverage with/without scale-up in OAT (5-20%) and ART (64-81%). We estimated the cost per disability-adjusted life-year (DALY) averted of current NGO provision over 2022-2041 compared to NGO activities stopping over 2022-2026, but restarting after that till 2041. We assumed average unit costs of US$80-90 per person-year of NGO contact for PWID. RESULTS: With existing coverage levels of NGOs, the model projects that NGOs have averted 20.0% (95% credibility interval: 13.3-26.1) and 9.6% (5.1-14.1) of new HIV and HCV infections among PWID over 1997-2021, respectively, and will avert 31.8% (19.6-39.9) and 13.7% (7.5-18.1) of HIV and HCV infections over 2022-2030. With NGO scale-up, HIV and HCV incidence will decrease by 54.2% (43.3-63.8) and 30.2% (20.5-36.2) over 2022-2030, or 86.7% (82.9-89.3) and 39.8% (31.4-44.8) if OAT and ART are also scaled-up. Without NGOs, HIV and HCV incidence will increase by 51.6% (23.6-76.3) and 13.4% (4.8-21.9) over 2022-2030. Current NGO provision over 2022-2026 will avert 102,736 (77,611-137,512) DALYs when tracked until 2041 (discounted 3% annually), and cost US$912 (702-1222) per DALY averted; cost-effective at a willingness-to-pay threshold of US$1548/DALY averted (0.5xGDP). CONCLUSIONS: NGO activities have a crucial preventative impact among PWID in Ukraine which should be scaled-up to help achieve HIV and HCV elimination. Disruptions could have a substantial detrimental impact.

Risk factors of HIV and variation in access to clean needles among people who inject drugs in Pakistan.

We identified key risk factors for HIV among people who inject drugs (PWID) in Pakistan and explored access to free clean needles. Multivariable logistic regression was used to investigate associations between HIV prevalence and demographic, behavioral, and socio-economic characteristics of PWID. Data came from the Government of Pakistan's Integrated Biological and Behavioral Surveillance (IBBS) Round 5 (2016-17; 14 cities). A secondary analysis investigated associations with reported access to clean needles. Unweighted HIV prevalence among 4,062 PWID (99% male) was 21.0%. Longer injecting duration (Odds ratio [OR] 1.06 [95% confidence interval: 1.02-1.10]; per year), higher injecting frequency (OR 1.67 [1.30-2.13]; per unit increase), and injecting heroin (OR 1.90 [1.11-3.25]) were positively associated with HIV prevalence. There was no association between using a used syringe at last injection and HIV. Having>10 years of education had lower odds of HIV than being illiterate (OR 0.58 [0.35-0.95]). Having a regular sexual partner (OR 0.74 [0.57-0.97]) or paying for sex with the opposite sex (OR = 0.62 [0.45-0.85]) had lower odds of HIV than not. Conversely, PWID paying a man/hijra for sex had higher odds of HIV (OR 1.20 [1.00-1.43]). Receipt of clean needles varied by city of residence (0-97% coverage), whilst PWID with knowledge of HIV service delivery programs had higher odds of receiving clean needles (OR 4.58 [3.50-5.99]). Injecting behaviors were associated with HIV prevalence among PWID, though risks related to paying for sex remain complicated. Geographical variation in access to clean needles suggests potential benefits of more widely spread public health services.

Key MessagesWhat is already known on this topicThe HIV epidemic in Pakistan is concentrated among key populations including people who inject drugs.What this study addsInjecting practices, sexual behaviors, and socio-economic factors are associated with HIV prevalence among people who inject drugs. Access to harm reduction services is varied in Pakistan.How this study might affect research, practice, or policyAccess to clean free needles, as well as service delivery programs, with a broad geographical reach remain important to curb the HIV epidemic among people who inject drugs in Pakistan.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

BACKGROUND: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. FINDINGS: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. INTERPRETATION: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.

BACKGROUND: The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards. METHODS: We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population. FINDINGS: Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per µL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per µL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7). INTERPRETATION: For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV. FUNDING: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.

Associations between the prevalence of chronic hepatitis B among people who inject drugs and country-level characteristics: An ecological analysis.

INTRODUCTION: Globally, hepatitis B virus (HBV) is a leading cause of liver disease. People who inject drugs (PWID) are at greater risk than the general population of contracting HBV. This risk could depend on societal factors in different countries. We investigated the associations between country-level chronic HBV prevalence in PWID with national indicators of development and prevalence of HIV and hepatitis C virus (HCV). METHODS: We used global systematic review data on chronic HBV prevalence (hepatitis B surface antigen-positive) among PWID and country-level sociodemographic characteristics from online databases. National random-effects meta-analysis estimates of HBV prevalence were the outcome in linear regression models testing for associations with country-level characteristics. RESULTS: The study included 131,710 PWID from 304 estimates in 55 countries: the pooled HBV prevalence among PWID in the countries analysed was 4.5% (95% CI 3.9-5.1), the highest regional pooled prevalence was in East and Southeast Asia (17.6% [13.3-22.3]), and the lowest was in Western Europe (1.7% [1.4-2.1]). In multivariable models, no indicators of development were associated with HBV prevalence, but there was evidence of positive associations between HBV prevalence in the general population and among PWID, and evidence of HIV and HCV prevalence in PWID being associated with HBV prevalence in PWID: multivariable coefficients 0.03 (95% CI 0.01-0.04); p < 0.001, and 0.01 (95% CI 0.00-0.03); p = 0.01, respectively. DISCUSSION AND CONCLUSIONS: HBV prevalence among PWID was associated with HIV and HCV prevalence among PWID and background HBV prevalence in the general population, highlighting the need for improving harm reduction in PWID and implementation of HBV vaccination, especially where HBV is endemic.

Impact of hepatitis C virus point-of-care RNA viral load testing compared with laboratory-based testing on uptake of RNA testing and treatment, and turnaround times: a systematic review and meta-analysis.

BACKGROUND: Point-of-care (POC) hepatitis C virus (HCV) RNA nucleic acid test viral load assays are being used increasingly as an alternative to centralised, laboratory-based standard-of-care (SOC) viral load assays to reduce loss to follow-up. We aimed to evaluate the impact of using POC compared with SOC approaches on uptake of HCV RNA viral load testing and treatment, and turnaround times from testing to treatment along the HCV care cascade. METHODS: We searched PubMed, Embase, and Web of Science for studies published in English between Jan 1, 2016, and April 13, 2022. We additionally searched for accepted conference abstracts (2016-20) not identified in the main search. The contacts directory of the WHO Global Hepatitis Programme was also used to solicit additional studies on use of POC RNA assays. We included studies if they evaluated use of POC HCV RNA viral load with or without a comparator laboratory-based SOC assay, and had data on uptake of viral load testing and treatment, and turnaround times between these steps in cascade. We excluded studies with a sample size of ten or fewer participants. The POC studies were categorised according to whether the POC assay was based onsite at the clinic, in a mobile unit, or in a laboratory. Studies using the POC assay or comparator SOC assays were further stratified according to four models of care: whether HCV testing and treatment initiation were performed in the same or different site, and on the same or a different visit. The comparator was centralised, laboratory-based HCV RNA SOC assays. For turnaround times, we calculated the weighted median of medians with 95% CIs. We analysed viral load testing and treatment uptake using random-effects meta-analysis. The quality of evidence was rated using the GRADE framework. This study is registered with PROSPERO, CRD42020218239. FINDINGS: We included 45 studies with 64 within-study arms: 28 studies were in people who inject drugs, were homeless, or both; four were in people incarcerated in prison; nine were in the general or mixed (ie, includes high-risk groups) populations; and four were in people living with HIV. All were observational studies. The pooled median turnaround times between HCV antibody test and treatment initiation was shorter with onsite POC assays (19 days [95% CI 14-53], ten arms) than with either laboratory-based POC assays (64 days [64-64], one arm) or laboratory-based SOC assays (67 days [50-67], two arms). Treatment uptake was higher with onsite POC assays (77% [95% CI 72-83], 34 arms) or mobile POC assays (81% [60-97], five arms) than with SOC assays (53% [31-75], 12 arms); onsite and mobile POC assay vs SOC assay p=0·029). For POC and SOC arms, higher RNA viral load testing uptake was seen with the same-site models for testing and treatment than with different-site models (all within-category p≤0·0001). For onsite and mobile POC arms, there was higher treatment uptake for same-site than different-site models (within-category p<0·0001). Four studies had direct within-study POC versus SOC comparisons for RNA viral load testing uptake (pooled relative risk 1·11 [95% CI 0·89-1·38]), and there were ten studies on treatment uptake (1·32 [1·06-1·64]). Overall, the quality of evidence was rated as low. INTERPRETATION: Compared with use of laboratory-based SOC HCV viral load testing, the use of POC assays was associated with reduced time from antibody test to treatment initiation and increased treatment uptake. The effect of POC viral load testing is greatest when positioned within a simplified care model in which testing and treatment are provided at the same site, and, where possible, on the same day. POC HCV RNA viral load testing is now recommended in WHO guidelines as an alternative strategy to laboratory-based viral load testing. FUNDING: Unitaid.