The HepHIV 2023 Madrid conference: A call to action for political leadership in reaching the sustainable development goals on earlier testing and linkage to care for HIV, viral hepatitis, and sexually transmitted infections.

INTRODUCTION AND OBJECTIVES: The HepHIV 2023 Conference, held in Madrid in November 2023, highlighted how Europe is not on track to meet the United Nations (UN) sustainable development goals and Joint UN Programme on HIV/AIDS (UNAIDS) targets. This article presents the outcomes of the conference, which focus on ways to improve testing and linkage to care for HIV, viral hepatitis, and other sexually transmitted infections. HIV-related stigma and discrimination, a major barrier to progress, was a key concept of the conference and on the agenda of the Spanish Presidency of the European Union. METHODS: The HepHIV 2023 organizing committee, alongside the Spanish Ministry of Health, oversaw the conference organization and prepared the scientific programme based on abstract rankings. Key outcomes are derived from conference presentations and discussions. RESULTS: Conference presentations covered the obstacles that HIV-related stigma and discrimination continue to pose to access to services, models for data collection to better monitor progress in the future, and examples of legislative action that can be taken at national levels. Diversification of testing approaches was also highlighted, to reach key populations, (e.g. migrant populations), to increase testing offered in healthcare settings (e.g. emergency departments), and to account for different stages of epidemics across the region. CONCLUSION: With a strong call for intensified action to address the impact of HIV-related stigma and discrimination on testing uptake, the conference concluded that strengthened collaboration is required between governments and implementers around testing and linkage to care. There is also an ongoing need to ensure sustainable political commitment and appropriate resource allocation to address gaps and inequalities in access for key populations and to focus on the implementation of integrated responses to HIV, viral hepatitis, and sexually transmitted infections.

Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19.

Remdesivir and molnupiravir were the only 2 repurposed antivirals that were approved for emergency use during the COVID-19 pandemic. Both drugs received their emergency use authorization on the basis of a single industry-funded phase 3 trial, which was launched after evidence of in vitro activity against SARS-CoV-2. In contrast, for tenofovir disoproxil fumarate (TDF), little in vitro evidence was generated, no randomized trials for early treatment were done, and the drug was not considered for authorization. Yet, by the summer of 2020, observational evidence suggested a substantially lower risk for severe COVID-19 in TDF users compared with nonusers. The decision-making process for the launching of randomized trials for these 3 drugs is reviewed. Observational data in favor of TDF was systematically dismissed, even though no viable alternative explanations were proposed for the lower risk for severe COVID-19 among TDF users. Lessons learned from the TDF example during the first 2 years of the COVID-19 pandemic are described, and the use of observational clinical data to guide decisions about the launch of randomized trials during the next public health emergency is proposed. The goal is that gatekeepers of randomized trials make better use of the available observational evidence for the repurposing of drugs without commercial value.

The impact of coronavirus disease 2019 on people with HIV.

PURPOSE OF REVIEW: The COVID-19 pandemic materialized in 2020, the year the international community had expected to meet the interim targets to end AIDS by 2030. Forty years into the HIV pandemic, the COVID-19 pandemic challenges the achievements made in HIV and may even reverse some of them. RECENT FINDINGS: This article provides an overview of the impact of COVID-19 on people with, and at risk of, HIV infection. It addresses where the global response to HIV was expected to be by 2020, analyzes the impact of COVID-19 on HIV-related outcomes and reviews the impact of HIV on COVID-19 related outcomes. SUMMARY: The COVID-19 pandemic has had a profound impact on the response to HIV infection through disruption of prevention, testing, and access to antiretroviral treatment, as well as on the management of long-term HIV and mental health. This negative impact has been unequal throughout the world and across populations and deepens inequities in health. HIV does not increase Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility once confounders are taken into account and inconsistencies are reported regarding its direct role on clinical severity. In post-COVID-19 scenarios, new models for HIV testing and care are likely to be consolidated. Monitoring responses needs high-quality epidemiological data and collaborative research.

Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19.

BACKGROUND: Recruitment into randomized trials of hydroxychloroquine (HCQ) for prevention of COVID-19 has been adversely affected by a widespread conviction that HCQ is not effective for prevention. In the absence of an updated systematic review, we conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19. METHODS: A search of PubMed, medRxiv, and clinicaltrials.gov combined with expert consultation found 11 completed randomized trials: 7 pre-exposure prophylaxis trials and 4 post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates. RESULTS: The pooled risk ratio estimate of the pre-exposure prophylaxis trials was 0.72 (95% CI: 0.58-0.90) when using either a fixed effect or a standard random effects approach, and 0.72 (95% CI: 0.55-0.95) when using a conservative modification of the Hartung-Knapp random effects approach. The corresponding estimates for the post-exposure prophylaxis trials were 0.91 (95% CI: 0.72-1.16) and 0.91 (95% CI: 0.62-1.35). All trials found a similar rate of serious adverse effects in the HCQ and no HCQ groups. DISCUSSION: A benefit of HCQ as prophylaxis for COVID-19 cannot be ruled out based on the available evidence from randomized trials. However, the "not statistically significant" findings from early prophylaxis trials were widely interpreted as definite evidence of lack of effectiveness of HCQ. This interpretation disrupted the timely completion of the remaining trials and thus the generation of precise estimates for pandemic management before the development of vaccines.

Prevalence and undiagnosed fraction of hepatitis C infection in 2018 in Spain: results from a national population-based survey.

BACKGROUND: A national strategy against hepatitis C virus (HCV) was implemented in Spain in 2015 with the aim of reducing associated morbidity and mortality. In order to improve our understanding of the epidemiology of HCV, we analysed the prevalence of HCV antibodies and active infection overall and by age and sex in the general population aged 20-80 years. We also aimed to report the undiagnosed fraction. METHODS: A national population-based seroprevalence survey was conducted in 2017-2018. A representative sample from the general population was selected using two-stage sampling. The prevalence of total HCV antibodies and of HCV RNA was calculated using inverse probability weighting based on bootstrapping. RESULTS: Overall, we approached 17 496 persons; 9103 agreed to participate and met the eligibility criteria and 7675 were aged 20-80. We obtained a prevalence of HCV antibodies of 0.85% [95% confidence interval (CI): 0.64-1.08%] and of active infection of 0.22% (95% CI: 0.12-0.32%). The prevalence of active HCV infection was highest in men aged 50-59 (0.86%; 95% CI: 0.28-1.57%) and in men aged 60-69 years (0.72%; 95% CI: 0.27-1.28%). Prevalence was below 0.20% in the remaining age groups. The undiagnosed fraction for active HCV infection was 29.4%. CONCLUSION: This study shows that prevalence of HCV in the general population in Spain is low and reflects the impact of scaling up treatment with direct acting antivirals, together with other prevention strategies, from 2015 onwards. The data reported can guide subsequent public health actions.

Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy : A Cohort Study.

BACKGROUND: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. OBJECTIVE: To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART. DESIGN: Cohort study. SETTING: HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020. PARTICIPANTS: 77 590 HIV-positive persons receiving ART. MEASUREMENTS: Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models. RESULTS: Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died. LIMITATION: Residual confounding by comorbid conditions cannot be completely excluded. CONCLUSION: HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV. PRIMARY FUNDING SOURCE: Instituto de Salud Carlos III and National Institutes of Health.

Cause-specific mortality after diagnosis of cancer among HIV-positive patients: A collaborative analysis of cohort studies.

People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause-specific mortality rates (MR) after diagnosis of specific cancers and compared 5-year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006-2015: ADMs 102 (95% CI 92-113) per 1,000 years versus 88 (78-100), viral NADMs 134 (106-169) versus 111 (93-133) and nonviral NADMs 264 (232-300) versus 226 (206-248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19-39%]), lung (18% [13-23%]) and cervical (75% [63-84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67-81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS.

Content analysis of Spanish judgements addressing the sexual transmission of HIV: 1996-2016.

This study performed a content analysis of the language of the Spanish judgements addressing the sexual transmission of HIV in order to determine its possible interrelationship with HIV-related stigma. All judgements and writs dictated by Spanish penal and civil jurisdictions between 1981 and December 2016 were obtained through a systematic search of the Spanish legal databases. The inclusion criterion was that the possible transmission of HIV was judged as an individual infraction, regardless of whether other infractions were involved. Twenty judgements were selected and analysed through direct content analysis assisted by the software MAXQDA 12. The majority of the cases (85%) were brought before the penal jurisdiction. Most of the judgements applied the crimes of bodily harm or grievous bodily harm (75%). Aspects closely related to the determinants of HIV-related stigma, such as the perception of HIV as a severe and easily transmitted infection, and attributions of responsibility and blame to people with HIV, were found in the judgements' reasoning. They were associated with outdated scientific and technical knowledge. Furthermore, some arguments found are repeated literally and successively in several judgments from different years, ignoring medical advances. Most plaintiffs were unaware of their sexual partner's HIV status. The scarce results found regarding the concealment of HIV status suggested that fear of stigma could be the reason thereof. The results suggested that training legal professionals in the epidemiological, clinical, and social aspects of HIV could influence stigma reduction, leading to a more objective consideration of the characteristics of this infection.

Assessing quality of life in people with HIV in Spain: psychometric testing of the Spanish version of WHOQOL-HIV-BREF.

BACKGROUND: The assessment of health-related quality of life (HRQoL) in people living with HIV (PLHIV) has become crucial to evidence-based practice. The goals of this study are to analyze the psychometric properties and evidence of the validity of the Spanish version of WHOQOL-HIV-BREF in a sample of PLHIV in Spain and to examine the more impaired HRQoL facets and dimensions and identify the PLHIV who show the most vulnerable profile. METHODS: A total of 1462 PLHIV participated in an observational cross-sectional ex-post-facto study. Data were collected at 33 Spanish sites through an online survey. In addition to measuring HRQoL, the study used other tools to measure treatment adherence (CEAT-VIH 2.0 version), psychological well-being (GHQ-12) and HIV-related stigma (HSSS). Cronbach's alpha, first- and second-order confirmatory factor analysis (CFA), the Pearson coefficient and one-way ANOVA were used to evaluate reliability, construct validity and concurrent and known-group validity, respectively. Differences according to the socio-demographic and epidemiological profiles of participants were analyzed. RESULTS: First- and second-order CFAs confirmed a six-domain first-order structure of the Spanish version of WHOQOL-HIV-BREF and one second-order factor related to overall HRQoL with an acceptable fit to the data, although some minor changes would improve it. The six-domain structure showed an acceptable internal consistency (Cronbach's alpha ranged from .61 to .81). Significant moderate to large correlations between domains and overall HRQoL, adherence, psychological well-being and negative self-image were found. Significant differences were found according to participants' self-reported CD4+ cell count in several HRQoL facets and domains. Being female, heterosexual, having low socio-economic and educational statuses, having acquired HIV through an unsafe injection and living more years with HIV were related to poorer HRQoL. PLHIV older than 50 presented lower scores in 19 HRQoL facets. CONCLUSIONS: This study demonstrates that the Spanish version of the WHOQOL-HIV-BREF is a valid instrument. It also presents the most recent data about HRQoL in PLHIV in Spain with the largest sample to date.

Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.

Background: Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results: Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions: These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.

Molecular Tracing of the Geographical Origin of Human Immunodeficiency Virus Type 1 Infection and Patterns of Epidemic Spread Among Migrants Who Inject Drugs in Athens.

BACKGROUND: High numbers of human immunodeficiency virus type 1 (HIV-1) infections among people who inject drugs (PWID) have been diagnosed in Athens, Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection for migrants who inject drugs and to investigate whether transmissions occur more frequently among migrants than among Greek nationals. METHODS: Multiple cross-sectional studies were pooled to assemble all persons diagnosed with HIV-1 in Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used maximum likelihood estimation. The hypothesis of ethnic compartmentalization was tested by reconstructing ancestral states of characters at the tips using the criterion of parsimony over a set of bootstrap trees. RESULTS: Of 2274 persons, 38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID-specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non-Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the origin of their infection was assumed to be in Greece (postmigration). For PWID infected within LTNs, transmissions for subtype A and CRF14_BG occurred more frequently among migrants than would be expected by chance (phyloethnic study). CONCLUSIONS: Our analysis showed that the majority of infections among migrants occurred postmigration. The existence of significant transmission networking among migrants highlights that this population is a priority for HIV prevention. As molecular analysis can estimate the probable country of HIV infection, it can help to inform the design of public health strategies.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges.

BACKGROUND.: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. METHODS.: Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. RESULTS.: In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%-0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. CONCLUSIONS.: European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

Lack of decline in hepatitis C virus incidence among HIV-positive men who have sex with men during 1990-2014.

BACKGROUND & AIMS: Hepatitis C virus (HCV) incidence among HIV-positive men who have sex with men (MSM) has increased since 2000, although there are regional differences. We aimed to 1) estimate trends in HCV incidence among HIV-positive MSM, 2) assess the association between incidence and geographical region, age and HIV-related measurements and, 3) assess temporal changes from HIV seroconversion to HCV infection. METHODS: Data was used from MSM with well-estimated dates of HIV seroconversion from the CASCADE Collaboration (1990-2014). Smoothly varying trends in HCV incidence over time were allowed, using restricted cubic splines. The association of calendar year, age, CD4 count (lagged), HIV RNA (lagged), geographical region and HIV infection stage (recent vs. chronic) with HCV incidence were assessed using Poisson regression. RESULTS: Of 5,941 MSM, 337 acquired HCV during follow-up. HCV incidence significantly increased from 0.7/1,000 person-years in 1990 to 18/1,000 person-years in 2014. Recent calendar years, younger age, recent HIV infection and higher HIV RNA levels were significantly associated with HCV incidence, while CD4 count was not. Trends differed by geographical region; while incidence appeared to have stabilized in Western Europe and remained stable in Southern Europe, it continued to increase in Northern Europe in recent years. Time from HIV to HCV infection significantly decreased over time (p<0.001). CONCLUSIONS: HCV has continued to spread among HIV-positive MSM in recent years, but trends differ by geographical region. Interventions to decrease the risk of HCV acquisition and increase early diagnosis are warranted. LAY SUMMARY: Hepatitis C virus infection continues to spread among HIV-positive men who have sex with men, especially among younger individuals. However, trends seem to differ by European region in recent years. Furthermore, men who have sex with men with a higher HIV RNA load were more likely to get infected with the hepatitis C virus. During recent HIV infection, MSM appear to be at higher risk of acquiring hepatitis C.

The distribution of hepatitis B virus exposure and infection in a population-based sample of U.S. Hispanic adults.

UNLABELLED: Little is known regarding the prevalence and distribution of hepatitis B virus (HBV) infection in U.S. Hispanics/Latinos. We sought to determine the prevalence of HBV exposure (serum HBV core antibody; anti-HBc), active HBV infection (serum HBV surface antigen; HBsAg), and vaccine-induced HBV immunity (antibody against HBV surface antigen; anti-HBs) in U.S. Hispanics/Latinos and consider how these data inform clinical screening recommendations. Our analysis included 11,999 women and men of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based, household survey in four urban communities (Bronx, NY; Miami, FL; Chicago, IL; and San Diego, CA) of U.S. civilian, noninstitutionalized self-identifying Hispanic/Latino adults ages 18-74. Vaccine-induced immunity was defined as detection of anti-HBs, but not anti-HBc. However, if anti-HBc were present, it was considered evidence of exposure to HBV, with detection of HBsAg used to distinguish those with active HBV infection. Mean age was 45.7 years, and 7,153 were women. Vaccine-induced immunity was greatest among those ages 18-29 years (60.2% in women, 54% in men) and decreased with increasing age, regardless of country of birth. The prevalence of active HBV infection was 0.29% (95% confidence interval: 0.19-0.43), but varied by country of birth. Those born in the Dominican Republic had the highest prevalence of HBV exposure (20.3% in women, 29.7% in men) and active HBV infection (0.95%). CONCLUSIONS: The overall age-standardized prevalence of active HBV infection in Hispanic/Latino adults (0.29%) was no different from the general U.S. population estimate (0.27%) and did not exceed 2%, regardless of country of birth. These data do not support targeting HBV screening to US Hispanic/Latino adults based upon background.

Implementing and expanding HIV testing in immigrant populations in Europe: Comparing guideline's recommendations and expert's opinions.

Immigrant populations, especially those from endemic countries, living in the European Union (EU) suffer a disproportionate burden of HIV, delayed diagnosis and poorer access to antiretroviral treatment. While International Organisations are developing recommendations aimed at increasing the uptake of HIV testing, the feasibility and real outcomes of these measures remain unexplored. The aim of this review was, firstly to identify the recommendations of the main International Organisations (IO) on HIV testing in immigrants. Secondly, to describe the challenges for implementing and expanding HIV testing and counselling interventions targeting immigrants by interviewing key informants. The importance of HIV testing in immigrants is discussed, along with the appropriateness of universal HIV testing approaches vs most at risk targeted approaches. Also addressed is, pre- and post-HIV test counselling characteristics and community initiatives suitable to reach this population and, finally the legal issues regarding access to treatment for illegal immigrants.

Executive summary: Pre-exposure prophylaxis for prevention of HIV infection in adults in Spain: July 2016.

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out.

Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study.

BACKGROUND: CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. METHODS: We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. RESULTS: A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94-1.00; P = .054) and 1.02 (95% CI, .98-1.07; P = .32) among patients followed for 5-9.9 and ≥10 years, respectively. CONCLUSIONS: After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts.