Incidence of AIDS-Defining and Other Cancers in HIV-Positive Children in South Africa: Record Linkage Study.

BACKGROUND Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa. METHODS We linked the records of five ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age, and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria. RESULTS Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI 55-122). The most frequent cancers were Kaposi Sarcoma (34 per 100,000 person-years) and Non Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR 0.29, 95%CI 0.09-0.86), and increased with age at enrolment (>10 versus <3 years: HR 7.3, 95% CI 2.2-24.6) and immunodeficiency at enrolment (advanced/severe versus no/mild: HR 3.5, 95%CI 1.1-12.0). The HR for the effect of ART from complete case analysis was similar but ceased to be statistically significant (p=0.078). CONCLUSIONS Early HIV diagnosis and linkage to care, with start of ART before advanced immunodeficiency develops, may substantially reduce the burden of cancer in HIV-positive children in South Africa and elsewhere.

Modelling the impact of deferring HCV treatment on liver-related complications in HIV coinfected men who have sex with men

BACKGROUND AND AIMS Hepatitis C (HCV) is a leading cause of morbidity and mortality in people who live with HIV. In many countries, access to direct acting antiviral agents to treat HCV is restricted to individuals with advanced liver disease (METAVIR stage F3 or F4). Our goal was to estimate the long term impact of deferring HCV treatment for men who have sex with men (MSM) who are coinfected with HIV and often have multiple risk factors for liver disease progression. METHODS We developed an individual-based model of liver disease progression in HIV/HCV coinfected men who have sex with men. We estimated liver-related morbidity and mortality as well as the median time spent with replicating HCV infection when individuals were treated in liver fibrosis stages F0, F1, F2, F3 or F4 on the METAVIR scale. RESULTS The percentage of individuals who died of liver-related complications was 2% if treatment was initiated in F0 or F1. It increased to 3% if treatment was deferred until F2, 7% if it was deferred until F3 and 22% if deferred until F4. The median time individuals spent with replicating HCV increased from 5 years if treatment was initiated in F2 to almost 15 years if it was deferred until F4. CONCLUSIONS Deferring HCV therapy until advanced liver fibrosis is established could increase liver-related morbidity and mortality in HIV/HCV coinfected individuals, and substantially prolong the time individuals spend with replicating HCV infection.

Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study

BACKGROUND Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. METHODS Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. FINDINGS Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). INTERPRETATION Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. FUNDING EU Seventh Framework Programme.

Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study

Background.  Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods.  Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results.  Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), higher education (OR, 4.03; 95% CI, 2.47-7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20-2.80). Older age (OR, 0.55; 95% CI, .42-.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13-.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998-2001 to 41.2% in 2009-2012, but the employment rates did not increase. Conclusions.  Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV.

Absence of Hepatitis Delta Infection in a Large Rural HIV Cohort in Tanzania

OBJECTIVES The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in sub-Saharan Africa are ill-defined. We determined the prevalence of HDV infection in HIV/hepatitis B virus (HBV)-co-infected individuals in rural Tanzania. DESIGN AND METHODS We screened all hepatitis B virus (HBV)-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) for anti-HDV antibodies. In positive samples, we performed a second serological test and nucleic acid amplification. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and positive patients. RESULTS Among 222 HIV/HBV-coinfected patients on ART, 219 (98.6%) had a stored serum sample available and were included. Median age was 37 years, 55% were female, 46% had WHO stage III/IV HIV disease and median CD4 count was 179 cells/μL. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8%-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS We found no confirmed case of HDV infection among over 200 HIV/HBV-co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test.

Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia.

BACKGROUND Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.

Retention in care of HIV-infected pregnant and lactating women starting art under Option B+ in rural Mozambique.

OBJECTIVE In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analyzed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. METHODS We compared ART outcomes in pregnant ("B+pregnant"), lactating ("B+lactating") and non-pregnant-non-lactating women of childbearing age starting ART after clinical and/or immunological criteria ("own health") between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health center), age, WHO stage and time from HIV diagnosis to ART. RESULTS Over 333 person-years of follow-up (of 243 "B+pregnant", 65″B+lactating" and 317 "own health" women), 3.7% of women died and 48.5% were lost to follow-up. "B+pregnant" and "B+lactating" women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; p<0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; p<0.001) than "own health" women. In adjusted analyses, risk of being lost to follow-up was higher in "B+pregnant" (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; p<0.001) and "B+lactating" (asHR: 1.94; 95% CI: 1.37-2.74; p<0.001). Type 2 health center was the only additional significant risk factor for loss to follow-up. CONCLUSIONS Retaining pregnant and lactating women in option B+ ART was poor; losses to follow-up were mainly early. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counseling and retention measures, especially at the beginning of treatment. This article is protected by copyright. All rights reserved.

In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-exposed Uninfected Children in Brazil.

BACKGROUND There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV-exposed but uninfected (HEU) children. The aim of this study was to evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first 2 years of life. METHODS This cohort study was conducted among HEU infants born between 1996 and 2010 in Tertiary children's hospital in Rio de Janeiro, Brazil. Weight was measured by mechanical scale, and height was measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. RESULTS A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared with infants exposed later: adjusted differences were -0.52 (95% confidence interval [CI]: -0.99 to -0.04, P = 0.02) at birth and -0.22 (95% CI: -0.47 to 0.04, P = 0.10) during follow-up. LAZ were lower during follow-up: -0.35 (95% CI: -0.63 to -0.08, P = 0.01). There were no differences in weight-for-length scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. CONCLUSIONS In HEU children, early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

OBJECTIVE To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa.

INTRODUCTION Although hepatitis C virus (HCV) screening is recommended for all HIV-infected patients initiating antiretroviral therapy, data on epidemiologic characteristics of HCV infection in resource-limited settings are scarce. METHODS We searched PubMed and EMBASE for studies assessing the prevalence of HCV infection among HIV-infected individuals in Africa and extracted data on laboratory methods used. Prevalence estimates from individual studies were combined for each country using random-effects meta-analysis. The importance of study design, population and setting as well as type of test (anti-HCV antibody tests and polymerase chain reactions) was examined with meta-regression. RESULTS Three randomized controlled trials, 28 cohort studies and 121 cross-sectional analyses with 108,180 HIV-infected individuals from 35 countries were included. The majority of data came from outpatient populations (55%), followed by blood donors (15%) and pregnant women (14%). Based on estimates from 159 study populations, anti-HCV positivity prevalence ranged between 3.3% (95% confidence interval (CI) 1.8-4.7) in Southern Africa and 42.3% (95% CI 4.1-80.5) in North Africa. Study design, type of setting and age distribution did not influence this prevalence significantly. The prevalence of replicating HCV infection, estimated from data of 29 cohorts, was 2.0% (95% CI 1.5-2.6). Ten studies from nine countries reported the HCV genotype of 74 samples, 53% were genotype 1, 24% genotype 2, 14% genotype 4 and 9% genotypes 3, 5 or 6. CONCLUSIONS The prevalence of anti-HCV antibodies is high in HIV-infected patients in Africa, but replicating HCV infection is rare and varies widely across countries.

Immune recovery in HIV-infected patients after candida esophagitis is impaired despite long-term antiretroviral therapy.

OBJECTIVE Candida esophagitis belongs to the most common AIDS-defining diseases, however, a comprehensive immune pathogenic concept is lacking. DESIGN We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients to 3 groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4 counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4 counts >500 cells/μl, CD4 nadir >350 cells/μl and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group), and 20 healthy individuals. METHODS We investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and ELISpot. RESULTS We found that patients with Candida esophagitis had nearly abolished CD4 proliferation in response to C. albicans, significantly increased percentages of dysfunctional CD4 cells, significantly decreased cytotoxic NK-cell counts and peripheral innate lymphoid cells and significantly reduced IFN-γ and IL-17 production compared to the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery. CONCLUSIONS Our data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects.

Dually Active HIV/HBV Antiretrovirals Protect Against Incident Hepatitis B Infections: Potential for Prophylaxis.

BACKGROUND  Hepatitis-B virus (HBV) has a detrimental effect on HIV natural course, and HBV vaccination is less effective in the HIV infected. We examine the protective effect of dually active antiretroviral therapy (DAART) for HIV/HBV (Tenofovir/Lamivudine/Emtricitabine) in a large cohort encompassing heterosexuals, men-who-have-sex-with-men (MSM), and intravenous drug users (IDU), who are HIV-infected yet susceptible to HBV, with comprehensive follow-up data about risky behavior and immunological profile. METHODS  We defined an incident HBV infection as the presence of any of HBV serological markers (HBsAg/AntiHBc/HBV-DNA) following a negative baseline AntiHBc test. Patients with positive AntiHBs were excluded. Cox proportional hazard models were utilized, with an incident case of HBV infection as the outcome variable. RESULTS  We analyzed 1,716 eligible patients from the Swiss HIV Cohort Study with 177 incident HBV cases. DAART was negatively associated with incident HBV infection (hazard ratio 0.4, 95%CI 0.2-0.6). This protective association was robust to adjustment (0.3, 0.2-0.5) for condomless sex, √CD4 count, drug use, and patients' demographics. Condomless sex (1.9,1.4-2.6), belonging to MSM (2.7,1.7-4.2) or IDU (3.8,2.4-6.1) were all associated with higher HBV hazard. CONCLUSIONS  Our study suggests that DAART, independently of CD4 count and risky behavior, has a potentially strong public health impact including pre-exposure prophylaxis of HBV co-infection.

HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa.

BACKGROUND Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa. METHODS Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates.

Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland.

Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8-2.1), female gender (OR: 1.6; 95% CI: 1.4-1.7), black ethnicity (OR: 1.9; 95% CI: 1.7-2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6-2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS'. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance.

Trends in incidences and risk factors for hepatocellular carcinoma and other liver events in HIV and hepatitis C virus co-infected individuals from 2001 to 2014: a multi-cohort study.

BACKGROUND  While liver-related deaths in HIV and hepatitis C virus (HCV) co-infected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We described the epidemiology of HCC and other liver events in a multi-cohort collaboration of HIV/HCV co-infected individuals. METHODS  We studied all HCV antibody-positive adults with HIV in the EuroSIDA Study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort Study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios. RESULTS  Our study comprised 7,229 HIV/HCV co-infected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval (CI): 1.3, 2.0) and 8.6 (95% CI: 7.8, 9.5) cases per 1,000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI: 4%, 19%) and decreased 4% for other liver events (95% CI: 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. High age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events. CONCLUSIONS  In HIV/HCV co-infected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.