Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.

BACKGROUND The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. METHODS We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. RESULTS A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. CONCLUSIONS Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

Delayed HIV diagnosis and initiation of antiretroviral therapy: inequalities by educational level, COHERE in EuroCoord.

OBJECTIVES In Europe and elsewhere, health inequalities among HIV-positive individuals are of concern. We investigated late HIV diagnosis and late initiation of combination antiretroviral therapy (cART) by educational level, a proxy of socioeconomic position. DESIGN AND METHODS We used data from nine HIV cohorts within COHERE in Austria, France, Greece, Italy, Spain and Switzerland, collecting data on level of education in categories of the UNESCO/International Standard Classification of Education standard classification: non-completed basic, basic, secondary and tertiary education. We included individuals diagnosed with HIV between 1996 and 2011, aged at least 16 years, with known educational level and at least one CD4 cell count within 6 months of HIV diagnosis. We examined trends by education level in presentation with advanced HIV disease (AHD) (CD4 <200 cells/μl or AIDS within 6 months) using logistic regression, and distribution of CD4 cell count at cART initiation overall and among presenters without AHD using median regression. RESULTS Among 15 414 individuals, 52, 45,37, and 31% with uncompleted basic, basic, secondary and tertiary education, respectively, presented with AHD (P trend <0.001). Compared to patients with tertiary education, adjusted odds ratios of AHD were 1.72 (95% confidence interval 1.48-2.00) for uncompleted basic, 1.39 (1.24-1.56) for basic and 1.20 (1.08-1.34) for secondary education (P < 0.001). In unadjusted and adjusted analyses, median CD4 cell count at cART initiation was lower with poorer educational level. CONCLUSIONS Socioeconomic inequalities in delayed HIV diagnosis and initiation of cART are present in European countries with universal healthcare systems and individuals with lower educational level do not equally benefit from timely cART initiation.

A Bundle of Services Increased Ascertainment of Tuberculosis among HIV-Infected Individuals Enrolled in a HIV Cohort in Rural Sub-Saharan Africa.

OBJECTIVES To report on trends of tuberculosis ascertainment among HIV patients in a rural HIV cohort in Tanzania, and assessing the impact of a bundle of services implemented in December 2012, consisting of three components:(i)integration of HIV and tuberculosis services; (ii)GeneXpert for tuberculosis diagnosis; and (iii)electronic data collection. DESIGN Retrospective cohort study of patients enrolled in the Kilombero Ulanga Antiretroviral Cohort (KIULARCO), Tanzania.). METHODS HIV patients without prior history of tuberculosis enrolled in the KIULARCO cohort between 2005 and 2013 were included.Cox proportional hazard models were used to estimate rates and predictors of tuberculosis ascertainment. RESULTS Of 7114 HIV positive patients enrolled, 5123(72%) had no history of tuberculosis. Of these, 66% were female, median age was 38 years, median baseline CD4+ cell count was 243 cells/µl, and 43% had WHO clinical stage 3 or 4. During follow-up, 421 incident tuberculosis cases were notified with an estimated incidence of 3.6 per 100 person-years(p-y)[95% confidence interval(CI)3.26-3.97]. The incidence rate varied over time and increased significantly from 2.96 to 43.98 cases per 100 p-y after the introduction of the bundle of services in December 2012. Four independent predictors of tuberculosis ascertainment were identified:poor clinical condition at baseline (Hazard Ratio (HR) 3.89, 95% CI 2.87-5.28), WHO clinical stage 3 or 4 (HR 2.48, 95% CI 1.88-3.26), being antiretroviralnaïve (HR 2.97, 95% CI 2.25-3.94), and registration in 2013(HR 6.07, 95% CI 4.39-8.38). CONCLUSION The integration of tuberculosis and HIV services together with comprehensive electronic data collection and use of GeneXpert increased dramatically the ascertainment of tuberculosis in this rural African HIV cohort.

Gender inequalities in the response to combination antiretroviral therapy over time: the Swiss HIV Cohort Study

OBJECTIVES Gender-specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders in a setting of equal access to cART over a 14-year period. METHODS Analyses included treatment-naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men. RESULTS A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV-1 RNA copies/mL at 1 year (75.2% versus 78.1% of men; P = 0.029) and at 2 years (77.5% versus 81.1%, respectively; P = 0.008), whereas no difference between sexes was observed at 5 years (81.3% versus 80.5%, respectively; P = 0.635). The probability of virological suppression increased in both genders over time (test for trend, P < 0.001). The median increase in CD4 cell count at 1, 2 and 5 years was generally higher in women during the whole study period, but it gradually improved over time in both sexes (P < 0.001). Women also were more likely to switch or stop treatment during the first year of cART, and stops were only partly driven by pregnancy. In multivariate analysis, after adjustment for sociodemographic factors, HIV-related factors, cART and calendar period, female gender was no longer associated with lower odds of virological suppression. CONCLUSIONS Gender inequalities in the response to cART are mainly explained by the different prevalence of socioeconomic characteristics in women compared with men.

Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period.

OBJECTIVES The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. METHODS We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. RESULTS A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/μL and 15% (six of 41) a CD4 count < 200 cells/μL at their return. CONCLUSIONS A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.

Age in antiretroviral therapy programmes in South Africa: a retrospective, multicentre, observational cohort study.

BACKGROUND As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status. METHODS In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age. FINDINGS Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older. INTERPRETATION Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV. FUNDING National Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis.

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.

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.

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.

Relevant drug to drug interactions between itraconazole and non-nucleoside reverse transcriptase inhibitors in HIV-infected patients on maintenance therapy for disseminated histoplasmosis

Objective. Itraconazole is recommended life-long for preventing relapse of disseminated histoplasmosis in HIV-infected patients. I sought to determine if serum itraconazole levels are affected by the type of Highly Active Anti-Retroviral Therapy (NNRTI or PI) being taken concomitantly to treat HIV. ^ Design. Retrospective cohort. ^ Methods. De-identified data were used from an IRB-approved parent study which identified patients on HAART and maintenance itraconazole for confirmed disseminated histoplasmosis between January 2003 and December 2006. Available itraconazole blood levels were abstracted as well as medications taken by each patient at the time of the blood tests. Mean itraconazole levels were compared using the student's t-test. ^ Results. 11 patients met study criteria. Patient characteristics were: median age 36, 91% men, 18% white, 18% black, 55% Hispanic and 9% Asians, median CD4 cell count 120 cells/mm3. 14 blood levels were available for analysis—8 on PI, 4 on NNRTI and 2 on both. 8/8 itraconazole levels obtained while taking concomitant PI were therapeutic (>0.4 μg/mL) in contrast to 0/4 obtained while taking NNRTI. Two patients switched from NNRTI to PI and reached therapeutic levels. Mean levels on NNRTI (0.05 μg/mL, s.d. 0.0) and on PI (2.45 μg/mL, s.d. 0.21) for these two patients were compared via a paired t-test (t = 16.00, d.f. = 1, P = 0.04). Remaining patient levels were compared using an unpaired t-test. Mean itraconazole on concomitant PI (n = 6) was 1.37 μg/mL (s.d. 0.74), while the mean on concomitant NNRTI was 0.05 μg/mL (s.d. 0.0), t = 2.39, d.f. = 6, P = 0.05. ^ Conclusions. Co-administration of NNRTI and itraconazole results in significant decreases in itraconazole blood levels, likely by inducing the CYP3A4 enzyme system. Itraconazole drug levels should be monitored in patients on concomitant NNRTI. PI-based HAART may be preferred over NNRTI-based HAART when using itraconazole to treat HIV-infected patients with disseminated histoplasmosis. ^

Tuberculosis in HIV-infected individuals in Ho Chi Minh City, Vietnam

Early and accurate detection of TB disease in HIV-infected individuals is a critical step for a successful TB program. In Vietnam, the diagnosis of TB disease, which is based predominantly on the clinical examination, chest radiography (CXR) and acid fast bacilli (AFB) sputum smear, has shown to be of low sensitivity in immunocompromised patients. The sputum culture is not routinely performed for patients with AFB negative smears, even in HIV-infected individuals.^ In that background, we conducted this cross-sectional study to estimate the prevalence of sputum culture-confirmed pulmonary tuberculosis (PTB), smear-negative PTB, and multidrug-resistant TB (MDR-TB) in the HIV-infected population in Ho Chi Minh City (HCMC), the largest city in Vietnam where both TB and HIV are highly prevalent. We also evaluated the diagnostic performance of various algorithms based on routine available tools in Vietnam such as symptoms screening, CXR, and AFB smear. Nearly 400 subjects were consecutively recruited from HIV-infected patients seeking care at the An Hoa Clinic in District 6 of Ho Chi Minh City from August 2009 through June 2010. Participants’ demographic data, clinical status, CXR, and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and PTB. ^ The prevalence of smear-positive TB, smear-negative TB, resistant TB, and MDR-TB were 7%, 2%, 5%, 2.5%, and 0.3%, respectively. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were 3.17, 32.04, and 4.28, respectively. Clinical findings alone had poor sensitivity, but the combination of CD4+ cell count, sputum smear, and CXR proved to perform a more accurate diagnosis.^ This study results support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Vietnam. When routine sputum culture is not available, an algorithm combining CD4+ cell count, sputum smear, and CXR is recommended for diagnosing PTB. Future studies on more affordable, rapid, and accurate tests for TB infection would also be necessary to timely provide specific treatments for patients in need, reduce mortality, and minimize TB transmission to the general population.^

Anal warts and their predictors among HIV-infected women

Human papillomavirus (HPV) is a necessary cause of cervical cancer and is also strongly associated with anal cancer. While different factors such as CD4+ cell count, HIV RNA viral load, smoking status, and cytological screening results have been identified as risk factors for the infection of HPV high-risk types and associated cancers, much less is known about the association between those risk factors and the infection of HPV low-risk types and anogential warts. In this dissertation, a public dataset (release P09) obtained from the Women's Interagency HIV Study (WIHS) was used to examine the effects of those risk factors on the size of the largest anal warts in HIV-infected women in the United States. Linear mixed modeling was used to address this research question. ^ The prevalence of anal warts at baseline for WIHS participants was higher than other populations. Incidence of anal warts in HIV-infected women was significantly higher than that of HIV-uninfected women [4.15 cases per 100 person-years (95% CI: 3.83–4.77) vs. 1.30 cases per 100 person-years (95% CI: 1.00–1.58), respectively]. There appeared to be an inverse association between the size of the largest anal wart and CD4+ cell count at baseline visit, however it was not statistically significant. There was no association between size of the largest anal wart and CD4+ cell count or HIV RNA viral load over time among HIV-infected women. There was also no association between the size of the largest anal wart and current smoking over time in HIV-infected women, even though smokers had larger warts at baseline than non-smokers. Finally, even though a woman with Pap smear results of ASCUS/LGSIL was found to have an anal wart larger than a woman with normal cervical Pap smear results the relationship between the size of the largest anal wart with cervical Pap smear results over time remains unclear. ^ Although the associations between these risk factors and the size of the largest anal wart over time in HIV-infected women could not be firmly established, this dissertation poses several questions concerning anal wart development for further exploration: (1) the role of immune function (i.e., CD4+ cell count), (2) the role of smoking status and the interaction between smoking status with other risk factors (e.g., CD4+ cell count or HIV RNA viral load), (3) the molecular mechanism of smoking on anal warts over time, (4) the potential for development of a screening program using anal Pap smear in HIV-infected women, and (5) how cost-effective and efficacious would an anal Pap smear screening program be in this high-risk population. ^

Interferon β transduction of peripheral blood lymphocytes from HIV-infected donors increases Th1-type cytokine production and improves the proliferative response to recall antigens

We are developing a gene therapy method of HIV infection based on the constitutive low production of interferon (IFN) β. Peripheral blood lymphocytes (PBL) from HIV-infected patients at different clinical stages of infection were efficiently transduced with the HMB-HbHuIFNβ retroviral vector. The constitutive low production of IFN-β in cultured PBL from HIV-infected patients resulted in a decreased viral production and an enhanced survival of CD4+ cells, and this protective effect was observed only in the PBL derived from donors having a CD4+ cell count above 200 per mm3. In IFN-β-transduced PBL from healthy and from HIV-infected donors, the production of the Th1-type cytokines IFN-γ and interleukin (IL)-12 was enhanced. In IFN-β-transduced PBL from HIV-infected donors, the production of IL-4, IL-6, IL-10, and tumor necrosis factor α was maintained at normal levels, contrary to the increased levels produced by the untransduced PBL. The proliferative response to recall antigens was partially restored in IFN-β-transduced PBL from donors with an impaired antigen response. Thus, in addition to inhibiting HIV replication, IFN-β transduction of PBL from HIV-infected donors improves several parameters of immune function.

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.

Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders

Objectives The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. Methods This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. Results Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. Conclusions MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.