Jodie L. Guest

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

BACKGROUND Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. METHODS The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated. FINDINGS 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, respectively. 2056 (4.7%) deaths were observed during the study period, with crude mortality rates decreasing from 16.3 deaths per 1000 person-years in 1996-99 to 10.0 deaths per 1000 person-years in 2003-05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36.1 (SE 0.6) years to 49.4 (0.5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32.6 [1.1] years vs 44.7 [0.3] years in 2003-05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32.4 [1.1] years for CD4 cell counts below 100 cells per muL vs 50.4 [0.4] years for counts of 200 cells per muL or more). INTERPRETATION Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries.

Hepatitis C Virus Coinfection Increases Mortality in HIV-Infected Patients in the Highly Active Antiretroviral Therapy Era: Data from the HIV Atlanta VA Cohort Study

BACKGROUND We compared survival among patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) with that among patients infected solely with HIV. METHODS Descriptive, bivariate, and survival analyses were conducted using data for all HIV-positive patients who were seen during the period of January 1997 through May 2001 in the HIV Atlanta VA Cohort Study (HAVACS) and who had been tested for HCV antibody since 1992 (n=970). RESULTS The prevalence of HCV coinfection was 31.6%, and coinfected patients were significantly more likely to be older, black, and injection drug users. In multivariate analysis, the duration of survival from the time of diagnosis of acquired immunodeficiency syndrome (AIDS) was significantly shortened for HIV-HCV-coinfected patients (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.09-3.10), as was time from HIV diagnosis to death (HR, 2.47; 95% CI, 1.26-4.82). Recovery of CD4+ cell count from the time of initiation of HAART did not differ significantly by coinfection status. CONCLUSIONS HCV coinfection is common in this HIV-infected population and negatively affects survival from the time of both HIV and AIDS diagnoses, although this is apparently not associated with a difference in CD4+ cell recovery while receiving HAART. These findings differ from those of a previous study that was conducted in this cohort in the pre-HAART era, which found no association between HIV-HCV coinfection and HIV disease progression.

Impact of Risk Factors for Specific Causes of Death in the First and Subsequent Years of Antiretroviral Therapy Among HIV-Infected Patients

Among HIV-infected patients who initiated antiretroviral therapy (ART), patterns of cause-specific death varied by ART duration and were strongly related to age, sex, and transmission risk group. Deaths from non-AIDS malignancies were much more frequent than those from cardiovascular disease.

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

BACKGROUND Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. METHODS We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. CONCLUSIONS Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Durability of first ART regimen and risk factors for modification, interruption or death in HIV-positive patients starting ART in Europe and North America 2002-2009.

Objectives:To estimate the incidence of and risk factors for modifications to first antiretroviral therapy (ART) regimen, treatment interruption and death. Methods:A total of 21 801 patients from 18 cohorts in Europe and North America starting ART on regimens including at least two nucleoside reverse transcriptase inhibitors and boosted protease inhibitor or non-nucleoside reverse transcriptase inhibitor during 2002–2009 were included. Incidence of modifications (change of drug class, substitution/addition within class, or switch to nonstandard regimen), interruption or death and associations with patient characteristics were estimated using competing-risks methods. Results:During median 28 months follow-up, 8786 (40.3%) patients modified first ART, 2346 (10.8%) interrupted and 427 (2.0%) died before changing regimen. Three-year cumulative percentages of modification, interruption and death were 47, 12 and 2%, respectively. After adjustment, rates of interruption were highest for IDUs and lowest for MSM, and higher for patients starting ART with CD4 cell count above 350 cells/&mgr;l than other patients. Compared to efavirenz, patients on lopinavir and other protease inhibitors had higher rates of modification and interruption, on atazanavir had lower rates of class change, and on nevirapine higher rates of interruption. Those on tenofovir/emtricitabine backbone had lowest rates of substitutions and switches to nonstandard regimen, and on abacavir/lamivudine lowest rates of interruption. Rates of substitution and switches to nonstandard regimen were lower in 2006–2009. Conclusion:Rates of modification and interruption were high, particularly in the first year of ART. Decreased rates of substitutions or switches to nonstandard regimen in recent years may be linked to greater use of well tolerated once-daily drugs.

Response to hepatitis A vaccine in HIV patients in the HAART era.

We evaluated the development of hepatitis A antibody after vaccination in a large cohort of patients studied in a clinical setting after the introduction of HAART. Overall, 130 of 214 vaccinated individuals developed hepatitis A antibody. In a multivariate analysis, only the CD4 cell count at the time of vaccination was associated with an absence of response. The lack of association with the nadir CD4 cell count suggests that patients will respond to vaccine after immunological reconstitution in response to HAART.

Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70,000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).

Prevalence and Predictors of Food Insecurity in Migrant Farmworkers in Georgia

We examined the prevalence of food insecurity in migrant farmworkers in Georgia. Of these workers 62.83% did not have enough food, and non-H-2A workers had an adjusted risk of food insecurity almost 3 times higher than did H-2A workers. Lack of access to cooking facilities, transportation problems, and having children were additional risk factors. Migrant farmworkers are at extreme risk for food insecurity, although being an H-2A guestworker was protective within this population. Policy interventions are needed to protect these vulnerable farmworkers.

Methicillin-Resistant Staphylococcus aureus Colonization of the Groin and Risk for Clinical Infection among HIV-infected Adults

Data on the interaction between methicillin-resistant Staphylococcus aureus (MRSA) colonization and clinical infection are limited. During 2007–2008, we enrolled HIV-infected adults in Atlanta, Georgia, USA, in a prospective cohort study. Nares and groin swab specimens were cultured for S. aureus at enrollment and after 6 and 12 months. MRSA colonization was detected in 13%–15% of HIV-infected participants (n = 600, 98% male) at baseline, 6 months, and 12 months. MRSA colonization was detected in the nares only (41%), groin only (21%), and at both sites (38%). Over a median of 2.1 years of follow-up, 29 MRSA clinical infections occurred in 25 participants. In multivariate analysis, MRSA clinical infection was significantly associated with MRSA colonization of the groin (adjusted risk ratio 4.8) and a history of MRSA infection (adjusted risk ratio 3.1). MRSA prevention strategies that can effectively prevent or eliminate groin colonization are likely necessary to reduce clinical infections in this population.

Differences in rates of diarrhea in patients with human immunodeficiency virus receiving lopinavir-ritonavir or nelfinavir.

Study Objective. To determine and compare rates of diarrhea in patients receiving an antiretroviral regimen containing lopinavir‐ritonavir versus nelfinavir and in patients who received these drugs sequentially.