(See the editorial commentary by Peters and Marston, on pages 166–8.)
Background. Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.
Methods. Participants with HIV diagnosis seroconversion window of ≤3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.
Results. Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15–2.71); 3.27 (2.71–3.84); 3.75 (2.25–5.25); and 5.41 (3.41–7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20–2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94–1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75–1.75).
Conclusions. HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.
To evaluate whether elevated CD8 counts are associated with increased risk of virologic treatment failure in HIV-infected individuals.
Retrospective cohort study.
U.S. Military HIV Natural History Study participants who initiated HAART in 1996-2008, had 6- and 12-month post-HAART HIV RNA <400 c/ml, ≥2 subsequent HIV viral loads and a baseline CD8 count were eligible (n=817). Baseline was 12 months after HAART start, virologic failure was defined as confirmed HIV RNA ≥400 c/ml, and CD8 counts ≥1200 cells/mm3 were considered elevated. Cox models were used to examine the effect of baseline and time-updated CD8 counts on virologic failure.
There were 216 failures for a rate of 5.6 per 100 person-years (95% confidence interval [CI] 4.9-6.4). Among those initiating HAART in 2000-2008, participants with elevated baseline CD8 counts had significantly greater risk of virologic failure compared to those with baseline CD8 counts ≤600 cells/mm3 (hazard ratio [HR] = 2.68, 95% CI 1.13 – 6.35). Participants with elevated CD8 counts at >20% of prior 6-month follow-up visits had greater risk of failure at the current visit than those who did not (HR = 1.53, 95% CI 1.14 - 2.06). Those with CD8 counts that increased after HAART start had greater risk of failure than those with CD8 counts that decreased or remained the same (HR = 1.59, 95% CI 1.19 – 2.13).
Initial or serial elevated CD8 counts while on HAART or an increase in CD8 counts from HAART initiation may be early warnings for future treatment failure.
Human immunodeficiency virus; CD8 count; antiretroviral therapy; HIV viral load suppression; HIV virologic failure
Background. Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)–infected adults.
Methods. We retrospectively studied HIV-infected adults who had received 2 doses of HAV vaccine. We analyzed blood specimens taken at 1 year, 3 years, and, when available, 6–10 years postvaccination. HAV immunoglobulin G (IgG) values of ≥10 mIU/mL were considered seropositive.
Results. We evaluated specimens from 130 HIV-infected adults with a median age of 35 years and a median CD4 cell count of 461 cells/mm3 at or before time of vaccination. Of these, 49% had an HIV RNA load <1000 copies/mL. Initial vaccine responses were achieved in 89% of HIV-infected adults (95% confidence interval [CI], 83%–94%), compared with 100% (95% CI, 99%–100%) of historical HIV-uninfected adults. Among initial HIV-infected responders with available specimens, 90% (104 of 116; 95% CI, 83%–95%) remained seropositive at 3 years and 85% (63 of 74; 95% CI, 75%–92%) at 6–10 years. Geometric mean concentrations (GMCs) among HIV-infected adults were 154, 111, and 64 mIU/mL at 1, 3, and 6–10 years, respectively, compared with 1734, 687, and 684 mIU/mL among HIV-uninfected persons. Higher GMCs over time among HIV-infected adults were associated with lower log10 HIV RNA levels (β = −.12, P = .04).
Conclusions. Most adults with well-controlled HIV infections had durable seropositive responses up to 6–10 years after HAV vaccination. Suppressed HIV RNA levels are associated with durable HAV responses.
Human immunodeficiency virus (HIV)-infected persons are at risk for severe influenza infections. Although vaccination against the H1N1 pandemic influenza strain is recommended, currently, there are no data on the durability of post-vaccination antibody responses in this population.
HIV-infected and HIV-uninfected adults (18–50 years old) received a single dose of monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1). Antibody levels to the 2009 H1N1 pandemic strain were determined at day 0, day 28, and 6 months by hemagglutination-inhibition assay. A seroprotective response was a post-vaccination titer of ≥1:40 among those with a pre-vaccination level of ≤1:10. Geometric mean titers (GMT) and factors associated with higher levels were also evaluated.
We studied 127 participants with a median age of 35 (interquartile range (IQR) 28, 42) years. Among the HIV-infected arm (n=63), the median CD4 count was 595 (IQR 476, 819) cells/mm3 and 83% were receiving HAART. Thirty-five percent of all participants had a pre-vaccination level of >1:10. HIV-infected compared to HIV-uninfected adults were less likely to generate a seroprotective response at day 28 (54% vs. 75%, adjusted OR 0.23, p=0.021) or have a durable response at 6 months post-vaccination (28% vs. 56%, adjusted OR 0.19, p=0.005). Additionally, although pre-vaccination GMT were similar in both arms (median 7 vs. 8, p=0.11), the GMT at 6 months was significantly lower among HIV-infected versus HIV-uninfected adults (median 20 vs. 113, p=0.003). Among HIV-infected persons, younger age (p=0.035) and receipt of HAART (p=0.028) were associated with higher GMTs at 6 months.
Despite vaccination, most HIV-infected adults do not have durable seroprotective antibody responses to the 2009 influenza A (H1N1) virus, and hence may remain vulnerable to infection. In addition to HAART use, more immunogenic vaccines are likely needed for improving protection against influenza in this population.
influenza; pandemic 2009 H1N1; vaccine responses; HIV; durability; long-term immunity
We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/μL greater for cases than controls (p=0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change −0.04 (±0.18) log10 copies/mL; p=0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination.
Measles; Mumps; MMR Vaccine; Human Immunodeficiency Virus; Vaccines; Vaccination
To determine whether hepatitis E virus (HEV) is a cause of hepatitis among HIV-infected persons, we evaluated 1985–2009 data for US military beneficiaries. Evidence of acute or prior HEV infection was detected for 7 (4%) and 5 (3%) of 194 HIV-infected persons, respectively. HEV might be a cause of acute hepatitis among HIV-infected persons.
Hepatitis E virus; HIV; epidemiology; hepatitis; military; viruses
Microbial resistance has reached alarming levels, threatening to outpace the ability to counter with more potent antimicrobial agents. In particular, methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of skin and soft-tissue infections and PVL-positive strains have been associated with necrotizing pneumonia. Increasing reports of growing resistance to glycopeptides have been noted, further limiting the efficacy of standard antibiotics, such as vancomycin. Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum activity against Gram-positive bacteria, including MRSA and extensively-resistant strains, such as vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and vancomycin-resistant S. aureus (VRSA). In addition to being an exciting new agent in the anti-MRSA armamentarium, ceftaroline provides efficacy against many respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Ceftaroline (600 mg intravenously every 12 hours) has been shown effective in phase III studies in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia. To date, this unique antibiotic exhibits a low propensity for inducing resistance and has a good safety profile, although further post-marketing data and clinical experience are needed. In summary, ceftaroline provides an additional option for the management of complex multidrug resistant infections, including MRSA.
Ceftaroline; antibiotic; cephalosporin; methicillin-resistant Staphylococcus aureus; MRSA; multidrug resistant organisms
Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality.
We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel.
Cumulative mortality was 5%, 10% and 18% at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years [PY]) in those with ≤ 50 CD4+ cells/mm3 before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with ≥ 500 CD4+ cells/mm3). In multivariate analysis, factors significantly (p < 0.05) associated with post-HAART mortality included: increasing age among those ≥ 40 years (Hazard ratio [HR] = 1.32 per 5 year increase), clinical AIDS events before HAART (HR = 1.93), ≤ 50 CD4+ cells/mm3 (vs. CD4+ ≥ 500, HR = 2.97), greater HIV RNA level (HR = 1.36 per one log10 increase), hepatitis C antibody or chronic hepatitis B (HR = 1.96), and HIV diagnosis before 1996 (HR = 2.44). Baseline CD4+ = 51-200 cells (HR = 1.74, p = 0.06), and hemoglobin < 12 gm/dL for women or < 13.5 for men (HR = 1.36, p = 0.07) were borderline significant.
Although treatment has improved HIV survival, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory correlates of poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.
Highly active antiretroviral therapy; mortality; CD4+ lymphocyte count
To assess associations between the timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and vaccine effectiveness, US Military HIV Natural History Study cohort participants without HBV infection at the time of HIV diagnosis were grouped by vaccination status, retrospectively followed from HIV diagnosis for incident HBV infection, and compared using Cox proportional hazards models. A positive vaccine response was defined as hepatitis B surface antibody level ≥10 IU/L. Of 1,877 participants enrolled between 1989 and 2008, 441 (23%) were vaccinated prior to HIV diagnosis. Eighty percent of those who received vaccine doses only before HIV diagnosis had a positive vaccine response, compared with 66% of those who received doses both before and after HIV and 41% of those who received doses only after HIV (P < 0.01 for both compared with persons vaccinated before HIV only). Compared with the unvaccinated, persons vaccinated only before HIV had reduced risk of HBV infection after HIV diagnosis (hazard ratio = 0.38, 95% confidence interval: 0.20, 0.75). No reduction in HBV infection risk was observed for other vaccination groups. These data suggest that completion of the vaccine series prior to HIV infection may be the optimal strategy for preventing this significant comorbid infection in HIV-infected persons.
hepatitis B vaccines; hepatitis B virus; HIV; immunization; vaccination
Background. Limited data exist on the immunogenicity of the 2009 influenza A (H1N1) vaccine among immunocompromised persons, including those with human immunodeficiency virus (HIV) infection.
Methods. We compared the immunogenicity and tolerability of a single dose of the monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1) between HIV-infected and HIV-uninfected adults 18–50 years of age. The primary end point was an antibody titer of ≥1:40 at day 28 after vaccination in those with a prevaccination level of ≤1:10, as measured by hemagglutination-inhibition assay. Geometric mean titers, influenza-like illnesses, and tolerability were also evaluated.
Results. One hundred thirty-one participants were evaluated (65 HIV-infected and 66 HIV-uninfected patients), with a median age of 35 years (interquartile range, 27–42 years). HIV-infected persons had a median CD4 cell count of 581 cells/mm3 (interquartile range, 476–814 cells/mm3) , and 82% were receiving antiretroviral medications. At baseline, 35 patients (27%) had antibody titers of >1:10. HIV-infected patients (29 [56%] of 52), compared with HIV-uninfected persons (35 [80%] of 44), were significantly less likely to develop an antibody response (odds ratio, .20; P = .003). Changes in the median geometric mean titer from baseline to day 28 were also significantly lower in HIV-infected patients than in HIV-uninfected persons (75 vs 153; P = .001). Five influenza-like illnesses occurred (2 cases in HIV-infected persons), but none was attributable to the 2009 influenza H1N1 virus. The vaccine was well tolerated in both groups.
Conclusions. Despite high CD4 cell counts and receipt of antiretroviral medications, HIV-infected adults generated significantly poorer antibody responses, compared with HIV-uninfected persons. Future studies evaluating a 2-dose series or more-immunogenic influenza A (H1N1) vaccines among HIV-infected adults are needed (ClinicalTrials.gov NCT00996970).
Prior studies have shown that weight may impact immune cell counts. However, few data exist about the relationship of weight and immune cell counts among HIV-infected patients. We examined documented HIV seroconverters (mean window, 15.7 months) in a prospective U.S. Military HIV Natural History Study (1 January 1986 to 20 January 2010). We estimated the association of the time-updated body mass index (BMI) category with changes in immune cell counts from HIV diagnosis across time (mean follow-up of 5.1 years) using multiply adjusted longitudinal linear mixed-effects models. Of 1,097 HIV seroconverters, 448 (41%) were overweight and 93 (8%) were obese at HIV diagnosis. Immune cell counts at HIV diagnosis did not significantly differ by BMI category. In the longitudinal models for those diagnosed before the advent of the highly active antiretroviral therapy (HAART) era, mean postdiagnosis decreases in the white cell count, total lymphocyte count, CD4 count, CD4 percentage, and CD4/CD8 ratio were less as the BMI category increased (all with P values of <0.05). Among HIV seroconverters diagnosed in the HAART era, obese compared to normal-weight patients had significantly smaller increases in CD4 counts, CD4 percentages, and the CD4/CD8 ratio (all with P values of <0.05). Similar findings were also noted among underweight versus normal-weight patients. In conclusion, although BMI was not associated with immune cell levels at the time of HIV diagnosis, weight appears to affect immune cells counts over the course of infection. In the HAART era, being either underweight or obese was associated with smaller increases in several important immune cell levels, including the CD4/CD8 ratio.
We evaluated longitudinal rates of Kaposi sarcoma (KS) and trends in CD4 counts at the time of KS diagnosis during the HIV epidemic (1985–2008). Although rates of KS have decreased, cases are now occurring at higher CD4 counts over time, with more than a third of cases diagnosed in 2002–2008 occurring at CD4 counts ≥350 cells/mm3. These data support future studies evaluating the impact of HAART initiation at higher CD4 counts to further reduce KS.
Ethnicity may be associated with the incidence of pneumococcal infections and the frequency of protective vaccine responses. Earlier studies have suggested that HIV-infected persons of black ethnicity develop less robust immune responses to pneumococcal vaccination that may relate to their higher incidence of invasive disease. We evaluated the association of ethnicity with capsule-specific antibody responses to pneumococcal revaccination, with either the pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccines among 188 HIV-infected adults. The proportion of the 77 African Americans (AA) and 111 Caucasians with comparable virologic and immunologic parameters who achieved a positive immune response (≥2-fold rise in capsule-specific IgG from baseline with post-vaccination value ≥1 µg/mL for ≥2 of 4 serotypes) at day 60 after revaccination was similar (43% vs. 49%, respectively, p=0.65). Results were also similar when vaccine types (PPV and PCV) were examined separately. Mean changes in log10 transformed IgG levels from baseline to days 60 and 180 post-vaccination were also not significantly different between AA and Caucasians. In summary, in this ethnically diverse cohort with equal access to care, we did not observe differential antibody responses between AA and Caucasian HIV-infected adults after pneumococcal revaccination.
HIV-infected persons are at heightened risk for recurrent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but there are limited data regarding the molecular characterization of these events. We describe an HIV-infected patient with 24 soft tissue infections and multiple colonization events. Molecular genotyping from 33 nonduplicate isolates showed all strains were USA300, Panton-Valentine leukocidin (PVL) and arginine catabolic mobile element (ACME) positive, and genetically related.
The risk of pneumococcal disease persists and antibody responses to revaccination with the 23-valent polysaccharide vaccine (PPV) are low among HIV-infected adults. We determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses.
In a randomized clinical trial, we compared the immunogenicity of revaccination with PCV (n=131) or PPV (n=73) among HIV-infected adults (median CD4 count 533 cells/mm3) vaccinated with PPV 3–8 years earlier. HIV-uninfected adults (n=25) without prior pneumococcal vaccination received one dose of PCV. A positive response was defined as a ≥2-fold rise (baseline to day 60) in capsule-specific IgG with a post-vaccination level value ≥1000 ng/ml for at least 2 of the 4 serotypes.
HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV vs. PPV (57% vs. 36%, p=0.004) and greater IgG concentration mean changes from baseline to day 60 for serotypes 4, 9V, and 19F (all p<0.05), but not for serotype 14. However by day 180 both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected compared with those in HIV-infected adults.
Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults.
Cryptococcus remains an important opportunistic infection in HIV patients despite considerable declines in prevalence during the HAART era. This is particularly apparent in sub-Saharan Africa, where Cryptococcus continues to cause significant mortality and morbidity. This review discusses the microbiology, epidemiology, pathogenesis, and clinical presentation of cryptococcal infections in HIV patients. Additionally, a detailed approach to the management of cryptococcosis is provided.
Cryptococcus; HIV; diagnosis; treatment
Infectious myositis is defined as an infection of a skeletal muscle. Infectious myositis is most commonly caused by bacteria; however, a variety of viral, parasitic, and fungal agents may also cause myositis. The pathogenesis of nonbacterial infectious myositis is via direct infection of the musculature or immune mechanisms. Symptoms typically include muscular pain, tenderness, swelling, and/or weakness. The diagnosis of the specific microbe is often suggested by the presence of concordant clinical signs and symptoms, a detailed medical/travel history, and laboratory data. For example, immunocompromised hosts have a heightened risk of fungal myositis, whereas the presence of a travel history to an endemic location and/or eosinophilia may suggest a parasitic cause. Definitive diagnosis requires detecting the organism by specific laboratory testing including serologies, histopathology, and/or cultures. Treatment entails antimicrobial agents against the pathogen, with consideration for surgical drainage for focal purulent collections within the musculature.
Infectious myositis; nonbacterial myositis; viral; fungal; parasitic; influenza; coxsackievirus; human immunodeficiency virus; rhabdomyolysis; Candida; cryptococcus; histoplasmosis; Aspergillus; trichinosis; cysticercosis; toxoplasmosis; Microsporidia
Ileitis, or inflammation of the ileum, is often caused by Crohn’s disease. However, ileitis may be caused by a wide variety of other diseases. These include infectious diseases, spondyloarthropathies, vasculitides, ischemia, neoplasms, medication-induced, eosinophilic enteritis, and others. The clinical presentation of ileitis may vary from an acute and self-limited form of right lower quadrant pain and/or diarrhea, as in the majority of cases of bacterial ileitis, but some conditions (ie, vasculitis or Mycobacterium tuberculosis) follow a chronic and debilitating course complicated by obstructive symptoms, hemorrhage, and/or extraintestinal manifestations. Ileitis associated with spondylarthropathy or nonsteroidal anti-inflammatory drugs is typically subclinical and often escapes detection unless further testing is warranted by symptoms. In a minority of patients with long-standing Crohn’s ileitis, the recrudescence of symptoms may represent a neoplasm involving the ileum. Distinguishing between the various forms of ileitis remains a test of clinical acumen. The diagnosis of the specific etiology is suggested by a detailed history and physical examination, laboratory testing, and ileocolonoscopy and/or radiologic data.
Ileitis; Crohn’s disease; Infectious ileitis; Yersinia; Salmonella; Clostridium difficile; Typhlitis; Mycobacterium tuberculosis; Mycobacterium avium; actinomycosis; Anisakiasis; Cytomegalovirus; Histoplasmosis; Spondyloarthropathies; Vasculitis; Ischemia; Neoplasms; Drug-induced; NSAID enteropathy; Eosinophilic enteritis; Sarcoidosis; Amyloidosis; Backwash ileitis
To evaluate the incidence rates of anal cancer over the HIV epidemic and assess the impact of HAART use on anal cancer events.
We evaluated the incidence of and factors associated with anal cancer using longitudinal data from the prospective U.S. Natural History Study (1985-2008). Poisson regression and Cox proportional hazard models were utilized.
Among 4,506 HIV-infected males with 37,806 person-years (PY) of follow-up, anal cancer rates (per 100,000 PY) increased 5-fold, from 11 in the pre-HAART to 55 in the HAART era, p=0.02. Rates continued to increase, reaching 128 in 2006-2008. Persons with HIV infection for >15 years had a 12-fold higher rate than those with <5 years (348 vs. 28, p<0.01). At cancer diagnosis (n=19), median age was 42 years, median CD4 count was 432 cells/mm3, 74% had a CD4 nadir <200 cells/mm3, 42% had a prior AIDS event, and 74% had received HAART. From separate models, prior AIDS event (HR 3.88, p=0.01) and lower CD4 nadir (HR 0.85 per 50 cell, p=0.03) were associated with anal cancer, with a trend for a history of gonorrhea (HR 2.43, p=0.07). Duration of HAART use was not associated with a reduced risk of anal cancer (HR 0.94, p=0.42).
Incidence rates of anal cancer have progressively increased during the HIV epidemic. Persons with a longer duration of HIV infection have a substantially higher rate of anal cancer. Since HIV-infected persons are experiencing longer life expectancies and HAART does not appear protective of anal cancer, studies on preventive strategies are needed.
HIV; anal cancer; incidence rates; antiretroviral therapy; HAART; epidemiology
Declining rates of hospitalizations occurred shortly after the availability of HAART. However, trends in the late HAART era are less defined, and data on the impact of CD4 counts and HAART use on hospitalizations are needed.
We evaluated hospitalization rates from 1999–2007 among HIV-infected persons enrolled in a large U.S. military cohort. Poisson regression was used to compare hospitalization rates per year and to examine factors associated with hospitalization.
Of the 2,429 participants, 822 (34%) were hospitalized at least once with 1,770 separate hospital admissions. The rate of hospitalizations (137 per 1,000 PYs) was constant over the study period (relative rate, RR 1.00 per year change, 95% CI, 0.98–1.02). The hospitalization rates due to skin infections (RR 1.50, p=0.02), MRSA (RR 3.19, p=0.03), liver disease (RR 1.71, p=0.04), and surgery (RR 1.17, p=0.04) significantly increased over time, while psychological causes (RR 0.60, p<0.01) and trauma (RR 0.54, p<0.01) decreased. In the multivariate model, higher nadir CD4 (RR 0.92 per 50 cells, P<0.01) and higher proximal CD4 counts (RR of 0.71 for 350–499 vs. <350 cells/mm3 and RR 0.67 for >500 vs. <350 cells/mm3, both P<0.01) were associated with lower risk of hospitalization. Risk of hospitalization was constant for proximal CD4 levels above 350 (RR 0.94 P=0.51, CD4 ≥500 vs. 350–499). HAART was associated with a reduced risk of hospitalization among those with a CD4 <350 (RR 0.72, P=0.02), but had smaller estimated and non-significant effects at higher CD4 levels (RR 0.81, P=0.33 and 1.06, P=0.71 for CD4 350–499 and ≥500, respectively).
Hospitalizations continue to occur at high rates among HIV-infected persons with increasing rates for skin infections, MRSA, liver disease, and surgeries. Factors associated with a reduced risk of hospitalization include CD4 counts >350 cells/mm3 and HAART use among patients with a CD4 count <350 cells/mm3.
HIV; hospitalization; morbidity; complications; MRSA infections; surgery; epidemiology
Histoplasma capsulatum; histoplasmosis; presumed ocular histoplasmosis syndrome
To assess the effect of obesity on CD4 counts, we estimated the association of time-updated BMI categories with CD4 changes among 1,001 documented HIV seroconverters. During the pre-HAART era, a higher BMI was associated with less reduction in CD4 counts over time. However during the HAART era, obese versus normal weight patients had smaller increases in CD4 counts (+69 v. +116 cells, p=0.01). Lower CD4 counts may now be another adverse consequence of obesity.
HIV; immunology; obesity; CD4 counts; antiretroviral therapy
To assess the association of HBV vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees.
Observational cohort study
Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan-Meier survival curves and Cox proportional hazards models.
During 11,632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75–2.27) /100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted HR 0.86, 95% CI 0.7–1.1; adjusted HR 1.08, 95% CI 0.8–1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (HR 0.96; 95% CI 0.56–1.64). Among 409 vaccinees with HBsAb <10 IU/L, 46 (11.2%) developed HBV infection compared to 11 of 217 (5.1%) vaccinees with HBsAb ≥10 IU/L (HR 0.51; 95% CI 0.3–1.0). In participants with initial HBsAb <10 IU/L, 16/46 (35%) infections were chronic, compared to 0/11 in those with initial HBsAb ≥10 IU/L (p=0.02).
Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients.
Hepatitis B virus; hepatitis B vaccine; human immunodeficiency virus; vaccination; immunization
The epidemiologic trends of hepatitis B virus (HBV) infection in HIV-infected patients over the last twenty years are largely unknown.
Prevalence and risk factors for HBV infection overall, at the time of HIV infection, and following HIV infection were examined in an ongoing observational HIV cohort study. Risk factors for HBV infection at the time of HIV diagnosis were evaluated using logistic regression, and risk for incident HBV infection following HIV diagnosis was evaluated using Cox proportional hazards models.
Of the 2769 evaluable participants, 1078 (39%) had HBV infection, of which 117 (11%) had chronic HBV. The yearly cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995 to 36% in 2008 (p<0.001). HBV prevalence at the time of HIV diagnosis decreased between 1989 and 2008 from 34% to 9% (p<0.001). The incidence of HBV infection following HIV diagnosis decreased from 4.0/100 person-years in the pre-HAART era to 1.1/100 person-years in the HAART era (p<0.001), but has remained unchanged from 2000 through 2008 (p=0.49), with over 20% of incident HBV infections having chronic HBV. Decreased risk of HBV infection following HIV diagnosis was associated with higher CD4 cell counts and the use of HBV-active HAART. Receipt of ≥1 dose of HBV vaccine was not associated with reduced risk of HBV infection after HIV diagnosis.
While the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection following HIV diagnosis raises concern that more effective prevention strategies may be needed to significantly reduce HBV infections in this patient population.
Hepatitis B Virus; Human Immunodeficiency Virus; Sexually Transmitted Infections; Highly Active Antiretroviral Therapy; Hepatitis B Vaccine