In a cohort of men who have sex with men, most of whom were infected with human immunodeficiency virus, men chronically infected with hepatitis B were 2-fold more likely to die a liver-related death than those chronically infected with hepatitis C.
Background. It is not known whether chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C) carries a greater risk of liver-related mortality. This study compared rates of liver-related mortality between these 2 groups in the Multicenter AIDS Cohort Study (MACS).
Methods. Six hundred eighty men with CH-B (n = 337) or CH-C (n = 343) at study entry into the MACS were prospectively followed to death, last follow-up visit, or 30 March 2010, whichever came first. Four hundred seventy-two (69.4%) of these men were infected with human immunodeficiency virus type 1 (HIV-1). Causes of death were obtained from death registry matching and death certificates. Liver-related and all-cause mortality rates (MRs) were compared between groups using Poisson regression and adjusted for potential confounders and competing risks.
Results. In 6728 person-years (PYs) of follow-up, there were 293 deaths from all causes (43.5 per 1000 PYs), of which 51 were liver-related (7.6 per 1000 PYs). The all-cause MR was similar between those with CH-B and CH-C; however, the liver-related MR was significantly higher in those with CH-B (9.6 per 1000 PYs; 95% confidence interval [CI], 6.9–13.2) than those with CH-C (5.0 per 1000 PYs; 95% CI, 3.0–8.4). In the HIV-infected subgroup, which had 46 (90.2%) of the liver-related deaths, the liver-related MR remained higher from CH-B after adjusting for potential confounders (incidence rate ratio, 2.2; P = .03) and competing risks (subhazard rate ratio, 2.4; P = .02). Furthermore, among HIV-infected subjects, CD4 cell counts <200 cells/mm3 were associated with a 16.2-fold (95% CI, 6.1–42.8) increased risk of liver-related death compared with CD4 cell counts >350 cell/mm3.
Conclusions. Chronic hepatitis B carries a higher risk of death from liver disease than does CH-C, especially in HIV-infected men with greater immunosuppression.
Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.
We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.
Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women.
African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.
African American; Hispanic; Acute hepatitis C; Female
Background. Although liver disease commonly causes morbidity and mortality among human immunodeficiency virus (HIV)–infected individuals, data are limited on its prevalence in HIV monoinfection. We used the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of hepatic fibrosis to characterize liver disease in the Multicenter AIDS Cohort Study.
Methods. Men were categorized based on their HIV and viral hepatitis status: uninfected (n = 1170), HIV monoinfected (n = 509), viral hepatitis monoinfected (n = 74), and HIV–viral hepatitis coinfected (n = 66).
Results. The median APRI in the HIV-monoinfected group was similar to that in the hepatitis-monoinfected group (0.42 vs 0.43; P > .05), higher than in the uninfected group (0.42 vs 0.27; P < .001) but lower than in the coinfected group (0.42 vs 1.0; P < .001). On multivariable analysis, HIV infection (1.39-fold increase [FI]; P < .001), viral hepatitis infection (1.52-FI; P < .001), and the interaction between HIV and viral hepatitis infections were independently associated with a higher APRI (1.57-FI; P < .001). Among the HIV-infected men, viral hepatitis coinfection (2.34-FI; P < .001), HIV RNA ≥100 000 copies/mL (1.26-FI; P = .007), and CD4 count ≤200 cells/mL (1.23-FI; P = .022) were independently associated with a higher APRI.
Conclusions. HIV and viral hepatitis are independently associated with an increased APRI. Further studies are needed to understand the biological basis for the association between HIV and liver disease.
To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).
Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.
Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.
Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001).
HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.
The incidence of Kaposi’s sarcoma (KS) and non-Hodgkin’s lymphoma (NHL) among human immunodeficiency virus (HIV)-infected individuals declined following the introduction of highly active antiretroviral therapy (HAART) in the mid 1990s, but the cancer risk associated with HIV infection during the HAART era remains to be clarified.
We compared cancer incidence among HIV-infected and -uninfected participants in the Multicenter AIDS Cohort Study (MACS) between 1984 and 2007 to the expected incidence using US population-based data from the Surveillance, Epidemiology, and End Results (SEER) Program, and we compared age and race adjusted cancer incidence rates by HIV status and over time within the MACS. Exact statistical methods were used for all analyses.
933 incident cancers were observed during 77,320 person-years of follow-up. Compared to SEER, MACS HIV-infected men had significantly (p<0.05) elevated rates of KS (standardized incidence ratio (SIR)=139.10), NHL (SIR=36.80), Hodgkin’s lymphoma (HL) (SIR=7.30), and anal cancer (SIR=25.71). Within MACS, HIV infection was independently associated with each of these cancers across the entire follow-up period, and KS (incidence rate ratio (IRR)=54.93), NHL (IRR=11.18), and anal cancer (IRR=18.50) were each significantly elevated among HIV-infected men during the HAART era. Among these men, the incidence of KS and NHL declined (IRR=0.13 and 0.23, respectively), anal cancer incidence increased (IRR=5.84), and HL incidence remained statistically unchanged (IRR=0.75) from the pre-HAART to the HAART era.
Cancer risk remains elevated among HIV-infected men who have sex with men, highlighting the continuing need for appropriate cancer screening in this population.
HIV infection; cancer incidence; malignancy; AIDS-defining malignancy; HAART
We previously reported an increased risk of all-cause and AIDS mortality among HIV-infected women with albuminuria (proteinuria or microalbuminuria) enrolled in the Women’s Interagency HIV Study (WIHS) prior to the introduction of highly active antiretroviral therapy (HAART).
The current analysis includes 1,073 WIHS participants who subsequently initiated HAART. Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria from two consecutive study visits prior to HAART initiation were categorized as follows: confirmed proteinuria (both specimens positive for protein), confirmed microalbuminuria (both specimens positive with at least one microalbuminuria), unconfirmed albuminuria (one specimen positive for proteinuria or microalbuminuria), or negative (both specimens negative). Time from HAART initiation to death was modeled using proportional hazards analysis.
Compared to the reference group of women with two negative specimens, the hazard ratio (HR) for all-cause mortality was significantly elevated for women with confirmed microalbuminuria (HR 1.9; 95% CI 1.2–2.9). Confirmed microalbuminuria was also independently associated with AIDS death (HR 2.3; 95% CI 1.3–4.3), while women with confirmed proteinuria were at increased risk for non-AIDS death (HR 2.4; 95% CI 1.2–4.6).
In women initiating HAART, pre-existing microalbuminuria independently predicted increased AIDS mortality, while pre-existing proteinuria predicted increased risk of non-AIDS death. Urine testing may identify HIV-infected individuals at increased risk for mortality even after the initiation of HAART. Future studies should consider whether these widely available tests can identify individuals who would benefit from more aggressive management of HIV infection and comorbid conditions associated with mortality in this population.
HIV; microalbuminuria; proteinuria; mortality; non-AIDS death
Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group.
To identify factors associated with ALT elevations in an HIV-HBV co-infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (≥2.5×ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4–13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA ≥2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04–4.11, p = 0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03–4.79, p = 0.04) were independently associated with ALT elevation.
In this HIV-HBV co-infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations.
Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited.
We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared.
In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tacrolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contrast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat refractory rejection in three patients from the CLI-treated arm. Concern has been raised in the literature about the possibility of tacrolimus being a direct hepatotoxin and an accelerant of allograft obliterative arteriopathy. However, no evidence to support either of these contentions was detected in this patient population. In contrast, tacrolimus is clearly nephrotoxic, although similar to cyclosporine in this regard.
Tacrolimus is an effective immunosuppressive drug for heart transplantation. The cardiac allograft histopathologic study of patients treated with tacrolimus immunosuppression does not significantly differ from those given conventional, cyclosporine-based triple therapy with lympholytic induction.
Background and purpose
Human immunodeficiency virus (HIV)-infected persons taking highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons taking HAART compared to HAART-naïve and HIV-uninfected persons.
Between 2004 and 2006, we performed high resolution B-mode ultrasound on 2,789 HIV-infected and HIV-uninfected participants of the Women’s Interagency HIV Study (WIHS; 1865 women) and the Multicenter AIDS Cohort Study (MACS; 924 men) and determined carotid arterial distensibility, a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4+ cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics.
In multivariable analysis, distensibility was 4.3% lower (95% confidence interval (CI): -7.4% to -1.1%) among HIV-infected versus uninfected participants. Among HIV-infected participants with fewer than 200 CD4+ cells, distensibility was 10.5% lower (95% CI: -14.5% to -6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among MACS participants but not among WIHS participants.
Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.
atherosclerosis; cardiovascular disease; carotid arteries; HIV; epidemiology
HIV infection has a significant impact on the natural progression of hepatitis B virus (HBV) related liver disease. In HIV-HBV co-infected patients, little is known about mutations in the HBV genome, which can influence severity of liver disease. The aim of this study was to characterize and to determine the frequency of known clinically-significant mutations in the HBV genomes from HIV-HBV co-infected patients and from HBV mono-infected patients. To accomplish this, genomic length HBV sequencing was performed in highly-active anti-retroviral therapy (HAART) –naïve HIV-HBV co-infected patients (n= 74) and in anti-HBV therapy-naïve HBV mono-infected patients (n=55).
The frequency of HBV mutations differed between the co-infected and mono-infected patients when comparing patients with the same genotype. BCP mutations A1762T and G1764A were significantly more frequent in HBV genotype C mono-infection and the −1G frameshift was significantly more frequent in co- infection and was only observed in HBV genotype A co-infection. PreS2 deletions were observed more frequently in the setting of co-infection. Further work is needed to determine if these mutational patterns influence the differences in liver disease progression in HIV-HBV co-infected and HBV mono-infected patients.
Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy.
Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria were performed in specimens from two consecutive visits in 1,547 HIV-infected women enrolled in the Women’s Interagency HIV Study in 1994–1995. Time to death was modeled using proportional hazards analysis.
Compared to women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with one (HR 3.4; 95% CI 2.2–5.2) or two specimens positive for either proteinuria or microalbuminuria (HR 3.9; 95% CI 2.1–7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR 5.8; 95% CI 3.4–9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death.
We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.
HIV; microalbuminuria; proteinuria; mortality
To characterize predictors of isolated hepatitis B core antibody (anti-HBc) among human immunodeficiency virus (HIV)–infected and HIV-uninfected women, we compared 702 women with anti-HBc and hepatitis B surface antibody (anti-HBs) with 490 women with isolated anti-HBc (1.8% of whom had detectable hepatitis B virus [HBV] DNA). Factors independently associated with isolated anti-HBc without viremia were detectable hepatitis C virus (HCV) RNA, HIV positivity, history of injection drug use, >10 lifetime sex partners, and HIV RNA level >100,000 copies/mL. Anti-HBs levels were lower among anti-HCV–positive women. Isolated anti-HBc was rarely explained by occult HBV in this cohort but may be explained by the influence of viral coinfections on anti-HBs level or durability.
We assessed the prevalence and predictors of latent Toxoplasma infection in a large group of human immunodeficiency virus (HIV)–infected and HIV-uninfected at-risk US women. The prevalence of latent Toxoplasma infection was 15% (380 of 2525 persons) and did not differ by HIV infection status. HIV-infected women aged ≥50 years and those born outside of the United States were more likely to have latent Toxoplasma infection, with prevalences of 32% and 41%, respectively.
Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS).
A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III.
Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III.
HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.
Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women's Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV− women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different (p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.
Hepatitis B; antiviral therapy; HIV infection; liver disease
Chronic hepatitis B (CH-B) is common among HIV-infected individuals and increases liver-related mortality in the absence of highly active antiretroviral therapy (HAART). The impact of CH-B on long-term HAART outcomes has not been fully characterized.
To address this question, HAART initiators enrolled in the Multicenter AIDS Cohort Study (MACS) were retrospectively analyzed. Subjects were classified by hepatitis B category based on serology at the time of HAART initiation. The association of CH-B with mortality, AIDS defining illnesses, CD4 rise, and HIV suppression was assessed using regression analysis.
Of 816 men followed for a median of 7 years on HAART, 350 were never HBV infected, 357 had past infection, 45 had CH-B, and 64 were only core-antibody positive. Despite HAART, AIDS-related mortality was the most common cause of death (8.3/1000 person-years (PYs)). It was highest in those with CH-B (17/1000 PYs, 95% CI 7.3, 42) and lowest among never HBV infected (2.9/1000 PYs, 95% CI 1.4, 6.4). In a multivariable model, patients with CH-B had a 2.7-fold higher incidence of AIDS-related mortality compared to those never infected (P=0.08). Non-AIDS-related mortality was also highest among those with CH-B (22/1000 PYs), primarily due to liver disease (compared to never infected, adjusted HR 4.1, p=0.04). There was no significant difference in AIDS defining events, HIV RNA suppression, and CD4 increase.
In HIV-infected patients receiving long-term HAART, HBV status did not influence HIV suppression or CD4 increase. However, mortality was highest among those with CH-B and was mostly due to liver disease despite HBV-active HAART.
hepatitis B; HIV; HAART; CD4; mortality; isolated core hepatitis B
Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women’s Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV− women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different ( p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.
To estimate the incidence of invasive cervical cancer (ICC) in women with human immunodeficiency virus (HIV) and compare it to that in HIV-uninfected women.
In a cohort study of HIV infected and uninfected women who had Pap tests obtained every six months, pathology reports were retrieved for women with biopsy or self-report of ICC. Histology was reviewed when reports confirmed ICC. Incidence rates were calculated and compared to those in HIV-negative women.
After a median follow-up of 10.3 years, three ICCs were confirmed in HIV seropositive women, none in seronegative women. The ICC incidence rate was not significantly associated with HIV status (HIV negative: 0/100,000 person-years vs. HIV positive: 21.4/100,000 person-years; p=0.59). A calculated incidence rate ratio standardized to expected results from the Surveillance Epidemiology and End Results database restricted to the HIV-infected WIHS participants was 1.32 (95% CI: 0.27, 3.85; p=0.80).
Among women with HIV in a prospective study incorporating cervical cancer prevention measures, ICC incidence was not significantly higher than in a comparison group of HIV-negative women.
Cervical cancer; HIV in women; cancer prevention
Treatment guidelines recommend all HIV/HCV-co-infected persons be considered for hepatitis C virus (HCV) treatment, yet obstacles to testing and accessing treatment for HCV continue for women.
To assess awareness of HCV, and describe diagnostic referrals and HCV treatment among women in the Women’s Interagency HIV Study (WIHS).
Prospective epidemiologic cohort.
Of 3,768 HIV-infected and uninfected women in WIHS, 1,166 (31%) were HCV antibody positive.
MEASUREMENTS AND MAIN RESULTS
Awareness of HCV infection and probability of referrals for diagnostic evaluations and treatment using logistic regression. Follow-up HCV information was available for 681 (390 died, 15 withdrew, 80 missed visit) in 2004. Of these 681, 522 (76.7%) reported knowing their HCV diagnosis. Of these, 247 of 522 (47.3%) stated their providers recommended a liver biopsy, whereas 139 of 247 or 56.3% reported having a liver biopsy. A total of 170 of 522 (32.6%) reported being offered treatment and 74.1% (n = 126 of 170) reported receiving HCV treatment. In multivariate regression analyses, African-American race, Hispanic/Latina ethnicity, poverty, and current crack/cocaine/heroin use were negatively associated with treatment referrals, whereas elevated alanine aminotransferase (ALT) was associated with increased likelihood of referral and increased likelihood of treatment.
One quarter of women with HCV in this cohort were not aware of their diagnosis. Among those aware of their HCV, 1 in 4 received liver biopsy and treatment for HCV. Both provider and patient education interventions regarding HCV testing and HCV treatment options and guidelines are needed to enhance HCV awareness and participation in HCV evaluation and treatment.
women; hepatitis C; HIV; race; drug use; therapy
Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.
We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use.
Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before.
In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.
Human papillomavirus (HPV) is an etiologic agent for both oropharyngeal and cervical cancers, yet little is known about the interrelationship between oral and cervical HPV infections. Therefore, we compared the prevalences and type distributions of oral and cervical HPV infections and evaluated infection concordance in a cross-sectional study within the Women's Interagency HIV Study cohort. Oral rinse and cervical-vaginal lavage samples were concurrently collected from a convenience sample of 172 human immunodeficiency virus (HIV)-positive and 86 HIV-negative women. HPV genomic DNA was detected by PGMY09/11 L1 consensus primer PCR and type specified by reverse line blot hybridization for 37 HPV types and β-globin. Only 26 of the 35 HPV types found to infect the cervix were also found within the oral cavity, and the type distribution for oral HPV infections appeared distinct from that for cervical infections (P < 0.001). Oral HPV infections were less common than cervical infections for both HIV-positive (25.2% versus 76.9%, P < 0.001) and HIV-negative (9.0% versus 44.9%, P < 0.001) women. Oral HPV infections were more common among women with a cervical HPV infection than those without a cervical HPV infection (25.5% versus 7.9%, P = 0.002). The majority of women (207; 93.7%) did not have simultaneous oral and cervical infections by the same HPV type; however, the number of women who did (14; 6.3%) was significantly greater than would be expected by chance (P = 0.0002). Therefore, the oral and cervical reservoirs for HPV infection are likely not entirely independent of one another.
Three-hundred ninety-two adult Dermacentor variabilis were collected from six Maryland counties during the spring, summer, and fall of 2002. Infection prevalence for spotted fever group Rickettsia was 3.8%, as determined by polymerase chain reaction. Single strand conformational polymorphism (SSCP) analysis followed by sequencing indicated that all infections represented a single rickettsial taxon, Rickettsia montanensis.
SFG Rickettsia; Dermacentor variabilis; Rickettsia montanensis; Rocky Mountain Spotted Fever; dispatch
At the CC (β) chemokine receptor 2 (CCR2) and CCR5 loci, combinations of common single-nucleotide polymorphisms (SNPs) and a 32-bp deletion (Δ32) form nine stable haplotypes (designated A through G*2). The distribution of these CCR2-CCR5 haplotypes was examined among 703 participants in the Multicenter AIDS Cohort Study (MACS), the District of Columbia Gay (DCG) Study, and the San Francisco Men’s Health Study (SFMHS). Highly exposed and persistently seronegative (HEPS; n = 90) Caucasian men from MACS more frequently carried heterozygous G*2 (Δ32) genotypes (especially A/G*2) and less frequently carried the homozygous E/E genotype compared with 469 Caucasian seroconverters (SCs) from the same cohort (P = 0.004 to 0.042). Among 341 MACS Caucasian SCs with 6- to 12-month human immunodeficiency virus type 1 (HIV-1) seroconversion intervals and no potent antiretroviral therapy, mean plasma HIV-1 RNA level during the initial 42 months after seroconversion was higher in carriers of the E/E genotype and lower in those with the 64I-bearing haplotype F*2 or the Δ32-bearing haplotype G*2 (and especially genotypes A/G*2 and F*2/G*2). A multivariable model containing these CCR markers showed significant composite effects on HIV-1 RNA at each of four postconversion intervals (P = 0.0004 to 0.050). In other models using time to AIDS as the endpoint, the same markers showed more modest contributions (P = 0.08 to 0.24) to differential outcome during 11.5 years of follow-up. Broadly consistent findings in the larger MACS Caucasian SCs and the smaller groups of MACS African-American SCs and the DCG and SFMHS Caucasian SCs indicate that specific CCR2-CCR5 haplotypes or genotypes mediate initial acquisition of HIV-1 infection, early host-virus equilibration, and subsequent pathogenesis.