Suchergebnisse

IntroductionDelayed‐type hypersensitivity (DTH) testing is an in vivo assessment of cell‐mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)‐suppressive HAART in the U.S. Military HIV Natural History Study.MethodsTreatment‐naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0–1) or non‐anergic (≥2). Pre‐HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation.ResultsNon‐anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non‐anergic and anergic participants in pre‐HAART CD4 count (409 cells/μL, interquartile range (IQR) 315–517 vs. 373 cells/μL, IQR 228–487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.4–4.9 vs. 4.4 log10 copies/mL, IQR 3.6–5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non‐anergic (220 cells/μL, IQR 115–358) and anergic groups (246 cells/μL, IQR 136–358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post‐HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283).ConclusionsDTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre‐HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL‐suppressive HAART.

OBJECTIVES: To determine long-term predictors of health-related quality of life (HRQOL) and evaluate the treatment effect of highly active antiretroviral therapy (HAART) on HRQOL in the US Military HIV Natural History Study (NHS) cohort. METHODS: Participants were a nested cohort of the NHS who responded to the Rand Short Form 36 questionnaire administered from 2006–2010. Physical component summary scores (PCS) and mental component summary scores (MCS) were computed using standard algorithms. HAART-status was categorized as non-protease inhibitor-based (NPI-HAART), protease inhibitor-based (PI-HAART), HAART-naïve, or off-HAART. Mixed linear random effects models were used to estimate changes in PCS and MCS over time for treatment and covariates (including CD4 count, HIV viral load, medical and mental comorbidities). RESULTS: 812 participants met the inclusion criteria. There was no difference in PCS or MCS between those on PIHAART compared to NPI-HAART. Significant predictors of PCS were CD4 count <200 cells/mm3 (β= −2.90), CD4 count 200–499 cells/mm3 (β= −0.80), and mental comorbidity (β= −3.23). Others were medical comorbidity, AIDS-defining illness, being on NPI-HAART, HAART-naïve, age, and rank. Those with medical comorbidities experienced yearly improvement in PCS. Predictors of MCS were CD4 count <200 cells/ mm3 (β= −2.53), mental comorbidity (β= −4.58), and being African American (β= 2.59). CONCLUSION: HRQOL was significantly affected by low CD4 count, medical and mental comorbidities. Addressing these modifiable factors would be expected to improve the physical and mental HRQOL of the cohort. Our study did not find any treatment benefit of NPI-HAART over PI-HAART on HRQOL in the long term.

Abstract Background Hepatitis B virus (HBV) vaccine antibody response has been associated with reduced risk of AIDS or death. However, it is unknown whether HBV vaccine responsiveness is associated with improved immune reconstitution during treatment with combination antiretroviral therapy (cART). We evaluated the relationship between HBV vaccine response status and CD4 reconstitution on cART in the U.S Military HIV Natural History Study. Methods Participants with viral load 350 cells/mm 3 at cART initiation, participants with CD4 < 200 and 200–350 cells/mm 3 had significantly reduced CD4 gains in both groups by longitudinal mixed models, but there was no difference in CD4 recovery according to HBV vaccine seroresponse. Conclusions Although HBV vaccine responsiveness is associated with a reduction in HIV disease progression, HBV vaccine responders do not achieve greater CD4 gains during the first year of cART. Additional clinical markers are needed to predict the magnitude of post-cART immune recovery.

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.

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.

Vaccination against human papillomavirus (HPV) is recommended to prevent cervical cancer among women, but the benefits of HPV vaccination for males are less obvious. This study characterized HPV acquisition among male military members by evaluating both seroprevalence at entry into service and seroincidence of HPV infection after ten years of service. At entry, 29 of 200 (14.6%) male service members were positive for HPV serotypes 6, 11, 16, or 18. Of 199 initially seronegative for at least one of the four HPV serotypes, 68 (34.2%) seroconverted to one or more serotypes at ten years; more than one-third of these were seropostive for oncogenic HPV serotypes. This estimate of HPV seroprevalence among male military accessions is higher than that reported among U.S. civilian males. Vaccination to prevent genital warts and cancers resulting from HPV infection may decrease health care system burdens. Further analyses are warranted to understand the potential costs and benefits of a policy to vaccinate male service members.

The influence of highly active antiretroviral therapy (HAART) upon hepatitis B virus (HBV) vaccine responses in HIV-infected individuals is unclear. After classification of vaccinees as non-responders (HBsAb <10 IU/L) or responders (HBsAb ≥10 IU/L) in our HIV cohort, multivariate logistic regression was used to assess factors associated with subsequent vaccine response. Of 626 participants vaccinated from 1988–2005, 217 (35%) were vaccine responders. Receipt of ≥3 doses of vaccine (OR 1.83, 95% CI 1.24–2.70), higher CD4 count at vaccination (OR 1.09, 95% CI 1.05–1.13 per 50 cells/μl increase), and use of HAART (OR 2.37, 95% CI 1.56–3.62) were all associated with increased likelihood of developing a response. However, only 49% of those on HAART at last vaccination responded, and 62% of those on HAART, with CD4 count ≥350, and HIV RNA <400 copies/mL responded. Compared to those on HAART with CD4 count ≥350, those not on HAART with CD4 count ≥350 had significantly reduced odds of developing a vaccine response (OR 0.47, 95% CI 0.30–0.70). While HAART use concurrent with HBV immunization was associated with increased probability of responding to the vaccine, the response rate was low for those on HAART. These data provide additional evidence of HAART benefits, even in those with higher CD4 counts, but also highlight the need for improving HBV vaccine immunogenicity.

IntroductionHIV controllers (HICs) experience relatively low‐level viraemia and CD4 preservation without antiretroviral therapy (ART), but also immune activation that may predispose to adverse clinical events such as cardiovascular disease and hospitalization. The objective of this study was to characterize the rates and reasons for hospitalization among HICs and persons with medically controlled HIV.MethodsSubjects with consistently well‐controlled HIV were identified in the U.S. Military HIV Natural History Study. ART prescription and HIV‐1 RNA data were used to categorize subjects as HICs or medically controlled as defined by ≥3 HIV‐1 RNA measurements ≤2000 or ≤400 copies/mL, respectively, representing the majority of measurements spanning ≥12 months. Hospitalizations were tallied and assigned diagnostic categories. All‐cause hospitalization rates were compared between groups using negative binomial regression.Results and discussionOf 3106 subjects followed from 2000 to 2013, 221 were HICs, including 33 elite (1.1%) and 188 viraemic (6.0%) controllers, who contributed 882 person‐years (PY) of observation time. An additional 870 subjects with medically controlled HIV contributed 4217 PY. Mean hospitalization rates were 9.4/100 PY among HICs and 8.8/100 PY among medically controlled subjects. Non‐AIDS‐defining infections were the most common reason for hospitalization (2.95/100 PY and 2.70/100 PY, respectively) and rates of cardiovascular hospitalization were similar in both groups (0.45/100 PY and 0.76/100 PY). There was no difference in hospitalization rate for HICs compared with subjects with medically controlled HIV (adjusted incidence rate ratio 1.15 [95% confidence interval 0.80 to 1.65]).ConclusionsAll‐cause and cardiovascular hospitalization rates did not differ between HICs and persons with medically controlled HIV. Non‐AIDS defining infections were common in this young, healthy, predominantly male cohort of military personnel and beneficiaries.

PURPOSE: There are few reports of refractive surgery on human immunodeficiency virus-positive (HIV+) patients; we sought to assess the frequency of refractive surgery complications in HIV+ individuals and related risk factors. SETTINGS: Multiple centers in the United States DESIGN: Prospective observational cohort study METHODS: The U.S. Military HIV Natural History Study is a prospective observational cohort study of HIV+ Servicemembers and beneficiaries. Participants were selected who had CPT codes for LASIK, PRK, and other refractive surgeries. The frequency of complications was determined using ICD-9 codes. Covariates included age, gender, antiretroviral therapy, time since HIV diagnosis, history of AIDS, and CD4 and viral load. Statistical analysis was completed using univariate (Chi-square and Wilcoxon-Mann-Whitney tests) and multivariate analyses. RESULTS: Seventy-nine out of 2073 participants had refractive surgery. 53 subjects underwent PRK, 23 LASIK, two radial keratotomy (RK), and one astigmatic correction. Complications occurred in 6/79 (7.6%) of participants, including five subjects who underwent PRK and one following RK, occurring between eight to 217 days after surgery. Five ulcers and one unspecified keratitis were noted. In univariate analysis, type of surgery (p=0.02) and history of AIDS (p=0.02) were risk factors for complications. In logistic regression analysis, no variables were found to be risk factors for complications. CONCLUSION: Complications were infrequent among HIV+ participants following refractive surgery. Point estimates suggest that PRK may have more complications than LASIK and that advanced HIV, reflected by prior AIDS, may be associated with an increased risk of complications. Further study will be needed to confirm these findings.

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

BackgroundSleep disturbances are reportedly common among persons infected with human immunodeficiency virus (HIV), but recent data, including comparisons with HIV-uninfected persons, are limited.MethodsWe performed a cross-sectional study among early-treated HIV-infected military beneficiaries (n = 193) to determine the prevalence and factors associated with insomnia (Pittsburgh Sleep Quality Index [PSQI]) and daytime sleepiness (Epworth Sleepiness Scale [ESS]). Data were compared with HIV-uninfected persons (n = 50) matched by age, sex, race or ethnicity, and military rank.ResultsForty-six percent of HIV-infected persons had insomnia (PSQI >5), and 30% reported daytime drowsiness (ESS ≥10). The prevalence of insomnia and daytime sleepiness was not significantly higher compared with the HIV-uninfected group (38% [P = .30] and 20% [P = .18], respectively). In the multivariate model, factors associated with insomnia among HIV infected patients included depression (odds ratio [OR], 16.8; 95% confidence interval [CI], 2.0-142.1; P = .01), increased waist size (OR, 2.7; 95% CI, 1.4-5.1; P = .002), and fewer years of education (OR, 0.8; 95% CI, .7-.95; P = .006). Neurocognitive impairment (diagnosed in 19% of HIV-infected participants) was not associated with insomnia; however, HIV-infected persons with insomnia were 3.1-fold more likely to have a decline in activities of daily living than those without insomnia (23% vs 9%; P = .01). Only 18% of HIV-infected persons reported using a sleep medication at least weekly.ConclusionsHIV-infected persons have a high prevalence of insomnia, but among an early-treated cohort this rate was not significantly higher compared with HIV-uninfected persons. Factors associated with insomnia among HIV-infected patients include depression and increased waist size. Prompt diagnosis and treatment of sleep disturbances are advocated and may improve quality of life.

BackgroundSleep disturbances are reportedly common among persons infected with human immunodeficiency virus (HIV), but recent data, including comparisons with HIV-uninfected persons, are limited.MethodsWe performed a cross-sectional study among early-treated HIV-infected military beneficiaries (n = 193) to determine the prevalence and factors associated with insomnia (Pittsburgh Sleep Quality Index [PSQI]) and daytime sleepiness (Epworth Sleepiness Scale [ESS]). Data were compared with HIV-uninfected persons (n = 50) matched by age, sex, race or ethnicity, and military rank.ResultsForty-six percent of HIV-infected persons had insomnia (PSQI >5), and 30% reported daytime drowsiness (ESS ≥10). The prevalence of insomnia and daytime sleepiness was not significantly higher compared with the HIV-uninfected group (38% [P = .30] and 20% [P = .18], respectively). In the multivariate model, factors associated with insomnia among HIV infected patients included depression (odds ratio [OR], 16.8; 95% confidence interval [CI], 2.0-142.1; P = .01), increased waist size (OR, 2.7; 95% CI, 1.4-5.1; P = .002), and fewer years of education (OR, 0.8; 95% CI, .7-.95; P = .006). Neurocognitive impairment (diagnosed in 19% of HIV-infected participants) was not associated with insomnia; however, HIV-infected persons with insomnia were 3.1-fold more likely to have a decline in activities of daily living than those without insomnia (23% vs 9%; P = .01). Only 18% of HIV-infected persons reported using a sleep medication at least weekly.ConclusionsHIV-infected persons have a high prevalence of insomnia, but among an early-treated cohort this rate was not significantly higher compared with HIV-uninfected persons. Factors associated with insomnia among HIV-infected patients include depression and increased waist size. Prompt diagnosis and treatment of sleep disturbances are advocated and may improve quality of life.

BACKGROUND AND METHODS: Active duty US Army and Air Force military personnel undergo mandatory biennial HIV antibody screening. We compared pre- and post-HIV seroconversion health status by conducting a case-control study, which evaluated all medical encounters and sociodemographic factors among incident HIV seroconverters and HIV-negative controls from June 2000 through February 2004. RESULTS: A total of 274 HIV seroconverters and 6205 HIV-negative personnel were included. In multivariate analysis restricted to male personnel (cases = 261, controls = 5801), single marital status (adjusted odds ratio [AOR] = 14.37), clinical indicators or symptoms within four years of HIV diagnosis (AOR = 6.22), black race (AOR = 5.88), nonindicator clinical syndromes within 2 years of HIV diagnosis (AOR = 3.31), any mental disorder within 4 years of HIV diagnosis (AOR = 3.04), increasing service-connected time (AOR = 1.69), and older age (AOR = 1.12) were associated with HIV diagnosis among males. A prior history of a sexually transmitted infection (STI) was associated with post-HIV seroconversion STI (OR(M-H) = 4.10). Similarly, a prior history of mental disorder was associated with post-HIV seroconversion mental disorder (OR(M-H) = 4.98). Forty-seven (18%) male cases were hospitalized at least once after HIV diagnosis; infectious diseases, and mental disorders made up 53% of initial admissions. CONCLUSIONS: HIV seroconversion was associated with increased health care-seeking behavior, STIs, and mental disorders, some of which may be amenable to screening. The higher STI rate after HIV diagnosis may partially be a consequence of monitoring, but secondary transmission of STI and possibly HIV require further definition and subsequent tailored preventive interventions.

OBJECTIVES: We sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs. METHODS: Male US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode. RESULTS: A total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1–12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85–5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83–3.64). CONCLUSIONS: PDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens.

BACKGROUND: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and Caucasians before HIV seroconversion, and before and after initiation of antiretroviral therapy (ART). METHODS: We analyzed D-dimer levels, clinical and laboratory data in 192 participants enrolled in the U.S. Military HIV Natural History Study, a 30 year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at three time points: 1) pre-HIV seroconversion (Pre-SC), 2) =6 months post-HIV seroconversion but prior to ART initiation (Post-SC), and 3) =6 months post-ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis. RESULTS: Compared to Caucasians (n=106), African Americans (n=86) had higher D-dimer levels post-SC (p=0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (p=0.40 and p=0.99 respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration of time on ART. CONCLUSIONS: Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.