Contribution of intestinal barrier damage, microbial translocation and HIV-1 infection status to an inflammaging signature.

BACKGROUND: Systemic inflammation is a characteristic of both HIV-1 infection and aging ("inflammaging"). Intestinal epithelial barrier damage (IEBD) and microbial translocation (MT) contribute to HIV-associated inflammation, but their impact on inflammaging remains unclear. METHODS: Plasma biomarkers for IEBD (iFABP), MT (LPS, sCD14), T-cell activation (sCD27), and inflammation (hsCRP, IL-6) were measured in 88 HIV-1 uninfected (HIV(neg)) and 83 treated, HIV-1-infected (HIV(pos)) adults from 20-100 years old. RESULTS: Age positively correlated with iFABP (r = 0.284, p = 0.008), sCD14 (r = 0.646, p = <0.0001) and LPS (r = 0.421, p = 0.0002) levels in HIV(neg) but not HIV(pos) subjects. Age also correlated with sCD27, hsCRP, and IL-6 levels regardless of HIV status. Middle-aged HIV(pos) subjects had elevated plasma biomarker levels similar to or greater than those of elderly HIV(neg) subjects with the exception of sCD14. Clustering analysis described an inflammaging phenotype (IP) based on iFABP, sCD14, sCD27, and hsCRP levels in HIV(neg) subjects over 60 years of age. The IP in HIV(neg) subjects was used to develop a classification model that was applied to HIV(pos) subjects to determine whether HIV(pos) subjects under 60 years of age were IP+. HIV(pos) IP+ subjects were similar in age to IP- subjects but had a greater risk of cardiovascular disease (CVD) based on Framingham risk score (p =  0.01). CONCLUSIONS: We describe a novel IP that incorporates biomarkers of IEBD, MT, immune activation as well as inflammation. Application of this novel IP in HIV-infected subjects identified a group at higher risk of CVD.

Association between opioid use and health care utilization as measured by emergency room visits and hospitalizations among persons living with HIV.

BACKGROUND: Epidemiologic studies in the non-human immunodeficiency virus (HIV) positive population have shown greater health care utilization among persons with chronic non-cancer pain on opioid therapy. However, we are not aware of any similar data in the HIV positive population. METHODS: We evaluated health care utilization, as measured by emergency room (ER) visits and hospitalizations, among persons with HIV and chronic pain seen at an academic medical center, during the calendar year 2005. We compared these outcomes between patients on chronic opioid therapy with those not on opioids. RESULTS: In univariate models chronic opioid therapy was associated with both ER visits and hospitalization: ER visits odds ratio (OR)=2.18 (95% confidence interval [CI], 1.30-3.66), hospitalization OR=1.90 (95% CI, 1.03-3.51). After multivariate analyses only nonsignificant trends remain: ER visits OR=1.71 (95% CI, 0.95-3.08); hospitalization OR=1.28 (95% CI, 0.66-2.49). CONCLUSIONS: In our study HIV positive individuals with chronic pain were more likely to be seen in the ER and be hospitalized if they were on opioids. However, after controlling for other variables, the association with opioids no longer remained significant.

Variables associated with decreasing pain among persons living with human immunodeficiency virus: a longitudinal follow-up study.

BACKGROUND: Pain is common among persons with human immunodeficiency virus (HIV); however, there are minimal data on its natural history, or the long-term efficacy of analgesic therapies. METHODS: We performed an observational study between 2001 and 2009. Pain was defined on a 0 to 10 scale; 0=no pain; 10=worst pain possible. Patients were included if they were HIV positive, had a chronic pain diagnosis, a median pain score during the first year of observation of ≥1.0, ≥2 years of follow-up, and ≥3 recorded pain scores. Two models were used to describe decreasing pain. Model 1 defined decreasing pain as a negative slope to the best fit line through all recorded pain scores. Model 2 defined decreasing pain as a median pain score of zero during the last year of follow-up. RESULTS: Using model 1, decreasing pain was negatively associated with a history of being abused (odds ratio=0.29) and positively associated with peripheral neuropathy (3.54). Using model 2, decreasing pain was positively associated with highly active antiretroviral therapy (3.71) and negatively associated with opioid analgesic use (0.24). CONCLUSIONS: We found social and HIV-related variables associated with decreasing pain. We failed to show a positive association between analgesic use and decreasing pain.

Factors associated with initiation of prolonged analgesic use among patients in the HIV Outpatient Study (HOPS).

BACKGROUND: Analgesic use is common but remains poorly described among human immunodeficiency virus (HIV)-infected persons in the highly active antiretroviral therapy era. METHODS: We studied HIV Outpatient Study participants during 1996 to 2008. We used Cox proportional hazards regression to assess variables associated with initiation of prolonged analgesia (≥90 consecutive days of analgesics); logistic regression to explore variables associated with initiation of prolonged opioid analgesia among those taking any prolonged analgesia; and linear regression to determine temporal trends in prolonged analgesia. RESULTS: Among 4180 patients, 931 (22%) initiated prolonged analgesia. Factors independently associated (P<0.05) with prolonged analgesia included: age above 40 years (hazard ratio=1.20), female sex (1.43), injection drug use as an HIV risk factor (1.33), public healthcare payer (1.88), nadir CD4+ less than 200 cells/mm (1.29), tobacco use (1.43), prior opportunistic infection(s) (1.25), antidepressant use (1.76), and anxiolytic use (1.51). Independent correlates of prolonged opioid analgesia were white race (odds ratio=1.64), baseline CD4+ less than 350 cells/mm (1.88), and anxiolytic use (1.87). Prolonged analgesia ranged from 11% to 15% each year. CONCLUSIONS: In the highly active antiretroviral therapy era, up to 15% of HIV Outpatient Study patients used prolonged analgesic therapy each year. Variables associated with the initiation of prolonged analgesia included HIV and non-HIV-related factors.

Mycobacterium avium complex cervical lymphadenitis in an immunocompetent adult.

Nontuberculosis mycobacterial cervical lymphadenitis is a relatively common disease in immunocompetent children but a rare disease in immunocompetent adults. We report the diagnosis and treatment of Mycobacterium avium complex cervical lymphadenitis in an adult female. Our evaluation of immune competence, including gamma interferon (IFN-gamma) and interleukin-12 (IL-12) signaling, found no evidence of deficiency.

Ongoing pain despite aggressive opioid pain management among persons with HIV.

BACKGROUND: Chronic pain is a common problem among persons living with HIV and opioids are frequently used in its treatment. However, data on the variables associated with opioids use and the efficacy of this practice are lacking. METHODS: We performed a cross-sectional cohort study of self-reported pain during the year 2005 in our clinic. Patients were grouped into 3 cohorts: those receiving daily opioid therapy for chronic pain (cohort 1, n=115), those with a chronic pain diagnosis but not on daily opioid therapy (cohort 2, n=209), and those without a chronic pain diagnosis (cohort 3, n=796). RESULTS: In multivariate analysis comparing cohorts 1 and 2, patients in cohort 1 were significantly more likely to be on a benzodiazepine or gamma-aminobutyric receptor agonist [odds ratio (OR)=15.2], have injection drug use as a HIV risk factor (OR=4.27), lack private insurance (OR=3.51), have been abused (OR=3.08), have a history of AIDS (OR=2.21), and be seen more frequently (OR=1.18). Patients in cohort 1 reported significantly more pain [mean pain scores (0 to 10): 4.3 cohort 1; 1.9 cohort 2; 0.7 cohort 3], and were more likely to have pain that was of moderate or greater severity (58.6% cohort 1; 15.5% cohort 2; 4.9% cohort 3). CONCLUSIONS: Psychosocial variables and a history of AIDS were associated with opioid use in our clinic. Persons on opioids continued to experience significantly more pain than other patients in our clinic.

Ochrobactrum anthropi septic arthritis: case report and implications in orthopedic infections.

Ochrobactrum anthropi is a rare cause of orthopedic infections. We report the second case of Ochrobactrum anthropi septic arthritis in the literature. Our case highlights the ability of Ochrobactrum anthropi to cause septic arthritis and its relevance in the field of orthopedic infections.

Bronchioloalveolar carcinoma presenting as chronic progressive pulmonary infiltrates in a woman with HIV: a diagnosis worth making.

A 52-year-old woman with human immunodeficiency virus (HIV) developed weight loss, cough, and breathing difficulties, accompanied by extensive bilateral pulmonary infiltrates. A lengthy infectious disease and autoimmune workup failed to reveal the etiology or produce benefit. Expert pathology review raised the possibility of pure bronchioloalveolar carcinoma. The patient was treated with erlotinib and achieved a dramatic and prolonged response to treatment. After 14 months a solitary lung nodule developed which was excised. This demonstrated an invasive adenocarcinoma with an activating epidermal growth factor receptor mutation (exon 19 deletion). As this nodule had developed in the presence of erlotinib, this deletion is only presumed to reflect the initial driver of erlotinib sensitivity. Known acquired resistance mechanisms were explored, but the lesion was negative for both exon 20 T790M gatekeeper mutations and cMET gene copy number alterations. An as yet unknown mechanism of acquired resistance is therefore assumed to be involved in this case. We discuss the diagnosis and treatment of lung cancer in HIV-positive populations and review the general and specific characteristics of bronchioloalveolar carcinoma, including response to epidermal growth factor receptor inhibitors, and known mechanisms of acquired resistance. The predilection for lung cancer in HIV-positive patients, the diffuse nature of bronchioloalveolar carcinoma that can mimic infectious etiologies and the potential for dramatic responses to therapy make this an important diagnosis to consider in this setting.

Short-term overfeeding increases resting energy expenditure in patients with HIV lipodystrophy.

BACKGROUND: HIV lipodystrophy and other lipodystrophy syndromes are characterized by extensive loss of subcutaneous adipose tissue. Lipodystrophy syndromes are also associated with increased resting energy expenditure (REE). This hypermetabolism may be an adaptive response to an inability to store triacylglycerol fuel in a normal manner. OBJECTIVE: This study was done to determine whether REE increases significantly after short-term overfeeding in patients with HIV lipodystrophy. DESIGN: REE was measured in HIV-infected patients with lipodystrophy (n = 9) and in HIV-infected (n = 10) and healthy (n = 9) controls after 3 d on a eucaloric diet and again after 3 d on a diet of similar composition but increased in calories by 50%. RESULTS: After 3 d of eucaloric feeding, REE was significantly higher in patients with HIV lipodystrophy [33.2 +/- 0.27 kcal/kg lean body mass (LBM)] than for both HIV-infected and healthy controls (29.9 +/- 0.26 and 29.6 +/- 0.27 kcal/kg LBM, respectively; P < 0.01). Furthermore, after 3 d of overfeeding, REE increased significantly in patients with HIV lipodystrophy but not in the control groups (33.2 +/- 0.27 vs 34.7 +/- 0.27 kcal/kg LBM; P < 0.01). Finally, postprandial thermogenesis did not differ among the groups after a "normal" test meal but tended to be higher in patients with HIV lipodystrophy than in healthy controls after a large test meal. CONCLUSIONS: Adaptive thermogenesis in the resting component of total daily energy expenditure and in the postprandial period may be a feature of the HIV lipodystrophy syndrome and may be due to an inability to store triacylglycerol fuel in a normal manner.

Short-term energy restriction reduces resting energy expenditure in patients with HIV lipodystrophy and hypermetabolism.

We have previously shown that resting energy expenditure (REE) is increased in patients with HIV lipodystrophy. This hypermetabolism could be the result of an inadequate storage capacity for lipid fuel secondary to atrophy of the subcutaneous adipose tissue depot. Therefore, energy restriction may be able to alleviate this hypermetabolism. To test this hypothesis, we measured REE in HIV-infected patients with lipodystrophy and hypermetabolism and in HIV-infected and healthy controls. Measurements were taken during the overnight fasted state after 3 days on a eu-energetic diet and again after 3 days on a diet of similar composition but reduced in energy by 50%. After 3 days of eu-energetic feeding, REE was significantly higher in HIV-infected patients with lipodystrophy compared with healthy controls (139.5 +/- 1.3 vs 117.2 +/- 1.3 kJ/kg lean body mass, P < .001) and tended to be higher compared with HIV-infected subjects without lipodystrophy (139.5 +/- 13 vs 127.3 +/- 1.4 kJ/kg lean body mass, P = .06). Furthermore, energy restriction caused a significant decline in REE in patients with HIV lipodystrophy (P < .001). This dietary manipulation did not lead to a significant reduction in REE in either HIV-infected or healthy controls. This suggests that energy intake and REE may be uniquely coupled in patients with lipodystrophy as a means to dissipate energy that cannot be stored in a normal manner. A better understanding of this coupling would have important implications for weight regulation in general.

CD4+ T cell targeting of human immunodeficiency virus type 1 (HIV-1) peptide sequences present in vivo during chronic, progressive HIV-1 disease.

We previously detected HIV-1 Gag-specific CD4+ T cells recognizing reference strain viral epitopes in subjects with progressive, chronic infection. To test whether these CD4+ T cells persist in vivo by failing to recognize autologous HIV-1 epitopes, we compared autologous plasma HIV-1 p24 nucleotide sequences with targeted HXB.2 strain Gag p24 CD4+ T cell epitopes in nine chronically infected, untreated subjects. In five responding subjects, 10 of 26 HXB.2 strain p24 peptides targeted by CD4+ T cells exactly matched autologous plasma viral sequences. Four subjects with plasma viral loads >100,000 copies/mL had no measurable p24-specific CD4+ T cell responses despite carrying HIV-1 strains that matched HXB.2 sequences at predicted epitopes. These results show that HIV-1-specific CD4+ T cells can persist in chronic HIV-1 infection despite recognition of epitopes present in vivo. However, with high-level in vivo HIV-1 replication, CD4+ T cells targeting autologous HIV-1 may be non-responsive or absent.

Apparent resolution of type 2 diabetes mellitus after initiation of potent antiretroviral therapy in a man from Africa with HIV infection.

We describe a 52-year-old African man with human immunodeficiency virus infection and type 2 diabetes mellitus whose diabetes resolved as viral replication was suppressed with protease inhibitor-based antiretroviral therapy. This case suggests that human immunodeficiency virus infection itself can precipitate overt diabetes mellitus.

HIV-1-specific CD4+ T-cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia.

OBJECTIVES: To determine whether increased sequence variation occurs in regions of endogenous HIV-1 targeted by HIV-1-specific CD4 T cells. The presence of increased variation would be suggestive of immune evasion by HIV-1. DESIGN: We performed a cross-sectional study of untreated HIV-1-infected subjects measuring HIV-1-specific interferon (IFN)-gamma-secreting CD4 T-cell responses against epitopes in Gag p17 and p24 and concurrent endogenous plasma HIV-1 RNA epitope sequence variation. METHODS: CD8- depleted IFNgamma enzyme-linked immunospot assays were used to identify regions of HIV-1 Gag recognized by CD4 T cells. Reverse transcriptase polymerase chain reaction and TA cloning were used to sequence endogenous plasma HIV-1 virus and identify variants. RESULTS: CD4 T-cell epitopes in Gag p17 and p24 were identified in 5 individuals, and concurrent sequence information on endogenous HIV-1 was obtained in 4 of these individuals. Endogenous plasma HIV-1 RNA sequencing revealed no intrapatient amino acid sequence variation through identified epitopes. CONCLUSIONS: In these chronically infected viremic subjects, circulating IFNgamma-secreting CD4 T-cell responses were directed against epitope sequences found in the predominant strain of endogenous circulating plasma HIV-1, suggesting that escape from CD4 T-cell responses is not a common process in vivo.

Mycobacterium avium complex peritonitis in the setting of cirrhosis: case report and review of the literature.

Mycobacterium avium complex is a rare cause of peritonitis. We report here the fourth case in the literature of MAC peritonitis associated with cirrhosis in the absence of AIDS, and discuss the possibility of different etiologies in persons with and without AIDS.