HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

OBJECTIVE: The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART). METHODS: A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME). RESULTS: Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001). CONCLUSIONS: Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared therapeutic approach.

Offering HIV testing in an acute medical admissions unit in Newcastle upon Tyne.

The objective of this study was to offer HIV testing to all patients attending the acute medical admissions unit (AMU) in Newcastle upon Tyne to assess feasibility, acceptability and point prevalence in accordance with the 2008 UK National HIV testing guidelines. A prospective audit was performed offering HIV testing to all patients with the capacity to give verbal consent who attended the AMU. In total, 3,753 eligible patients were admitted during the audit period and 586 (15.6%) were considered for testing. Of those approached, 108 (18.4%) were clinically ineligible to test and 478 were offered a test. In the 396 patients who consented (82.8%), there were two new HIV diagnoses (point prevalence 0.5%). Offering HIV testing in an AMU setting is feasible and acceptable to patients. The high uptake rate but low proportion of admissions tested suggests a lack of confidence of medical staff in offering a test. Misconceptions regarding HIV testing remain and greater education is required for healthcare workers.

Missed opportunities to diagnose syphilis prior to the development of sight-losing uveitis.

The incidence of syphilis in the UK is rapidly rising. Uveitis (intraocular inflammation) usually occurs in the secondary or later stages of syphilis infection and is sight-threatening. Methods A retrospective analysis of the demographics, presentation, diagnosis, treatment and outcomes of patients with syphilitic uveitis managed in Newcastle from 2005-2016 was carried out. Results Ten males (19 eyes) with syphilitic uveitis had a generally good visual and serological response to penicillin treatment. In eight of the patients there had been a failure to test for syphilis during assessments by various medical practitioners for unexplained symptoms that were attributable to syphilis prior to the eye involvement. Conclusion Uveitis associated with syphilis can be sight-threatening but responds well to treatment. In our case series there were multiple missed opportunities to diagnose syphilis prior to presentation with eye disease, with a general failure of healthcare professionals to take an adequate sexual history.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Bronchial responsiveness in AIDS patients with Pneumocystis carinii pneumonia.

OBJECTIVE: To study bronchial responsiveness to inhaled histamine among HIV-infected patients. DESIGN: A prospective study in a regional infectious diseases unit. METHODS: Three groups of patients were studied. Group A consisted of AIDS patients (n = 7) who had had Pneumocystis carinii pneumonia (PCP), group B of AIDS patients (n = 7) not known to have had PCP, and group C of asymptomatic HIV-positive patients (n = 7). Inhalational histamine challenge in cumulative doses (0.03-3.91 mumol) was administered by a nebulizer. It was stopped when the forced expiratory volume in 1 sec (FEV1) had fallen by more than 20% of the baseline value or when the cumulative dose administered exceeded 3.91 mumol. Response was measured as percentage change in FEV1 from the baseline value, and plotted on a linear scale against log dose histamine to enable the dose of histamine causing a 20% fall in FEV1 (PD20-FEV1) to be determined. Statistical analysis was performed by analysis of variance. RESULTS: AIDS patients previously infected with PCP (group A) had a significantly lower PD20-FEV1 [(mean, 0.31 mumol; range, 0.07-0.95; s.d., 0.31; s.e., 0.12; 95% confidence interval (CI), 0.03-0.60)] than AIDS patients without PCP (group B; mean, 1.01 mumol; range, 0.20-2.00; s.d., 0.67; s.e., 0.25; 95% CI, 0.39-1.64) or asymptomatic HIV-positive patients (group C; mean, 1.28 mumol; range, 0.49-1.80; s.d., 0.51; s.e., 0.19; 95% CI, 0.81-1.76) (P < 0.05). There was no significant difference between groups B and C. All patients recorded PD20-FEV1 within the asthmatic range of bronchial hyper-responsiveness. CONCLUSIONS: These results suggest that development of PCP in a small group of HIV-infected patients induces a significantly greater degree of bronchial hyper-responsiveness.

Retrospective study of CMV retinitis in patients with AIDS.

OBJECTIVES: To study the characteristics of clinical presentations and treatment outcome of patients with HIV infection who developed cytomegalovirus(CMV) retinitis. METHODS: A retrospective study for the period 1986-97 at the regional Unit of Infectious Diseases, Newcastle General Hospital; a teaching hospital in the north-east of England. Twenty-seven patients with advanced HIV disease and clinically confirmed CMV retinitis were studied. The mean age was 40.8 years, standard deviation +/-6.3 years. The male : female ratio was 25 : 2. Twenty-six of the patients were white Caucasians and one was of Afro-Caribbean origin. RESULT: The median time between the first AIDS-defining diagnosis and development of CMV retinitis was 1.5 years and the CD4+ cell count at the time of diagnosis of CMV retinitis was 7/mm3. After 14 months of treatment. 80% of patients on mono antiretroviral therapy had impairment of sight (visual acuity 3/60) versus 30% for those on triple antiretroviral therapy. In the same period, the survival rate was 18 versus 70% for mono versus triple antiretroviral therapy, respectively. CONCLUSION: The outcome for patients with CMV retinitis was significantly better for those who were on triple than for those on mono antiretroviral therapy.

Greater emotional distress is associated with accelerated CD4+ cell decline in HIV infection.

An investigation was conducted to explore the relationship between emotional distress and HIV progression. One hundred twenty-five homosexual, HIV-positive males participated in a 12-month longitudinal investigation. Psychosocial data were collected at 6-month intervals and CD4+ data were collected from diagnosis to the end of the investigation. Principal component analyses were performed initially to identify factors of emotional distress and health status. In addition, CD4+ reliability assessments were performed to ensure the validity of the prognostic assessments made. As a result of these analyses, 47 individuals were eligible for the main analyses. The results from a stepwise regression revealed that disease progression was significantly predicted by CD4+ count at diagnosis (32% of variance) and emotional distress (17% of variance), but was unrelated to subjective perceptions of health. The data suggest that some of the variability in HIV progression can be attributed to emotional distress.

Mortality and survival trends in patients with AIDS in north east England from 1984-1992.

OBJECTIVE: to study trends in mortality and survival in patients with AIDS attending an ID unit. METHOD: retrospective analysis of patients developing an AIDS-defining illness between April 1984, and November 1992. Survival was analysed by calculation of survival product-limit. RESULTS: 71 patients were analysed (including four women), 23 of whom are still alive. Pneumocystis carinii pneumonia (PCP) was the most frequent AIDS-index diagnosis: n = 36 (51%); 24 of these patients have died. HIV encephalopathy was the most frequent diagnosis at death; n = 16 (22.5%), followed by mycobacterial infection; n = 11 (15.5%), and PCP and CMV infection, each occurring in 10 (14%). One-, 2- and 3-year survival probabilities for patients with AIDS before 1987 were 0.46, 0.15 and 0 compared with probabilities of 0.63, 0.5 and 0.3 in those diagnosed after 1987; log rank -P < 0.01. One- and 2-year survival probabilities in patients who received at least 3 months' zidovudine (AZT) therapy were 0.76 and 0.53 in those who are still alive compared with 0.55 and 0.33 in the deceased, while values for deceased AZT-naive patients were 0.29 and 0.1; -P < 0.01. Thirteen (27%) deaths occurred within 2 months of an AIDS-index disease. In 10 patients this was their first presentation to the department. PCP accounted for 8 (61%) of these deaths. CONCLUSIONS: survival in patients with AIDS has increased since 1987, when AZT was introduced. Early AIDS-related deaths are frequent in patients who have had no prior medical care. This has implications for education and provision of care in individuals with asymptomatic HIV infection.

Risks and behaviour in patients requesting HIV tests.

A prospective survey to assess reasons for requesting HIV tests, perceived HIV risk and sexual behaviour in genitourinary medicine clinic attenders was carried out. Overall 123 (38.6%) were concerned about casual sexual contacts. Homosexual and bisexual men may have changed their sexual behaviour as a result of public health campaigns but publicity had little immediate effect on prompting people to have an HIV test.

Cryptococcosis: an unusual opportunistic infection complicating B cell lymphoproliferative disorders.

We report two cases of cryptococcosis in patients with Waldenstrom's macroglobulinaemia and chronic lymphocytic leukaemia that responded to prolonged therapy with systemic amphotericin and flucytosine. Cryptococcosis, although more common in those with impaired cell mediated immunity, should also be considered as a complication in patients with impaired antibody responses.

Cytomegalovirus cholecystitis and colitis associated with the acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) is an important cause of acalculous gangrenous cholecystitis in immunocompromised persons. We report a case of acalculous acute cholecystitis and active colitis associated with CMV in a patient suffering from the acquired immune deficiency syndrome. The condition was treated successfully with surgery and 9-(1,3,-dihydroxy-2-propoxymethyl)guanine intravenously.

The role of aerosol pentamidine prophylaxis.

Pneumocystis carinii pneumonia (PCP) is the most frequent opportunistic infection in patients with AIDS, occurring in 80% and recurring in 50% of patients within 12 months of the first episode. Prophylaxis for PCP is recommended if the CD4+ cell count is < 200 x 10(6)/l or 20% of the total lymphocyte count, or after an episode of PCP. The most effective prophylactic agent currently is trimethoprim-sulphamethoxazole and should be the drug of choice but alternatives such as aerosol pentamidine are being increasingly used for patients who cannot tolerate this combination or other oral preparations. If aerosol pentamidine is used and administered via a Respigard II Marquest nebulizer, the dosage should be higher than the currently recommended monthly dosage of 300 mg.

A UK centre's experience of mycobacterial infections in HIV-infected patients.

A descriptive retrospective review of 26 patients with mycobacterial infection; 7 Mycobacterium tuberculosis (MTB), 17 Mycobacterium avium complex (MAC), one M. xenopei and one M. kansasii. Diagnosis of non-tuberculous mycobacteria (NTM) was made mainly from blood in 68%, with biopsy material initially useful in 68%. All MTB were fully sensitive. No patients received MAC chemoprophylaxis, yet resistance to rifabutin, ciprofloxacin and ethambutol was noted. It is important to examine the UK experience of mycobacterial infection; individual centres may find it useful to review infecting organisms and resistance patterns.

Retrospective study of malaria cases treated in Newcastle General Hospital between 1990 and 1996.

BACKGROUND: Malaria, in particular Falciparum malaria, continues to pose a substantial risk to travelers to endemic areas. METHODS: In this study we examined 93 case notes of patients with malaria treated in our department between 1990 and 1996. RESULTS: Forty-seven (50.5%) patients had infection with Plasmodium falciparum, 41 (44.1%) had Plasmodium vivax and 5 (5.4%) had Plasmodium ovale. One of these patients had a dual infection with P. falciparum and P. vivax. None of our patients had Plasmodium malariae. Forty-four of the P. falciparum cases (93.6%) were imported from sub-Saharan Africa, 33 of the P. vivax cases (78.5%) were imported from the Indian subcontinent. All the P. ovale cases were imported from sub-Saharan Africa. Fifty-four of our patients (58.1%) did not take any form of chemoprophylaxis. Forty-two out of 93 (45.2%) of the "travelers" were settled immigrants in the UK. Seventy-eight percent of travelers of British caucasian origin took prophylaxis whereas only 13.5% of travelers of ethnic minorities origin took prophylaxis. CONCLUSIONS: Greater awareness of the risk of malaria by travelers and medical practitioners in UK must be encouraged and in particular appropriate chemoprophylaxis instituted for travelers to chloroquine-resistant areas.

A case of hypersensitivity to gelafundin.

We report a case of cardiovascular collapse after gelafundin infusion, a commonly used colloid. Risk factors for such a reaction and suggested alternative are reviewed. Awareness of this reaction is highlighted in view of its increasing popularity.