Alison Morris

A Prospective, Blinded Study of Quantitative Touch-Down Polymerase Chain Reaction Using Oral-Wash Samples for Diagnosis of Pneumocystis Pneumonia in HIV-Infected Patients

Oral-wash samples obtained during 113 episodes of suspected Pneumocystis pneumonia (PCP) in human immunodeficiency virus-infected patients were tested by use of a quantitative touch-down PCR (QTD PCR) assay. QTD PCR had a sensitivity of 88% and a specificity of 85%. Treatment for PCP prior to oral wash collection had an impact on the sensitivity, and PCR-positive oral-wash samples obtained within < or =1 day of treatment from patients without PCP had significantly fewer copies per tube than did those from patients with PCP; thus, application of a post hoc cut-off value of 50 copies/tube increased the specificity to 100%. QTD PCR of oral-wash samples can be an accurate and noninvasive method for diagnosis of PCP.

HIV and Chronic Obstructive Pulmonary Disease: Is It Worse and Why?

Smoking-related diseases, such as chronic obstructive pulmonary disease (COPD), are of particular concern in the HIV-infected population. Smoking rates are high in this population, and long-term exposure to cigarette smoke in the setting of HIV infection may increase the number of complications seen. Before the era of combination antiretroviral therapy, HIV-infected persons were noted to have an accelerated form of COPD, with significant emphysematous disease seen in individuals less than 40 years old. Unlike many of the AIDS-defining opportunistic infections, HIV-associated COPD may be more common in the current era of HIV because it is frequently reported in patients without a history of AIDS-related pulmonary complications and because many aging HIV-infected individuals have had a longer exposure to smoking and HIV. In this review, we document the epidemiology of HIV-associated COPD before and after the institution of combination antiretroviral therapy, review data suggesting that COPD is accelerated in those with HIV, and discuss possible mechanisms of HIV-associated COPD, including an increased susceptibility to chronic, latent infections; an aberrant inflammatory response; altered oxidant-antioxidant balance; increased apoptosis associated with HIV; and the effects of antiretroviral therapy.

Pneumocystis colonisation is common among hospitalised HIV infected patients with non-Pneumocystis pneumonia

Background: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis, although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii. Methods: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing. Results: 68% (117/172) of all patients were colonised with Pneumocystis. No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count ⩽50 cells/μl (unadjusted OR 2.4, 95% CI 1.09 to 5.48; pu200a=u200a0.031) and using PCP prophylaxis (unadjusted OR 0.55, 95% CI 0.29 to 1.07; pu200a=u200a0.077) were associated with Pneumocystis colonisation, although the latter association may have been due to chance. After adjustment for CD4+ T cell count, use of PCP prophylaxis was associated with a decreased odds of colonisation (adjusted OR 0.45, 95% CI 0.21 to 0.98; pu200a=u200a0.045). 11 patients who were colonised were subsequently readmitted for evaluation of a second episode of pneumonia; three were found to be colonised again, but none had PCP. Conclusions: The majority of hospitalised HIV infected patients with non-PCP pneumonia are colonised with Pneumocystis. Failure to use co-trimoxazole prophylaxis and severe immunosuppression are associated with an increase in the odds of colonisation. Pneumocystis colonisation among hospitalised patients does not commonly lead to PCP.

Low tidal volume ventilation is associated with reduced mortality in HIV-infected patients with acute lung injury

Background: Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A study was undertaken to identify therapies and clinical factors associated with mortality in acute lung injury among HIV-infected patients with respiratory failure in the period 1996–2004. A secondary aim was to compare mortality before and after introduction of a low tidal volume ventilation protocol in 2000. Methods: A retrospective cohort study was performed of 148 consecutive HIV-infected adults admitted to the ICU at San Francisco General Hospital with acute lung injury requiring mechanical ventilation. Demographic and clinical information including data on mechanical ventilation was abstracted from medical records and analysed by multivariate analysis using logistic regression. Results: In-hospital mortality was similar before and after introduction of a low tidal volume ventilation protocol, although the study was not powered to exclude a clinically significant difference (risk difference −5.4%, 95% CI −21% to 11%, pu200a=u200a0.51). Combination antiretroviral therapy was not clearly associated with mortality, except in patients with Pneumocystis pneumonia. Among all those with acute lung injury, lower tidal volume was associated with decreased mortality (adjusted odds ratio 0.76 per 1 ml/kg decrease, 95% CI 0.58 to 0.99, pu200a=u200a0.043), after controlling for Pneumocystis pneumonia, serum albumin, illness severity, gas exchange impairment and plateau pressure. Conclusions: Lower tidal volume ventilation is independently associated with reduced mortality in HIV-infected patients with acute lung injury and respiratory failure.

Pneumocystis carinii Dihydropteroate Synthase Genotypes in HIV‐infected Persons Residing in San Francisco: Possible Implications for Disease Transmission

ion was designed to examine this possibility. Alternatively, the high frequency of DHPS mutations seen in our cohort, including those patients who had never used PCP prophylaxis, may be the result of transmission of P. curinii mutant DHPS genotypes, either from another person or fra an as yet unidentified environmental source. Whether the reservoir of human P. carinii resides solely in humans or also in the environment and whether PCP results from reactivation of a latent infection acquired early in childhood or from a more recent exposure and infection remains unclear. The current study cannot determine whether FCP in humans results from person to person transmission of P. curinii. However. our finding that patients who resided in a certain area of San Francisco were significantly more likely to present with a PCP specimen that contained a mutant DHPS genotype than patients who resided outside of this area argues for the possibility that at least some PCP cases result from a recent infection since mutant DHPS genotypes are virtually never seen in PCP specimens prior to 1990. Furthermore, the influence of geography on DHPS genotype in this and other studies [ 1,3] suggests that the specific factors that are involved in disease transmission might include ones found to a greater degree in certain geographic regions and in certain areas of San Francisco. Future studies should be conducted to explore explanations for the presence of mutant DHPS genotypes in persons without PCP prophylaxis, including the influence of sulfa medication for reasons unrelated to PCP prophylaxis and the possibility that the disease in humans may result from person to person transmission.

Pandemic (H1N1) 2009 and HIV Infection.

To the Editor: In the United States during spring and fall of 2009, pandemic (H1N1) 2009 influenza A virus resulted in 2 major outbreaks of disease. Initial reports identified immunosuppression, including HIV infection, as a risk factor for the development of severe influenza (1–5). Subsequent reports did not confirm this association, but the number of HIV-infected patients in these studies was small (6,7). We describe the clinical course of pandemic (H1N1) 2009 in HIV-infected persons in a US hospital. n nDuring 2009, 23 cases of laboratory-confirmed pandemic (H1N1) 2009 in HIV-infected persons were identified at Harborview Medical Center (Seattle, WA, USA) by querying the University of Washington HIV Information System (a database that enables complete capture of all HIV testing results at Harborview Medical Center) and by querying the Harborview Infection Control Registry for influenza subtype H1N1 infections. Most cases occurred during October and November. Baseline patient characteristics are noted in the Table. Most patients who sought care had fever and cough; median duration of symptoms before seeking care was 4 days. Overall mortality rate for the entire cohort was 8.7%. n n n nTable n nBaseline characteristics for HIV-infected patients with pandemic (H1N1) 2009, Seattle, Washington, USA, 2009* n n n nOf the 23 patients, only 2 were not treated for influenza; each had mild signs and symptoms and neither required hospital admission. Each of the remaining 13 outpatients received a 5-day course of treatment with oseltamivir. The 8 patients who required hospitalization received therapy for a median of 6 (range 1–22) days. n nOverall mortality rate among HIV-infected patients hospitalized for pandemic (H1N1) 2009 infection was 25% (2 of 8 patients). The 2 inpatients who died had each received >14 days of therapy with oseltamivir. Three inpatients were admitted to the intensive care unit (ICU); of these, 2 had hypoxemic respiratory failure and bilateral infiltrates at the time of admission and a later diagnosis of acute respiratory distress syndrome, and 1 was hospitalized with fever and hemodynamic instability. Each patient with acute respiratory distress syndrome subsequently died; 1 had methicillin-resistant Staphylococcus aureus pneumonia at the time of admission, and 1 had severe hypoxemic respiratory failure requiring the use of rescue therapies (e.g., prone positioning and inhaled nitric oxide) and later treatment for ventilator-associated pneumonia. Of the 2 patients who died, 1 had concurrent conditions, including preexisting interstitial lung disease (believed to be associated with crack cocaine use) and a low CD4 cell count of 127 cells/µL, and 1 had a preserved CD4 cell count >1,000 cells/µL, but 8 days passed before anti-influenza therapy was started, and thrombotic complications developed before death. The lengths of ICU stay for the patients who died were 13 and 29 days. n nOur findings are similar to those reported by others, suggesting that HIV infection alone does not appear to be a risk factor for severe pandemic (H1N1) 2009, provided that patients are not severely immunocompromised, do not have other risk factors associated with poor outcomes, and are treated for influenza soon after signs and symptoms develop (6–9). Most of the 23 patients described here had mild disease and were treated as outpatients. Only 3 required ICU admission, and 2 of these died. Although the mortality rate reported here is higher than that reported in other studies, our sample size was relatively small, and the patients who died had additional risk factors for poor outcomes. n nOur study has several limitations. It is a retrospective study, and HIV-infected patients at Harborview Medical Center were not all prospectively tested for pandemic (H1N1) 2009. Most pandemic (H1N1) 2009 virus was detected by reverse transcription PCR of nasal swab specimens; this testing was only available after October 2009, during the second wave of influenza. Infections occurring during the spring were diagnosed by insensitive testing with fluorescent antibody and culture, diagnosed by clinical criteria alone and not included in this analysis, or missed altogether. n nBecause of differences in pandemic (H1N1) 2009 virus testing, we were unable to compare the incidence of pandemic (H1N1) 2009 virus infection and outcomes between HIV-infected and HIV-uninfected patients. A total of 189 persons received a diagnosis of pandemic (H1N1) 2009 at Harborview Medical Center in 2009, and 79 were hospitalized. A total of 8 (10%) of 79 patients with pandemic (H1N1) 2009 died, including the 2 HIV-infected patients reported here. However, during the peak of the epidemic, many HIV-infected outpatients, who were receiving antiretroviral therapy and had preserved CD4 cell counts, were advised to remain at home if they had mild influenza-like symptoms and were therefore not tested for influenza. This circumstance could have produced a bias toward diagnosing and reporting only more severe disease. Outpatients who had influenza-like symptoms were tested and treated empirically pending test results. Our case series of HIV-infected patients with pandemic (H1N1) 2009 at a single institution in the United States suggests that HIV itself does not appear to be as major a risk factor for severe disease as are other previously reported concurrent conditions, delays in treatment, and development of secondary bacterial pneumonia.