Co-infection of Pneumocystis jirovecii pneumonia and pulmonary CMV in a infant with X-linked severe combined immunodeficiency.

We herein report a rare case of co-infection of Pneumocystis jirovecii pneumonia and pulmonary CMV in a 3-month-old infant with X-linked severe combined immunodeficiency, in which diagnostic clues were obtained from the bronchoalveolar lavage fluid. We focus on the value of cytological diagnosis of P. jirovecii pneumonia and pulmonary CMV in the bronchoalveolar lavage fluid. Recognizing morphological characteristics of these pathogenic microorganisms is important to get timely diagnosis and treatment for the patients. Furthermore, repeated severe infections in infants should remind us to screen for immunosuppressed states.

Outcomes of HIV-associated pneumocystis pneumonia at a South African referral hospital.

HIV-associated pneumocystis pneumonia (PCP) is increasingly recognized as an important cause of severe respiratory illness in sub-Saharan Africa. Outcomes of HIV-infected patients with PCP, especially those requiring intensive care unit (ICU) admission, have not been adequately studied in sub-Saharan Africa. The aim of this study was to describe the clinical phenotype and outcomes of HIV-associated PCP in a group of hospitalized South African patients, and to identify predictors of mortality. We conducted a retrospective record review at an academic referral center in Cape Town. HIV-infected patients over the age of 18 years with definite (any positive laboratory test) or probable PCP (defined according to the WHO/CDC clinical case definition) were included. The primary outcome measure was 90-day mortality. Logistic regression and Cox proportional hazards models were constructed to identify factors associated with mortality. We screened 562 test requests between 1 May 2004 and 31 April 2015; 124 PCP cases (68 confirmed and 56 probable) were included in the analysis. Median age was 34 years (interquartile range, IQR, 29 to 41), 89 (72%) were female, and median CD4 cell count was 26 cells/mm3 (IQR 12 to 70). Patients admitted to the ICU (n = 42) had more severe impairment of gas exchange (median ratio of arterial to inspired oxygen (PaO2:FiO2) 158 mmHg vs. 243 mmHg, p < 0.0001), and increased markers of systemic inflammation compared to those admitted to the ward (n = 82). Twenty-nine (23.6%) patients were newly-diagnosed with tuberculosis during their admission. Twenty-six (61.9%) patients admitted to ICU and 21 (25.9%) admitted to the ward had died at 90-days post-admission. Significant predictors of 90-day mortality included PaO2:FiO2 ratio (aOR 3.7; 95% CI, 1.1 to 12.9 for every 50 mgHg decrease), serum LDH (aOR 2.1; 95% CI, 1.1 to 4.1 for every 500 U/L increase), and concomitant antituberculosis therapy (aOR 82; 95% CI, 1.9 to 3525.4; P = 0.021). PaO2:FiO2 < 100 mmHg was significantly associated with inpatient death (aHR 3.8; 95% CI, 1.6 to 8.9; P = 0.003). HIV-associated PCP was associated with a severe clinical phenotype and high rates of tuberculosis co-infection. Mortality was high, particularly in patients admitted to the ICU, but was comparable to other settings. Prognostic indictors could be used to inform ICU admission policy for patients with this condition.

Multicenter study of trimethoprim/sulfamethoxazole-related hepatotoxicity: incidence and associated factors among HIV-infected patients treated for Pneumocystis jirovecii pneumonia.

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Prevalence of Pneumocystis jirovecii pneumonia (2010-2013): the first Croatian report.

Pneumocystis jirovecii is an important cause of interstitial pneumonia particularly among immunocompromised hosts. We analysed the prevalence of P. jirovecii pneumonia (PCP) among HIV-infected and HIV-uninfected patients presented with interstitial pneumonia or acute respiratory syndrome hospitalized in six Croatian tertiary care hospitals. Over four-year period (2010-2013), a total of 328 lower respiratory tract samples: 253 (77.1%) bronchoalveolar lavage fluid, 43 (13.1%) tracheal aspirates and 32 (9.8%) bronchial aspirates from 290 patients were examined by real-time polymerase chain reaction (PCR). PCP was detected in 23 (7.9%) patients. The prevalence of PCP differed significantly among tested groups (χ2 = 95.03; d.f. = 3; p < 0.001). HIV-infected patients were more often positive (56.6%, 95%CI = 37.3-72.4) compared to other groups (patients with malignant disease 7.7%, 95%CI = 2.6-20.3; transplant patients 7.7%, 95%CI = 2.2-24.1; patients with other diagnosis 1.5%, 95%CI = 0.5-4.4). Majority of HIV-positive patients (80%) were newly diagnosed cases. Our results indicate that HIV-infected patients still represents the main risk group for P. jirovecii infection. PCP is responsible for pneumonia in 56.6% HIV-positive patients in Croatia, primarily those who do not know that they are HIV infected.

The prevalence of airway obstruction among Japanese HIV-positive male patients compared with general population; a case-control study of single center analysis.

BACKGROUND AND OBJECTIVE: Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. METHODS: Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. RESULTS: Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/µL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. CONCLUSIONS: HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.

Pneumocystis jirovecii pneumonia in HIV-negative patients: a prospective study with focus on immunosuppressive drugs and markers of immune impairment.

Pneumocystis jirovecii pneumonia (PCP) is emerging in HIV-negative patients, for whom the prognosis is significantly worse than in HIV-infected patients and risk factors are poorly characterized. We performed an observational, multi-centre, prospective study of 56 consecutive cases of documented PCP in HIV-negative patients, and found that: (1) the main underlying conditions were haematological malignancies (43%), solid tumours (25%), inflammatory diseases (20%), and solid organ transplantation (7%); (2) most patients (80%) had received prolonged corticosteroids, with a mean daily dose of 47.3 ± 32.8 mg equivalent prednisone when PCP was diagnosed, and a mean cumulative dose of 5807 ± 5048 mg over the last 12 months; and (3) the median CD4 cell count was 0.12 × 109/l (range 0.0-1.42), with a median CD4/CD8 ratio of 1.32 (0.0-6.4). These findings may be used to better target PCP prophylaxis according to the level of risk and contribute to decrease the burden of PCP in HIV-negative patients.

Outcomes of non-HIV-infected patients with Pneumocystis pneumonia and concomitant pulmonary cytomegalovirus infection.

BACKGROUND: The pathogenic effect of concomitant pulmonary cytomegalovirus (CMV) infection on morbidity and mortality of Pneumocystis jirovecii pneumonia (PCP) has been questioned in the case of non-HIV-infected patients. METHODS: We conducted a retrospective cross-sectional study of patients who were diagnosed with PCP by bronchoalveolar lavage. We compared demographics, clinical characteristics, morbidity, and mortality in non-HIV-infected PCP patients with (n = 31) and without (n = 75) pulmonary CMV infection. Morbidity was assessed by length of hospital stay, admission to the intensive care unit, and use of mechanical ventilation. Mortality was defined as 30-day and 90-day all-cause mortality. RESULTS: Morbidity and mortality did not differ between PCP patients with and without pulmonary CMV infection. In multivariate analysis using the Cox proportional hazard model, haematological malignancy (relative risk (RR) 0.20, 95% confidence interval (95% CI) 0.06-0.71), PCP treatment duration (RR 0.81, 95% CI 0.75-0.88), changing to a second-line regimen due to treatment failure (RR 4.51, 95% CI 1.61-12.64), and mechanical ventilation (RR 17.99, 95% CI 4.83-67.04) were independently associated with 30-day all-cause mortality. Being a solid organ transplant recipient (RR 0.17, 95% CI 0.05-0.56) and the use of mechanical ventilation (RR 6.49, 95% CI 2.84-14.83) were independently associated with 90-day all-cause mortality. However, concomitant pulmonary CMV infection was not associated with either 30-day or 90-day mortality. CONCLUSIONS: Our results suggest that concomitant pulmonary CMV infection does not significantly affect the prognosis of PCP, as indicated by morbidity and mortality in non-HIV-infected patients with PCP. Based on this result, we propose that it is not essential to administer an anti-CMV regimen when CMV is co-isolated from the bronchoalveolar lavage in patients with PCP.

Métodos diagnósticos tintoriales para pneumocystis jirovecii / Diagnostic methods staining for Pneumocystis jirovecii

Se realizó una búsqueda en base de datos Cabdirect bajo los términos ®Pneumocystis-stain¼ entre los años 1990 a 2010., revisándose 109 trabajos relacionados al diagnóstico y estudio de la neumocistosis. Las metodologías empleadas fueron clasificadas en 6 grupos según su frecuencia: Tinción con Gomori-Grocott; Giemsa; Azul de toluidina; Otras tinciones (pap, blanco de calcofluor, gram, may grunwald giemsa);además de inmunofluorescencia directa y PCR (en cualquiera de sus variantes). Se observó una constante en el empleo de las tinciones histológicas en ambas décadas, mayormente con las tinciones de Gomori-Grocott y Giemsa. Sin embargo y como es de esperar, aumenta en la segunda década la tendencia del diagnóstico a través de técnicas moleculares.

Was performed a database search Cabdirect under the terms "pneumonia-stain" between the years 1990 to 2010, 109 papers being revised, and study related to the diagnosis of pneumocystosis. The methodologies used were classified into six groups according to their frequency: Gomori-Grocott stain, Giemsa, toluidine blue, Other stains (pap, calcofluor white, Gram, May Grunwald Giemsa), in addition to direct immunofluorescence and PCR (in any of their variants). There was a constant in the use of histological stains in both decades, mostly with Gomori Grocott staining and Giemsa. However, as expected, increases in the second decade, the trend of diagnosis using molecular techniques.

Immunohistochemical and ultra-structural detection of Pneumocystis in wild boars (Sus scrofa) co-infected with porcine circovirus type 2 (PCV2) in Southern Brazil.

Pneumocystis spp. are fungi that are able to infect a variety of host species and, occasionally, lead to severe pneumonia. Porcine circovirus type 2 (PCV2) is an important viral pathogen which affects both swine and wild boar herds worldwide. Co-infection between PCV2 and other pathogens has been reported, and the secondary immunodeficiency caused by the virus may predispose to these co-infections. In the present study, postmortem tissue samples obtained from wild boar herds in Southern Brazil were analyzed by histopathology, ultra-structural observation, and immunohistochemistry. Forty-seven out of seventy-eight (60%) wild boars showed clinical signs, gross, and histopathological lesions characteristic of infection by PCV2. Pneumocystis was detected by immunohistochemistry in 39 (50%) lungs and viral antigens of PCV2 were found in 29 (37.2%) samples. Concomitant presence of Pneumocystis and PCV2 were observed in 16 (20.5%) of the wild boars. Cystic and trophic forms of Pneumocystis were similar to previously described ultra-structural observations in other mammals.

Lessons learned about opportunistic infections in southeast Asia.

Southeast Asia is a region where the number of people infected with HIV/AIDS is one of the fastest growing in the world. Tuberculosis (TB) has grown along with the HIV epidemic. TB is not only the most common AIDS-defining illness but is also the leading cause of morbidity and mortality in AIDS patients. Cryptococcosis (meningitis or disseminated) is one of the most common opportunistic infections in AIDS patients. Cryptococcal meningitis is the first in the differential diagnosis considered with meningeal irritation. Penicillosis, a unique systemic mycosis, is an important emerging public health problem and has been classified as an AIDS defining illness in endemic areas like Thailand. Pneumocystis carinii (jiroveci) pneumonia has been one of the most important opportunistic infections in AIDS patients. Among parasitic infections, cryptosporidiosis is the most common intestinal protozoan infection relating to diarrhea in AIDS patients and toxoplasmosis is the only parasitic infection of the nervous system with a substantial incidence, up to 14.8%. Cytomegalovirus (CMV) retinitis has a lower prevalence compared to other opportunistic infections. In the era of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has significantly reduced in the past few years. Subsequently, the phenomena of immune restoration inflammatory syndrome (IRIS) in AIDS patients has been reported in this region as a result of HAART.

Progressive multifocal leukoencephalopathy in a patient with B-cell lymphoma during rituximab-containing chemotherapy: case report and review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyomavirus. We describe a rare case of PML in a 48-year-old female patient with diffuse large B-cell lymphoma who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy. While she was undergoing five cycles of R-CHOP, she noticed gradually progressive neurological symptoms, such as slurred speech and gait disturbance, and she eventually developed high-grade fever. She also developed Pneumocystis jiroveci pneumonia. The neurological symptoms deteriorated thereafter, and she developed spastic quadriparesis and bulbar palsy. Magnetic resonance imaging showed hyperintensity within the right cerebellar hemisphere on T2-weighted images. Polymerase chain reaction-based tests of the cerebrospinal fluid revealed the presence of the JC virus. Despite intravenous and intrathecal cytarabine treatment, the patient died of PML 5 months after it was diagnosed. Retrospective analysis of her laboratory data showed that her CD4(+) T-cell count before R-CHOP therapy had decreased to 68 microL(-1). Thus, when administering rituximab-containing chemotherapy, even to patients with no prior history of opportunistic infections, attention should be paid to the potential occurrence of PML, particularly in patients with low CD4(+) T-cell counts.

Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4.

OBJECTIVE: HIV-1 isolates are prominently CD4-dependent and, to date, only a few laboratory-adapted CD4-independent strains have been reported. Therefore, whether CD4-independent viruses may exist in HIV-1-infected patients has remained unclear. Here, we report the successful isolation of a CD4-independent clinical HIV-1 strain, designated SDA-1, from the viral quasispecies of a therapy-naive HIV-1 and Pneumocystis jirovecii pneumonia patient in the late-stage of AIDS with extremely low CD4 cell count (CD4 = 1/microl). We characterized this virus and further explored whether it could infect or induce pathological effects in human hepatocytes. DESIGN AND METHODS: To determine coreceptor usage and CD4-independent infection, the HIV-1 envelope (Env)-pseudotypes and Env-chimeric viruses were used. RESULTS: SDA-1 was able to infect CD4 cell lines through either chemokine (C-X-C motif) receptor 4 or CCR5. It still maintained the ability to infect CD4 cells through multiple coreceptors of chemokine (C-X-C motif) receptor 4, chemokine (C-C motif) receptor 5, chemokine (C-C motif) receptor 3 and chemokine (C-C motif) receptor 8. Productive infection by SDA-1 was noted in both CD4-negative hepatoma cells and primary cultured human hepatocytes. Moreover, we demonstrated that SDA-1 could efficiently infect human hepatocytes on both static and mitotic phases through chemokine (C-X-C motif) receptor 4, without inducing apoptotic cell death. CONCLUSION: The present study provides evidence that emergence of CD4-independent HIV-1 virus in vivo may occur in HIV-1-infected patients. In addition, these results shed light on the mechanisms involved in liver damage in HIV-1-infected individuals, which could have important implications concerning the range of mutability and the pathogenesis of AIDS.

S-adenosylmethionine levels in the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection.

BACKGROUND: S-adenosylmethionine (AdoMet) is a key molecule involved in methylation reactions and polyamine synthesis. Pneumocystis carinii are unable to synthesize this molecule and have been shown to scavenge this metabolic intermediate from the plasma of rats during active infection. A prior study involving humans strongly suggested that low levels of plasma AdoMet are sensitive and specific indicators of acute infection. METHODS: From March 2004 through January 2006, we collected plasma AdoMet levels from patients with human immunodeficiency virus (HIV) infection and either confirmed Pneumocystis carinii pneumonia (PCP), confirmed pulmonary tuberculosis, or confirmed bacterial pneumonia. We compared levels in patients with PCP with those in patients with other diseases and also monitored changes in levels during treatment of PCP. RESULTS: Initial AdoMet levels were significantly lower in patients with PCP, and there was no overlap between the groups. Among patients with PCP, levels of AdoMet increased with successful treatment. CONCLUSIONS: Measurement of plasma AdoMet levels in patients with HIV infection who have pulmonary infections can identify those with PCP.

Pneumocystis jiroveci pneumonia (PCP) in HIV-1-negative patients: a retrospective study 2002-2004.

A retrospective study was conducted to describe risk factors associated with Pneumocystis jiroveci pneumonia (PCP) among HIV-negative patients. During 2002-2004, 50 cases of PCP were identified at Rigshospitalet University Hospital on the basis of histology, PCR and clinical symptoms of PCP. Predisposing conditions included haematological malignancy (72%), inflammatory diseases (14%), solid organ transplantation (6%) and other conditions associated with immunodeficiency (8%). The most common treatment related risk factors were steroid usage (76%) and chemotherapy (72%). In 88% of patients who received steroids, dosage was either lowered or given as pulse-therapy in the 2 weeks preceding the onset of symptoms. Only 1 patient was on PCP prophylaxis at diagnosis and only 8 (16%) patients had previously been given PCP prophylaxis. At diagnosis, 78% of patients were lymphopenic. CD4 counts were available in 17 patients. Only 9 patients (52%) had CD4 count values below 300 cells/microl. The overall mortality attributable to PCP was 14% and was significantly associated with delayed diagnosis and treatment. Among immunocompromized HIV-negative patients, PCP should be particularly suspected in the context of steroid treatment and lymphopenia. Although low CD4 count is associated with a higher risk of PCP, the use of CD4 count as guidance for risk identification or prophylaxis among HIV-negative patients appears insufficient.

Non-tuberculosis opportunistic infections and other lung diseases in HIV-infected infants and children.

The diagnosis and management of human immunodeficiency virus (HIV) infected infants and children who do not respond to recommended empiric therapy for acute or chronic pneumonia is a frequent clinical challenge, especially as the greatest burden of childhood HIV-related lung disease occurs in low-income regions where options for investigation and treatment are limited. Lung disease is due to a wider spectrum of causes in HIV-infected than non-infected children. Bacterial pneumonia, viral pneumonia and pulmonary tuberculosis (TB) are common in children throughout the developing world, and the added impact of HIV infection on the incidence and outcome of these diseases is covered in companion articles. This review focuses on lung diseases that are more specifically HIV-related. Pneumocystis jirovecii pneumonia (PJP) is a major cause of pneumonia and death in HIV-infected infants, especially in regions where maternal HIV status is often not known and the provision of PJP prophylaxis for HIV-exposed infants is unusual. Cytomegalovirus is commonly found in the lungs of HIV-infected infants, with implications for the use of corticosteroids for PJP. Lymphoid interstitial pneumonitis, a common cause of persistent respiratory symptoms in HIV-infected children, must be differentiated from pulmonary or miliary TB. The incidence of uncommon causes such as fungal pneumonia or HIV-related pulmonary malignancy varies among regions. The burden of lung disease due to opportunistic infections would be significantly reduced by more widely applying available measures that reduce mother-to-child HIV transmission, by providing cotrimoxazole prophylaxis for HIV-exposed infants, and by increasing the availability of antiretroviral therapy.

Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection.

In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomyopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.

Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003.

OBJECTIVES: To examine changes over a 2-year period in both the mortality rate and the causes of death in a geographically defined HIV-infected population. METHODS: A database search of primary care information for the dates and causes of death for all patients documented with HIV infection and living in Southern Alberta between 1984 and 2003 was undertaken. Sociodemographic and clinical characteristics were obtained. Causes of death were then individually confirmed by reviewing the patients' hospital charts, autopsy reports, or death certificates and coded using the International Classification of Diseases, 9th Revisions. AIDS deaths were reconciled with Public Health Reports. The time span was divided into pre-highly active antiretroviral therapy (HAART) (1984-1996) and current HAART (1997-2003) periods. RESULTS: Between 1984 and 2003, there were 560 deaths in the 1987 individuals living with HIV infection in Southern Alberta. Of these, 436 deaths (78%) occurred pre-HAART and 124 (22%) in the current HAART period. The crude mortality rate declined from 117 deaths per 1000 patient-years pre-HAART to 24 in the current HAART period. In the pre-HAART era, 90% of all deaths were AIDS related whereas only 67% were AIDS related in the current HAART era. The leading causes of AIDS deaths were AIDS multiple causes (31%), Mycobacterium avium complex (18%), Pneumocystis pneumonia (10%) and non-Hodgkin's lymphoma (7%). The proportion of non-AIDS related deaths increased from 7% pre-HAART to 32% in the current HAART era. Accidental deaths, including drug overdose (29%), suicide (7%) and violence (3%), hepatic disease (19%), non-AIDS related malignancies (19%), and cardiovascular disease (16%) accounted for the majority of non-AIDS related deaths. No deaths directly caused by drug toxicity were found. Overall, 21% of patients who died were antiretroviral (ARV)-naive. A total of 14% of patients dying from AIDS were ARV-naive in contrast to 35% dying from non-HIV related conditions. Of all those dying from AIDS, 23% died<3 months after their initial diagnosis, reflecting late presentation. In the current HAART era, 87% of patients who died from AIDS were extensively treated, reflecting HAART treatment failures due mostly to multiclass drug resistance (42%), inexorable disease progression despite ARV (32%), lack of ability or interest to be maintained on a lifelong HAART programme (21%) and, rarely, drug intolerance (<1%). CONCLUSIONS: Deaths from AIDS-related causes have decreased significantly, but deaths from non-AIDS related conditions have increased, both as an absolute number of deaths and as a proportion of all deaths in HIV-infected patients. The increasing age of the HIV population, and the increased mean CD4 count, increased proportion of intravenous drug users, increased hepatitis B virus and hepatitis C virus coinfection rate, and increased history of smoking seen in our population also influenced the mortality rate and causes of death. These factors must also be considered in projecting future trends in mortality of an HIV-infected population.

T cytotoxic-1 CD8+ T cells are effector cells against pneumocystis in mice.

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes. A hallmark of HIV infection is Pneumocystis carinii (PC) pneumonia. Recently, CD8+ T cells, which are recruited to the lung in large numbers in response to PC infection, have been associated with some level of host defense as well as contributing to lung injury in BALB/c mice. In this study, we show that CD8+ T cells that have a T cytotoxic-1 response to PC in BALB/c mice, as determined by secretion of IFN-gamma, have in vitro killing activity against PC and effect clearance of the organism in adoptive transfer studies. Moreover, non-T cytotoxic-1 CD8+ T cells lacked in vitro effector activity and contributed to lung injury upon adoptive transfer. This dichotomous response in CD8+ T cell response may in part explain the clinical heterogeneity in the severity of PC pneumonia.