Antifungal Susceptibilities of Cryptococcus neoformans

Susceptibility profiles of medically important fungi in less-developed countries remain uncharacterized. We measured the MICs of amphotericin B, 5-flucytosine, fluconazole, itraconazole, and ketoconazole for Cryptococcus neoformans clinical isolates from Thailand, Malawi, and the United States and found no evidence of resistance or MIC profile differences among the countries

AIDS-defining illnesses among patients with HIV in Singapore, 1985 to 2001: results from the Singapore HIV Observational Cohort Study (SHOCS)

BACKGROUND: The objective was to describe the causes of initial and overall AIDS-defining disease episodes among HIV patients in Singapore. METHODS: A retrospective observational cohort study was performed of all adult patients seen at the national HIV referral center between 1985 and 2001. Data were extracted from the patients' records by ten trained healthcare workers. AIDS-defining conditions were established using predefined criteria. RESULTS: Among 1504 patients, 834 had experienced one or more AIDS-defining diseases. The most frequent causes of the initial AIDS-defining episode were Pneumocystis carinii pneumonia (35.7%), Mycobacterium tuberculosis (22.7%) and herpes simplex (7.4%). In total 1742 AIDS-defining episodes occurred. The most frequent causes were Pneumocystis carinii pneumonia (25.1%), Mycobacterium tuberculosis (16.2%) and cytomegalovirus retinitis (9.5%). CONCLUSIONS: The most frequent causes of AIDS-defining illnesses in Singapore are similar to those reported in the West, prior to the introduction of anti-retroviral therapy. Opportunistic infections remain the most frequent AIDS-defining illnesses

Integration of antiretroviral therapy with tuberculosis treatment.

Background. We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved. Methods. We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier- ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here. Results. At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P = 0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P = 0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P = 0.006). Conclusions. Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death

Pneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression

Objective: Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings. Design Systematic review and meta-regression. METHODS: Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies). RESULTS: The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10 3/ ml. CONCLUSIONS: There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii , ubiquitous in all settings, then becomes a greater relative threat

A prospective study of AIDS-associated cryptococcal meningitis in Thailand treated with high-dose amphotericin B.

OBJECTIVE: To assess kinetic of cryptococci in the cerebrospinal fluid (CSF) and outcome of AIDS-associated cyptococcal meningitis after high-dose amphotericin B. PATIENTS AND METHODS: A prospective study involving Thai adults (n=106) with cryptococcal meningitis associated with AIDS was conducted to determine the kinetic of cryptococci in CSF and prognostic factors affecting survival after high-dose amphotericin B (0.7 mg/kg/day) followed by oral azole treatment. Cerebrospinal fluids were collected for cryptococcal count and culture at weekly intervals for at least 2 weeks or until CSF cultures were negative for cryptococci. All patients were followed monthly for 1 year or until death in order to detect relapse or occurrence of any other opportunistic infection. RESULTS: A total of 106 AIDS patients with cryptococcal meningitis were enrolled. The geometric mean (range) total and viable cryptococcal counts in CSF on admission were 430,000 (1000 to 3.4 x 10(7)) and 31,000 (10 to 1.4 x 10(7)) per ml, respectively. Both total and viable cryptococcal counts declined monoexponentially with an elimination half life of 4 days. The cumulative CSF yeast clearance rates were 38% and 56% at 2 and 4 weeks, respectively. Early death was associated significantly with previous history of weight loss [relative risk (RR)=2.2; 95% CI, 1.2-3.9], Glasgow Coma Score &lt;13 (RR=2.33; 95% CI, 1.55-3.50), and hypoalbuminaemia (P&lt;0.001). Later mortality was associated delayed CSF yeast clearance (RR=3.6; 95% CI, 1.9--6.4) and relapse (RR=3.9; 95% CI, 1.4-10.8). CONCLUSION: High-dose amphotericin B was not as effective as previously thought. Cumulative mortality at 2 weeks, 4 weeks and 1 year were 16%, 24% and 76%, respectively

Long-term efficacy and safety of first-line therapy with once-daily saquinavir/ritonavir

BACKGROUND: The aim of this study was to assess the long-term efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: A total of 272 antiretroviral-naive patients with a CD4+ T-cell count of 200-350 cells/mm3 were treated with two NRTIs and saquinavir/ritonavir 1,600/100 mg per day for 400 copies/ml, with a median HIV RNA decline of -2.89 (IQR 3.31--2.37) log10 copies/ml (P > 0.001) and a median rise in CD4+ T-cell count of 192 (IQR 117-317) cells (P > 0.001). At weeks 24, 48, 72 and 96, 249/272 (91.5%), 157/164 (95.7%), 113/126 (89.7%) and 84/90 (93.3%) had HIV RNA > 400 copies/ml, respectively; at the same time points, 83.8%, 92.7%, 85.7% and 85.6% had HIV RNA > 50 copies/ml. Drug-related adverse events were reported in 6.30%. Significant rises in total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein were seen. CONCLUSION: First-line highly active antiretroviral therapy with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy