Coping with COVID: risk and resilience factors for mental health in a German representative panel study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare. METHODS: In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting. RESULTS: PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes. CONCLUSIONS: We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART.

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44% received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2% and 20.2%, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44 percent received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2 percent and 20.2 percent, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial.

OBJECTIVES: To compare change from baseline in HIV RNA and fasting low-density lipoprotein (LDL) cholesterol levels in protease inhibitor (PI)-experienced patients receiving unboosted atazanavir 400 mg once daily versus lopinavir 400 mg boosted with ritonavir 100 mg twice daily, with two nucleoside reverse transcriptase inhibitors (NRTIs). Secondary objectives included virologic response, CD4 cell count changes, other lipid changes, safety, and tolerability. METHODS: Randomized, open-label, multinational, 48-week study in patients with one PI-regimen failure, HIV RNA > or = 1000 copies/mL, and CD4 count > or = 50 cells/mm3. RESULTS: Three hundred patients were randomized; 290 treated (144 atazanavir, 146 lopinavir/ritonavir). Lopinavir/ritonavir resulted in a significantly greater reduction in HIV RNA than unboosted atazanavir (-2.02 vs -1.59 log10 copies/mL, p < 0.001) at week 48. Secondary efficacy endpoints also favored lopinavir/ritonavir; the differences in efficacy between regimens were also observed in secondary analyses comparing those subjects who were susceptible and those subjects who were resistant to their respective PIs at baseline. However, both regimens were equally effective in subjects who had no baseline NRTI mutations. From baseline to week 48, atazanavir resulted in either no change or decreases in fasting LDL cholesterol, total cholesterol, and fasting triglycerides (-6%, -2%, and +1%), whereas lopinavir/ritonavir resulted in increases (+3%, +12%, and +53%) (p < 0.05, all between-treatment comparisons). Fewer patients were administered lipid-lowering therapy in the atazanavir arm (6% vs 20% for lopinavir/ritonavir). Both regimens were safe and well tolerated. CONCLUSIONS: While both treatments demonstrated good antiviral efficacy, relatively greater antiviral suppression was observed with lopinavir/ritonavir. In those patients with no NRTI mutations at baseline, both regimens demonstrated comparable virologic suppression. Atazanavir-treated patients demonstrated a superior lipid profile and required less frequent lipid-lowering treatment.

Discrepant results in the interpretation of HIV-1 drug-resistance genotypic data among widely used algorithms.

OBJECTIVES: The aim of this study was to assess the concordance on the interpretation of HIV-1 drug-resistance genotypic data by three widely used algorithms: Stanford University Database (SU), TruGene (Visible Genetics, Canada) (VG) and VirtualPhenotype (Virco, Belgium) (VP). METHODS: Genotypic data from 293 HIV-1-infected individuals with treatment failure was interpreted for 14 antiretroviral drugs by the three algorithms. RESULTS: Complete concordant results among the three systems for all the drugs studied were found in 40/293 (13.7%) samples. Low concordance in the interpretation was observed for most nucleoside reverse transcriptase inhibitors (NRTIs), while results agreed highly for all nonnucleoside reverse transcriptase inhibitors (NNRTIs) and most protease inhibitors (PIs). In pair-wise comparisons, discordant interpretations between SU and VP were found in over 50% of the samples for didanosine, zalcitabine, stavudine and abacavir, and the level of disagreement between VG and VP exceeded 40% for the same drugs. Major discrepancies (high-level resistance interpretation by one algorithm with sensitive interpretation by another) were observed between VG and VP in over 10% of the cases for didanosine, zalcitabine, stavudine and abacavir. On the other hand, the three algorithms had concordant results for lamivudine in over 90% of the cases. CONCLUSIONS: This work demonstrates the great level of discordance in the interpretation of genotyping results among algorithms, clearly showing the necessity for clinical validation. Moreover, these results suggest that a joint effort from the scientific community as well as national and international HIV societies is needed to achieve a consensus for the interpretation of genotypic data.

Resistance profiles to antiretroviral drugs in HIV-1 drug-naive patients in Argentina.

The drug resistance profile of treatment-naive HIV-infected individuals living in Buenos Aires, Argentina, was studied. Samples taken from 94 drug-naive individuals with established HIV infection and 13 patients with primary HIV infection were assessed by nucleotide sequencing and LIPA. The prevalence of drug-associated primary mutations in individuals with established infection was very low. In the viral protease region, 1/86 (1.2%) individuals carried the D30N mutation, whereas 1/85 (1.2%) had the M41L mutation in the reverse transcriptase (RT) region. Secondary mutations in both the protease and RT regions were found in almost 90% of the individuals. In individuals with primary infection, primary mutations were detected in 2/13 (15.4%) patients, one of them carrying M461 mutation in the protease while the other patient had a mutation at codon 184 of the RT. In accordance with current drug resistance testing guidelines, the results of this study suggest that susceptibility tests need not be performed at this time prior to initiation of antiretroviral therapy in HIV-1-infected people in Argentina. However, the public health implications of this subject warrant follow-up studies that will examine a larger number of drug-naive patients, not only in Buenos Aires but also in other major Argentinian cities and in rural areas.

Role of hydroxyurea in treatment of disease due to human immunodeficiency virus infection.

The potential role of hydroxyurea in the treatment of human immunodeficiency virus (HIV) infection was first supported by in vitro experiments that demonstrated control of viral production in activated and resting T cells. More recently, controlled clinical trials demonstrated that the addition of hydroxyurea to nucleoside-including regimens (chiefly of didanosine but also of stavudine and lamivudine) enhances their antiviral potency. It is believed that the cytostatic effect of hydroxyurea is at least partially responsible for its antiviral effect, through the down-modulation of cellular proliferation. Such an effect has also been credited for the blunted CD4 T cell responses that are characteristically observed when hydroxyurea is added to nucleoside-including regimens. The adjunctive antiviral effect of hydroxyurea-as well as its favorable dosing schedule, safety profile, and cost-makes it a very attractive addition to our therapeutic armamentarium. Further research is urgently needed to delineate the most appropriate use of this compound in the setting of HIV antiretroviral therapy.

Human immunodeficiency virus-infected persons with mutations conferring resistance to zidovudine show reduced virologic responses to hydroxyurea and stavudine-lamivudine.

The baseline predictors of poor virologic response (<0.5 log decrease in plasma virus load) were examined in two 1996 pilot trials of combination nucleoside-analogue therapy. One trial examined the addition of hydroxyurea to didanosine therapy; the other examined stavudine-lamivudine in combination. In both, predictors of virologic response included the presence of mutations associated with zidovudine resistance. For hydroxyurea, the odds ratio (OR) of failure to achieve a short-term (4 weeks) virologic response in a bivariate logistic regression model was 30.8 (95% confidence interval [CI], 1.75-543; P=.02) for use of lower dose hydroxyurea (500 mg/day) and 14.7 (95% CI, 1.1-200; P=.04) for the presence of a zidovudine-related mutation. For the stavudine-lamivudine study, the OR of failure to achieve a virologic response at 4 weeks in a multivariate logistic regression model was 23 (95% CI, 2.7-199; P=.004) for the presence of a mutation at codon 215.

Determinants of short- and long-term outcome in patients with respiratory failure caused by AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVES: To determine (1) predictors of in-hospital mortality and long-term survival in patients with acute respiratory failure (ARF) caused by acquired immunodeficiency syndrome-related Pneumocystis carinii pneumonia (PCP) and (2) long-term survival for patients with ARF relative to those without ARF. METHODS: A retrospective medical chart review was conducted of all cases of PCP-related ARF for which the patient was admitted to the intensive care unit of a single tertiary care institution between 1991 and 1996. Data were extracted regarding physiologic scores, relevant laboratory values, and duration of previous maximal therapy with combined anti-PCP agents and corticosteroids at entry to the intensive care unit. Duration of survival was determined by Kaplan-Meier methods from date of first hospital admission and compared for patients with and without ARF. RESULTS: There were 41 admissions to the intensive care unit among 39 patients, with 56.4% in-hospital mortality. Higher physiologic scores (Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Lung Injury, and modified Multisystem Organ Failure scores) were predictive of in-hospital mortality. Duration of previous maximal therapy also predicted in-hospital mortality (45% for patients with <5 days of previous maximal therapy vs 88% for those with > or =5 days of previous maximal therapy; P = .03). Combining physiologic scores and duration of previous maximal therapy enhanced prediction of in-hospital mortality. There was no difference in long-term survival between patients with PCP with ARF and those without ARF (P = .80), and baseline characteristics did not predict long-term survival. CONCLUSIONS: In-hospital mortality of patients with acquired immunodeficiency syndrome-related PCP and ARF is predicted by duration of previous maximal therapy and physiologic scores, and their combination enhances predictive accuracy. Long-term survival of patients with ARF caused by PCP is comparable to that of patients with PCP who do not develop ARF, and determinants of in-hospital mortality do not predict long-term survival.

Treatment of primary HIV infection: a pilot study of stavudine and didanosine plus nevirapine with or without hydroxyurea.

Treatment of primary human immunodeficiency virus (HIV) infection (PHI) may provide an opportunity to achieve a long lasting suppression of viral replication. Although there is growing evidence of the benefit of treating PHI, clinical data are still very limited. Special therapeutic considerations in this clinical setting include the prevalence of resistant viruses in the community, complexity of regimens and their long-term toxicity. In addition, adjunctive therapies aimed at exploring the role of immune modulation and intensification of antiretroviral therapy are becoming areas of great interest. In this regard, the role of hydroxyurea, a cytostatic agent that potentiates the antiviral effect of didanosine, and possibly of stavudine is being investigated. A pilot study to assess the antiviral effect of a combination of didanosine plus stavudine plus nevirapine with or without hydroxyurea in the treatment of PHI is currently under way. Preliminary results on 22 patients who completed at least 36 weeks of therapy suggest that the combination is safe, well tolerated and effective for the treatment of PHI.

Validation of the modified multisystem organ failure score as a predictor of mortality in patients with AIDS-related Pneumocystis carinii pneumonia and respiratory failure.

STUDY OBJECTIVES: To validate a previously developed multisystem organ failure (MSOF) score with and without the addition of the lactate dehydrogenase (LDH) level as a predictor of survival to hospital discharge in patients with AIDS-related Pneumocystis carinii pneumonia (PCP) and acute respiratory failure (ARF). DESIGN: Retrospective chart review between April 1, 1991, and September 30, 1996. SETTING: University-affiliated tertiary care center in downtown Vancouver, British Columbia, Canada. PATIENTS: All patients with PCP-related ARF admitted to the ICU of St. Paul's Hospital during the study period. INTERVENTIONS: As putative prognostic instruments, data were extracted regarding the APACHE II (acute physiology and chronic health evaluation II), acute lung injury (ALI), AIDS, and modified MSOF scores, as well as LDH levels, at entry to the ICU. Patients were stratified based on an LDH level of < or > or = 2,000 U/L and this threshold was assessed in its predictability of outcome when added to each of the above scores. For APACHE II, the score was categorized in six groups and evaluated with and without inclusion of the LDH. Receiver operating characteristic curves were constructed for LDH and for each score with and without the LDH level to assess accuracy of prediction. The area under each curve was calculated and compared to estimate the statistical significance of observed differences. MEASUREMENTS AND RESULTS: There were 40 admissions to the ICU of 38 patients with 52.5% mortality. The ALI and AIDS scores were not predictive of outcome. The modified MSOF and APACHE II scores were significant predictors of survival and the performance of both was enhanced by the addition of LDH. CONCLUSIONS: Both the APACHE II and the modified MSOF scores were significant predictors of outcome in the patient population studied. These results validate the modified MSOF score as an effective predictor of survival to hospital discharge among patients with AIDS-related PCP who develop ARF and the performance of the score is enhanced by the addition of the LDH level.

Is there anything left to learn? A report on the Fifth International Workshop on HIV Drug Resistance.

Although insight into the viral dynamics of human immunodeficiency virus (HIV) infection has increased dramatically over the past year, there remains much to learn in the field of antiretroviral drug resistance. Transmission of isolates with primary drug resistance is increasingly recognized. With respect to reverse transcriptase inhibitors, it appears that the use of drugs in combination may forestall the development of resistance once therapy has been initiated. Further, certain findings, particularly with respect to zidovudine and lamivudine, suggest that emergence of resistance to one agent may lead to increased susceptibility to another. These data may allow evaluation of innovative treatment strategies to avoid the development of multidrug resistance, which has now been reported in a number of settings. Protease inhibitors (PIs) are, on an individual basis, the most potent antiretroviral compounds available today. A number of studies have shown that resistance to these agents develops after the accumulation of several mutations in the protease gene of HIV. As with reverse transcriptase inhibitors, the use of PIs in the context of regimens designed to suppress viral replication as much as possible appears to forestall, perhaps indefinitely, the development of drug resistance. Although different patterns of resistance mutations have been described for the different PIs available, the issue of cross-resistance remains unresolved. For the time being, it may be best to consider all PIs as a single agent that must always be used in a regimen designed to maximally suppress viral load. In conclusion, research in the field of antiretroviral drug resistance has never been more active and productive. It is hoped that such research will lead to the development of an integrated model of the clinical and laboratory management of HIV-infected individuals.

Stavudine plus lamivudine in advanced human immunodeficiency virus disease: a short-term pilot study.

The short-term effects of stavudine (d4T) plus lamivudine (3TC) were evaluated among 48 human immunodeficiency virus-infected patients for whom zidovudine therapy had failed or who could not tolerate zidovudine. Patients were followed for 8 weeks after initiation of open-label d4T plus 3TC. Four patients discontinued therapy, because of neutropenia (1), hepatitis (1), or neuropathy (2). Reduction in virus load was -0.86 (+0.3 to -3.4) log10 copies/mL and CD4 cell increase was 30 (-100 to +290) cells/mm3. Virologic response was associated with a higher CD4 cell count, no prior exposure to d4T and 3TC, and no previous AIDS-defining illness. Virus load reduction for patients naive to 3TC and d4T was -1.47 (-0.14 to -3.37) log10 copies/mL. Short-term use of d4T plus 3TC is safe, well-tolerated, and associated with virologic and substantial immunologic benefits. Further evaluation of d4T and 3TC in combination is warranted.

A pilot study of hydroxyurea among patients with advanced human immunodeficiency virus (HIV) disease receiving chronic didanosine therapy: Canadian HIV trials network protocol 080.

To assess the in vivo short-term antiretroviral effect of hydroxyurea in human immunodeficiency virus (HIV)-infected persons chronically treated with didanosine (ddI), 26 patients with CD4 cell counts between 100 and 350 were enrolled in a 12-week, open-label pilot study and randomly assigned to receive 500 or 1000 mg/day hydroxyurea. Clinical status, laboratory toxicities, CD4 lymphocyte count, and HIV RNA plasma virus load were assessed weekly. Median declines from baseline of 0.02 and 0.63 log10 HIV-1 RNA copies/mL of plasma were observed for the 500- and 1000-mg/day groups, respectively (P = .02). CD4 cell counts did not change significantly with the addition of hydroxyurea; however, a small but statistically significant decrease in counts was observed during the washout phase. Both doses of hydroxyurea were well-tolerated. These results demonstrate a substantial decrease in plasma virus load when 1000 mg of hydroxyurea is administered over 1 month as adjunctive therapy to ddI among HIV-infected persons with 100-350 CD4 cells/mm3.

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adherence to guidelines for the prevention of HIV-related respiratory diseases.

In this study we characterized the pattern of use of preventive therapies for specific respiratory diseases within a cohort of homosexual men and assessed the impact of targeted feedback on the level of compliance with guidelines for these diseases. All human immunodeficiency virus seronegative (HIV-) (n=169) and acquired immune deficiency syndrome (AIDS)-free human immunodeficiency virus seropositive (HIV+) (n=154) participants in our cohort, who completed four annual visits between October 1989 and December 1993, were identified. Information about the use of purified protein derivative (PPD) (tuberculin) testing, history of pneumococcal vaccinations, influenza vaccinations, use of Pneumocystis carinii pneumonia (PCP) prophylaxis, symptoms and CD4 counts was obtained yearly for each subject. In 1992, participating physicians were provided with feedback regarding the overall levels of compliance with contemporary guidelines for the prevention of respiratory disease. As part of this exercise, the guidelines were distributed and discussed. The percentage of HIV+ patients who underwent PPD testing increased from 43 to 65% during the study (p=0.001). Significantly more HIV+ than HIV- patients underwent PPD testing (p<0.001). A total of 144 (94%) HIV+ men received at least one influenza vaccination compared to 60 (35%) HIV- men (p<0.001). Utilization of influenza vaccination in the HIV+ group significantly increased from 78% in 1992 to 92% in 1993 (p<0.001). A total of 104 (68%) HIV+ men received pneumococcal vaccination compared to 2 (1%) HIV- men (p<0.001). Among HIV+ individuals whose absolute CD4+ count was less than 200 cells x mm(-3), the percentage of men who received primary PCP prophylaxis was 0, 86, 72 and 88 for the years 1990-1993, respectively. Among HIV+ patients whose only eligibility criterion for PCP prophylaxis was a CD4+ percentage <20%, compliance was 55, 30, 37 and 50% for the years 1990-1993, respectively. Among HIV+ subjects, increases in the compliance level were noted for all preventive therapies after targeted feedback was provided during the last quarter of 1992. However, only utilization of influenza vaccine exceeded a 90% compliance in 1993. These data demonstrate that a suboptimal level of compliance with current guidelines for the prevention of respiratory disease among human immunodeficiency virus-infected individuals can be significantly improved using targeted feedback. Although it is likely that similar effects could be achieved in other populations or the community at large, this remains to be demonstrated.

HTLV type I and HTLV type II infection among Indians and natives from Argentina.

Endemic foci for HTLV-II infection have been identified in several Amerindian populations. To determine HTLV-I and/or HTLV-II infection among Amerindians living in Argentina we studied 454 sera or plasmas from Indians and natives from different areas of our country. All samples were tested by the particle agglutination technique, and positive reactions were confirmed by the immunofluorescence assay (IFA). IFA titration was used to differentiate HTLV-I and HTLV-II antibodies. Twenty-three of 222 samples (10.4%) were found positive among the Tobas Indians; 22 samples were typed as HTLV-II and 1 as HTLV-I. Antibodies for HTLV-I were found in the serum and CSF of three natives from Salta with a TSP diagnosis. No positive samples were found among 96 Mapuche Indians and 133 natives from San Luis. Our results indicate that HTLV-II is endemic among the Tobas Indians. In this study, infection by these retroviruses in Argentinian Amerindians seems to have a marked geographic distribution.

Early diagnosis of toxoplasmic encephalitis in AIDS patients by dot blot hybridization analysis.

Central nervous system toxoplasmosis is a life-threatening infection with a mortality rate of higher than 60%. An early and rapid diagnosis is important for effective treatment of the disease. A new approach for detection of cerebral toxoplasmosis is described here. DNAs extracted from cells in cerebrospinal fluid samples (0.3 to 0.8 ml) of patients suspected of having cerebral toxoplasmosis were analyzed by a dot blot hybridization technique. A highly repetitive DNA sequence of Toxoplasma gondii (ABGTg4) was nonisotopically labelled with digoxigenin-dUTP and used as a specific DNA probe. Four of six patients analyzed gave positive signals in our hybridization assay. Two of them recovered with pyrimethamine-sulfadiazine, a drug recommended for treatment of toxoplasmosis. The other two patients with positive signals died soon after diagnosis. Patients with negative signals were found to suffer from mycobacterial infection (patient 1) or varicella-zoster virus infection (patient 6).