Junko Tanuma

Serum (1→3) β-d-Glucan as a Noninvasive Adjunct Marker for the Diagnosis of Pneumocystis Pneumonia in Patients with AIDS

High serum (1-->3) beta-D-glucan levels are described in patients with Pneumocystis pneumonia (PCP). We evaluated the diagnostic value of beta-D-glucan in 111 patients with AIDS who had PCP and confirmed its usefulness. However, it does not correlate with disease severity and is not suitable for monitoring response to treatment.

Impact of small body weight on tenofovir-associated renal dysfunction in HIV-infected patients: a retrospective cohort study of Japanese patients.

Background Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. Methods In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. Results The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; p<0.001)(per 1 kg/m2 decrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058). Conclusion The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir.

Short Communication: Effects of Low HIV Type 1 Load and Antiretroviral Treatment on IgG-Capture BED-Enzyme Immunoassay

The IgG-capture BED-enzyme immunoassay (BED-CEIA) is used widely at present to detect recent HIV-1 seroconversion. However, antibody levels and antibody kinetics are impacted by HIV-1 load and antiretroviral treatment, which may have a significant effect on the assay results. In this study, we analyzed serial samples from 11 patients with recent infection, including four patients treated by structured treatment interruption (STI), and compared the results with those of 10 untreated and 7 treated patients with chronic infection. The BED-CEIA missidentified one long-term nonprogressor hemophiliac with an extremely low HIV-1 load and five patients with chronic infection who received antiretroviral treatment. We also found that the ODn values increased slowly in patients with recent infection and low HIV-1 loads and that the ODn values fluctuated in parallel with HIV-1 load during STI. Our data indicate that the results of BED-CEIA are influenced by HIV-1 load and antiretroviral treatment. Care should be taken when interpreting the results of BED-CEIA, especially in individuals with low HIV-1 loads. Those on antiretroviral treatment should be excluded from BED-CEIA testing to improve the predictive value of detecting recent infections.

Renal function declines more in tenofovir- than abacavir-based antiretroviral therapy in low-body weight treatment-naïve patients with HIV infection.

Objective To compare the rate of decline of renal function in tenofovir- and abacavir-based antiretroviral therapy (ART) in low-body weight treatment-naïve patients with HIV infection. Design We conducted a single-center retrospective cohort study of 503 Japanese patients who commenced on either tenofovir- or abacavir-based initial ART. Methods The incidence of renal dysfunction, defined as more than 25% fall in estimated glomerular filtration rate (eGFR) from the baseline, was determined in each group. The effect of tenofovir on renal dysfunction was estimated by univariate and multivariate Cox hazards models as the primary exposure. Changes in eGFR until 96 weeks were estimated in both groups with a repeated measures mixed model. Results The median body weight of the cohort was 64 kg. The estimated incidence of renal dysfunction in the tenofovir and the abacavir arm was 9.84 per 100 and 4.55 per 100 person-years, respectively. Tenofovir was significantly associated with renal dysfunction by univariate and multivariate analysis (HR = 1.747; 95% CI, 1.152–2.648; p = 0.009) (adjusted HR = 2.080; 95% CI, 1.339–3.232; p<0.001). In subgroup analysis of the patients stratified by intertertile baseline body weight, the effect of tenofovir on renal dysfunction was more evident in patients with lower baseline body weight by multivariate analysis (≤60 kg: adjusted HR = 2.771; 95%CI, 1.494–5.139; p = 0.001) (61–68 kg: adjusted HR = 1.908; 95%CI, 0.764–4.768; p = 0.167) (>68 kg: adjusted HR = 0.997; 95%CI, 0.318–3.121; p = 0.995). The fall in eGFR was significantly greater in the tenofovir arm than the abacavir arm after starting ART (p = 0.003). Conclusion The incidence of renal dysfunction in low body weight patients treated with tenofovir was twice as high as those treated with abacavir. Close monitoring of renal function is recommended for patients with small body weight especially those with baseline body weight <60 kg treated with tenofovir.

Detection of HIV Type 1 Load by the Roche Cobas TaqMan Assay in Patients with Viral Loads Previously Undetectable by the Roche Cobas Amplicor Monitor

OR, 6.2; 95% CI, 2.5–15.4). There was no increase in the risk of T. vaginalis infection among women who were infected with T. vaginalis during the immediately preceding interval (4.4%), compared with women who were not (3.9%). However, 13 (62%) of 21 new infections occurred in women who had been previously infected with T. vaginalis, and 11 (85%) of 13 had negative test results during the immediately preceding interval (figure 1). Some of the women might have acquired infections during sexual contact that they did not report, and some might have had infections that were not detected at the baseline visit. However, many women were treated for infection, had negative test results, and then had positive test results again, which suggests that T. vaginalis was undetected by testing but still present for months after treatment. The possibility of long-term asymptomatic carriage is consistent with the age distribution of infected women; T. vaginalis is found more often in older women [8, 9]. This pattern is different from the pattern for bacterial sexually transmitted diseases but similar to that for incurable viral infections, such as herpes simplex virus type 2 [10]. Trials have suggested cure rates of 190%, but most have tested women once within a few weeks after treatment [11]. When women were tested again a few months after treatment, some of the previously cured women had infection detected again [11], and none of the studies continued testing women beyond a few months. Cultures might not detect infections if the concentration of T. vaginalis is low, which would be expected in asymptomatic infections [6, 12, 13]. Nucleic acid amplification tests may be better, but reports are inconsistent and the tests are not commercially available in the United States [14]. Similarly, self-obtained vaginal swab specimens occasionally miss infections, but the sensitivity of tests performed with self-obtained specimens has compared favorably with that of tests performed with clinician-obtained specimens [15]. Treatment failure could explain many of our findings, because 13 women had a documented preceding infection. However, our results were not simply attributable to treatment failure. Most of the women ( ) had an intervening negn p 11 ative test result before having a positive result during an interval when they reported not having sex. This suggests that, after treatment, T. vaginalis infection can become nondetectable for months and then reappear. Because these findings were unexpected and obtained with a small number of participants, additional studies are needed to confirm or refute these observations.

Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up.

Objectives:To investigate the effect of long-term tenofovir disoproxil fumarate (TDF) use on renal function, especially in patients with low body weight who are vulnerable to TDF nephrotoxicity. Design:A single-center, observational study in Tokyo, Japan. Methods:We performed a 10 years cohort study of 792 HIV-1-infected patients. The effect of long-term TDF use on estimated glomerular filtration rate (eGFR) was investigated on treatment-naive patients who started TDF-containing antiretroviral therapy (n = 422) and those who started abacavir-containing antiretroviral therapy as control (n = 370). Three renal endpoints were examined by the logistic regression model: decrement in eGFR of higher than 10 ml/min per 1.73 m2 relative to the baseline, more than 25% decrement in eGFR, and eGFR lower than 60 ml/min per 1.73 m2 at least 3 months apart. The loss in eGFR was estimated using linear mixed models for repeated measures. Results:The median weight at baseline was 63 kg. TDF use increased the risk of all three renal outcomes compared with the control group: higher than 10 ml/min per 1.73 m2 decrement in eGFR [adjusted odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.45–3.14, P < 0.001], more than 25% decrement (adjusted OR = 2.1, 95% CI 1.50–2.90, P < 0.001), and eGFR lower than 60 ml/min per 1.73 m2 at least 3 months apart (adjusted OR = 3.9, 95% CI 1.62–9.36, P = 0.002). The cumulative mean loss relative to the control after 1, 2, 3, 4, and 5 years of TDF exposure was −3.8, −3.6, −5.5, −6.6, and −10.3 ml/min per 1.73 m2, respectively, indicating that the loss in eGFR increased over time (P < 0.001). Conclusion:In this cohort of patients with low body weight, TDF exposure increased the risk of renal dysfunction. Furthermore, the loss in eGFR relative to the control increased continuously up to 5 years.

Prophylactic Effect of Antiretroviral Therapy on Hepatitis B Virus Infection

BACKGROUND Hepatitis B virus (HBV) infection is common in individuals infected with human immunodeficiency virus, especially in men who have sex with men (MSM). Almost all currently used regimens of antiretroviral therapy (ART) contain lamivudine (LAM) or tenofovir disoproxil fumarate (TDF), both of which have significant anti-HBV activity. However, the prophylactic effect of ART on HBV infection has not been assessed previously. METHODS Non-HBV-vaccinated HIV-infected MSM were serologically evaluated for HBV infection using stocked serum samples. Cases negative for HBV surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HBV core antigen (anti-HBc) in first serum samples were serologically followed until last available stocked samples. HBV genotype and LAM-resistant mutation (rtM204V/I) were analyzed in cases that became HBsAg-positive. RESULTS The first stocked samples were negative for all analyzed HBV serological markers in 354 of 1434 evaluated patients. The analysis of their last samples indicated HBV incident infection in 43 of them during the follow-up period. The rate of incident infections was lower during LAM- or TDF-containing ART (0.669 incident infections in 100 person-years) than during no ART period (6.726 incident infections in 100 person-years) and other ART (5.263 incident infections in 100 person-years) (P < .001). Genotype A was most prevalent (76.5%), and LAM-resistant HBV was more frequent in incident infections during LAM-containing ART (50.0%) than in those during no ART and other ART (7.1%) (P = .029). CONCLUSIONS LAM- and TDF-containing ART regimens seem to provide prophylaxis against HBV infection, although drug-resistant strains seem to evade these effects.

Amebiasis in HIV-1-Infected Japanese Men: Clinical Features and Response to Therapy

Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection.

Profile of HIV Type 1 Infection and Genotypic Resistance Mutations to Antiretroviral Drugs in Treatment-Naive HIV Type 1-Infected Individuals in Hai Phong, Viet Nam

We evaluated the prevalence and profile of antiretroviral treatment (ART)-associated resistance mutations among HIV-1 strains in northern Vietnam by genotypically analyzing strains isolated from ART-naive individuals in Hai Phong, a city in which HIV-1 is highly prevalent. Plasma samples were collected from injecting drug users (IDU, n = 760), female sex workers (FSW, n = 91), seafarers (n = 94), pregnant women (n = 200), and blood donors (n = 210), and screened for HIV-1 antibodies. Plasma viral RNA was extracted from HIV-1-positive samples, amplified by reverse transcriptase (RT)-PCR of protease and RT genes, and analyzed for genotypes and ART-associated resistance mutations. HIV-1 prevalence among IDU, FSW, seafarers, pregnant women, and blood donors was 35.9%, 23.1%, 0%, 0.5%, and 2.9%, respectively. Phylogenetic analyses revealed that the most prevalent HIV-1 subtype was CRF01_AE (98.3%), similar to strains prevalent in southern China. Four (1.4%) subtype B strains and one (0.3%) unique recombinant between subtypes B and C were also identified. We found protease inhibitor-associated major resistance mutations in one of the 294 cases analyzed (0.3%; mutation M46I). We found RT inhibitor-associated major resistance mutations in 7/273 cases (2.6%; one occurrence each of L74I, M184I, and K219E; three cases of K103N; and two cases of G190E). One CRF01_AE strain harboring a protease codon 35 insertion was first identified in Vietnam. Thus, monitoring of drug-resistant HIV-1 and establishment of a database are required for the proper selection of ART in Vietnam.

Dilated Cardiomyopathy in an Adult Human Immunodeficiency Virus Type 1–Positive Patient Treated with a Zidovudine-Containing Antiretroviral Regime

We describe an adult woman infected with human immunodeficiency virus type 1 (HIV-1) who developed dilated cardiomyopathy (DCM) with histologically confirmed mitochondrial damage while receiving anti-HIV-1 combination therapy that included nelfinavir, lamivudine, and zidovudine. DCM resolved after discontinuation of the regimen, and cardiac function remained normal after initiation of treatment with nelfinavir, lamivudine, and abacavir, which indicates that DCM was induced by mitochondrial toxicity, most likely caused by zidovudine.