Pre-exposure prophylaxis: awareness, acceptability and risk compensation behaviour among men who have sex with men and the transgender population.

OBJECTIVES: This exploratory study examined the facilitators of and barriers to acceptance of pre-exposure prophylaxis (PrEP) and potential risk compensation behaviour emerging from its use among men who have sex with men (MSM) and transgender individuals (TGs) in India. METHODS: A questionnaire was administered to 400 individuals registered with a targeted intervention programme. Logistic regression models were used to identify facilitators of and barriers to PrEP acceptance. RESULTS: The respondents consisted of 68% MSM and 32% TGs. Risk behaviour categorization identified 40% as low risk, 41% as medium risk and, 19% as high risk for HIV infection. About 93% of the respondents were unaware of PrEP, but once informed about it, 99% were willing to use PrEP. The facilitators of PrEP acceptance were some schooling [odds ratio (OR) 2.16; P = 0.51], being married or in a live-in relationship (OR 2.08; P = 0.46), having a high calculated risk (OR 3.12; P = 0.33), and having a high self-perceived risk (OR 1.8; P = 0.35). Increasing age (OR 2.12; P = 0.04) was a significant barrier. TGs had higher odds of acceptance of PrEP under conditions of additional cost (OR 2.12; P = 0.02) and once-daily pill (OR 2.85; P = 0.04). Individuals identified as low risk for HIV infection showed lower odds of potential risk compensation, defined as more sexual partners (OR 0.8; P = 0.35), unsafe sex with new partners (OR 0.71; P = 0.16), and decreased condom use with regular partners (OR 0.95; P = 0.84), as compared with medium-risk individuals. The associations, although not statistically significant, are nevertheless important for public health action given the limited scientific evidence on PrEP use among MSM and TGs in India. CONCLUSIONS: With high acceptability and a low likelihood of risk compensation behaviour, PrEP can be considered as an effective prevention strategy for HIV infection among MSM and TGs in India.

Kidney Transplantation from a Hepatitis C Virus-positive Donor to a Hepatitis C Virus-negative Recipient.

Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.

General hygiene, sexual risk behaviour and HIV prevalence in truck drivers from Andhra Pradesh, South India: implications for prevention interventions.

The relationships between hygiene, sexual behaviour and HIV infection are poorly understood. We examine these relationships in Indian truck drivers, a group at high risk for HIV infection. Truck drivers (n = 189) were recruited into an integrated HIV and hygiene Information Motivation (IM) programme. Sociodemographic characteristics, sexual and hygiene behaviour and HIV prevalence were determined. Multivariate logistic regression and linear generalized estimating equation models were utilized. At baseline, 2.1% of drivers were HIV infected and 34% who reported having contact with female sex workers (FSWs) had contact within the previous six months. Those who washed their hands postdefecation were less likely to report genital symptoms (OR 0.02; P = 0.01) and have sex with an FSW (OR [odds ratio] 0.21; P = 0.05). After an IM intervention, there were no changes in sexual risk-taking behaviour (coefficient -0.15 to -0.02; P = 0.13-0.75); however, hygiene behaviour improved from baseline (coefficient 0.09-0.31; P < 0.01 to P = 0.03). Personal hygiene habits, like handwashing, seem to be a modifiable behaviour after a modest intervention, whereas HIV risk-taking behaviour was not. The association between hygiene and HIV risk-taking suggests the need for further evaluation of the relationship and that of other hygiene practices in high-risk men in India.

HIV infection dynamics in rural Andhra Pradesh south India: a sexual-network analysis exploratory study.

The southern state of Andhra Pradesh (AP) has one of the highest rates of HIV-1 infection in India. Estimates of HIV infection in rural areas have begun to approximate the urban. Methods of HIV transmission in rural India are poorly understood. We examined risk factors for HIV transmission in a group of rural villages in AP through the use of a sexual-network analysis survey - the Indian Health and Family Life Survey (IHFLS). The study sample included 20 HIV-positive and 40 HIV-negative matched controls randomly selected from a population-based, voluntary counselling and testing program in rural AP. HIV-1 status was confirmed by Western Blot. The 405-item IHFLS is based upon the National Health and Life Survey which has been validated in the US and China. The sample mean age was 37 years and 22% were of a tribal caste. Among female respondents, none were commercial sex workers (CSWs) and there were no significant social or behavioral associations with HIV infection. Among male respondents, ever having bought sex and having more than one lifetime partner were found to be significantly associated with HIV infection (p=0.002 and p=0.017). Amongst sub-populations, all men who had sex with men (MSM) were married. Tribals were more likely to report a concurrent sexual relationship (p=0.04). All high-risk men, including MSM, men who buy sex and men with multiple lifetime female partners did not use condoms. Public health interventions aimed at reducing HIV transmission in rural AP should consider targeting sub-populations of men who engage in covert MSM or CSW, high-risk tribal caste members and at-risk wives.

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

BACKGROUND: We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. METHODS: Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. RESULTS: Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. CONCLUSION: The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Identification of the asexual state of Rhizopus species on histologic tissue sections in a patient with rhinocerebral mucormycosis.

Mucormycosis is an infection caused by a group of fungi in the order Mucorales in the phylum Zygomycota. The most well-known form of this disease is rhinocerebral mucormycosis, which usually develops in diabetic or immunocompromised patients. The fungal hyphal elements are easily detected in biopsy specimens by direct or histologic examination. However, the confirmatory identification of the genus or species requires culture of the specimen. This article presents a case of rhinocerebral mucormycosis in which presumptive identification of the genus was made without microbiologic cultures and was based on the extraordinarily rare appearance of fungal sporangia and sporangiospores in histologic tissue sections. Identification of these structures allowed an early and accurate diagnosis of rhinocerebral invasive mucormycosis.

Pharmacoeconomic analysis of liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients.

PURPOSE: In a randomized, double-blind, comparative, multicenter trial, liposomal amphotericin B was equivalent to conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients, using a composite end point, but was more effective in reducing proven emergent fungal infections, infusion-related toxicities, and nephrotoxicity. The purpose of this study was to compare the pharmacoeconomics of liposomal versus conventional therapy. PATIENTS AND METHODS: Itemized hospital billing data were collected on 414 patients from 19 of the 32 centers that participated in the trial. Hospital length of stay and costs from the first dose of study medication to the time of hospital discharge were assessed. RESULTS: Hospital costs from the time of first dose to discharge were significantly higher for all patients who received liposomal amphotericin B ($48,962 v $43,183; P =.022). However, hospital costs were highly sensitive to the cost of study medication ($39,648 v $43,048 when drug costs were not included; P =.416). Using decision analysis models and sensitivity analyses to vary the cost of study medications and the risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients. CONCLUSION: The cost of liposomal amphotericin B and patient risk for developing nephrotoxicity play large roles in determining whether liposomal amphotericin B is cost-effective as first-line empirical therapy in persistently febrile neutropenic patients.

Refractory post-transplant airway strictures: successful management with wire stents.

OBJECTIVE: Bronchial stenosis, malacia and dehiscence are major airway complications of lung transplantation. Our success in managing this problem evolved from the use of semi-rigid dilators, to balloon dilation and placement of a stent, which were initially silicone, thereafter wire balloon-expandable and finally wire self-expandable. METHODS: From May, 1994 until July 1997, we performed a total of 49 single and 58 bilateral lung transplants. Symptoms of shortness of breath, verified by a drop in the forced expiratory volume in one second (FEV1), led to bronchoscopic inspection of the airway in lung transplant patients. Eighteen patients (16%) suffered a severe form of airway complication (dehiscence or stenosis) in 24 of 151 airways at risk (15.9%). These anastomotic strictures were recalcitrant to conventional therapy. Intervention consisted of rigid bronchoscopy, dilation of the stricture and placement of a stent. Flexible bronchoscopy and fluoroscopy were used for precise placement of the stent. As the initial stent, the Hood silicone stent was placed five times in four patients and the Dumont studded stent five times in four patients. The Palmaz wire stent was used as the initial stent 10 times in seven patients and the Wallstent used eight times in seven patients. Four patients had multiple stents. Balloon inflation moulded the wire stent to the airway. RESULTS: There was no mortality resulting from the airway complication or any intervention. The most serious complication was a perforation of the airway using the semi-rigid dilator that necessitated immediate thoracotomy and re-anastomosis of the bronchus. Other complications necessitated repeat interventions due to restenosis or failure of the stents. The success of the stent placement was measured subjectively by the immediate ease of breathing enjoyed by each patient and objectively by the significant increase of the FEV1 from a pre-operative mean of 1.19 l (SD 0.64 l) to a post-operative mean of 2.06 l (SD 0.70 l) (P < 0001). The mean number of interventions according to the type of wire stent first used was significantly fewer with Wallstent insertion (1.28 (SD 0.48)) than in those patients in whom a Palmaz stent was inserted (5.22 (SD 2.38)) (P < 0008). CONCLUSION: The airway complication of stricture, broncho-malacia or dehiscence following lung transplantation can be managed effectively and easily with the use of balloon catheter dilation followed by precise placement of a self-expandable wire stent. The Wallstent is the superior stent for this application.

Effective oral ganciclovir prophylaxis against cytomegalovirus disease in heart transplant recipients.

The presented data show the combined sequential use of i.v. G for 14 days followed by PO G for 90 days is a much more effective prophylaxis for CMVD after heart transplantation than use of i.v. G for 14 days followed by PO A for 90 days. A need for hospitalization due to CMVD is significantly reduced by this new strategy. The follow-up in group II is shorter than in group I but is now at least 6 months in group II, without any new cases in the first 6 months after cardiac transplantation. Some currently unknown adverse effect of prolonged PO G, which may be present, is not identified in this analysis.

Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients.

The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections.

Molecular analysis of human cytomegalovirus strains from two lung transplant recipients with the same donor.

A total of four cytomegalovirus (CMV) isolates were obtained from two CMV seronegative patients, each of whom received a lung transplant from the same seropositive donor. CMV was isolated from Patient 1 from two bronchial alveolar lavage (BAL) specimens, one obtained during treatment with ganciclovir (GCV) and a second during later treatment with foscarnet. Both of these isolates are sensitive to GCV and foscarnet. CMV was isolated from Patient 2 from a blood and a BAL specimen obtained during treatment with GCV. Both of these isolates are resistant to GCV and show reduced GCV phosphorylation. Patient 1 is still alive 33 months posttransplant. Patient 2 died 6 1/2 months posttransplant. Although the four strains differ with respect to GCV susceptibility and phosphorylation, their DNA restriction fragment hybridization patterns and UL97 kinase gene sequences indicate that they are closely related. The restriction fragment hybridization patterns are identical among the strains, while these patterns differ markedly from those of unrelated strains. The DNA sequences of the UL97 genes of the strains from Patient 2 differ by only one nucleotide from those of Patient 1. The same comparison with unrelated strains shows a minimum of 12 nucleotide differences. The nucleotide change in the strains from Patient 2 produces an amino acid substitution of serine for leucine at residue 595, a substitution that was previously shown to transfer GCV resistance. Both patients, therefore, were apparently infected with the same donor strain, but during the course of GCV prophylaxis and treatment, a GCV-resistant mutant strain was selected in Patient 2.

Postmortem findings in lung transplant recipients.

Lung transplantation is now an accepted modality for treating end-stage lung disease. To better understand the factors limiting the survival of these patients, we reviewed the autopsy findings in 37 patients who received lung transplants. Between 1986 and 1995, 131 patients have undergone lung transplantation at our institution, including 4 patients with repeat transplantations. Of these, 48 (36.6%) died, 37 (77%) of whom had an autopsy. The autopsied patients were divided into three groups on the basis of post-transplantation interval: early (< 30 d), intermediate (31-365 d), and late (> 365 d). Of the 12 patients in the early group, 6 died of intra- and postoperative complications and 6 of bacterial infection with pneumonia in the transplanted lung. There were 18 patients in the intermediate group, of whom 11 died of infection (5 of cytomegalovirus, 5 of nonviral infections of the transplanted lung, and 1 of encephalomyelitis), 3 of post-transplantation lymphoproliferative disorder, 3 of chronic airway rejection, and one of unrelated cause. Of the seven patients in the late group, four died of chronic airway rejection, two of unrelated causes, and one of bacterial infection. Native lungs examined in 23 patients showed, in addition to the primary disease, bacterial pneumonia in 5, post-transplantation lymphoproliferative disorder in 3, cytomegalovirus in 2, and aspergillosis in 1. In this series of 37 autopsied patients, chronic rejection was the cause of death in 7 and was concomitantly seen in 3 patients (27%). In summary, the most common cause of death was infection (48%), followed by chronic rejection (19%), surgical complications (19%), post-transplantation lymphoproliferative disorder (7%), and unrelated causes (7%); rejection was not a major cause of death in the early and intermediate post-transplantation periods; in 30% of native lungs, significant pathologic findings were present in addition to the primary disease; and in the intermediate post-transplantation period, significant left ventricular hypertrophy occurred, which may be attributable to cyclosporine-induced hypertension but which needs to be further studied.

Aspergillus and lung transplantation.

BACKGROUND: Aspergillus infection is a known complication of transplantation. METHODS: We describe our experience with 37 patients who received lung transplants over 2 years at Loyola University Medical Center. All patients who had evidence of aspergillus on culture of clinical specimens or had biopsies with hyphal forms consistent with aspergillus were categorized according to the clinical manifestations. Important risk factors were analyzed in comparison with other lung transplant recipients during the same period. RESULTS: The incidence of invasive aspergillosis was high (16%). No patient with disseminated disease survived. Locally invasive disease responded well to treatment with amphotericin B and itraconazole. CONCLUSIONS: Lung transplantation patients may have a higher incidence of aspergillosis as compared with other transplantation groups. Prophylactic measures need to be explored.

Common infections complicating lung transplantation.

Infections are the most common cause of early and late morbidity and mortality in lung transplant recipients. Viral infections, in particular, have been linked to acute rejection, chronic rejection, and development of lymphoproliferative diseases.

Molecular evolution of the urate oxidase-encoding gene in hominoid primates: nonsense mutations.

Nucleotide sequences of portions of second and fifth exons of urate oxidase encoding gene (UOX) of chimpanzee, gorilla, orangutan, rhesus monkey and squirrel monkey obtained following amplification by polymerase chain reaction have been compared with corresponding sequences of human, baboon and rat UOX. Two or more nonsense mutations are found in the coding regions of this UOX gene thus far analyzed in human, chimpanzee, gorilla and orangutan, but not in the baboon, rhesus monkey and squirrel monkey. Of these nonsense mutations, the stop codon at amino acid position 33 is constant in the human and the three great apes suggesting that this may be the original mutation responsible for the inactivation of the UOX gene during hominoid evolution.

In-vitro and in-vivo studies of trimethoprim-sulphamethoxazole against multiple resistant Staphylococcus aureus.

Methicillin and gentamicin resistant strains of Staphylococcus aureus (MRSA) remains a cause of significant morbidity and mortality. Vancomycin is usually effective against these strains, but toxicity and expense are significant drawbacks. Resistance to the new quinolones has been demonstrated in vitro and during clinical therapeutic trials. Trimethoprim-sulphamethoxazole has proved to be effective in vitro against staphylococcal strains that are resistant to gentamicin, methicillin, and quinolones. As determined by time-kill kinetic studies, trimethoprim-sulphamethoxazole was rapidly bactericidal. Clinical evaluation of trimethoprim-sulphamethoxazole against MRSA in patients with osteomyelitis is under study. We believe that our data support the use of trimethoprim-sulphamethoxazole as a potentially economical and effective alternative for the treatment of infections caused by MRSA.