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Biomedical subjects

Michelle E Roland

Publications and source records attributed to Michelle E Roland.

At least 19 recordsLinked to original sources
PubMed2007

Postexposure prophylaxis after sexual exposure to HIV.

PURPOSE OF REVIEW: HIV postexposure prophylaxis is often recommended following potential sexual exposure to HIV. Recent data address the effectiveness of postexposure prophylaxis and prevention counseling, cost-effectiveness, antiretroviral options, challenges with nonoccupational postexposure prophylaxis among adolescents and children and following sexual assault in high HIV prevalence areas, and a successful program in Amsterdam. RECENT FINDINGS: Postexposure prophylaxis is not completely protective. Seroconversion may result from antiretroviral failure or from ongoing exposures. Postexposure prophylaxis associated risk reduction counseling results in reductions in subsequent risk behavior. Programs that target outreach and limit prescriptions to those with exposure sources who are at risk of being HIV infected are cost-effective. Less restrictive guidelines result in more prescriptions for low-risk exposures; this practice is not cost-effective. The ideal antiretrovirals for postexposure prophylaxis use have not been established. Tenofovir has several attractive properties. Developing systems to support the effective delivery of postexposure prophylaxis among children and adolescents and following sexual assault in high HIV prevalence, resource limited settings is challenging. SUMMARY: Numerous national and international guidelines recommend postexposure prophylaxis following potential sexual exposure to HIV. Maximizing adherence and minimizing subsequent HIV exposures will be critical to enhancing the effectiveness of this HIV prevention intervention.

Anti-HIV Agents↗
PubMed2006

Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation.

The outcome of patients with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) referred for liver transplantation (LT) is unknown. A high frequency of lamivudine-resistant (LAM-R) HBV infection may increase the risk of liver-related death pre-transplantation and prophylaxis failure post-transplantation. We evaluated the association of LAM-R HBV on pre-transplant survival and post-transplant outcomes in 35 consecutive HIV-HBV coinfected patients referred for LT between July 2000 and September 2002. At the time of referral, the median CD4 count was 273/mm, MELD was 14, and LAM-R HBV infection was present in 67%. Among these referred patients, 26% were listed, 29% not listed due to relative/absolute contraindications; 26% not listed as too early for LT; 9% not listed as too sick for LT; and 11% died during transplant evaluation. Of the 9 listed patients, 4 remained listed, 1 died 18 months post-referral, and 4 were transplanted (11% of total) 3 to 40 months after listing. Of 17 evaluated but not listed patients, 5 died (p=0.38 compared to listed group) and all deaths were liver-related. All the HBV-HIV coinfected patients, who were transplanted, are HBsAg negative and have undetectable HBV DNA levels on prophylactic therapy using hepatitis B immune globulin (HBIG) plus lamivudine, with and without tenofovir or adefovir, with median 33.1 months follow-up. Late referral and the presence of LAM-R HBV pre-transplantation are common in referred HIV-HBV patients. In HIV-HBV coinfected patients undergoing LT, HBV recurrence is successfully prevented with combination prophylaxis using HBIG and antivirals.

Adult↗
PubMed2006

Solid organ transplantation is a reality for patients with HIV infection.

Recent policies, guidelines, and laws reflect promising preliminary outcomes among transplant recipients with HIV infection, and ethical analyses suggest that it is not justifiable to deny solid organ transplantation based solely on HIV-infection status. These studies consistently describe stable HIV disease following liver and kidney transplantation. Despite good graft survival, kidney allograft rejection occurs frequently, and serious non-AIDS-defining infections requiring hospitalization are common following antirejection therapy. Profound interactions between immunosuppressants and antiretroviral drugs require careful monitoring, dose adjustment, and highly effective communication between the patient and a multidisciplinary group of health care providers. Despite these scientific and policy advances, many health care providers and patients remain unaware of ongoing progress in this field. The implications are critical, as late referral for liver transplant evaluation increases the pretransplant mortality risk. Because important patient selection and clinical management questions remain, it is critical that ongoing studies are completed quickly.

Anti-HIV Agents↗
PubMed2006

Liver transplantation in HIV-infected recipients.

Although human immunodeficiency virus (HIV)-infected patients are living longer and dying less often from complications related to acquired immunodeficiency syndrome (AIDS), they are experiencing significant morbidity and mortality related to end-stage liver disease. Advances in the management of HIV disease have made it difficult to continue denying transplantation to this population based upon futility arguments alone. Patient and graft survival rates in HIV-infected study subjects appear similar to those in large transplant databases. There are no reports suggesting significant HIV disease progression. There are substantial interactions between immunosuppressants and antiretroviral drugs that require careful monitoring and dose adjustment. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team and the primary HIV care provider. It is critical that HIV clinicians and hepatologists are aware that liver transplantation is an option for HIV-infected patients at many transplant centers as delays in referral result in unnecessary mortality during the pretransplantation evaluation process.

AIDS-Related Opportunistic Infections↗
PubMed2006

Solid organ transplantation: referral, management, and outcomes in HIV-infected patients.

Advances in HIV management make it difficult to deny solid organ transplantation to HIV-infected patients based on futility arguments. Preliminary studies suggest that both patient and graft survival are similar in HIV-negative and HIV-positive transplant recipients. While there has been no significant HIV disease progression, substantial interactions between immunosuppressants and antiretroviral drugs necessitate careful monitoring. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team, the primary HIV care provider, and the patient. Timely referral for transplant evaluation will prevent unnecessary mortality during the pre-transplant evaluation process.

HIV Infections↗
PubMed2005

Seroconversion following nonoccupational postexposure prophylaxis against HIV.

BACKGROUND: The efficacy of antiretroviral postexposure prophylaxis (PEP) against infection with human immunodeficiency virus (HIV) following occupational exposures has prompted the use of PEP after nonoccupational exposures. There are, however, important differences between occupational and nonoccupational exposures, and the effectiveness of PEP following nonoccupational exposure is unknown. We sought to describe the occurrence and circumstances of HIV seroconversion following nonoccupational PEP. METHODS: HIV uninfected individuals reporting potential sexual or injection drug use exposures to HIV in the preceding 72 h received a 28-day regimen of antiretroviral therapy and counseling in a nonrandomized trial. The level of HIV antibody was measured 12 weeks after PEP initiation. RESULTS: Of 877 exposed subjects, 702 were evaluable 12 weeks after exposure. Seroconversion was detected in 7 subjects (1%; 95% confidence interval, 0.4%-2%). Three seroconverters reported having no exposures after PEP initiation and, thus, probably represent evidence of chemoprophylactic failure. In the other 4 subjects, additional exposures to HIV after PEP initiation or detection of HIV RNA in plasma specimens obtained at baseline precluded determination of the source of seroconversion. No exposure source was available to assess genetic concordance with the seroconverter's virus. CONCLUSIONS: As for occupational exposure, PEP is not completely effective in preventing HIV infection following nonoccupational exposure. Therefore, primary prevention remains essential. In contrast to the occupational setting, the potential source of exposure is rarely available for testing in the nonoccupational setting, and exposures are often not isolated. Thus, it is often impossible to determine whether seroconversion resulted from failure of PEP or from other exposures, posing difficulties for future comparative studies seeking to evaluate the effectiveness of PEP.

Anti-HIV Agents↗
PubMed2005

Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients.

BACKGROUND: With advances in antiretroviral therapy, many human immunodeficiency virus (HIV)-infected individuals are living longer and developing end-stage renal or hepatic disease requiring transplantation. Maintaining the viability of the transplant and suppressing HIV replication requires concomitant use of immunosuppressants (e.g., cyclosporine) and antiretrovirals (e.g., protease inhibitors or nonnucleoside reverse transcriptase inhibitors), which leads to drug interactions. To assist in appropriate clinical management of HIV-infected transplant recipients, the authors describe the pharmacokinetic interactions between cyclosporine and the antiretroviral medications, and required modifications of cyclosporine dosing. METHODS: Eighteen HIV-infected subjects with end-stage kidney or liver disease underwent transplantation. Subjects had pharmacokinetic studies before transplantation and for up to 2 years posttransplantation (at weeks 2-4, 12, 28, 52, and 104). Protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and cyclosporine concentrations were measured by liquid chromatography-mass spectrometry in plasma and whole blood, respectively. RESULTS: Subjects using protease inhibitors and cyclosporine had a threefold increase in cyclosporine area under the curve (4,190+/-2,180-11,900+/-1,600 ng*hr/mL, P<0.01), necessitating an 85% reduction in cyclosporine dose over a 2-year period (1.3+/-1.5-0.2+/-0.0 mg/kg/dose), leading to a progressive increase in oral cyclosporine bioavailability (R=0.92, P<0.02). Subjects on nonnucleoside reverse-transcriptase inhibitors showed minimal interactions with cyclosporine, and subjects on both HIV treatments had intermediate responses. CONCLUSIONS: HIV-infected transplant recipients on protease inhibitors require markedly lower doses of cyclosporine, with continued lowering of the cyclosporine dose over time and ongoing cyclosporine trough monitoring because of progressively increasing cyclosporine bioavailability. Medication changes must be carefully managed to avoid insufficient immunosuppression or toxicity resulting from drug interactions.

Adolescent↗
PubMed2004

Cost-effectiveness of HIV postexposure prophylaxis following sexual or injection drug exposure in 96 metropolitan areas in the United States.

OBJECTIVES: To evaluate the cost-effectiveness of HIV postexposure prophylaxis (PEP) following sexual or injection-related exposures in 96 metropolitan statistical areas in the United States (MSA). DESIGN: Empirical, model-based cost-effectiveness analysis. METHODS: Epidemiological and population size estimates from the literature were combined with information about the distribution of exposure types, PEP completion rate, proportion of source partners known to be HIV infected, and PEP program costs obtained from a feasibility study of PEP in San Francisco to estimate the cost-effectiveness of hypothetical PEP programs in each of the 96 MSA. The effectiveness of combination antiretroviral therapy following sexual or drug use-related exposures, which is presently not known, was assumed equal to the effectiveness of zidovudine monotherapy in the occupational setting. The main outcome measure was the cost-utility ratio, defined as the cost per quality-adjusted life year (QALY) saved by the PEP intervention. RESULTS: The cost-utility ratios for the 96 MSA ranged from 4137 dollars to 39,101 dollars per QALY saved; only two of the ratios exceeded 30,000 dollars per QALY saved. Combined across the 96 MSA, the hypothetical PEP programs would reach nearly 20,000 clients at a total cost of approximately 22 million dollars. The overall cost-utility ratio across MSA was 12,567 dollars per QALY saved. The majority of the HIV infections prevented by PEP were among men and women who reported receptive anal intercourse exposure. CONCLUSIONS: PEP following sexual or drug use-related exposures could be a cost-effective complement to existing HIV-prevention efforts in most MSA across the United States.

Chemoprevention↗
PubMed2004

HIV RNA testing in the context of nonoccupational postexposure prophylaxis.

BACKGROUND: The specificity and positive predictive value of human immunodeficiency virus (HIV) RNA assays have not been evaluated in the setting of postexposure prophylaxis (PEP). METHODS: Plasma from subjects enrolled in a nonoccupational PEP study was tested with 2 branched-chain DNA (bDNA) assays, 2 polymerase chain reaction (PCR) assays, and a transcription-mediated amplification (TMA) assay. Assay specificity and positive predictive value were determined for subjects who remained negative for HIV antibody for >or=3 months. RESULTS: In 329 subjects examined, the lowest specificities (90.1%-93.7%) were seen for bDNA testing performed in real time. The highest specificities were seen with batched bDNA version 3.0 (99.1%), standard PCR (99.4%), ultrasensitive PCR (100%), and TMA (99.6%) testing. Only the 2 assays with the highest specificities had positive predictive values >40%. For the bDNA assays, increasing the cutoff point at which a test is called positive (e.g., from 50 copies/mL to 500 copies/mL for version 3.0) increased both specificity and positive predictive values to 100%. CONCLUSIONS: The positive predictive value of HIV RNA assays in individuals presenting for PEP is unacceptably low for bDNA-based testing and possibly acceptable for PCR- and TMA-based testing. Routine use of HIV RNA assays in such individuals is not recommended.

Anti-HIV Agents↗
PubMed2004

Use of postexposure prophylaxis against HIV infection following sexual exposure does not lead to increases in high-risk behavior.

BACKGROUND: The effectiveness of postexposure prophylaxis (PEP) following occupational exposure to HIV has prompted advocacy for PEP following sexual or drug-use exposures. OBJECTIVE: To evaluate the concern that the availability of PEP for sexual or drug-use exposures might result in behavioral disinhibition. DESIGN: Non-randomized trial of 397 adults with high-risk sexual or drug-use exposures within the prior 72 h. INTERVENTIONS: Antiretroviral medication for 4 weeks and five counseling sessions. MAIN OUTCOME MEASUREMENTS: Participants were followed for 12 months for repeat request for PEP and for changes compared with pre-enrollment in overall high-risk behavior and the acquisition of sexually transmitted diseases (STD) and HIV. RESULTS: After 12 months following receipt of PEP, the majority of participants (83%) did not request a repeat course of PEP. At 12 months after exposure, 73% of participants reported a decrease compared with baseline in the number of times they had performed high-risk sexual acts; 13% reported no change, and 14% had an increase. Most participants (85%) had no change in the incidence of STD; 8.5% had a decrease and 6.8% an increase. Three homosexual men seroconverted for HIV (none associated with the presenting exposure) for a rate of 1.2/100 person-year, equivalent to rates in San Francisco among all homosexual men. CONCLUSIONS: After receipt of PEP consisting of antiretroviral medication and behavioral counseling following a potential sexual exposure to HIV, most individuals do not increase high-risk behavior. Coupled with prior safety and feasibility data, this lack of behavioral disinhibition suggests that use of PEP should be routinely considered following high-risk sexual exposures.

Adult↗
PubMed2004

Cost-effectiveness of postexposure prophylaxis after sexual or injection-drug exposure to human immunodeficiency virus.

BACKGROUND: The cost-effectiveness of interventions that provide human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) to individuals after sexual or injection-drug use exposures depends on the distribution of exposure routes, prevalence of infection among source partners, adherence to PEP regimens, medical care costs, and prevailing epidemiologic contexts, among other factors. OBJECTIVE: To determine the cost-effectiveness of a comprehensive program to prevent HIV infection after sexual or injection-drug use exposure for 401 persons seeking PEP in an urban community. METHODS: We conducted a retrospective cost analysis to evaluate the cost of the PEP intervention, then combined this information with model-based effectiveness estimates to determine the PEP program's "cost-utility ratio," which is the ratio of net program costs to the total number of quality-adjusted life-years (QALYs) saved by the program. RESULTS: The average cost of the PEP regimen was $1222, and the total cost of the program was $450 970. The PEP program prevented an estimated 1.26 HIV infections, saved 11.74 QALYs, and averted $281 323 in future HIV-related medical care costs. The overall cost-utility ratio was $14 449 per QALY saved. When analysis was restricted to men reporting receptive anal intercourse, the savings in averted HIV-related medical care costs exceeded the cost of the program. The results were generally robust to changes in key parameter values but were sensitive to assumptions about the HIV transmission probability for receptive anal intercourse. CONCLUSIONS: For this study population, HIV PEP was cost-effective by conventional standards and cost-saving for persons seeking PEP after male-male receptive anal intercourse.

Anti-HIV Agents↗
PubMed2003

Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have historically been excluded from consideration for transplantation out of concern for the effects of immunosuppression on the progression of HIV disease. Improvements in HIV-related morbidity and mortality with the use of highly active antiretroviral therapy (HAART) have prompted a reevaluation of transplantation as a treatment option for HIV-infected patients with end-stage kidney and liver disease. METHODS: Eligible patients met standard transplant criteria. They had undetectable plasma HIV-1 RNA levels (viral load) for 3 months (kidney) or were predicted to achieve viral load suppression posttransplantation if unable to tolerate HAART (liver); a CD4+ T-cell count of more than 200 cells/microL (kidney) or more than 100 cells/microL (liver) for 6 months; and no history of opportunistic infections and neoplasm. Standard immunosuppression included prednisone, mycophenolate mofetil (CellCept, Roche Pharmaceuticals, Basel, Switzerland), and cyclosporine (Neoral, Novartis, East Hanover, NJ). RESULTS: Fourteen patients received transplants (10 kidney transplants, mean follow-up 480 days; four liver transplants, mean follow-up 380 days). All of the kidney transplant recipients (100%) are alive and with functioning grafts, and three of four liver transplant patients (75%) are alive and well with functioning grafts (all liver transplant patients with normal liver function tests). The one death occurred 445 days posttransplantation in a liver recipient coinfected with hepatitis C virus, who died as the result of its rapid reoccurrence. Rejection occurred in 5 of 10 kidney transplant recipients but did not occur in any of the four liver transplant recipients. HIV viral loads have remained undetectable in all patients maintained with HAART. CD4 counts have remained stable in patients not treated for rejection. Patients receiving protease inhibitors require 25% of the dose of cyclosporine compared with patients receiving nonnucleoside reverse transcriptase inhibitors. CONCLUSIONS: There has been no evidence of significant HIV progression and no adverse effect of HIV on allograft function. Rejection is a concern in kidney transplant recipients, as is the possible poor outcome in hepatitis C virus-coinfected liver transplant recipients. Preliminary data are encouraging and indicate that transplantation should be a treatment option for individuals with well-controlled HIV disease.

Adult↗
PubMed2003

Kidney and liver transplantation in HIV-infected patients: case presentations and review.

Until recently, HIV-infected patients have been excluded from consideration for solid organ transplantation. The relatively high mortality rates among HIV-infected transplant recipients observed in the era prior to the use of highly active antiretroviral therapy (HAART), coupled with long waiting times for cadaveric organs, made it difficult to support organ transplantation in this patient group. However, in response to the marked reductions in morbidity and mortality associated with HIV infection, several transplant centers have developed pilot studies or revised their clinical criteria to allow transplantation in this group of patients. We describe two cases, one kidney and one liver transplant recipient, and review the major clinical and research issues related to this topic. Reports of transplantations in the pre-HAART era highlight two important findings. First, some HIV-infected transplant recipients did very well with long survival periods. However, overall progression to AIDS and death appeared accelerated. We recently reported on our preliminary experience with 45 selected transplant recipients in the HAART era. One-year patient survival rates were similar to unmatched survival data from the United Network for Organ Sharing (UNOS) database. Median CD4+ T-cell counts remained stable in the follow-up period compared to pretransplant. HIV-1 RNA nearly uniformly continued to be suppressed below the limits of detection. Preliminary data are promising and support the current efforts to evaluate patient and graft survival among HIV-infected transplant recipients and to explore the mechanisms underlying the many potential complications of transplantation in this population.

Adult↗