Opportunities to Increase Access to HIV Prevention: Evaluating the Implementation of Pharmacist-Initiated Pre-exposure Prophylaxis in California.

Background: Pharmacies are a promising setting through which to expand access to human immunodeficiency virus (HIV) prevention, including pre-exposure and post-exposure prophylaxis (PrEP and PEP, respectively). We aimed to evaluate and inform the implementation of California's Senate Bill 159 (2019), allowing pharmacists to independently prescribe PrEP and PEP. Methods: From October through December 2022, we conducted a cross-sectional study of 919 California pharmacists and pharmacy students, primarily recruited via the email listservs of professional organizations. Participants completed an online survey assessing the implementation of pharmacist-initiated PrEP/PEP, including knowledge, attitudes, practices, perceived barriers, and implementation preferences elicited through a discrete choice experiment. Results: Among 919 participants (84% practicing pharmacists, 43% in community pharmacies), 11% and 13% reported that pharmacists at their pharmacy initiate PrEP and PEP, respectively. Most believed that pharmacist-initiated PrEP/PEP is important (96%) and were willing to provide PrEP (81%); fewer (27%) had PrEP/PEP training. Common implementation barriers were lack of staff/time and payment for pharmacist services. Participants preferred PrEP implementation models with in-pharmacy rapid oral HIV testing and pharmacists specifically hired to provide PrEP services. Conclusions: Despite pharmacists' supportive attitudes, Senate Bill 159 implementation in California pharmacies remains limited, in part due to policy-level and organizational-level barriers. Ensuring PrEP/PEP-related payment for services and sufficient workforce capacity is key to leveraging pharmacists' role in HIV prevention.

Patterns of Prescribing Antiretroviral Therapy Upon Discharge to Psychiatry Inpatients With HIV/AIDS at a Large Urban Hospital.

BACKGROUND: HIV infection is more prevalent among people with severe mental illness (SMI) than in the general population. People with SMI may lack access to recommended antiretroviral therapy (ART), and inpatient psychiatric admissions may be opportunities to ensure that individuals receive recommended treatment. OBJECTIVE: To evaluate ART prescription patterns on an inpatient psychiatry service. METHODS: In this retrospective, observational study, patient and admission characteristics and ART prescriptions were obtained for 248 HIV-positive inpatients between 2006 and 2012. Receipt of any ART, any recommended ART regimen, and ART with potentially harmful adverse events and drug interactions were examined. General estimating equation models were used to evaluate prescription patterns in relation to patient and admission characteristics. RESULTS: ART was prescribed at 39% of discharges and increased by 51% during the study. Prescription was more common in admissions with an AIDS diagnosis and age greater than 29 years and less common in admissions associated with a psychotic diagnosis and shorter inpatient stays. When ART was prescribed, regimens were consistent with guideline recommendations 91% of the time. Prescription of potentially harmful regimens was limited. CONCLUSION AND RELEVANCE: In an acute inpatient psychiatry setting in an urban HIV/AIDS epicenter, where psychotic disorders and brief and involuntary admissions were the norm, guideline-recommended ART regimens were prescribed at almost 60% of discharges by the end of the study. Future studies should explore interventions to increase ART for high-risk subpopulations with SMI, including younger individuals or those with brief inpatient psychiatry hospitalizations.

Community pharmacy delivered PrEP to STOP HIV transmission: An opportunity NOT to miss!

In the United States, 1.1 million persons are living with human immunodeficiency virus (HIV), and approximately 37,800 new infections occur annually. Ending the HIV epidemic requires reducing HIV transmissions by 90% within the next 10 years and requires expanded HIV testing, antivirals for persons infected with HIV, and scale-up of pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) to prevent new infections. Community pharmacies are widely accessible and employ highly trained health care professionals on-site who can initiate PrEP and PEP. Recommendations are offered to implement a community pharmacy PrEP program. Pharmacy, government, and HIV prevention leaders must be prepared to support and promote transformative changes, including (1) modification or expansion of existing state-specific scope of practice to initiate PrEP and PEP, (2) encouraging pharmacist education about PrEP and PEP, (3) identification and screening of candidates for PrEP eligibility, (4) incorporating pharmacy laboratory ordering and monitoring logistics, (5) adjusting workflow and ensuring confidential spaces for sensitive discussions, and (6) addressing reimbursement to maintain pharmacist-delivered PrEP and PEP programs. HIV disproportionately affects minority communities and younger individuals who may not be engaged in the health care system. Community pharmacies are accessible and can help increase PrEP use. Expansion of community pharmacy PrEP programs are needed to help end the HIV epidemic. Implementation of PrEP requires adaptation of the pharmacy profession to support incorporation of PrEP in a community pharmacy. Endorsement and support of community pharmacists are needed to implement PrEP to increase HIV prevention efforts and expand pharmacists' scope of practice.

Implementation of pre-exposure prophylaxis at a community pharmacy through a collaborative practice agreement with San Francisco Department of Public Health.

OBJECTIVE: To discuss the design and implementation of a community pharmacy-initiated HIV pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) program developed in collaboration with the San Francisco Department of Public Health (SFDPH). SETTING: A community pharmacy in San Francisco and the SFDPH developed a collaborative practice agreement (CPA) that allowed community pharmacists to initiate PrEP and PEP to prevent HIV acquisition and increase uptake in vulnerable populations. PRACTICE DESCRIPTION: A community pharmacy in San Francisco's Mission District, an urban, historically Hispanic/Latino/Latinx neighborhood. The primary collaborative practice team consisted of 1 community pharmacy technician, 4 community pharmacists, and 1 designated overseeing physician at SFDPH. PRACTICE INNOVATION: The pharmacy and the SFDPH collaborated together for 20 months from start to implementation of the CPA and the PrEP program. An interdisciplinary team of pharmacists, pharmacy personnel, public health physicians, and health department staff members worked together to design, launch, and maintain the program. Pharmacists were trained by SFDPH staff members on HIV testing and counseling and implementation of the PrEP protocol, including PEP initiation and sexually transmitted disease testing. A Department of Public Health secure portal was used to share patient information. An SFDPH physician reviewed patients' charts regularly and communicated with PrEP pharmacists as needed. RESULTS: Between April 2018 and the end of March 2019, 6 patients received PEP and 53 patients completed a PrEP initiation visit, of whom 96% (n = 51) filled their prescription. Approximately 47% (n = 24) of clients who started PrEP self-identified as Hispanic or Latino, 10% (n = 5) were black or African American, and 82% (n = 42) identified as men who have sex with men. CONCLUSION: Implementation of a CPA between a community pharmacy and a local health department enabled the launch of pharmacist-delivered PrEP, further expanding the landscape of access points to vulnerable populations in San Francisco.

Outcome of challenging HIV case consultations provided via teleconference by the Clinician Consultation Center to the Federal Bureau of Prisons.

OBJECTIVES: To describe the collaboration and prospective outcome of challenging human immunodeficiency virus (HIV) cases presented by Board of Prisons (BOP) pharmacists in consultation with Clinician Consultation Center (CCC) clinical pharmacists and physicians to improve correctional patient care. SETTING: Federal correctional facilities. PRACTICE DESCRIPTION: Pharmacists improve care of incarcerated persons infected with HIV. PRACTICE INNOVATION: Pharmacists evaluate, implement, and provide successful oversight of HIV/hepatitis C virus (HCV) care. EVALUATION: Retrospective review of the clinical outcomes of HIV and HCV coinfected cases implemented by BOP pharmacists following CCC clinical consultations from 2010 through 2012. RESULTS: Most cases focused on selecting optimal antiretroviral therapy (ART) regimens in patients experiencing treatment failure by interpreting resistance tests, limiting ART toxicity, identifying adherence strategies, and managing HIV/HCV coinfection. In 32 of the 34 cases presented, 87.5% (28/32) of CCC recommendations were implemented, resulting in 89% of those patients (25/28) achieving optimal virologic or clinical outcome. Complete virologic suppression occurred in 64% (18/28), and significant viral load reductions in 25% (7/28) of the cases. No changes occurred in 2 patients, and data were not available in 2 others lost to follow-up. BOP participation has increased since its inception from 6 to 12-15 pharmacists per call. Discussions also included updates in antiretroviral guidelines, screening and management of patients coinfected with HIV and HCV, and implications for BOP guidelines. CONCLUSION: BOP clinical consultant pharmacists can successfully implement CCC recommendations to achieve desired clinical outcomes. Consultations and educational efforts from CCC experts assist BOP pharmacists in ensuring excellence in management of complex HIV/HCV issues and medication regimens to achieve desired outcomes. CCC collaboration and BOP pharmacist involvement have improved patient care. Using a team approach to include BOP clinical pharmacists and obtaining expert opinion in management of other chronic illnesses may be a model that can be considered to improve correctional care.

Pharmacists performing hepatitis C antibody point-of-care screening in a community pharmacy: A pilot project.

OBJECTIVES: To describe the first community pharmacy-based hepatitis C antibody (HCV-Ab) point-of-care (POC) screening program and its outcomes in California. SETTING: Community pharmacy. PRACTICE DESCRIPTION: Community pharmacists perform HCV-Ab POC testing, counsel patients about HCV transmission and prevention, and provide linkage to care. PRACTICE INNOVATION: Pharmacists implement an HCV-Ab POC screening program in collaboration with the local public health department. EVALUATION: Descriptive data of the demographics of the persons receiving HCV-Ab POC screening and qualitative assessment of the attitudes and knowledge of the trained pharmacists involved in its implementation. RESULTS: During the 3-month pilot, 6 community pharmacists performed 83 HCV-Ab rapid POC tests with 1 positive result (1.2%). Risk factors for the positive result included injection drug use, crack cocaine or methamphetamine use, and being in the high-risk birth cohort. Although some expressed reservations, pharmacists attested to the feasibility of incorporating HCV screening into their routine pharmacy work. Two major barriers identified by pharmacists for implementing HCV screening included getting non-pharmacy customers into the pharmacy for testing and balancing the time required to review test results within the normal pharmacy workflow. CONCLUSION: This pilot demonstrated that trained and motivated community pharmacists in partnership with the Department of Public Health could perform needed rapid HCV-Ab POC screening for potentially high-risk patients not currently in care. Community pharmacies are viable locations for screening and linkage to care owing to their easy access to knowledgeable pharmacists and accessible locations.

Initial Management of Patients with HIV Infection.

Human immunodeficiency virus (HIV) infection has become a treatable chronic disease with near-normal life expectancy when patients receive antiretroviral therapy (ART). Family physicians and other primary care clinicians commonly provide long-term comprehensive care for persons with HIV infection. This article describes the scope of initial care, including obtaining a thorough history; physical examination for HIV-associated manifestations; attention to HIV-specific immunization schedules; routine and HIV-specific laboratory evaluation; and ensuring standard health care maintenance to prevent HIV- and non-HIV-related morbidity and mortality. Clinicians should encourage combination ART as early as possible, although careful assessment of patient readiness and ability to sustain lifelong treatment must be weighed. After ART initiation, monitoring viral load and CD4 lymphocyte response is essential to ensure viral suppression and evaluate immune system restoration. Opportunistic infections are now less common than in the past because ART usually prevents or markedly delays progression to advanced HIV disease. The most important reasons for consultation or comanagement with an HIV expert include management of antiretroviral drug resistance or drug toxicities, as well as special circumstances such as viral hepatitis coinfection or pregnancy.

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are nucleoside reverse transcriptase inhibitors approved as pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). Prophylactic TDF-based regimens have been shown to reduce the risk of HIV infection by 74 to 92% among participants with detectable drug levels. Adverse events observed in clinical trials include nausea, elevated creatinine and liver enzymes, and decreased bone mineral density. AREAS COVERED: This article reviews the pharmacology, pharmacokinetics, and the safety profile of TDF and FTC used as PrEP for HIV infection. EXPERT OPINION: TDF-FTC can have a large impact in preventing HIV infections among high risk individuals when taken daily. Although TDF-FTC is associated with adverse events, they can be minimized with clinician-guided monitoring.

Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection: Joint Opinion of the GI/Liver/Nutrition and Infectious Diseases Practice and Research Networks of the American College of Clinical Pharmacy.

The objective of this opinion paper was to identify and describe potential clinical pharmacists' services for the prevention and management of patients infected with the hepatitis C virus (HCV). The goals of this paper are to guide the establishment and development of pharmacy services for patients infected with HCV and to highlight HCV research and educational opportunities. Recommendations were based on the following: a review of published data on clinical pharmacist involvement in the treatment and management of HCV-infected patients; a consensus of clinical pharmacists who provide direct patient care to HCV-infected patients and practice in different pharmacy models, including community-based and academic settings; and a review of published guidelines and literature focusing on the treatment and management of HCV infections. The recommendations provided in this opinion paper define the areas of clinical pharmacist involvement and clinical pharmacy practice in the treatment and management of patients with HCV. Clinical pharmacists can promote preventive measures and education about reducing HCV transmission, improve medication adherence, assist in monitoring clinical and adverse effects, recommend treatment strategies to minimize adverse effects and drug interactions, and facilitate medication acquisition and logistics that positively improve patient outcomes and reduce the health care system costs.

Reporting of critical information in studies of pharmacists in HIV care.

OBJECTIVE: To evaluate manuscripts documenting HIV pharmacist interventions and assess adequacy of reporting as defined by CONSORT and STROBE criteria. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, BIOSIS Previews, and PsycINFO databases were searched from inception - 1 June 2011. Studies were included if pharmacists performed an intervention to improve HIV patient care, and the study evaluated the intervention's impact. Qualitative studies, non-English language reports, abstracts and studies where the pharmacist did not intervene were excluded. Manuscripts were independently evaluated by two reviewers for the presence, absence or lack of applicability of STROBE (observational studies) or CONSORT (randomized studies) criteria, for presence or absence of description of pharmacist's duties, CD4+ cell count, HIV viral load and adherence measurement. Reviewers met to discuss the rationale behind their evaluation; a third arbiter was consulted when reviewers could not agree on a particular criterion. KEY FINDINGS: Twenty-two manuscripts met inclusion criteria. Observational studies of HIV pharmacists (n = 19) included 56% of applicable STROBE criteria. Randomized studies of HIV pharmacists (n = 3) adhered more closely to CONSORT reporting guidelines (average 80% of applicable criteria). Manuscripts published after 2004 more consistently evaluated pharmacist impact on HIV outcomes such as CD4+ and viral load. CONCLUSIONS: Thorough reporting increases the reader's ability to critically evaluate manuscripts of HIV pharmacist services. Increasing pharmacist awareness of manuscript guidelines such as CONSORT and STROBE may improve clarity of reporting in studies of HIV pharmacist interventions and clinical programmes.

Center for the Advancement of Pharmacy Education 2013 educational outcomes.

An initiative of the Center for the Advancement of Pharmacy Education (formerly the Center for the Advancement of Pharmaceutical Education) (CAPE), the CAPE Educational Outcomes are intended to be the target toward which the evolving pharmacy curriculum should be aimed. Their development was guided by an advisory panel composed of educators and practitioners nominated for participation by practitioner organizations. CAPE 2013 represents the fourth iteration of the Educational Outcomes, preceded by CAPE 1992, CAPE 1998 and CAPE 2004 respectively. The CAPE 2013 Educational Outcomes were released at the AACP July 2013 Annual meeting and have been revised to include 4 broad domains, 15 subdomains, and example learning objectives.

The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review.

OBJECTIVE: Due to the rapid proliferation of human immunodeficiency virus (HIV) treatment options, there is a need for health care providers with knowledge of antiretroviral therapy intricacies. In a HIV multidisciplinary care team, the HIV pharmacist is well-equipped to provide this expertise. We conducted a systematic review to assess the impact of HIV pharmacists on HIV clinical outcomes. METHODS: We searched six electronic databases from January 1, 1980 to June 1, 2011 and included all quantitative studies that examined pharmacist's roles in the clinical care of HIV-positive adults. Primary outcomes were antiretroviral adherence, viral load, and CD(4) (+) cell count and secondary outcomes included health care utilization parameters, antiretroviral modifications, and other descriptive variables. RESULTS: Thirty-two publications were included. Despite methodological limitation, the involvement of HIV pharmacists was associated with statistically significant adherence improvements and positive impact on viral suppression in the majority of studies. CONCLUSION: This systematic review provides evidence of the beneficial impact of HIV pharmacists on HIV treatment outcomes and offers suggestions for future research.

Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women.

OBJECTIVES: To estimate nevirapine (NVP) pharmacokinetics and examine its association with rash and/or hepatotoxicity in women starting antiretroviral treatment in the AIDS Clinical Trials Group A5208/OCTANE study in Africa. DESIGN: In HIV-infected, nonpregnant women with screening CD4 cell count less than 200 cells/µl randomized to NVP (twice daily, after 14-day once-daily lead-in period) and tenofovir/emtricitabine, single NVP blood samples were collected 14 and 28 days following randomization. Rash and hepatotoxicity that occurred during therapy, or within 7 days after the last dose of NVP, were defined as toxicity. METHODS: NVP pharmacokinetics were modeled by population pharmacokinetic analysis. Individual Bayesian pharmacokinetic estimates were used to calculate clearance, 24-h area under the curve, and predicted plasma concentrations. RESULTS: Median week 4 NVP clearance was 2 l/h. Among the 359 women, 194 (54%) developed a rash of any grade; 82 (23%) had grade 2+ and nine (3%) had grade 3+ rash. Median clearance was 1.7 l/h for participants exhibiting 3+ rash versus 2 l/h in women without 3+ rash (P = 0.046). The odds of developing 3+ rash was 50% higher for every 20% decrease in clearance (P = 0.046). NVP discontinuation due to rash/liver toxicity was significantly more common among women with pretreatment CD4 cell count more than 250 cells/µl (P = 0.003). CONCLUSION: In this study, HIV-infected African women starting a NVP-based antiretroviral regimen had a lower NVP clearance compared to previous reports. Severe rash, but not hepatotoxicity, was associated with higher NVP exposure. Albeit observed in a small number of women, baseline CD4 cell count at least 250 cells/µl was significantly associated with NVP toxicity.

Health care provider satisfaction with telephone consultations provided by pharmacists and physicians at the National HIV/AIDS Clinicians' Consultation Center.

BACKGROUND: The federally funded National HIV/AIDS Clinicians' Consultation Center (NCCC) offers US health care providers expert telephone consultations for managing HIV/AIDS and occupational exposures to blood-borne pathogens through 3 telephone services: the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline), the National HIV Telephone Consultation Service (Warmline), and the Perinatal HIV Hotline. Callers to the NCCC receive consultation from either a clinical pharmacist (PharmD) or a physician (MD) with HIV expertise. OBJECTIVE: To compare the satisfaction of NCCC callers who received clinical consultations from clinical pharmacists and physicians with HIV expertise. METHODS: We prospectively mailed 1256 satisfaction surveys to NCCC health care provider callers during a 7-month period. Survey recipients were not aware that satisfaction surveys compared PharmD and MD consultation services. Respondents rated their level of agreement with 8 statements about the quality of consultation, the quality of clinical information given, and future calls to the NCCC. RESULTS: Survey return rates were 43% for PEPline and 40% for Warmline and Perinatal HIV Hotline combined. Overall, caller satisfaction with the telephone consultation service was extremely high (>4 in all categories on a 1-5 Likert scale). There was no significant difference in PEPline caller satisfaction ratings between PharmD and MD consultations. Callers to the Warmline and Perinatal HIV Hotline agreed with all 8 satisfaction statements. For the following 3 statements, however, satisfaction was higher when Warmline and Perinatal HIV Hotline consultation was provided by an MD: "Overall, I was pleased with the quality of my consultation" (p = 0.04); "I would use this service again" (p < 0.02); and "I am likely to recommend this service to my colleagues" (p = 0.02). CONCLUSIONS: Health care provider callers to the NCCC were highly satisfied with the information obtained from this HIV/AIDS telephone consultation service. By measuring callers' survey response to PharmD and MD consultations, the importance of the clinicians' contributions to this advanced HIV/AIDS consultation service is documented.

Raltegravir: the first HIV integrase inhibitor.

BACKGROUND: The availability of new classes of antiretroviral drugs has made it possible for HIV-infected individuals who are highly treatment experienced to achieve the goals of immunologic recovery and virologic suppression. Raltegravir is the first integrase inhibitor to be approved by the US Food and Drug Administration for use in antiretroviral treatment- experienced adult patients with viral resistance. OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, tolerability, resistance profile, drug interactions, and dosing and administration of raltegravir. METHODS: Searches of MEDLINE and International Pharmaceutical Abstracts from 1964 to July 2008 were conducted using the terms integrase, raltegravir, and MK-0518. Relevant information was extracted from the identified clinical trials and review articles. Abstracts from the Conference on Retroviruses and Opportunistic Infections (1998-2008); Interscience Conference on Antimicrobial Agents and Chemotherapy (1999-2007); International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (2001-2007); and European AIDS Conference (2001-2007) were also searched. RESULTS: Raltegravir blocks HIV replication by inhibiting essential strand-transfer activities of integrase. Raltegravir is rapidly absorbed, with a median T(max) of approximately 4 hours in the fasting state. No dose adjustment is recommended in patients with moderate renal or hepatic insufficiency, and raltegravir may be taken without regard to meals. In Phase II studies in treatment-naive patients, raltegravir had efficacy similar to that of standard initial therapies. In 2 interrelated Phase III clinical studies in treatment-experienced patients with drug-resistant disease, the addition of raltegravir to an optimized background regimen significantly lowered HIV RNA compared with optimized background treatment alone (62.1% vs 32.9%, respectively; P < 0.001). Raltegravir was generally well tolerated. The most common adverse effects reported in Phase II/III trials in treatment-experienced patients were diarrhea (16.6%), nausea (9.9%), and headache (9.7%). Cytochrome P450-related drug interactions are not expected, as raltegravir is not a CYP substrate, inducer, or inhibitor. However, to prevent failure of raltegravir, the drug should not be coadministered with rifampin. CONCLUSION: Raltegravir is a potent and generally well tolerated antiretroviral agent that may play an important role in the treatment of patients harboring resistance to other antiretrovirals.

Immunologic benefits of enfuvirtide in patients enrolled in a drug assistance program.

BACKGROUND: Randomized clinical trials have demonstrated that enfuvirtide plus an optimized background regimen can cause a significant increase in CD4+ cell counts and a reduction in HIV RNA levels. OBJECTIVE: To describe and analyze CD4+ cell count and HIV RNA changes in HIV-infected patients receiving enfuvirtide and a prescribed background regimen (PBR) in a primarily clinical setting. METHODS: A retrospective review from September 1998 through August 2005 of CD4+ cell counts and HIV RNA changes from baseline was conducted in patients receiving enfuvirtide. Data were stratified and analyzed according to baseline CD4+ cell count and HIV RNA. RESULTS: A mean CD4+ cell count increase of approximately 102 cells/mm(3)was observed, regardless of baseline CD4+ cell count, in 187 patients receiving enfuvirtide during a mean of 19.4 months of follow-up. During 3 years of follow-up, patients initiating enfuvirtide at CD4+ cell counts less than 100 cells/mm(3)never achieved absolute CD4+ cell counts comparable to the counts in patients starting enfuvirtide at CD4+ cell counts of 100 cells/mm(3)or more. In 38.3% of patients achieving an undetectable HIV RNA level, a mean CD4+ cell count increase of 185 cells/mm(3)was observed. An unexpected finding was that a mean CD4+ cell count increase of 76 cells/mm(3)occurred in 61.7% of patients not achieving complete viral suppression. CONCLUSIONS: Immunologic benefits were observed in subjects continuing enfuvirtide plus a PBR irrespective of baseline CD4+ cell count, complete viral suppression, or antiretroviral susceptibility data. Data suggest that initiation of enfuvirtide at CD4+ cell counts greater than 100 cells/mm(3)may be immunologically advantageous and independent of complete virologic response.

Tipranavir: a protease inhibitor for HIV salvage therapy.

OBJECTIVE: To review the efficacy, safety, pharmacology, virology, pharmacokinetics, and resistance of the nonpeptidic protease inhibitor (PI) tipranavir. DATA SOURCES AND STUDY SELECTION: A PubMed search (1966-February 2006) was conducted using the key words tipranavir or PNU-140690, with the limitation of English-language reports. Pharmacokinetic and randomized clinical trials originating from major HIV conferences, such as the Conference on Retroviruses and Opportunistic Infections, International AIDS Society, European AIDS Conference, and Interscience Conference on Antimicrobial Agents and Chemotherapy, published only in abstract form, from 2000 to February 2006, were reviewed for relevance and included in this review. DATA SYNTHESIS: Phase III studies have shown that tipranavir is effective in the treatment of PI-resistant HIV compared with other PI-containing regimens. Adverse effects associated with tipranavir/ritonavir therapy include gastrointestinal reactions, hepatotoxicity, and elevations in cholesterol and triglyceride levels. Resistance data suggest that tipranavir/ritonavir should be reserved for salvage therapy in antiretroviral-experienced patients who have previously failed standard PI therapies. The potential for hepatotoxicity and drug interactions and the expense of tipranavir due to required ritonavir boosting may limit its widespread use. CONCLUSIONS: Tipranavir/ritonavir is an essential addition to the antiretroviral armamentarium for HIV-infected patients with limited treatment options.

Advances in human immunodeficiency virus therapeutics.

OBJECTIVE: To review recent advances in the management of persons infected with HIV. DATA SOURCES: A MEDLINE search (March 2003-February 2006) was done to identify recent articles on antiretroviral therapy research, adverse effects, and investigational products. Abstracts and programs of major HIV conferences, held from January 2003 to June 2005, were also reviewed for relevant material. STUDY SELECTION AND DATA EXTRACTION: Studies and observations conducted with either recently approved or investigational products were selected for inclusion, with conference abstracts primarily used. Excluded were topics covered in recent publications in The Annals. DATA SYNTHESIS: New modalities for treating HIV, including the CXCR4 and CCR5 receptor inhibitors, have so far shown promise in trial. Tipranavir, a recently approved protease inhibitor, has been shown to be effective in highly resistant patients, but may be unable to be combined with other protease inhibitors. Once-daily emtricitabine and tenofovir have shown superiority compared with lamivudine and zidovudine as backbone nucleoside analogs for combination antiretroviral therapy. Pharmacokinetic considerations for age, gender, race, and which agents are being discontinued have emerged. CONCLUSIONS: Much progress has been made in the treatment of HIV infection. Tolerability and adherence remain major obstacles to optimizing regimen longevity.

Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism.

BACKGROUND: Uncontrolled hyperparathyroidism (HPT), particularly HPT resulting from chronic kidney disease (CKD), is associated with significant morbidity and cardiovascular mortality. Traditional medical therapy (eg, vitamin D sterols, calcium, phosphate binders) has been inadequate for the management of HPT and its vascular and skeletal complications. OBJECTIVE: : The goal of this article was to review the efficacy and safety profile of cinacalcet, a second-generation calcimimetic, in the management of HPT secondary to CKD, primary HPT, and parathyroid carcinoma. METHODS: MEDLINE, Web of Science, and International Pharmaceutical Abstracts were searched from 1995 to July 2005 using the terms cinacalcet, AMG 073, KRN 1493, calcimimetics, hypercalcemia, and hyperparathyroidism. RESULTS: Compared with placebo, cinacalcet significantly reduced parathyroid hormone levels within 2 to 4 hours after administration (P < 0.05). In Phase III trials involving 1136 patients with secondary HPT, 56% of those who received cinacalcet achieved the National Kidney Foundation Kidney Disease Outcomes Quality Initiative target of a reduction in parathyroid hormone to <300 pg/mL, 65% achieved a calcium-phosphorus product <55 mg2/dL2, and a respective 49% and 46% achieved normalized serum calcium and phosphorus levels (P < 0.001). Cinacalcet's effects were similar regardless of patients' demographic characteristics, duration or mode of dialysis, severity of HPT, or use of concomitant medical therapy. Preliminary evidence suggests that cinacalcet may reverse cortical bone loss. Cinacalcet was well tolerated, with nausea (31%) and vomiting (27%) being the most commonly reported adverse effects. Hypocalcemia was transient in 5% of patients, was usually asymptomatic, and was corrected by dose reduction. CONCLUSIONS: Based on the available evidence, cinacalcet is effective and well tolerated in the treatment of secondary HPT and refractory parathyroid carcinoma. Its use in primary HPT appears promising. Further investigations are needed to determine if cinacalcet can prevent the long-term complications of HPT and reduce mortality.