Immune response to ART initiation in advanced HIV infection.

OBJECTIVES: Our objective was to compare the immunological responses to commonly used antiretroviral therapy (ART) regimens among people with advanced HIV in the USA and to assess virological outcomes and regimen persistence. METHODS: This study included ART-naïve adults with advanced HIV infection (CD4 cell count <200 cells/µL) initiating ART with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), boosted darunavir (bDRV), dolutegravir (DTG), or elvitegravir (EVG/c)-containing regimens between 1 January 2018 and 31 December 2020 in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. Cox proportional hazards models and linear mixed models with random intercept were fit with inverse probability of treatment weighting. RESULTS: Overall, 1349 people with advanced HIV (816 B/F/TAF, 253 DTG, 146 EVG/c, 134 bDRV) were followed for a median of 22 months. Compared with B/F/TAF, a lower likelihood of achieving a CD4 cell count ≥200 cells/µL was observed with bDRV (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.60-0.96), DTG (HR 0.82; 95% CI 0.69-0.98), and EVG/c (HR 0.73; 95% CI 0.57-0.93). All groups had a similar pattern of CD4:CD8 ratio changes: a rapid increase in the first 6 months (ranging from +0.15 to +0.16 units), followed by a slower increase thereafter. Only 40 individuals (4%) achieved CD4:CD8 ratio normalization (≥1). B/F/TAF was associated with a faster time to virological suppression (viral load <200 copies/mL) and a slower time to discontinuation compared with other regimens. CONCLUSIONS: Among people with advanced HIV infection, B/F/TAF initiation was associated with faster CD4 cell count recovery and favourable virological outcomes compared with bDRV-, DTG-, and EVG/c-based regimens, although no difference was observed in CD4:CD8 ratio changes over time across regimens.

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age.

OBJECTIVES: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study. METHODS: In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96. RESULTS: Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0-98.1) and 74.4% (64/86; 95% CI 63.9-83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR -2.3, 2.0). Median self-reported adherence was 100% (IQR 100-100%). CONCLUSIONS: Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population.

Advanced HIV Infection in Treatment-Naïve Individuals: Effectiveness and Persistence of Recommended 3-Drug Regimens.

BACKGROUND: Approximately 20% of newly diagnosed people with HIV (PWH) in the United States have advanced HIV infection, yet the literature on current antiretroviral therapy (ART) options is limited. The discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count <200 cells/µL). METHODS: ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)-, or elvitegravir/cobicistat (EVG/c)-based 3-drug regimen between January 1, 2018, and July 31, 2019, in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression (<50 or <200 copies/mL) was assessed using Cox proportional hazards models with inverse probability of treatment weights. RESULTS: Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/µL over a 16-month median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV: adjusted hazard ratio [aHR], 2.65; 95% CI, 1.75-4.02; DTG: aHR, 2.42; 95% CI, 1.75-3.35; EVG/c: aHR, 3.52; 95% CI, 2.44-5.07). Compared with B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (aHR, 0.72; 95% CI, 0.52-0.99) and <200 copies/mL (aHR, 0.55; 95% CI, 0.43-0.70); no statistically significant difference was detected with DTG or EVG/c. CONCLUSIONS: Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared with those on bDRV but not compared with those on other integrase inhibitors.

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial.

INTRODUCTION: We report the 48-week results of an ongoing study to assess the efficacy and safety of switching older people with HIV to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). METHODS: This was a 96-week, phase 3b, open-label, single-arm study (GS-US-380-4449; NCT03405935). Virologically suppressed individuals aged ≥ 65 years receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen were switched to B/F/TAF. Primary endpoint was the percentage of participants with HIV-1 RNA < 50 copies/ml at week 24. RESULTS: Eighty-six participants (median age 69 [range 65-80] years; 87% male; 95% white) were enrolled and treated in five European countries. Rates of virologic suppression were 97.7% at week 24 and 90.7% at week 48; none had HIV-1 RNA ≥ 50 copies/ml, and 100% had virologic suppression by missing = excluded analysis at both time points. No treatment-emergent resistance was observed. There were no grade 3-4 study drug-related adverse events (AEs) or study drug-related serious AEs or deaths. Three AEs led to premature discontinuation; one (moderate abdominal discomfort) was attributed to the study drug by the investigator. At week 48, median changes from baseline in weight and estimated glomerular filtration rate were + 0.1 kg (interquartile range [IQR] - 1.0, 2.3) and - 6.0 ml/min (IQR - 10.2, 0.0), respectively. There were no clinically relevant changes from baseline to week 48 in fasting lipid parameters. Treatment satisfaction improved, and health-related quality of life was maintained from baseline through week 48. Median adherence to the study drug was 98.6% (IQR 96.0, 100). CONCLUSIONS: Switching to B/F/TAF was effective and well tolerated through 48 weeks in virologically suppressed adults aged ≥ 65 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03405935.

Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation.

BACKGROUND: The ability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to maintain virologic suppression in participants with M184V and/or M184I resistance mutations from historical genotypic reports when switching from a tenofovir disoproxil fumarate-based or abacavir (ABC)-based regimen was investigated. SETTING: Phase IIIb, 48-week, open-label, single-arm, multicenter, clinical trial (NCT02616029). METHODS: Virologically suppressed adults with HIV and documented M184V/I on historical genotypic records switched to E/C/F/TAF from a tenofovir disoproxil fumarate-based or ABC-based regimen. The primary end point was HIV-1 RNA of <50 copies per milliliter at week 12 using pure virologic response (PVR). Secondary end points included HIV-1 RNA of <50 copies per milliliter at weeks 24/48 (PVR) and at weeks 12, 24, and 48 (Food and Drug Administration snapshot algorithm), and change in CD4+ count at weeks 12, 24, and 48. RESULTS: M184V alone was reported in 82.8% of 64 participants; 9.4% and 7.8% had M184I and M184V/I, respectively, and 43.8% had archived M184V/I (baseline DNA). All (62/62 with available data, 100%, 95% confidence interval 94.2% to 100%) participants maintained PVR at weeks 12, 24, and 48. By Food and Drug Administration snapshot algorithm, one participant had HIV-1 RNA of ≥50 copies per milliliter (week 12); confirmatory HIV-1 RNA was <50 copies per milliliter. No significant changes were observed in CD4+ cell count. Drug-related adverse events (AEs) were reported by 10 (15.6%) participants. Six (9.4%) and 5 (7.8%) participants had grade 3-4 AEs or serious AEs, respectively (none drug related). CONCLUSIONS: The presence of the resistance mutations M184V/I did not jeopardize the efficacy of switching to E/C/F/TAF in virologically suppressed adults. High rates of virologic suppression were maintained throughout 48 weeks of therapy and treatment was well tolerated.

A Pharmacist-Led Program to Evaluate and Reduce Polypharmacy and Potentially Inappropriate Prescribing in Older HIV-Positive Patients.

OBJECTIVE: The goal of this pharmacist-led study was to utilize two validated instruments, Beers Criteria and Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP), to assess potentially inappropriate prescribing (PIP) in older patients infected with the human immunodeficiency virus (HIV) and evaluate pharmacist interventions. DESIGN: Prospective randomized interventional trial. SETTING: Large urban clinic providing interdisciplinary primary and HIV care for ~2700 HIV-positive publicly insured patients. DATA SOURCE: A computerized electronic record search was conducted for all patients who met the two search criteria: 50 years and older, and a primary care appointment within the last 12 months. PATIENTS: After identification of 857 patients meeting the search criteria, 324 patients were randomly selected and contacted, resulting in 248 patients assessed. MEASUREMENTS AND MAIN RESULTS: Patients had a mean age of 58 years, 71% male, 44% white, and a mean CD4 count of 536 cells/mm3 . Common comorbidities included hypertension (56%), depression (52%), asthma/chronic obstructive pulmonary disease (48%), dyslipidemia (39%), coronary artery disease (27%), and diabetes (22%). Patients sampled were prescribed a mean of 11.6 ± 5.7 concomitant medications (excluding antiretrovirals) with 35% receiving at least 16 medications. PIP was identified in 54% and 63% of patients using the STOPP and Beers Criteria, respectively. Twenty-five contraindicated drug interactions were identified in 20 patients. After the pharmacist visit, at least 69% of patients had at least one medication discontinued with almost 10% having six or more medications discontinued. More than 40% of patients had at least one Beers or STOPP criteria that required immediate correction by the pharmacist. CONCLUSIONS: Results suggest that targeting individuals with 11 or more chronic medications would have the highest yield and greatest impact. Pharmacist-led review of medication prescribing using Beers and STOPP criteria revealed a large number of PIP, many amenable to immediate clinical pharmacist intervention.

Adherence and HIV RNA Suppression in the Current Era of Highly Active Antiretroviral Therapy.

BACKGROUND: We examined trends in adherence to highly active antiretroviral therapy (HAART) and HIV RNA suppression and estimated the minimum cutoff of adherence to newer HAART formulations needed for HIV RNA suppression by regimen type. METHODS: We used Veterans Affairs pharmacy dispensing data from the Veterans Aging Cohort Study Virtual Cohort between October 2000 and September 2010 and defined adherence as the duration of time the patient had the medications available, relative to the total number of days between refills for all antiretrovirals in a year. Temporal trends in adherence and viral load suppression were examined by the patient's most frequently used HAART regimen in the year. The minimum needed adherence was defined as the level at which the odds of suppression was not significantly different than that observed with ≥ 95% adherence using repeated-measures logistic regression. RESULTS: A total of 21,865 HAART users contributed 82,217 person-years of follow-up. There was a significant increase (P(trend) < 0.001) in the proportion virally suppressed even among those with <95% adherence (2001: 38% to 2010: 84%), and the trend was similar when restricting to their first HAART regimen. For nonnucleoside reverse transcriptase inhibitor multi-pill users, the odds of suppression did not differ for 85%-89% adherence compared to those with ≥ 95% adherence [odds ratios: 0.82 (0.64-1.04)], but for protease inhibitor users, the odds of suppression significantly differed if adherence levels were <95% compared to ≥ 95% adherence. CONCLUSIONS: Although all HIV-infected persons should be instructed to achieve perfect adherence, concerns of slightly lower adherence should not hinder prescribing new HAART regimens early in HIV infection.

Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection.

OBJECTIVES: To describe the frequency of medication-related problems in older adults with human immunodeficiency virus (HIV) infection. DESIGN: Retrospective chart review. SETTING: Community. PARTICIPANTS: HIV-positive individuals aged 60 and older and age- and sex-matched HIV-negative individuals. MEASUREMENTS: Total number of medications, potentially inappropriate medications (PIMs) according to the modified Beers Criteria, anticholinergic drug burden according to the Anticholinergic Risk Scale (ARS), and drug-drug interactions using the Lexi-Interact online drug interactions database. RESULTS: Of 89 HIV-positive participants, most were Caucasian (91%) and male (94%), with a median age of 64 (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and depression. Participants were taking a median of 13 medications (range 2-38), of which only a median of four were antiretrovirals. At least one PIM was prescribed in 46 participants (52%). Sixty-two (70%) participants had at least one Category D (consider therapy modification) drug-drug interaction, and 10 (11%) had a Category X (avoid combination) interaction. One-third of these interactions were between two nonantiretroviral medications. Fifteen participants (17%) had an ARS score of 3 or greater. In contrast, HIV-negative participants were taking a median of six medications, 29% had at least one PIM, and 4% had an ARS score of 3 or greater (P < .05 for each comparison, except P = .07 for anticholinergic burden). CONCLUSION: HIV-positive older adults have a high frequency of medication-related problems, of which a large portion is due to medications used to treat comorbid diseases. These medication issues were substantially higher than HIV-negative participants. Attention to the principles of geriatric prescribing is needed as this population ages in order to minimize complications from multiple medication use.

The next therapeutic challenge in HIV: polypharmacy.

With the adoption of combination antiretroviral therapy (ART), most HIV-infected individuals in care are on five or more medications and at risk of harm from polypharmacy, a risk that likely increases with number of medications, age, and physiologic frailty. Established harms of polypharmacy include decreased medication adherence and increased serious adverse drug events, including organ system injury, hospitalization, geriatric syndromes (falls, fractures, and cognitive decline) and mortality. The literature on polypharmacy among those with HIV infection is limited, and the literature on polypharmacy among non-HIV patients requires adaptation to the special issues facing those on chronic ART. First, those aging with HIV infection often initiate ART in their 3rd or 4th decade of life and are expected to remain on ART for the rest of their lives. Second, those with HIV may be at higher risk for age-associated comorbid disease, further increasing their risk of polypharmacy. Third, those with HIV may have an enhanced susceptibility to harm from polypharmacy due to decreased organ system reserve, chronic inflammation, and ongoing immune dysfunction. Finally, because ART is life-extending, nonadherence to ART is particularly concerning. After reviewing the relevant literature, we propose an adapted framework with which to address polypharmacy among those on lifelong ART and suggest areas for future work.

Does once-daily etravirine have a role in the management of HIV-1 infection?

When individualizing therapy for HIV-positive patients and for those in whom the 'preferred regimens' of the US Department of Health and Human Services HIV treatment guidelines are not appropriate, a once-daily non-nucleoside with a fixed-dose combination of two nucleosides may be considered in patients who are adherence challenged, intolerant to other regimens but with no viral resistance, or in those in whom the pill burden or actual pill size was too great to accept. Despite having a 30- to 40-h elimination half-life, etravirine was never considered for once-daily dosing during development due to an unacceptably high pill burden in phase II trials. However, a recently published study, SENSE, enrolled 157 HIV-positive patients in a multinational, randomized, placebo-controlled, double-blind trial that investigated 400 mg etravirine once daily with two nucleosides versus a comparator arm that included efavirenz and two nucleosides. The primary objective was to assess neuropsychiatric tolerability over the 48-week study period, with comparative efficacy as a secondary objective. Using the intent-to-treat time to loss of virologic response (ITT-TLOVR) analysis at 48 weeks, 76 % of patients receiving etravirine had an undetectable viral load of <50 copies/mL compared with 74 % of patients receiving efavirenz. This translates to a suppression rate difference of 1.6 % favouring etravirine (95 % CI -12.0-15.2) and met the non-inferiority criteria of a delta of -12 %. Baseline viral load was not observed to impact clinical response rates. Pharmacokinetically and clinically, studies indicate the efficacy and safety of utilizing once-daily etravirine in the treatment-naive population. While it is not appropriate for all patients, once-daily etravirine is best utilized for patients in whom caloric requirements, pill burden, pill size, potential adverse reactions, concomitant medications/drug interactions, psychosocial factors and patient preference preclude the use of a 'preferred' regimen. Etravirine dissolution in water allows for the flexibility of once-daily dosing with one fixed-dose combination tablet followed by an etravirine/water 'chaser'.

Coinfection with human immunodeficiency virus and hepatitis C virus: challenges and therapeutic advances. Insights from the Society of Infectious Diseases Pharmacists.

In the United States, approximately 30% of all human immunodeficiency virus (HIV)-positive patients are also infected with hepatitis C virus (HCV). Both viruses share similar routes of transmission. Unlike HIV or hepatitis B virus, HCV is curable if treated and the patient achieves a sustained virologic response. The impact of coinfection includes greater morbidity and mortality, with higher rates of opportunistic disease, development of cirrhosis, and death. The standard of treatment for HIV-HCV coinfection is similar to that for HCV monoinfection and consists of pegylated interferon alpha and ribavirin. As with HCV monoinfection, the best predictor of response to therapy for HIV-HCV coinfection is infection with an HCV genotype other than genotype 1 or 4. Adherence to treatment is critical for improving response to HCV therapy. However, considerable toxicities are associated with pegylated interferon alpha and ribavirin and pose particular problems in the coinfected patient. Coinfected patients are more likely to experience significant weight loss with HCV therapy. Neutropenia and anemia are both common laboratory abnormalities that necessitate dosage reductions and are concerns for development of acquired immunodeficiency syndrome-defining events. The effect of CD4(+) cell count has been evaluated both as a factor in response to HCV therapy and in stratification of risk for infection. Immunosuppression is not a contraindication to HCV therapy, although CD4(+) counts above 350 cells/mm(3) are associated with increased response rates in patients with HCV genotype 1 coinfection. Antiretroviral therapy does need to be adjusted to minimize adverse effects. Concomitant use of zidovudine is contraindicated because of its profound exacerbation of bone marrow suppression. The use of didanosine is also not indicated during HCV therapy because of the risks of hepatic decompensation. Controversy exists regarding the use of abacavir. Newer agents for HCV include the protease inhibitors telaprevir and boceprevir. Although results with the protease inhibitors are highly encouraging, their effects in coinfected patients have not been evaluated. Treatment for HCV in patients with HIV poses potential obstacles to success, but the benefits of viral eradication warrant the challenge of therapy.

Etravirine and rilpivirine: nonnucleoside reverse transcriptase inhibitors with activity against human immunodeficiency virus type 1 strains resistant to previous nonnucleoside agents.

Etravirine and rilpivirine are two new nonnucleoside reverse transcriptase inhibitors (NNRTIs) that have the distinct advantage of being able to be used in patients with exposure to previous NNRTIs (e.g., nevirapine or efavirenz). Etravirine was approved by the United States Food and Drug Administration to be used twice/day in treatment-experienced patients infected with the human immunodeficiency virus. The approval was based on phase III clinical studies in which 61% of etravirine-treated patients reached an undetectable viral load of less than 50 copies/ml compared with 40% of patients who received the optimized background regimen. Etravirine was well tolerated with a self-limiting skin rash being the most common toxicity, reported in 19% of patients. Rilpivirine, a once-daily NNRTI, is entering phase III studies; the drug appears to be effective against a broad range of NNRTI-resistant viruses including etravirine-resistant strains.

On the horizon: promising investigational antiretroviral agents.

Human immunodeficiency virus (HIV) infection affects close to 40 million individuals worldwide. Since 1981 when the first case reports of individuals dying from a then rare opportunistic infection were published, twenty million people have died from this epidemic. With 3 or more antiretrovirals as the standard of care, the prevalence of single, double and triple-class resistant HIV strains has increased significantly over the last 5 years due to the tremendous replicative capacity of HIV and selective drug pressure. With greater resistance comes the need for novel and effective antiretrovirals to treat these resistant strains. The purpose of this review is to highlight the most promising agents and classes in Phase II-III drug development by assessing the clinical efficacy, pharmacology, resistance and tolerability. Three out of the four existing antiretroviral classes (nucleosides, non-nucleosides, protease inhibitors) with agents in clinical trials will be discussed such as nucleoside reverse transcriptase inhibitors (D-d4FC, SPD754), non-nucleoside reverse transcriptase inhibitors (capravirine, TMC125) and protease inhibitors (tipranavir, TMC114). In the next several years, antiretrovirals from novel pharmacologic classes will enter the HIV armamentarium. Based on the early clinical studies, these promising agents will be reviewed from the following classes: attachment inhibitors (TNX-355, BMS-488043), CCR5 coreceptor antagonists (SCH-D, UK-427857, GW 873140) and a maturation inhibitor (PA-457). It is hoped that these agents will represent a therapeutic advance and better activity against HIV resistant strains by providing effective therapy that will reduce viral load, increase the CD4+ cell count and ultimately, prolong survival with minimal adverse effects.

Enfuvirtide: first fusion inhibitor for treatment of HIV infection.

PURPOSE: The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and availability of enfuvirtide are discussed. SUMMARY: To date, 20 antiretrovirals have been approved by FDA for the treatment of HIV infection. The recent approval of enfuvirtide offers a new and fourth class of antiretroviral agents called fusion inhibitors. Enfuvirtide is indicated for use in treatment-experienced patients who have evidence of viral replication despite receiving current therapy. The drug is a 36-amino-acid synthetic peptide that prevents completion of the HIV fusion sequence. Absolute bioavailability after subcutaneous injection is 84%. Clinical trials indicate that adding enfuvirtide to a salvage regimen in heavily treated patients may lead to an improved virologic response. Up to a 1.48 log decrease in the viral load was seen at 48 weeks when enfuvirtide was combined with an optimized background regimen. Patients who have at least two or more active drugs in the regimen, a CD4+ cell count of >100 cells/mm3, and previous exposure to two or more antiretrovirals prior to starting enfuvirtide appear to respond best. The most common adverse effect, occurring in 98% of all enfuvirtide recipients, is an injection-site reaction that generally can be managed nonpharmacologically. A much less common but more significant concern is an increased risk of bacterial pneumonia. Enfuvirtide is available through the Fuzeon Progressive Distribution Program. The annual cost of therapy is about 24,000 dollars. CONCLUSION: Enfuvirtide is the first fusion inhibitor available for the treatment of HIV infection. The drug is indicated for use with other antiretroviral agents in treatment-experienced patients who have evidence of HIV replication despite ongoing antiretroviral treatment.

Drug Interactions Among the Antiretrovirals.

There are 20 antiretroviral agents approved by the US Food and Drug Administration (FDA), four of which were approved in 2003. With 20 antiretrovirals FDA-approved, interactions occur when the medications alter the toxicity profile or efficacy of the other medication. In order to maintain clinical relevance, only the most significant interactions published within the past 12 months are highlighted in this article. Interactions discussed involve atazanavir, fosamprenavir, lopinavir/ritonavir, tenofovir, proton pump inhibitors, H(2)-blockers, clarithromycin, and vardenafil. Important interaction-management strategies also are discussed. The field of HIV pharmacology is constantly advancing, as are the drug interaction data. To screen, manage, dose adjust, and counsel, the physician and other health care professionals are highly advised and encouraged to consult with an infectious disease clinical pharmacist when managing patients receiving highly active antiretroviral therapy.

Valganciclovir: an advance in cytomegalovirus therapeutics.

OBJECTIVE: To review the pharmacology, pharmacokinetics, and preliminary clinical data for valganciclovir, a new oral agent for the therapy of cytomegalovirus (CMV) retinitis. DATA SOURCES: Relevant literature was extracted via MEDLINE/PUBMED and searchable abstracts from infectious diseases conferences covering the period from January 1990 to April 2002. Tertiary references provided background information. DATA SYNTHESIS: Current standard treatment for CMV retinitis consists of intravenous therapy, intraocular implant, and intraocular injection. The low bioavailability of oral ganciclovir restricts its use to prophylaxis and maintenance treatment. Oral valganciclovir, recently approved for both induction and maintenance therapy of CMV retinitis, may fill a niche for this disease. CONCLUSIONS: Although only 1 clinical study has been published for valganciclovir, its favorable pharmacokinetic profile, encouraging preliminary efficacy data, ease of administration, and lack of potential catheter-related complications make it a favorable option for the treatment of CMV retinitis in HIV-positive patients.