Roy M. Gulick, MD, MPH

Update on IAS-Paris: Focus on Antiretroviral Therapy (ART)

We may not have a cure for HIV, but the treatment options keep expanding and improving, and prevention strategies are working better than ever. This program targets the most recent advances in HIV treatment and prevention from the International AIDS Conference in Paris, including updates on what to start, how to switch, second and third line treatment options, and new NUCs, non-NUCs and integrase inhibitors in the drug development pipeline, as well as drugs with new mechanisms-of-action, such as an orally-dosed attachment inhibitor, an entry inhibitor and maturation inhibitor. So if you want to stay up to date and know what is in the horizon, do not miss this important program.

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Timothy J. Wilkin, MD, MPH

Advances in HIV Treatment and Prevention: CROI 2017

The annual Conference on Retroviruses and Opportunistic Infections (CROI) is known worldwide for its leadership in fostering and showcasing advances in the basic sciences, immunology, drug development, and clinical research for the prevention, treatment, and cure of HIV disease, as well as HIV-related coinfections and cancers. Don’t miss this important update from Tim Wilkin, focusing on the highlights from CROI 2017 that are most pertinent for our audience of HIV primary care providers.

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Rajesh T. Gandhi, MD

HIV Antiretroviral Therapy 2017: Clinical Controversies in When and What to Start

The field of HIV management is dynamic and staying up-to-date can be challenging. There are new questions and new answers to old questions that we must consider. Should all HIV-infected patients be treated, including elite controllers? Should HIV-infected patients initiate ART on the day of diagnosis? Should all newly-diagnosed HIV-infected patients be started on an integrase inhibitor-based regimen? Should TAF replace TDF for all patients? How should an ART regimen be chosen in patients with specific comorbidities or conditions? What regimen should you choose for a patient who cannot take ABC, TDF and TAF? Don't miss this important and thorough presentation on the art of initiating ART.

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Roy M. Gulick, MD, MPH

Update on IAS-Durban: Focus on ART

Fresh from the International AIDS Conference in Durban, Trip Gulick gives an engaging overview of new research in HIV treatment and prevention strategies, new formulations of existing antiretroviral drugs, new agents in the development pipeline, and better understanding of pharmacokinetics. Don’t miss this important review of new research that will contribute to the ever-changing, and improving field of HIV treatment and prevention.

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Roy M. Gulick, MD, MPH

Advances in the Treatment and Prevention of HIV Infection: CROI 2016, Focus on ART

Don’t miss this engaging review of the recent Conference on Retroviral and Opportunistic Infections (CROI 2016) spotlighting the latest research in HIV treatment and prevention strategies. Topics include prophylaxis, initiation of antiretroviral therapy in newly-diagnosed patients, switch-therapy to decrease toxicities, and choosing new therapeutic combinations for treatment-experienced patients with suboptimal responses. Also, new drugs in the development pipeline that may soon expand therapeutic options for our patients suffering from treatment failure are discussed, as well as research in longer-acting drugs for PrEP and other prevention modalities.

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Rajesh T. Gandhi, MD

Antiretroviral Treatment Guidelines: Where We Are Now and What's On the Horizon

It is encouraging that both national and international HIV treatment guidelines support early initiation of antiretroviral drugs, regardless of CD4 count, for the best long-term outcomes, and to decrease transmission. And the guidelines continue to evolve to support efficacy, tolerability and simplicity, while acknowledging scenarios where alternative regimens may be needed. Of course there are comorbidities, drug resistance, and immune failure to consider when choosing or changing regimens. And newer, safer drugs are still coming! Don’t miss this important review on the state-of-the-art and future of antiretroviral therapy for HIV.

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Christopher D. Pilcher, MD

Shooting the Rapids of the HIV Cascade: Outcomes of Initiating ART at Diagnosis

Isn’t it time to start treating HIV disease like the urgent medical and public health problem it is, rather than losing people step after step after step after step in a drawn-out cascade to treatment? In other words, why not start empiric treatment immediately on the same day as point-of-care diagnosis? In this presentation you will hear about the innovative work being done in San Francisco to hasten access to antiretroviral treatment in an effort to decrease loss-to-follow-up, speed treatment to undetectability and reduce transmission.

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Anne K. Monroe, MD, MSPH

Diagnosing and Managing Diabetes in HIV-infected Patients

With an estimated prevalence of up to 14% in HIV-infected patients, diabetes is a leading cause of cardiovascular disease, blindness, end-stage renal disease, amputations, and hospitalizations for our patients. Regular screening for diabetes is important, and extra diagnostic caution must be taken in people living with HIV. When diagnosed, changes in lifestyle are critical, and medical management requires individualization. This clinically oriented lecture focuses on therapeutic options including recently approved drugs from new classes of drugs for glycemic control, as well as treatment strategies for optimal management of diabetes and prevention of diabetic morbidities in HIV medicine.

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Dan R. Drozd, MD

Update on Cardiovascular Disease Risk, Management and Prevention in HIV

HIV disease is likely associated with a 50% increased risk for cardiovascular disease, but independent HIV-related risk factors suggest that early and continuous antiretroviral therapy may reduce atherosclerotic cardiovascular disease risk in HIV, especially type 1 myocardial infarctions caused by atherosclerotic plaque rupture. In addition to the direct relation of HIV disease to atherosclerotic disease, questions about reported associations of certain antiretroviral drugs with myocardial infarctions, and the potential use of statins to decreased inflammation and promote plaque regression are discussed in this important program.

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Roy M. Gulick, MD, MPH

Advances in the Treatment and Prevention of HIV Infection: CROI 2015. Focus on ART

The annual Conference on Retrovirology and Opportunistic Infections (CROI) is the most important international meeting on HIV. This year Trip Gulick reports on some of the highlights of CROI 2015 including the most up-to-date strategies for when to start treatment, what to start with, when to change and what to change to. In addition, he also touches on controversies of intolerance and toxicities, drug resistance, new drugs in the development pipeline, and finishes off with the most recent advances in HIV prophylaxis. If you are interested in the treatment and prevention of HIV disease, do not miss this engaging presentation.

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Ian M. McGowan, MD, PhD, FRCP

Update On Vaginal And Rectal Microbicides for HIV Prevention

Although oral PrEP can be highly successful in preventing HIV infection, more options for chemoprophylaxis are needed to meet the diverse needs of varying populations. The development of vaginal and rectal microbicides has been a bumpy road, and so far none have been licensed, but progress is being made. In this program, Ian McGowan, a leading researcher in the field, discusses the science and the studies that will hopefully lead to a variety of licensed microbicides for the prevention of vaginal and rectal transmission.

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Susan J. Little, MD

HIV Sexual Networks, Transmission Dynamics, and Drug Resistance

The early diagnosis and treatment of HIV during the acute or primary stage of infection has lasting benefits for each individual that starts and adheres to antiretroviral therapy, but there are also public health advantages for the community. Tracing the phylogenetics of HIV transmission networks provides insight to contagiousness, length of infection and severity, and transmission of drug resistant variants of HIV. In this exciting lecture, Susan Little, who runs the primary HIV infection program at UCSD demonstrates how early diagnosis and treatment of HIV interrupts network transmission, which may be the most powerful key to ending the HIV epidemic that we currently have.

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A. E. Radix, MD, MPH, FACP

HIV Prevention and Care in Transgender People

Transgender women are at extraordinarily high risk for HIV infection for a number of reasons. We will never be able to end the HIV epidemic if we cannot better serve the needs of transgender individuals in ways that are both culturally sensitive and inclusive. In this thought-provoking lecture, Dr. Radix targets the many challenges our transgender patients face and how we can improve the management and prevention of HIV in this most vulnerable population.

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François Clavel, MD

What Is It with HIV-2?

Now that we are all routinely testing for HIV-2 as part of the new HIV testing algorithm, it will be helpful to know more about how HIV-2 differs from HIV-1 pathogenically, and how treatment fro HIV-2 differs from standard therapy of HIV-1. And who could teach us better than the researcher who first discovered HIV-2, Fancois Clavel, in this fascinating lecture.

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Todd T. Brown, MD, PhD

Update on Hypogonadism in Aging HIV-infected Men

Is testosterone replacement for hypogonadism overprescribed in the United States? Is it safe? The diagnosis of hypogonadism is not uncommon in aging HIV-infected men. So understanding the optimal screening recommendations as well as the potential risks and benefits of testosterone therapy, particularly in older men, is extremely important to their well-being. Join us for this important update by Todd Brown.

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David J. Back, PhD

Drug-drug Interactions in HIV and HCV in an Aging Population

Awareness of drug-drug interactions between agents used to treat HIV, coinfections such as hepatitis C, and co-morbidities such cardiovascular, renal, respiratory and metabolic disease, has never been more important. And the risk of adverse interactions of polypharmacy will increase as our patients age and their problem lists get longer. This comprehensive view from David Back, known world-wide for his extensive work in drug interactions at the University of Liverpool, is a must for anybody caring for people living with HIV.

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Christina M. Wyatt, MD

Update on the Kidney in HIV Treatment and Prevention: Current Concepts

Who, among your HIV-positive patients, may be at higher risk for kidney disease? And what about your HIV-negative patients who have started or are thinking about PrEP? This program will help you recognize the limitations of current screening tests for kidney disease in your patients with and at risk for HIV disease, and understand the diagnosis and management of antiretroviral-associated nephrotoxicity.

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David M. Margolis, MD

Towards an HIV Cure: Real Progress And Real Problems

The advances in the management of chronic HIV disease have been extraordinary, but only one person—the Berlin patient—has ever achieved a “functional cure.” HIV cure research is a complicated yet exciting field, with recent setbacks, such as the failure of cure in the Mississippi baby. Purging latent reservoirs is necessary if the chronically infected are to ever be completely free of HIV infection. David Margolis, a leader in the field of cure research updates what is presently known as well as current research that may someday make eradication of HIV more easily achievable.

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Roy M. Gulick, MD, MPH

Advances in the Treatment and Prevention of HIV Infection: CROI 2014, Focus on ART

Hot on the heels of CROI 2014, this up-to-date review of HIV treatment and prevention strategies, antiretroviral initiation, options for treatment failure, and new agents in development, is not to be missed. Even if you attended this live meeting, we hope you will find this presentation by Trip Gulick helpful in your day-to-day decision-making.

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Tae-Wook Chun, PhD, and Michael C. Sneller, MD

Perspectives on Therapeutic Interventions Aimed at Eradicating HIV

In this program, Tae-Wook Chun reviews the mechanism by which HIV reservoirs persist in infected individuals on antiretroviral therapy and advances in HIV Cure research, followed by Mike Sneller who discusses a new therapeutic HIV vaccine trial, the THERAVAX Study, now enrolling HIV-infected individuals who were diagnosed and started on cART during the acute/early stage of HIV infection. If you have any patients that were diagnosed and initiated treatment during the acute/early stage of HIV disease, please view this program-- the NIAID/NIH needs your help to enroll this important trial.

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Asier Sáez-Cirión, PhD

Long-term Remission of HIV after Interruption of Very Early ART in Adults

Rarely, some individuals are able to control HIV without medication, while the overwhelming majority of people with HIV infection will progress to AIDS and death without lifelong antiretroviral therapy. But for this majority who are unlikely to control HIV spontaneously, is it possible to induce HIV control and prevent progression of disease without medication? The VISCONTI Study implies that this may be so. This important study in France has shown that very early diagnosis and initiation of combination antiretroviral therapy eventually led to virologic control after treatment interruption in a higher-than-expected proportion of study participants. Join us for Dr. Sáez-Cirión’s discussion of this important study and its contribution to research for a cure.

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Calvin Cohen, MD, MSc

How Many Ways Are There To Control HIV?

Antiretroviral therapy of HIV disease requires life-long adherence for optimal treatment outcomes and to prevent further transmission to uninfected partners. It is important for all prescribing clinicians to understand the principles of durable antiviral suppression, guidelines for initiating and changing antiretroviral regimens, and alternative strategies when these fail. Understanding the research behind alternative strategies is often necessary for long-term management of HIV-infection in the real world.

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Donna Futterman, MD

Youth and HIV: The Epidemic Accelerates

Each year the number of HIV infected youth is increasing. Join us to hear Donna Futterman describe the trends of this accelerating epidemic in young people, efforts to improve early diagnosis of HIV and other STIs in youth, and treatment challenges pertinent to optimal adolescent HIV care.

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Easing the Transition of HIV-Infected Adolescents to Adult Care

The expanding epidemic of HIV in young people, and their eventual move to the adult setting, poses many challenges to the quality and continuity of their medical care. In this program Joe Cervia targets the special needs and models of care that may ease the transitional challenges.

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Gero Hütter, MD

The Berlin Patient: Eradication of HIV with CCR5 Deficient Hematopoietic Stem Cells

Almost everybody has heard of the "Berlin Patient" and many may have also seen him on morning talk shows, but how many clinicians have had an opportunity to meet and listen to his doctor from Berlin? In this video you will hear Gero Hütter tell about his rationale for performing a bone marrow transplant with CCR5 deficient hematopoietic stem cells, the long term outcomes for his patient, further research to understand if he has been "cured," and attempts to repeat this unique success. Please also see PRN's video of Pablo Tebas, who spoke on gene therapy and other research based on Gero Hütter's "Berlin patient."

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Pablo Tebas, MD

Gene Therapy Studies for the Treatment of HIV Infection

Can HIV disease be cured? If a cure is defined as the permanent remission of HIV disease and its consequences in the absence of antiretroviral therapy, then Timothy Brown, the "Berlin patient,"was cured. (Also see the PRN video of Gero Hütter's detailed discussion of his Berlin patient.) And even though this remains an isolated case, the priority of NIH funding for HIV research has since shifted to a cure. In this presentation, Pablo Tebas highlights new research, in the aftermath of the Berlin patient, to identify HIV reservoirs and ways to eliminate them, gene therapy approaches that mimic the benefits of CCR5 deficient stem cell transplantation, and boosting the immune response with therapeutic vaccines an immune modulators. Yes, there is hope again, for a cure after all.

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Roy Gulick, MD, MPH

Strategies (And New Agents) For Antiretroviral Therapy Of HIV-1 Disease

The initiation and management of antiretroviral therapy is constantly improving, and periodic review of new data as well as changing treatment guidelines are imperative. In this lecture, Trip Gulick discusses important clinical studies that have led to changes in current guidelines as well as ongoing studies that may expand treatment options in the future.

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Andrew Talal, MD, MPH

Clinical Management Of Hepatitis C In Patients With And Without HIV Coinfection

There is great excitement about the introduction of directly acting agents for the treatment of chronic hepatitis C, and due to the experience that HIV clinicians already have with the use of antiretroviral agents, co-management of these diseases is optimal for patent care. In this lecture Andy Talal reviews recent advances in HCV monotherapy and implications for HIV-HCV coinfection.

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Joseph McGowan, MD and Sanjiv Shah, MD

Understanding HIV Tropism

The ability of HIV to bond to different coreceptors for cell entry is known as tropism. After attaching to CD4, HIV must also bind to one of two additional coreceptors. The predominant coreceptor is CCR5, especially early in the course of infection; alternately HIV may be able to bind to CXCR4, either instead of or in addition to CCR5. Viral and host cell factors determine viral tropism and the dynamics of viral attachment prior to cell entry. Tropism has critical implications for HIV care. This article explains tropism and explores how it may influence decisions regarding the use of CCR5 antagonists for disease management.

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Sharon Dian Lee, MD and Marjorie Williams, MPH

Selected Highlights from the Treatment and Management of HIV Infection in the US Conference

The PRN Notebook reports on sessions from the 2005 Treatment and Management of HIV Infection in the United States Conference. Comorbidities have become significant issues for hiv-positive people as they live longer, and patients face social and emotional obstacles as they chart their long lives with hiv infection. Dr. Sharon Lee discusses the need for chronic and lifelong care, and Marjorie Williams discusses social and emotional considerations in HIV.

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Teresa H. Evering, MD and Martin Markowitz, MD

HIV-1 Integrase Inhibitors

The integrase inhibitors are a welcome addition to the treatment armamentarium for HIV/AIDS in treatment-experienced patients failing available antiretroviral regimens. The promising efficacy and tolerability profile of the integrase inhibitors, absence of cross-resistance with other antiretroviral classes, and demonstrated synergism of the integrase inhibitors in combination with approved antiretroviral agents place them in a position to become important components of effective combination antiretroviral regimens in individuals living with HIV/AIDS.

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Athe Tsibris, MD

Update On CCR5 Inhibitors: Scientific Rationale, Clinical Evidence, and Anticipated Uses

The CCR5 antagonists are a welcome addition to the therapeutic armamentarium available for antiretroviral-experienced patients. Currently, their use in antiretroviral-naive patients should be restricted to enrollment in ongoing or planned clinical trials. The CCR5 antagonist maraviroc is FDA-approved for treatment-experienced patients with R5 virus (only), and no patient should receive maraviroc without first undergoing a tropism assay.

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Andrea Low, MD and Mark Muesing, PhD

Understanding and Inhibiting Integrase in the Treatment of HIV Disease

In light of the inability of HIV to propagate itself without integration of its genome into chromosomal DNA, the viral integrase protein has become an important potential therapeutic target. It is distinct mechanistically, independent of the catalytic activities of the viral protease, reverse transcriptase, or of virus cell fusion. It therefore has the potential for synergistic activity in combination with available protease and reverse transcriptase inhibitors, and with entry inhibitors now in development. In addition, because of their novel molecular structure, the cost of production of the new families of integrase inhibitors may be less than that of some of the current antiretrovirals which rely on protein-like compounds or nucleoside derivatives for their activity.

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Lawrence Siegel, MD, MPH and Wafaa El-Sadr, MD, MPH

New Perspectives in HIV Treatment Interruption: The SMART Study

The results of the SMART study showed that intermittent therapy compared with continuous therapy, was associated with increased risks of HIV disease progression or death, serious HIV disease progression, and severe complications. “These results were not affected by gender, race, baseline CD4+ cell count, or nadir CD4+ cell count… Episodic use of antiretroviral therapy based on CD4+ cell counts, as utilized in the SMART study design, is inferior to continuous antiretroviral therapy for the management of antiretroviral-experienced patients,” Dr. El-Sadr said. She added that an insufficient number of antiretroviral-naïve patients (5%) were included to make a conclusion about the use of intermittent therapy in this patient population.

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Kan Lu, PharmD

New Antiretrovirals for the Treatment of HIV: The View in 2006

To date, twenty-two antiretrovirals have been approved by the FDA for the treatment of HIV infection. In addition to the development of new drugs and drug classes with unique potency advantages, a number of older antiretrovirals have been reformulated to allow for more simplified dosing. Additionally, the development of fixed-dose combination tablets have considerably improved treatment acceptance. For the first time, a widely used complete drug regimen is available to take as one pill once per day. Even with increasingly simplified treatment regimens, challenges still remain in finding products with minimal toxicity and optimized resistance profiles. To achieve optimal viral suppression, there is also a need for agents that penetrate viral reservoirs and target new portions of the HIV lifecycle. Fortunately, the antiretroviral drug pipeline contains several promising agents that may address these needs.

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David Margolis, MD, FACP

Depletion of Latent HIV Infection & the Goal of Eradication

The discussion of eradication is certainly not new to the pages of The PRN Notebook. Early treatment, intensified treatment regimens, and immune-based therapies to achieve this goal have all been pursued—with limited success—and discussed in detail over the past ten years. Just as it seemed as if the possibility of eradicating HIV was nothing more than a pipe dream, exciting new research has emerged utilizing a truly novel approach and exploiting a very common compound—valproic acid—bringing the possibility of a cure to the forefront once again. PRN was pleased to host Dr. Margolis at its October meeting to explain the theory behind, and the data supporting, continued evaluation of this approach.

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Roy M. Gulick, MD, PhD

View from the Pipeline: The 2005 Review of Experimental Antiretrovirals

There are 20 unique medications approved for the treatment of HIV infection. Despite this impressive number, there is an indisputable need for new anti-HIV compounds that have potent and durable efficacy profiles, unique resistance patterns, patient-friendly dosing schedules, and minimal toxicities. What follows is an overview of some the newest antiretroviral contenders, discussed by Dr. Roy M. Gulick during a recent meeting of the Physicians’ Research Network.

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Athe MN Tsibris, MD and Charles Farthing, MD

Surviving Antiretroviral Drug Resistance: Strategies for Optimal Use of Therapeutic Agents

Constructing effective salvage therapy regimens for HIV-infected patients with highly resistant virus poses a daunting challenge to the practicing clinician. The recent approval of new protease inhibitors—tipranavir and darunavir—and the continuing development of new drug classes provide hope that patients can now be salvaged with at least a few active new drugs. This paper reviews the available clinical outcomes data for tipranavir and darunavir as well as the investigational CCR5 antagonists, 2nd-generation nonnucleoside reverse transcriptase inhibitors, and integrase inhibitors. Also discussed are salvage strategies in treatment-experienced patients with the goal of maximizing the chances of a patient receiving at least 2 active agents in combination.

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Laura A. Napolitano, MD

Advances in Immune-Based Therapies for HIV Disease

A great deal of research has established potent antiretroviral therapy as a way of drastically reducing HIV replication. Less is known about strategies to enhance T-cell production to preserve or restore immune function in HIV-infected patients, but much progress has been made. Not only do we better understand the mechanisms by which CD4+ cells are lost in HIV-infected individuals and then gained in response to antiretroviral therapy, research in this regard has given rise to a number of potential pharmacologic strategies that continue to be explored in studies.

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Marta Boffito, MD, PhD

From Concept to Care: Pharmacokinetic Boosting of Protease Inhibitors

Protease inhibitors have played an instrumental role in decreasing mortality and morbidity among people with HIV infection. At the same time, this class of antiretrovirals has been associated with a number of disadvantages. But now, pharmacokinetic “boosting”—primarily the use of ritonavir (Norvir) to boost concentrations of other protease inhibitors—has, in effect, rendered many of these drugs easier to take and more effective.

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Charles W. Flexner, MD

XEN and the Art of Pharmacology: New Learning from an Old Science

The future development of effective and safe antiretroviral agents—and the continued study of ways to maximize the utility of currently available therapies—are highly dependent on a scientific field that has evolved in recent years at an incredible rate: pharmacology. Very little has been published regarding the actual pharmacologic mechanisms responsible for host- and drug-related pharmacokinetics and pharmacodynamics variability. To help explain the science of drug metabolism and drug interactions—and how it is translating into new treatment strategies—PRN turned to Dr. Charles Flexner to discuss the latest developments and future directions of pharmacology in the much larger arena of HIV treatment research.

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François Clavel, MD

Mechanisms of HIV Drug Resistance: A Primer

Drug resistance of HIV to antiretroviral drugs is one of the most common causes for therapeutic failure in people infected with HIV. Fortunately, therapy can now be individualized, based on our evolving knowledge of drug resistance, drug-resistance testing, and state-of-the-art treatment approaches.

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Veronica Miller, PhD

Bangkok 2004: Progress In Spite of Protest?

When PRN approached Veronica Miller, PhD, Director of the Forum for Collaborative HIV Research, to write a summary of the recent XV International AIDS Conference in Bangkok, we knew that this would be a daunting task. For those interested in reading up on some of the basic science; clinical research, treatment, and care; and epidemiology and prevention data presented at the conference, we encourage readers to review the expert summaries posted on Medscape and Clinical Care Options. What Dr. Miller provides us with here has not been readily available through other clinician-based publications: a personal viewpoint of the IAC and, with it, a report on some of the Forum for Collaborative HIV Research activities at the highly charged conference.

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Joseph J. Eron, Jr., MD

View from the pipeline: The 2004 Review of Experimental Antiretrovirals

There are 26 medications approved for the treatment of HIV infection. This latest tally includes 19 unique antiretroviral agents, three prodrug/extended-release formulations of older drugs, and four fixed-dose combinations (including the most recent arrivals: Gilead’s Truvada and GlaxoSmithKline’s Epzicom). Despite these impressive numbers, there is an indisputable need for new anti-HIV compounds that have potent and durable efficacy profiles, unique resistance patterns, patient-friendly dosing schedules, and minimal toxicities. What follows is an overview of some the newest antiretroviral contenders, including some of the more recently approved agents and a number of the experimental agents in various stages of development.

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Daniel R. Kuritzkes, MD

HIV Drug Resistance: New Insight and Updated Practices

Significant amounts of data presented at scientific conferences have shed additional light on the mechanisms and clinical significance of antiretroviral drug resistance. These include new reports from studies evaluating the incidence and lingering consequences of transmitted drug-resistant HIV, the significance of the K65R mutation in reverse transcriptase, the persistence of minor HIV variants harboring drug-resistance mutations, the selection of TAM pathways, as well as some heartening data indicating that lamivudine retains some activity against HIV carrying the M184V mutation.

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Alice K. Pau, Pharm.D.

Antiretrovirals for the World: Needs and Challenges

At the XIII International AIDS Conference, held in 2002 in Barcelona, the World Health Organization (WHO) challenged the global HIV/AIDS community to expand access to care and treatment to at least half of those in immediate need—to put antiretroviral therapy into the hands of three million people in resource-limited settings by the end of 2005. On World AIDS Day 2003, WHO released a detailed and concrete plan to achieve this ambitious goal. The “3 by 5 Initiative,” as it has come to be known, has been heralded as the first big step towards universal access to AIDS care and treatment.

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Martin Markowitz, MD

Update on the Treatment of Acute and Early HIV Infection

The treatment of patients in the acute and early stage of HIV infection has long been a subject of intensive investigation. A handful of studies have evaluated immediate, short-term antiretroviral therapy during acute and early HIV infection in an effort to perturb the virus-host equilibrium with the intent of achieving long-term virologic control in the absence of antiretroviral therapy. This article summarizes a lecture focusing on acute and early HIV diagnosis and treatment delivered by Dr. Marty Markowitz, as well as data from the Massachusetts General Hospital primary HIV infection structured treatment interruption study, presented by Dr. Bruce Walker.

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David J. Back, PhD

Pharmacokinetics, Pharmacogenetics, and HIV: The Aim to Optimize Antiretroviral Therapy

Efforts are underway to better understand the pharmacology of antiretroviral therapy and how best to individualize treatment of HIV and AIDS to yield the safest, most effective results. According to Dr. David Back, this goal is evident in the recent move toward once daily regimens to simplify dosing as well as boosted protease inhibitor (PI) regimens to both simplify and improve the effectiveness of treatment. Most recently, there has also been growing interest in the potential role for host genotyping, stemming from the fascinating study of pharmacogenetics.

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Schlomo Staszewski, MD

Protease Inhibitor Therapy: Boosted and Double-Boosted Options to the Fore

Pharmacokinetic “boosting”—the use of ritonavir to boost concentrations of other protease inhibitors—has, in effect, rendered many of these drugs easier to take and more effective. Research is also emerging regarding the use of two protease inhibitors—both boosted using low-dose ritonavir—as a therapeutic option, which appears to hold promise, particularly for patients who have tried and failed protease inhibitor therapy in the past.

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Joseph S. Cervia, MD, FACP, FAAP

The Changing Face of HIV Infection in Children

The dramatic reduction of mother-to-child HIV transmission rates has been heralded as one of the most important breakthroughs in the history of HIV research. Yet an estimated 10,000-plus children in the United States were already infected with the virus. Today, thanks to early access to care and potent antiretroviral therapy, HIV-infected children can look forward to entering and graduating from high school and beyond. And with more information quickly emerging with respect to how HIV-infected children should be treated, we can expect continued improvements in prognosis.

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Judy Lieberman, MD, PhD

Shooting the Messenger: Harnessing RNA Interference to Combat HIV Infection

It all began less than ten years ago, when a team of researchers under the direction of Dr. Rich Jorgensen, who is currently an associate professor in the Department of Plant Sciences at the University of Arizona, was experimenting with petunias (Jorgensen, 1996). Dr. Jorgensen’s group was attempting to deepen the color of these household plants with the use of a pigment-producing gene. However, upon injecting the plants with the gene, the flowers actually lightened considerably, turning white in some cases. After some sleuthing, Dr. Jorgenson’s team suggested that what was being seen was “cosuppression”—the suppression of both the homologous endogenous gene and the introduced pigment-producing gene.

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Bernard M. Branson, MD

Understanding and Utilizing New Techniques for HIV Testing

The CDC also recognizes that, if they and other prevention groups are to be successful in stemming the tide of the epidemic, it is necessary to understand the ever-changing trends in HIV transmission. This requires monitoring the incidence of new HIV infections in various at-risk populations. To do this, the CDC has been implementing programs to take advantage of new testing strategies to identify newly infected individuals from among the scores of persons testing positive for HIV. This article intends to shed some light on rapid assays and sensitive/less-sensitive HIV-antibody testing strategies, based on a lecture delivered by Dr. Bernard Branson of the CDC to members of the Physicians’ Research Network in NYC.

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Mark Dybul, MD and Roy M. Gulick,MD MPH

State of the ART: The New DHHS HIV Treatment Guidelines and Current Controversies in Antiretroviral Therapy

Since their original publication on April 24, 1998, the Department of Health and Human Services’ Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents have undergone significant alterations. Research into the optimal times to start and switch therapy, along with the evaluation of both new and older antiretroviral regimens and laboratory assays, has evolved considerably over the past five years—a reflection of scientific discovery that continues to change the standard of care for HIV-infected individuals.

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Steven Deeks, MD

To Switch or Not to Switch: When Is It A Question?

When the first official Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents were published by the Department of Health and Human Services (DHHS) on April 24, 1998, the HIV treatment landscape was a different world: hitting the virus early still seemed like a logical idea, an apparent never-ending supply of protease inhibitors was flowing out of the drug-development pipeline, non-nucleoside reverse transcriptase inhibitors were coming into vogue as potent backbone options, nucleoside analogues did not appear to suffer much in the way of cross resistance, and an extraordinary percentage of HIV-positive individuals were still doing well on their first triple-drug regimens. In short, treatment options were plentiful and the DHHS was confident in its endorsement of pushing viral load to undetectable levels and keeping it there, using a succession of seemingly endless regimen switches to maintain this goal.

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Veronica Miller, PhD, Richard Haubrich, MD, and Daniel R. Kuritzkes, MD

Understanding Treatment-Resistant HIV

Resistance of HIV to antiretroviral drugs is one of the most common causes for therapeutic failure in people infected with HIV. Sadly, the emergence of drug-resistant HIV variants is usually an inevitable occurrence—even under the best of circumstances—given that no antiretroviral drug combination is completely effective in shutting down viral replication. And there is no shortage of data indicating that the emergence of HIV drug resistance is clearly associated with adverse treatment outcomes.

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David D. Ho, MD

HIV AIDS in Resource-Poor Settings: A Province In China

At the dawn of the third millennium, it is clear that humanity is facing one of the most devastating epidemics in human history-an epidemic that threatens development in major regions of the world. Since the 1960s, most countries have made impressive strides in human development. However, such achievements are being undermined as countries lose young, productive people to the epidemic.

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Scott M. Hammer, MD

View From the Pipeline: The 2003 Review of Experimental Antiretrovirals

Despite the fact that 16 antiretrovirals are approved for use in the United States, there is an indisputable need for new anti-HIV compounds that have potent and durable efficacy profiles, unique resistance patterns, patient-friendly dosing schedules, and minimal toxicities. To provide PRN with a glimpse of drugs currently snaking their way through the development pipeline—including three drugs currently being reviewed by the U.S. Food and Drug Administration (FDA) for marketing approval—Dr. Scott Hammer returned to the podium at the January 2003 PRN meeting to discuss his observations of data presented over the past few years. A summary of his presentation—along with key data presented at the 10th Conference on Retroviruses and Opportunistic Infections (CROI), held in February in Boston—is provided here.

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Donna Futterman, MD

Youth and HIV: The Epidemic Continues

HIV infection continues to increase among sexually active adolescents and young adults, who account for half of all new HIV infections in the United States and worldwide. However, only a fraction of these young people are actually aware of their HIV serostatus, and an even smaller number have been successfully linked to vital medical care and social services. It’s all about "Gettin’ Busy." The medical establishment, Dr. Donna Futterman argues, has much "Gettin’ Busy" to do. Now, more than ever, there is a great need to identify at-risk adolescents, to introduce them to counseling and testing as a component of HIV prevention, and to bring HIV-infected young people into care. "Gettin’ Busy"—a term that refers to having sex—still has enormous significance in the discourse of young people and it is something teenagers and adolescents are clearly doing. In the process, however, they are engaging in behavior that increases the risk of contracting or spreading sexually transmitted diseases, including HIV. Each year, 25% of sexually active adolescents contract an STD.

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Miriam Rabkin, MD, MPH

Identifying HIV Treatment and Research Priorities in Resource-Poor Settings

Not 20 years since it was identified as the cause of AIDS, the human immunodeficiency virus (HIV) has become the world's leading infectious cause of death. In the United States and other industrialized nations, the success of highly active antiretroviral therapy (HAART) has provided a partial reprieve from the epidemic. Yet in developing nations-home to 90% of those living with HIV in the world-antiretroviral treatment is beyond the reach of most people living with the disease.

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Mark Dybul, MD

HAART Interruption Strategies: How, When, and Why?

Although structured treatment interruptions (STIs) are no longer the most pressing topic among the many researchers who were initially charmed by their multifaceted potential, STIs very much remain in the hearts and minds of clinicians and people living with HIV. And why shouldn’t they? The reasons for wanting to halt therapy, even temporarily, are just as valid today as they once were. Even in this day and age, in which once-daily drug regimens with low pill burdens are plausible, there are countless patients who continue to grapple with adherence issues and treatment “burnout.” There is also the issue of long-term side effects, whether it’s preventing, delaying, or reversing their onset. Immune augmentation still remains a worthwhile goal, although its potential seems limited to those fortunate few diagnosed during the primary stages of infection. Finally, there is the possibility of using STIs to overcome drug-resistant virus in patients running low on fresh treatment options.

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Roy “Trip” Gulick, MD, MPH

New Antiretrovirals for the Treatment of HIV: The View in 2002

Despite the fact that 16 antiretrovirals are approved for use in the United States, there is an indisputable need for new anti-HIV compounds that have potent and durable efficacy profiles, unique resistance patterns, patient-friendly dosing schedules, and minimal toxicities. To provide PRN with a glimpse of drugs currently snaking their way through the development pipeline, Dr. Roy "Trip" Gulick returned to the podium at the February 2002 PRN meeting to discuss his observations of data presented over the past few years. A summary of his presentation-along with data presented at the 9th Conference on Retroviruses and Opportunistic Infections (CROI), held in February in Seattle-is provided here.

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Tim Horn

The Forum for Collaborative HIV Research

Tim Horn reports on The Forum for Collaborative HIV Research, which seeks and develops consensus from the diverse constituencies represented with the singular goal of moving hiv/aids research forward. Dr. Roy Gulick discusses how The Forum has been very successful in identifying, evaluating, and catalyzing the next steps in the key areas of HIV research.

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Alice K. Pau, Pharm.D

Polypharmacy Problems: Drug Interactions in the Multidrug Therapy of HIV Infection

Patients with HIV receive an abundance of daily medications, often including a triple-drug antiretroviral regimen, primary and/or secondary prophylactic drugs, and other compounds as needed (e.g., lipid-lowering drugs). Clinicians will be the first to admit that the proper use of these drugs has yielded highly desirable effects—including prolonged survival and fewer opportunistic infections—but will also attest to the burgeoning task of monitoring possible drug interactions.

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Joseph J. Eron, MD and Christine M. Hogan, MD

Entry and Fusion Inhibitors: An Update

Eradication of HIV has not been possible with currently available reverse transcriptase inhibitors and protease inhibitors; and multiclass drug-resistant mutants of HIV-along with a multitude of disabling and sometimes life-threatening side effects-are a growing threat. Thus, there is a great need for compounds that target non-protease and reverse transcriptase elements of the HIV lifecycle. Not only might such novel therapies increase the potency of initial HIV treatment, but they may also provide hope for patients who have exhausted current treatment options.

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Daniel R. Kuritzkes, MD

Nucleoside Reverse Transcriptase Inhibitors: Resistance, Cross-Resistance, and Resistance Testing

With so much emphasis being placed on protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) in recent years, it’s no wonder that key research involving the “old reliables”—the nucleoside reverse transcriptase inhibitors (NRTIs)—is often overlooked while thumbing through the pages of conference abstract books and peer-reviewed medical journals. Yet, just as there are remaining questions regarding how best to use PIs and NNRTIs, there are similar issues facing the NRTIs that have yet to be fully addressed—most notably, how best to sequence their use in light of their individual drug-resistance profiles. Ironically, this particular issue is becoming more complex as time goes on, given recent data suggesting that resistance within this class of drugs may not be as agent-specific as was originally suspected.

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Martin H. Markowitz, MD, Bharat Ramratnam, MD, Michael Louie, MD

The Road to Eradication: Is HAART Hard Enough?

At the ground-breaking 1996 International AIDS Conference, Markowitz and Ho, postulated 1.5--3 years of “maximally suppressive” antiretroviral therapy might eradicate HIV infection. Since then, research has shown that HAART may not completely shut down HIV replication, and that infection may persist in reservoirs. “But this does not mean that we should abandon concepts of eradication or remission,” stated Dr Markowitz at a meeting of PRN in NYC, “the shortcomings that we see today, especially the emergence of drug resistance, might be less of a concern if we can maximize the benefits of therapies that are now available, as well as those in development.”

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Joseph Eron, MD

New Drugs for the Treatment-Experienced Patient

Though much progress has been made in the treatment of HIV disease, most patients develop drug resistance over time, making new active agents necessary in order to sustain treatment success. Dr Joe Eron discusses HIV drugs-in-development in 2000, with attention to those that may benefit treatment-experienced patients with drug resistance and treatment failure on currently available agents.

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Elizabeth J. Phillips, MD, FRCPC

Approach to Hypersensitivity Syndromes Associated with Antiretroviral Agents

Life-threatening drug hypersensitivity reactions can occur with drugs used to treat HIV disease and its complications. This discussion of adverse drug reactions by Dr. Elizabeth Phillips, at a meeting of the Physicians’ Research Network in New York, focuses on the diagnosis and management of hypersensitivity to antiretroviral agents, including nevirapine, efavirenz, agenerase and abacavir, as well as to sulfamethoxazole used for treatment and prophylaxis of Pneumocystis pneumonia.

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Richard Hoetelmans, PHD

The Relevance of Pharmacologic Monitoring In HIV Disease

Virologic failure in the treatment of HIV disease, and the emergence of drug-resistant virus, often begins with subtherapeutic antiretroviral plasma concentrations, but the actual pharmacokinetics of individual drugs can also be blamed. Furthermore, plasma concentrations of antiretroviral agents exceeding therapeutic range may be associated with drug toxicity. This review of Dr Richard Hoetelmans’ presentation to the Physicians’ Research Network in New York focuses on the potential role of therapeutic drug monitoring (TDM) in individualizing antiretroviral therapy, preventing virologic failure, and avoiding drug toxicity.

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Kendall Smith, MD

Interleukin-2: Use in Immune Restoration and During Structured Treatment Interruption

Although structured treatment interruptions (STIs) are no longer the most pressing topic Structured treatment interruptions (STIs) are a clinical concern. Patients with underlying hiv drug-resistance mutations who initiate an STI while experiencing virologic failure on a HAART regimen essentially remove the selective pressure being exerted on the virus. This, in theory, should permit the “optimally fit” wild-type virus to outgrow drug resistant variants, thus having a dominant drug-sensitive phenotypic population. And once therapy is reinitiated, a profound and perhaps durable response to therapy would ensue. This article reviews treatment interruption strategies and studies, as well the benefits and drawbacks to STIs.

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