Pre-exposure prophylaxis, especially long-acting PrEP, affects the laboratory diagnosis of HIV. And the current diagnostic algorithm needs some updating anyway. In this presentation, Bernie Branson discusses the aging HIV diagnostic algorithm and ways to improve it, the difference between HIV RNA for diagnosis vs. monitoring, and which tests are necessary before initiating ART.
Every two years, HIV Research for Prevention (R4P) meets internationally and focuses solely on prevention modalities, technologies, and strategies. In this thought-provoking presentation, Craig Hendrix reviews the highlights of HIV R4P, including long-acting PrEP, on-demand PrEP, and multipurpose prevention technologies
What progress has been made world-wide in the prevention of new pediatric HIV infections? How has the COVID-19 pandemic impacted HIV services for pregnant women and infants? In this presentation by Elaine Abrams, we will gain insight into these critical questions along with an understanding of optimal antiviral regimens for use during pregnancy and breastfeeding, as well as gaps along the cascade of care for prevention of vertical HIV transmission.
How has the COVID-19 pandemic impacted efforts to end the HIV epidemic in New York City? In this presentation, Anisha Gandhi will discuss the most up-to-date epidemiology in New York City along with current strategies to end the epidemic.
The more effective PrEP options we have, the more we will reduce barriers to adherence and usage -- and the more we can succeed at reducing HIV transmission. People will benefit with improved success at preventing new infection. In this comprehensive review, Dr. Hendrix will present an update on microbicides, vaginal rings, long-term injectables, and other advances in new drug development and delivery that will expand on the existing options for PrEP.
One of the greatest challenges with the COVID 19 pandemic has been the availability, speed, and accuracy of diagnostic testing. In this presentation, Bernard Branson will discuss both HIV and COVID 19 testing. With COVID 19, you will learn to understand the fundamentals of laboratory tests as well as appreciate the role for serology testing in identifying exposure. As we have learned with HIV testing, it can and must get better. In fact, with recent advances in HIV testing, it may be time for a new HIV diagnostic algorithm. Learn which parameters affect the accuracy of tests for both COVID 19 and HIV.
Leveraging Imaging Approaches to Define the Dynamics of SIV/HIV During & After ART & Adapting this Approach to Study SARS-CoV-2
This captivating lecture by Tom Hope shows us how imaging approaches he has developed to study HIV, rebound reservoirs and latent cells after discontinuation of ART in non-human primates, can provide insight to HIV Cure research. And these same imaging approaches developed to study HIV have been adapted by Dr. Hope to study COVID-19, leading to a clearer understanding of pathogenesis and intervention for this new pandemic.
So just what are broadly neutralizing antibodies anyway? And why are bNAbs so promising for HIV prevention and treatment? This presentation by Marina Caskey, one of the most prominent researchers leading the way in this new field of immunotherapy, discusses their potential in prevention of HIV infection during sexual exposure or mother-to-child transmission, as alternatives or adjuncts to antiretroviral drug therapy in populations that face challenges in maintaining long-term compliance with daily ART regimens, as salvage therapy in individuals with multi-ARV resistance, and more. Don’t miss this exciting glimpse of what HIV treatment and prevention may look like in the future.
When you write an order for an HIV test, do you know what assay your facility or reference lab is using? And depending on what assay is being used, and whether the specimen is whole blood or plasma, how soon after exposure can HIV infection be detected? And how does this window of time to detection change in patients who do not take PrEP as prescribed, for one reason or another? Yes, it gets complicated. You probably ask yourself these questions every time you see somebody requesting PEP or PrEP, or struggling to answer these questions as accurately as you can when your patients ask you for your expert opinion. This presentation by Bernard Branson will help you understand the limitations and advantages of the various HIV tests currently available as well as new assays in the testing pipeline, so that you can answer all of these questions better, no matter who is asking.
At the most recent HIV Research for Prevention (HIVR4P) convention in Madrid, advocates from around the world were marching and chanting in support for more choices in HIV prevention modalities. And the prevention pipeline is very interesting! This presentation by Craig Hendrix targets the drugs, delivery systems, safety and efficacy of agents currently used for PrEP in diverse populations, including cisgender and transgender women, as well as the many agents in development that will help you in your next conversation with a patient wishing or waiting for more prevention choices.
What happens after genital or anal exposure to HIV, and how fast can infection take hold? When and where can this infection be stopped after exposure and what is the virus doing during the eclipse and window periods before it can be detected in blood? In this thought-provoking program, Tom Hope will sharpen your view of pathogenesis with his research into the earliest events of HIV transmission and dissemination utilizing non-human primate mucosal-challenge models, human tissue explant cultures, whole animal PET/CT and PET/MRI imaging, and electron microscopy.
Internet hook-up trends for gay men, in combination with recreational drugs, including crystal meth, to decrease inhibitions and increase sexual pleasure, are the drivers of what has become known as chemsex. This phenomenon is not limited to the UK and Europe, where the term was first used—it is international in scope, including New York City, and can lead to substance use disorders and mental illness. Chemsex also greatly increases the risk for non-adherence to HIV medication, PrEP, and condom use, while elevating the risk for transmission of HIV and other sexually transmitted diseases. How can we understand and help in a non-judgmental way? This program by Drs. Vaty Poitevien and Pierre Arty tackles this important and too-often overlooked problem.
We are making great strides in New York to end the HIV epidemic, as this presention by Demetre Daskalakis demonstrates. But how are the demographics changing? What are the emerging disparities? And how can we address the evolving needs of New Yorkers who are newly infected or at ongoing risk for transmission in all of our diverse communities? Don’t miss this important presentation on where we stand and the problems we currently face in the struggle to end the HIV epidemic once and for ALL by the end of 2020.
Efforts to prevent mother-to-child transmission of HIV are the oldest and most successful examples of HIV prophylaxis, and a model for post-exposure prophylaxis and the expanded efforts we now have, such as Treatment as Prevention. But even though it is rare, we still see mother-to-child transmission of HIV, especially when mothers become acutely infected during pregnancy or while nursing. It is important to understand the deficiencies and oversights in routine standards of care, if we hope to finally reduce perinatal HIV infection to zero.
“Queer Health Warrior,” Demetre Daskalakis, who also happens to be our Deputy Commissioner at the New York City Department of Health and Mental Hygiene, is serious about ending the HIV epidemic in New York. And so are we. So how are we doing? And how can we all work together to accomplish this goal by the end of 2020? Don’t miss this engaging update on the strategies and efforts currently underway to prevent HIV transmission and infection, and ways that you can help. After all, HIV is an emergency, so let’s treat it that way!
Just how fast and accurate are the rapid tests you are using at the point-of-care? And what about the laboratory tests you are ordering to confirm infection or sort out false positives from false negatives? The early diagnosis of HIV infection is critical to ending the epidemic, and our patients who seroconvert while on PrEP present a special challenge. Understanding the advantages as well as the limitations of current HIV diagnostic tests informs not only our interpretation of the tests results we receive, but the way we explain these results to our patients. We also have a commitment to diagnosing HCV in our patients with, or at risk for HIV. This presentation by Bernard Branson reviews and compares the current diagnostic tools available, as well as newer assays in the development pipeline.
For many years, stable heterosexual HCV discordant couples have failed to implicate HCV as a sexually transmissible disease. But more recently we have seen an epidemic of HCV in HIV-infected MSM, suggesting that sexual transmission is possible. In this program, Daniel Fierer discusses outcomes of studies showing the presence of HCV in semen as well as rectal secretions, and further suggests that sexual transmission of HCV in MSM is associated with condomless anal sex and use of non-injectable party-drugs, rather than physical trauma or shared needles.
In 2014, Governor Cuomo issued a three-point New York State plan to increase efforts to 1) diagnose people with HIV-infection and link them to ongoing care, 2) maximize viral suppression with antiretroviral therapy to keep HIV-positives healthy and reduce their risk of transmitting the virus to other people, and 3) facilitate access to antiretroviral pre-exposure prophylaxis (PrEP) for uninfected people at risk. Since then much has been done to achieve these goals, especially here in New York City. Don’t miss this exciting presentation by New York City’s dynamic queer health warrior, Demetre Daskalakis, who also happens to be our Acting Deputy Director of the Bureau of Disease Control at the New York City Department of Health and Mental Hygiene, as he inspires us to work together to end this frightful epidemic, once and for all.
The role of partner services and linkage to ongoing preventive and therapeutic medical services is critical in our efforts to slow and hopefully end the HIV epidemic. Providers cannot do this alone, but by partnering with local and regional departments of health and improving awareness of partner services within our practices and institutions, we can achieve broader and earlier diagnosis and assure access to care for partners needing treatment, if already HIV-infected, and pre-exposure prophylaxis, if not. This important presentation on the history and future of partner services underscores the responsibility we all have as health care providers to more effectively collaborate in larger public health efforts to end the epidemic in the sexual networks of the people we serve.
While many patients and clinicians focus on viral load and CD4 count in the chronic management of HIV disease, another important marker that is often overlooked is the CD8 count, and the resulting CD4/CD8 ratio. But it is the CD4/CD8 ratio that may be our best marker of immune recovery after initiation of treatment, especially in those treated during acute and early HIV infection. And it may also be our best marker for immune dysfunction, increased risk for non-AIDS morbidity and mortality, increased viral reservoir, and increased inflammation in the chronic management of HIV. This important lecture by Martin Hoenigl highlights the importance early intervention and the life-long benefits that this may have for people lucky enough to initiate ART early, with restoration of a more normal CD4/CD ratio.
The recent Zika epidemic in Puerto Rico presented challenges to the care of pregnant women that in many ways benefitted from previous lessons learned with HIV. In this presentation, Carmen Zorrilla, who has played an important role in the care of pregnant women in both epidemics, shares her experiences and insights on meeting the new challenges of Zika, while drawing from the effective actions taken against HIV in the past.
How and when are HIV reservoirs established in the central nervous system? What is the impact of early antiretroviral therapy on CNS HIV infection? Does HIV persist in the CNS compartment? If one of your patients develops an HIV-associated neurocognitive disorder, can ART intensification help? And how does what we are learning about the CNS impact HIV cure strategies? For answers to these and other questions about the human brain in HIV pathogenesis, management, and potential cure, don’t miss this important presentation by Serena Spudich.
Yes our HIV-positive patients and our HIV-negative patients in serodiscordant relationships can have healthy pregnancies and HIV-negative babies. And it is our responsibility as primary care providers to know how to assess, understand and counsel our patients about their reproductive aspirations with sensitivity and efficiency during a routine visit. In this program Karen Beckerman discusses the liberating advances in the safety and outcomes for HIV-positive and discordant couples wishing to have a child.
To end the HIV epidemic, all healthcare providers must be aware of and sensitive to the unique needs of each individual patient, based not simply on sexual orientation, but also on their gender identities and accompanying physical risk factors for sexually transmitted infections. How can we improve our communication skills in sexual history-taking in such situations? And what do we need to know about advances in gender-affirming surgery so that our trans-female, trans-male, and gender non-conforming patients feel that we are thorough, compassionate, and trustworthy? For some important updates on sexual health across the gender spectrum, don’t miss this important presentation by Dr. Asa Radix.
In the age of PrEP, do we really need an HIV vaccine anymore? Yes. In this presentation, Rick Koup, reminds us of the ongoing need for safe and effective HIV vaccines to stop this world-wide epidemic, the past failures in HIV vaccine trials that have been so disappointing, and the new era of more rational vaccine design that is presently emerging. If your patients ever ask about HIV vaccines, and we are sure they will, this program will help you respond positively.
The roll-out of pre-exposure prophylaxis to men who have sex with men is gaining momentum. But PrEP is for women at risk too, and barriers to care, including gender inequality, poverty, racism, gender-based violence, and transphobia must be overcome. Adherence and pharmacokinetics of the genital tract also play an important role in successful prophylaxis for women. This lecture targets the complexities and barriers to successful PrEP for women, as well as the exciting variety of research products in the PrEP pipeline that should provide women with more options for HIV prevention in the future.
Epidemiological Synergy: The High Risk of HIV Infection among Men with Sexually Transmitted Bacterial Infections
The New York City Department of Health and Mental Hygiene has data clearly demonstrating increased risk for HIV seroconversion during the months following the diagnosis of a bacterial STI, especially among men who have sex with men (MSM). So if you diagnose an HIV-negative patient with gonorrhea, Chlamydia or syphilis, do not let them out of sight until you have discussed HIV pre-exposure prophylaxis (PrEP). This is especially important in MSM with or at risk for anorectal STIs, and, if we are to end the HIV epidemic, the lag-time to initiation of HIV PrEP may be critical.
Preventing HIV transmission to uninfected individuals through the use of pre-exposure prophylactic medication works well when at-risk individuals take it as prescribed, and we are all hoping that PrEP will help stop this epidemic. But PrEP only works as well as adherence allows, and daily dosing is problematic for some people. This presentation details the common barriers to PrEP adherence, limiting side effects of currently recommended PrEP, and important research toward easier or more forgiving regimens, including IPERGAY and ADAPT studies of intermittent PrEP.
The laboratory testing for HIV and HCV have never been easier or faster. But do you really know what tests your lab is doing? And how to interpret the test results? And what to order next? The newer diagnostic algorithms are straightforward but in the real world, a deeper understanding of what commercially available tests really show is vital to identifying negatives, staging positives, and advising appropriate care and prevention. This presentation will help you understand the advances in routine laboratory testing for HIV and HCV and how to interpret them to improve of both patient and public health.
However bad the HIV epidemic may be in the US, it is worse in adolescents and young adults: 26% of new cases are among youth, ages 13-24. It is estimated that 14% of Americans don’t know they are infected, but among youth, it is estimated that 51% are unaware. And African-American youth are disproportionately affected. Don’t miss this important program on the diagnosis, treatment and prevention of HIV and other sexually transmitted diseases in young people who need our help to live longer, healthier and more productive lives.
Governor Cuomo has initiated a statewide effort to end the HIV epidemic in New York by 2020, known as EtE 2020. In this presentation, Bill Valenti, chair of the Care Committee of the Governor’s Task Force, reviews and discusses the major goals of EtE 2020, including: 1) identifying people with HIV who remain undiagnosed and linking them to health care, 2) linking and retaining people diagnosed with HIV to health care and getting them on anti-HIV therapy to maximize HIV virus suppression so they remain healthy and prevent further transmission; and 3) providing access to Pre-Exposure Prophylaxis (PrEP) for high-risk people to keep them HIV negative. We hope that you will view this program and join us in this effort so that by working together we can end the HIV/AIDS epidemic in New York State once and for all.
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.
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.
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.
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 both in pathogenesis and treatment. And who could teach us better than the researcher who first discovered HIV-2, Fancois Clavel, in this fascinating and important lecture.
Pre-exposure prophylaxis is currently our best possible means of slowing or perhaps stopping the HIV epidemic, but the success of currently available PrEP is strongly dependent on the adherence of each individual to a one-pill-a-day regimen. Longer-acting drugs in the research pipeline, with intermittent dosing up to 3 months apart, may help stabilize preventive levels of prophylactic antiretroviral agents more consistently over time, and may play an important role in the future of PrEP.
Get ready. If your HIV-negative patients have not already asked you about pre-exposure prophylaxis for the prevention of HIV infection, this presentation will help you answer their questions when they do. And if they already have started asking you for PrEP, this will help you fine-tune your responses, recommendations and management. The rate of new infections with HIV have remained constant over the last decade despite ongoing reminders for consistent condom use, and the use of antiretroviral drugs for PrEP is a new strategy that may greatly enhance ongoing efforts to reduce HIV transmission in vulnerable populations at highest risk for infection.
Are we ending the HIV/AIDS epidemic in New York? Rapid HIV tests are readily available and easy to use, oral consent for rapid HIV testing is allowed, pre-test counseling is no longer required, and New York State mandates that all primary care providers offer HIV testing to all patients 13-64 years of age and assure linkage to care for positives. So how are we doing? Join us to hear Blayne Cutler discuss the current trends in New York and the nation, advances in testing, management and prevention, and the critical role primary care plays in ending this epidemic.
Post-exposure prophylaxis (PEP) to prevent HIV infection has been around for a long time though the drugs used have fewer risks and side effects than in the past. But when patients present again and again for PEP, it is a great opportunity to discuss a newer and perhaps more effective way to prevent HIV infection in vulnerable patients with ongoing risk: pre-exposure prophylaxis (PrEP) with a single once-a-day tablet. In this presentation, Joe McGowan discusses the new recommendations for PEP in New York State including baseline lab tests and STD screening for PEP recipients, and how patients seeking serial PEP may benefit from ongoing PrEP with periodic follow-up and re-evaluation.
While HIV screening and testing have become more routine, the old testing algorithm made diagnosis during the most infectious acute stage difficult. The new HIV testing algorithm improves detection during acute HIV infection utilizing 4th generation assays that look for antigen as well antibody, and older confirmatory tests, that do not become positive until after the window of acute infection closes, are no longer recommended. Acute HIV infection plays a major role in sustaining onward HIV transmission, and the newer tests and testing algorithm, that can determine whether HIV infection is recent, will allow earlier treatment interventions that may more successfully slow this epidemic.
SPECIAL BRIEF REPORT: New guidelines for non-occupational Post-Exposure Prophylaxis (n-PEP) in New York State
This special presentation by Lyn Stevens highlights the recent changes to the guidelines for HIV non-occupational post-exposure prohylaxisis (n-PEP) in New York State. Clinicians need to be familiar with these recommendations so that they can respond promptly and knowledgably when patients present with recent risk of exposure to HIV, particularly within the last 36 hours when post–exposure prophylaxis is most likely to be effective in preventing infection. After you view this brief presentation, links to more detailed information will be provided.
The use of illicit drugs and consequent increased sexual risk-taking by gay and bisexual men plays an ongoing role in the sexual transmission bacterial and viral infections. This synergy between party drugs and unprotected sex drives the “syndemic” in the LGBT community, facilitating the spread of HIV, syphilis, gonorrhea, HPV, hepatitis C and other pathogens. Understanding these behaviors and their inherent risks, and intervening through the use of motivational techniques and holistic modalities may help decrease stigma and speed access to diagnosis, treatment and prevention of disease in this vulnerable community.
With the recently reported functional cure of a Mississippi child, infected with HIV at birth, diagnosed rapidly and treated early, we have further evidence that early diagnosis of HIV during the acute stage, with immediate initiation of combination antiretroviral therapy, contributed to the functional cure of this child after ARV treatment was interrupted. PRN is pleased to present Deborah Persaud with this groundbreaking report.
The number of people newly infected with HIV in the USA has remained steady, at around 50,000 per year, since the early 1990’s, despite the advances in the treatment of HIV and AIDS, and many efforts to promote safer sex. To further protect individuals at highest risk for acquiring HIV infection, pre-exposure prophylaxis with antiretroviral agents was recently approved by the FDA. Ongoing data analysis supporting PrEP as an intervention, current recommendations from the CDC, as well as new drugs and research studies in chemoprophylaxis are reviewed and discussed in this important presentation.
A safe and effective vaccine to prevent & control HIV infection will most likely require induction of broadly protective antibodies and cellular immune responses. As prevention technologies intersect, opportunities emerge to evaluate combination strategies to achieve incremental reduction in HIV incidence. HIV vaccine studies will become more complex but also more relevant and applicable to diverse populations in greatest need of prevention interventions.
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.
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.
The use of antiretroviral drugs to prevent HIV infection has created great hope worldwide, and pre-exposure prophylaxis, or PrEP, is an important addition to prevention efforts for seronegative patients with ongoing risk. It is important for all front-line providers to understand appropriate uses and limitations of PrEP, and to be aware of ongoing research. With her rich knowledge of antiretroviral pharmacokinetics in the anogenital tract, Angel Kashuba returns to PRN to discuss and compare data from clinical trials aimed at reducing the sexual transmission of HIV disease.
Historical Clues, Physical Signs, Laboratory Diagnosis & Treatment of Oral, Anogenital & Systemic STDs
Knowing when and how to successfully diagnose, treat, and counsel patients with sexually transmitted diseases is a skill that benefits our patients, their sexual partners and the public health. Syphilis, gonorrhea, Chlamydia, LGV, herpes, HPV, and even acute HIV can present in myriad ways, and the more efficient we are at suspecting, diagnosing, and treating these diseases, the better we are at preventing further spread.
HIV-1 coinfection and superinfection are not that uncommon, but few people talk about it, or the viral evolution that dual infections make possible. Davey Smith does talk about it, and if you have patients who think serosorting is safe, you will be better prepared to advise them about the risks and implications of HIV superinfection.
HIV-1 dual infection, coinfection or superinfection, happens and that it may happen rather frequently. Dual infection has identifiable consequences affecting clinical care of patients who already have HIV and are at continued risk of superinfection. To make matters worse, recombination can occur when two distinct viral variants infect the same cell, adding to the genetic diversity of HIV worldwide, and further complicating the development of a preventive vaccine.
Non-occupational Post-exposure Prophylaxis and Antiretroviral Pharmacokinetics in the Male and Female Genital Tracts
For sexual transmission, prophylaxis with antiretrovirals before a potential exposure—pre-exposure prophylaxis (PrEP)—or after the exposure occurs (PEP) is controversial and often leaves clinicians unsure of how to provide the best care to their at-risk patients. In March of 2006, Michelle Roland, MD, and Angela Kashuba, PharmD, were invited to a PRN meeting to discuss this complex issue. Dr. Roland discussed the challenges and opportunities she has experienced in PEP research, particularly focusing on the broader context of nonpharmacologic interventions that prevent transmission, and the current state of PEP in the United States and internationally. Dr. Kashuba focused on work being done to determine which antiretrovirals are optimal for PrEP and PEP applications, and to provide a rational framework for further policy making.
Health officials, clinic directors, and individual clinicians have been involved in initiatives to make confidential HIV testing a routine part of medical care with the use of new diagnostic technologies, including rapid HIV assays. These assays have been developed to make point-of-care (POC) HIV testing feasible providing immediate results. “When it comes to these assays,” Dr. Kevin Armington said in his introductory remarks, “if people can get a negative or preliminary positive result in twenty minutes, that’s the test most people are going to want.”
Proven, existing interventions could prevent one-half to two-thirds of HIV infections in New York City. Further reductions in transmission are also feasible through expanded community-based prevention efforts, prevention counseling for individual patients, supporting patients to facilitate return to care, and improving availability of effective treatment. The DOHMH is aware that its expanded public health initiatives may provoke controversy.
New York City remains the epicenter of the HIV/AIDS epidemic in the United States. Though NYC is home to less than 3% of the U.S. population, it accounts for 17% of national AIDS deaths. “We have more cases than Los Angeles, San Francisco, Miami, and Washington, D.C., combined,” Dr. Thomas Frieden noted in his presentation to the Physicians’ Research Network. “Our case rate is 60 times the national target for 2010, four times the U.S. average, and higher than any other city in the U.S.” While current funding levels are insufficient in terms of keeping up with care and prevention needs, Dr. Frieden argues that many of the services and programs currently available in New York City can be made more efficient.
PEPFAR targets $9 billion in new funding over five years to ramp up prevention, treatment, and care services in 15 of the most affected countries of the world, devotes $5 billion over five years to ongoing bilateral programs in more than 100 countries, and increases the U.S. Government’s pledge to the Global Fund by $1 billion over five years. We also intend this program to be sustainable. The heart and soul of PEPFAR is to support national strategies, to build capacity for the future.
The risk of mother to child transmission (MTCT ) of HIV infection can be reduced to below 2% by employing interventions that include antiretroviral therapy given to HIV-infected women during pregnancy and labor, as well as to exposed infants during the first weeks of life; the avoidance of breastfeeding; and delivery by elective Caesarean section. With all of these approaches, there are numerous questions and considerations.
Where is no shortage of data suggesting that people with primary HIV infection (PHI) are, unknowingly, significant contributors to the spread of HIV. In turn, public health initiatives surrounding PHI—whether its aggressive testing and counseling of acutely infected individuals, stepped-up contact tracing efforts, or the use of HAART—need to be considered carefully in the larger context of HIV/AIDS prevention efforts
The HIV medical community received an official wakeup call on July 30, 1998, when Dr. Frederick M. Hecht —a frequent PRN lecturer—and his colleagues published the first documented case of high-level protease inhibitor resistance in a recently infected, treatment-naïve, HIV-positive individual. Since this initial report, a number of researchers with close ties to primary HIV infection cohorts have not only confirmed that transmission of drug-resistant HIV is possible, but that it is occurring in up to 20% of all new HIV infections identified in North America in recent years (Little, 2002).
Advancing HIV Prevention: New CDC Strategies for a Changing Epidemic A Report from the U.S. Centers for Disease Control
In several U.S. cities, recent outbreaks of primary and secondary syphilis among men who have sex with men (MSM) (CDC, 2002), along with increases in newly diagnosed HIV infections among MSM and heterosexuals, have created concern that HIV incidence might be increasing. In addition, declines in HIV morbidity and mortality during the late 1990s attributable to HAART appear to have ended.
On the last day of the 7th Conference on Retroviruses and Opportunistic Infections in San Francisco in February 2000, shockwaves reverberated through the Moscone Convention Center. No, it was not an earthquake attributed to the cantankerous San Andreas Fault but rather an earth-shattering case report stemming from a Canadian HIV clinic situated 2500 miles away (Angel, 2000). The case report, presented by Dr. Jonathan Angel and his colleagues from the University of Ottawa, involved an antiretroviral-naïve HIV-positive male (patient A) who experienced rapid disease progression and high levels of viral resistance to multiple drugs after engaging in unprotected sexual activity with another HIV-positive male harboring a drug-resistant, possibly more virulent strain of HIV (patient B). Dr. Angel concluded that "Patient A was very likely infected with a resistant strain of HIV by Patient B," and went on to say: "I think there's enough information here to raise awareness regarding HIV superinfection and to say that this should be a public health issue if we can prove it."
The basic premise of the immune system is simple: to coordinate the activities of various cell types in order to provide extended, if not lifelong, protection against disease-causing pathogens. Usually, this system works flawlessly, quashing infections before they can kill their host and sparking immunity to provide protection against future attacks. Sometimes, however, the system fails and infection prevails--and there is, perhaps, no greater example of this than HIV, a pathogen that almost always succeeds in circumventing and manipulating the body's immune defense to facilitate its own survival. Immunology is still a relatively young research field, and there is still much to learn about its function, particularly as it relates to specific pathogens. One of the least-understood members of the immune system family is the dendritic cell. Accounting for only about 1% of all immune system cells, dendritic cells are nevertheless vital to both the initiation and control of immune responses.
Ever since HIV was first discovered in 1985, the bulk of research conducted has focused primarily on the pathogenesis of this virus in peripheral blood mononuclear cells (PBMCs). However, the mucosal-associated lymphoid tissues (MALT) are the largest source of lymphocytes, macrophages, and dendritic cells in the body, rendering them among the most important--and least understood--repositories of HIV. The significance of mucosal surfaces in the pathogenesis of HIV cannot be overstated. Mucosal surfaces--including those in the alimentary tract--are an important route by which HIV may gain access to blood and lymphoid tissue during heterosexual, homosexual, and perinatal transmission. What's more, the mucosa may be involved in the initial selection of viruses that are transmitted to adults and infants and may be a site where virus replication persists and drug-resistant viruses evolve during HAART.
At the ground-breaking 1996 international conference on AIDS in Vancouver, Drs. Martin Markowitz and David Ho, leading researchers at the Aaron Diamond aids Research Center (ADARC), gave presentations charting the gradual depletion of HIV reservoirs in a small group of patients treated with antiretroviral regimens. Dr. Ho went on to suggest that it might be possible to completely eradicate HIV by initiating aggressive antiretroviral, focusing first on a unique population of patients: individuals in the acute stages of HIV infection. The public consideration of what would be, in essence, a cure was met with enormous enthusiasm—and occasional criticism— by the international media, HIV-treating physicians and, of course, people living with HIV.
The treatment of patients in the acute stage of HIV infection has long been a contentious subject. While some data seem to indicate that the initiation of HAART during PHI is associated with few or no long-term advantages—which appears to have been the experience of Dr. Martin Markowitz and his colleagues at the Aaron Diamond aids Research Center (see page 16)—other research teams have gained extremely encouraging results, most notably Dr. Eric Rosenberg and his colleagues with the Partners AIDS Research Center at Massachusetts General Hospital (MGH). Not only has this research at mgh helped to define the immunologic significance of PHI, it has also led to a greater appreciation of the immune-boosting potential of antiretroviral therapy.
Reams of epidemiological and biological data are now available to suggest that people in the primary stages of HIV are, unknowingly, significant contributors to the spread of HIV and, consequently, the proliferation of the aids epidemic. However, the precise extent to which individuals with phi play into this unfortunate scenario remains unclear. To help make sense of the data that have emerged thus far—and to comment on its relevancy within the realm of public health—Dr. Christopher Pilcher shared his ongoing experiences and thoughts with PRN.
Without a doubt, public health initiatives surrounding PHI—whether it’s aggressive testing and counseling of acutely infected individuals, stepped-up contact tracing efforts, or the use of HAART—need to be considered carefully in the larger context ofHIV/AIDS prevention efforts. Yet our understanding of the public health consequences of “unchecked” viremia and risky sexual behavior during phi is still in its infancy, and even less is known about the cost-effectiveness of intervention programs, particularly when pricey diagnostic tests and antiretroviral therapies are involved.
As discussed throughout this special edition of THE PRN NOTEBOOK, a number of experts suggest that phi is a unique window of opportunity with respect to treatment, since it may be the optimal time to initiate haart to alter the long-term course of HIV disease. On a public-health level, correct diagnosis and medical intervention during PHI—a period in which viral load is exceptionally high—may be useful in halting the unintentional spread of the virus when someone is hypothesized to be most infectious. But, to take advantage of either the possible therapeutic or public health opportunities during phi, clinicians face a daunting task right from the start: actually connecting with and correctly diagnosing individuals in the initial throes of acute infection. While it is true that a growing number of people are likely to seek care immediately after possible exposure, given that the stigma and general sense of pessimism surrounding HIV infection has lessened, the most likely scenario involves patients who appear in the clinic only after symptoms of phi have surfaced— not necessarily aware that they may be connected to acute retroviral syndrome.
Just as the breakthroughs in basic research continue to pave the way for pharmaceutical companies and technology firms to develop novel therapeutics and laboratory tests, the advances of clinical research should serve as a reminder to all clinicians that the management of hiv disease is a work in progress and that new approaches in the diagnosis and care of hivpositive people are always on the horizon. This is certainly the case with primary hiv infection (phi). Chalked up by many as a relatively inconsequential period in the overall natural history of hiv disease, phi has now come to be recognized by some as a veritable window of opportunity for individuals fortunate enough to be diagnosed during the earliest stage of their infection.
The clinical syndrome of primary HIV infection was recognized and documented in 1985, about two years after the initial identification of the causative agent of aids. By 1991 it was known that this symptomatic period is associated with an explosive replication of the virus, which is then partially controlled as the illness resolves spontaneously. Reports in 1993 further showed the population of HIV during this early period of infection to be quite homogeneous, in distinct contrast to the diverse quasispecies that are typically found in chronically infected persons. This observation suggested not only the presence of selective forces operating during HIV transmission, but also the greater likelihood of therapeutic success in treating early infection.
Most HIV patients are diagnosed after the acute stage—primary HIV infection (PHI)—has come and gone. While the individual benefit of initiating HAART during PHI is uncertain, Drs. Christopher Pilcher & Jim Koopman arguet that there may also be unique public health advantage from the rapid diagnosis and treatment of PHI. “HIV shedding in genital secretions during the initial stage of infection is a major concern,” Dr. Pilcher said during his opening remarks at a meeting of PRN in NYC. “If we can step in with counseling and contact tracing, along with antiretroviral therapy, we may be able to diminish HIV shedding and, most importantly, interrupt epidemic spread in sexual networks.”
What factors increase and decrease the risk of transmission of HIV in discordant heterosexual couples? This review of an important meeting of the Physicians' Research Network in NYC points out the roles that male circumcision, control of concomitant sexually transmissible diseases, and decreased HIV viral load may have on HIV transmission risk.
What are the initial signs and symptoms of new HIV infection, how can HIV be diagnosed in its earliest stage of infection, and how risky is oral sex for HIV transmission? These and related issues are reviewed in detail by Dr Frederick Hecht at a meeting of the Physicians’ Research Network in New York.