Category Archives: News

From AIDSinfo

Download revision here:  [Download not found]

Download entire guidelines here:  [Download not found]

What’s New in the Guidelines?

Revisions to the October 14, 2011, version of the guidelines include both new sections and key updates to existing sections. The additions and updates, which are highlighted throughout the guidelines, are summarized below.

New Sections

The following new sections have been added to the guidelines.

HIV and the Older Patient
Effective antiretroviral therapy (ART) has led to greater longevity in HIV-infected individuals resulting in an increasing number of older individuals living with HIV infection. Compared with younger HIV-infected patients, older patients may have more comorbidities, which can complicate treatments of HIV and other diseases. This section focuses on HIV diagnosis and treatment considerations in the older HIV-infected patient.

Antiretroviral Drug Cost Table (Appendix C)
This new table lists the monthly average wholesale price (AWP) for U.S. Food and Drug Administration (FDA)-approved brand and generic antiretroviral (ARV) drugs, including fixed-dose combination products. (The AWP listed for an ARV may not represent the pharmacy acquisition price or the price paid by consumers for that drug.)

Key Updates to Existing Sections

Following are key updates to existing sections of the guidelines.

Initiating Antiretroviral Therapy in Treatment-Naive Patients

The Panel updated its recommendations on initiation of ART in treatment-naive patients. The changes are primarily based on increasing evidence showing the harmful impact of ongoing HIV replication on AIDS and non-AIDS disease progression. In addition, the updated recommendations reflect emerging data showing the benefit of effective ART in preventing secondary transmission of HIV. The updated section includes more in-depth discussion on the rationale for these recommendations and on the risks and benefits of long-term ART.

The Panel’s recommendations are listed below.

• ART is recommended for all HIV-infected individuals. The strength of this recommendation^a varies on the basis of pretreatment CD4 cell count:
• CD4 count <350 cells/mm³ (AI)
• CD4 count 350 to 500 cells/mm³ (AII)
• CD4 count >500 cells/mm³ (BIII)

• Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:
• Pregnancy (AI) (see perinatal guidelines for more detailed discussion)
• History of an AIDS-defining illness (AI)
• HIV-associated nephropathy (HIVAN) (AII)
• HIV/hepatitis B virus (HBV) coinfection (AII)

• Effective ART also has been shown to prevent transmission of HIV from an infected individual to a sexual partner. Therefore, ART should be offered to patients who are at risk of transmitting HIV to sexual partners (AI[heterosexuals] or AIII [other transmission risk groups]).

• Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.

HIV-Infected Women
This revised section includes an expanded discussion on the use of hormonal contraception in HIV-infected women. The discussion focuses on drug-drug interactions between combined oral contraceptives and ARV drugs as well as on recent data showing a possible association between hormonal contraceptive use and acquisition or transmission of HIV.

HIV/Hepatitis C Coinfection
Updates to this section focus on the newly approved HCV NS3/4A protease inhibitors (PIs) boceprevir and telaprevir, the known interactions between these drugs and ART, and interim results from current ongoing research in HIV/HCV coinfected patients. The updated section includes preliminary recommendations on coadministration of the HCV NS3/4A drugs and ART.

Mycobacterium Tuberculosis Disease with HIV Coinfection
This update provides recommendations for timing of initiation of ART in HIV-infected patients who have been diagnosed with tuberculosis (TB) and are not receiving ART. The recommendations are based on results from randomized controlled trials showing survival benefits (1) when ART was initiated during rather than after TB treatment and (2) when ART was started within 2 weeks of TB treatment in patients with pretreatment CD4 count <50 cells/mm³. The updated section provides more in-depth discussions on the evidence and rationale supporting the recommendations.

The Panel’s recommendations are as follows:

•  For patients with CD4 counts <50 cells/mm³, ART should be initiated within 2 weeks of starting TB treatment (AI).
•  For patients with CD4 counts >50 cells/mm³ with clinical disease of major severity as indicated by clinical evaluation (including low Karnofsky score, low body mass index [BMI], low hemoglobin, low albumin, organ system dysfunction, or extent of disease), the Panel recommends initiation of ART within 2 to 4 weeks of starting TB treatment (BI for CD4 count 50–200 cells/mm³ and BIII for CD4 count >200 cells/mm³).
•  For other patients with CD4 counts >50 cells/mm3, ART can be delayed beyond 2 to 4 weeks but should be initiated by 8 to 12 weeks of TB therapy (AI for CD4 count 50–500 cells/mm3; BIII for CD4 count >500 cells/mm3).

Drug Interaction Tables (Tables 14–16b)
These tables are updated with recent data on pharmacokinetic (PK) interactions between ARV drugs and other drugs commonly prescribed for HIV-infected patients and the Panel’s recommendations on coadministration of these drugs. The key updates include:

• Change in recommendation on dosing of rifabutin with HIV PIs
• New recommendation to not use HIV PIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) with rifapentine
• Addition of information on interactions of boceprevir and telaprevir with different ARV drugs and related recommendations
• Update of interactions between different ritonavir-boosted PI and HMG-CoA reductase inhibitors.

Prevention of Secondary HIV Transmission
This section is updated to discuss the role of effective ART in preventing HIV transmission. The updated section also indicates evidence-based interventions available to assist providers with HIV risk behavior identification and counseling.

Additional Updates

Minor revisions have also been made to the following sections:

• Treatment Goals
• What to Start: Initial Combination Regimens for the Antiretroviral-Naive Patient (new information regarding adverse effects of raltegravir)
• HIV and Illicit Drug Users (new drug interaction added to Table 11 included in the section)
• Adherence to Antiretroviral Therapy
• Adverse Effects of Antiretroviral Agents (and accompanying Table 13)
• Drug Characteristics Tables (Appendix B)

By Tim Horn

Published on March 23, 2o12 on AIDSMEDS

Although hepatitis C virus (HCV) is a common and serious coinfection among people living with HIV, it often goes undiagnosed, even in a major U.S. city with multiple HIV care providers and a clinic dedicated to caring for people with both infections. This is the finding of a Miami cohort study reported Tuesday, March 6, at the 19th Conference on Retroviruses and Opportunistic Infections in Seattle.

Conducted by Khaled Deeb, MD, of the University of Miami’s Miller School of Medicine and his colleagues, the analysis presented in Seattle involved a medical chart review of 14,900 people living with HIV, who were in care for more than a year during the period between 2000 and 2011.

Click HERE to read the full article at AIDSMEDS

Click HERE to view the Cohort Study

This articel is courtesy of AIDSMEDS

  By Oriol R. Gutierrez Jr.

Published March 27, 2012 on POZ Blogs

The 10th annual LGBT Health Awareness Week runs from March 26 to 30. The National Coalition for LGBT Health organizes the event, which is a call to action to recognize health and wellness as an essential part of the LGBT social justice movement.

“Come Out for Health” is this year’s theme. The goal is to advance four core LGBT health principles: consumer empowerment, culturally competent services, engaged communities and inclusive policymaking.

Click HERE to read the full article on POZ Blogs

Click HERE to read more about “Come Out for Health” on The National Coalition for LGBT Health’s website.

This article is courtesy of POZ Blogs

Treatment of Anal Intraepithelial Neoplasia in HIV⁺ MSM: A Triple-arm Randomized Clinical Trial of Imiquimod, Topical 5-Fluoruracil, and Electrocautery

Olivier Richel, H De Vries, C Van Noesel, M Dijkgraaf, and J Prins; Academic Med Ctr, Amsterdam, The Netherlands

Background:  Anal cancer is an increasing problem among HIV⁺ men-who-have-sex-with-men (MSM). Screening for its precursor lesion, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimal and have not been compared in a prospective trial. In this randomized clinical trial we compared efficacy and side effects of imiquimod, topical 5-fluoruracil (5-FU), and electrocautery for the treatment of AIN.

Methods:  We randomized 148 HIV⁺ MSM with histologically confirmed AIN among 16 weeks of imiquimod (3 times a week), 5-FU (twice a week), and monthly electrocautery for 4 months. Participants were evaluated by high-resolution anoscopy with biopsies 4 weeks and 6 months after treatment. Response rates were compared by c² analysis.

Results:  Of all patients, 57% had high-grade (HG) AIN. In an intent-to-treat analysis, imiquimod showed a response rate of 39% (95%CI 27 to 52), 5-FU of 29% (95%CI 18 to 43), and electrocautery of 48% (95%CI 34 to 62). Complete response was seen in 26% (95%CI 16 to 39), 17% (95%CI 8 to 30), and 41% (95%CI 28 to 56), respectively (p = 0.03), of which 25%, 57%, and 17% recurred 6 months after treatment. In a multivariate logistic regression, HGAIN, peri-anal AIN and high plasma CD4 cell count were significantly associated with response to treatment, with odds ratios of 3.5 (p = 0.003), 31.9 (p = 0.003), and 1.003 (per cell/µL; p = 0.002), respectively. Severe side effects were seen in 43% (imiquimod), 27% (5-FU), and 18% (ECA) (p = 0.02).

Conclusions: This study showed that regarding both efficacy and side effects electrocautery is superior to imiquimod and 5-FU in treatment of AIN, but recurrence rates are substantial.

____________________________________________________________________________________________________________________________________________________

An Article by Tim Horn at AIDSmeds.com

When it comes to treating precancerous anal lesions, electrocauterization is both more effective and, somewhat surprisingly, better tolerated than repeated topical applications of either Aldara (imiquimod) or Efudex (fluorouracil), according to data presented Thursday, March 8, at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.  Lead presenter Olivier Richel, MD, of the Academic Medical Center in Amsterdam noted, however, recurrence rates were high with all treatments tested in the study.

As explained by Richel, between 50 and 80 percent of HIV-positive men who have sex with men (MSM) will experience anal lesions—anal intraepithelial neoplasia (AIN)—caused by human papillomavirus (HPV) and that up to 50 percent will develop high-grade AIN, or HGAIN. HGAIN, cause by oncogenic strains of HPV, are precancerous lesions, with approximately 15 percent of HIV-positive MSM developing anal cancer within five years of developing high-grade lesions.

Numerous questions abound regarding the diagnosis and treatment of AIN. For example, it’s still not clear if aggressive screening for anal lesions has a profound effect on anal cancer rates, at least not to the extent that regular Pap smears have helped reduce cervical cancer rates among women. It is also unclear whether HIV-positive men and women should be screened for AIN using Pap smears or if more expensive and invasive direct visualization—high-resolution anoscopy, for example—should be the preferred first-line screening method.

As for treatment, Richel noted that numerous options exist. One option is cauterization—an outpatient procedure in which affected anal tissue is burned and destroyed. Cauterization, using either electric or infrared technology, is approximately 50 to 70 percent effective but ais associated with high recurrence rates. Aldara, when applied to tissue inside the anus, was found to be partially or completely effective in up to 29 percent of patients in a small study reported in 2010. Efudex was partially or completely effective in up to 39 percent of AIN patients in a small study reported in 2011.

Richel and his colleagues set out to compare these three options in a study involving 148 HIV-positive MSM with biopsy confirmed low-grade or high-grade AIN. The men averaged 47 years of age and had been diagnosed with HIV seven to 10 years prior. More than 80 percent were on an antiretroviral regimen upon entering the study and more than three-quarters had undetectable viral loads. Average CD4 cell counts were between 535 and 590.

Between 54 and 60 percent of the men had HGAIN and roughly 95 percent had evidence of AIN lesions inside their anuses.

Forty-six men were randomized to receive electrocauterization once a month for four months.  Among the 54 men allotted to the Aldara group, the cream was applied three times a week for 16 weeks. The 48 men in the Efudex group received topical treatment twice a week for 16 weeks.

Thirty six, 45 and 43 men, respectively, successfully completed the study as planned. Three men in the electrocauterization group, compared with 5 men in the Aldara group and 2 men in the Efudex group, discontinued treatment in the study because of side effects.

In the strict intent-to-treat analysis—which included all people randomized in the study, regardless of whether or not they completed their treatment course and follow-up appointments—electrocauterization proved most effective, with 41 percent achieving a complete response and 7 percent achieving a partial response. Seventeen percent, however, saw AIN recur within six months after treatment.

In the Aldara group, complete responses were seen in 26 percent and partial responses were documented in 13 percent.  Twenty-five percent of the partial or complete responders experienced AIN recurrence within six months.

As for those receiving Efudex, the complete response rate was 17 percent and the partial response rate was 13 percent. Fifty-seven percent experienced disease recurrence within six months.

As for side effects in the electrocauterization group, 60 percent experienced pain and 69 percent had bleeding, though Richel noted that these problems only lasted a few days following the procedure. In the Aldara and Efudex groups, side effects lasted for weeks, and included pain (60 to 67 percent), bleeding (30 to 40 percent), sudden bowel movement urges (Efudex; 26 percent), flatulence (Efudex; 15 percent), flu-like symptoms (Aldara; 13 percent) and fatigue (Aldara; 13 percent).

Richel also noted that severe side effects were more common in the Aldara group (43 percent) and Efudex group (27 percent) compared with the electrocauterization group (18 percent).

“This study showed that regarding both efficacy and side effects electrocautery is superior to [Aldara] and [Efudex] in treatment of AIN, but recurrence rates are substantial,” Richel and his colleagues concluded.

By Regina McEnery

Earvin “Magic” Johnson, the Los Angeles Lakers basketball star whose megawatt smile was about as famous as the dazzling moves that inspired his nickname, shocked the sports world on Nov. 7, 1991, when he announced that he had contracted HIV and would retire that day from the Lakers.

In a 90-minute documentary, entitled “The Announcement,” narrated by Johnson and produced by ESPN Films for the network’s entertainment television channels, the basketball legend recounts the tense private moments leading up to his explosive disclosure, describing, among other things, his anguish at the thought that he may have infected his wife, Cookie, and their unborn child. It turned out he had not. Still, Cookie was opposed to his making a public announcement. This was not surprising. The nation, and certainly the world of professional sports, hadn’t quite come to terms with the HIV epidemic.

But the diagnosis was not a death sentence, as many at the time assumed it would be. Thanks to a new class of HIV drugs called protease inhibitors and the development of highly active antiretroviral therapy (HAART), Johnson has lived a relatively healthy life with the virus for more than 20 years. He has in that time become an inspiring advocate for the treatment and prevention of HIV infection, working to remove the stigma associated with HIV, which today infects more than 33 million people worldwide. The documentary is as much about how Johnson has lived with his diagnosis as it is about the impact of his announcement, which shocked his friends and fans and left many in tears. The film first aired on March 11 and is scheduled to be shown through April 14.

A second documentary, “How to Survive a Plague,” by journalist and first-time director Donald France, examines how the activist group, AIDS Coalition to Unleash Power (ACT UP)—and the Treatment Action Group, an offshoot of ACT UP—drew attention to the HIV epidemic. Scores of gay activists, terrified by the specter of AIDS in the 1980s and 1990s, fought to save the sick and dying using a range of aggressive tactics that included not only protests at Capitol Hill but such antics as infiltrating the set of a nightly news broadcast and marching outside the home of Anthony Fauci, the director of the US Institute for Allergy and Infectious Diseases, which was funding many of the AIDS drug trials.

Fifteen years after the first cases of AIDS were detected, HAART was rescuing AIDS patients from the brink of death and transforming the US epidemic. ACT UP is credited with putting AIDS on the national health agenda and so speeding these developments. Two special screenings of the documentary were held in New York City in March—on the 25th anniversary of the very first ACT UP demonstration. It is due to open in theatres this fall.

This article is from VAX: The Bulletin on AIDS Vaccine Research.  Download the full March bulletin here:[Download not found]

What are some of the challenges in developing viral vector-based vaccine candidates and how are scientists trying to overcome these challenges?

Many of the current AIDS vaccine candidates that are being tested in clinical trials utilize viral vectors to shuttle HIV fragments into the body that can stimulate an immune response (see VAXSep. 2004 Primer on Understanding Viral Vectors). Some of the viral vector-based candidates are being tested in prime-boost combinations with other approaches (see Global News, this issue). Several different viruses have been used to develop vectors for HIV vaccine candidates, including adenovirus, a common cold virus, and pox viruses, such as modified vaccinia Ankara virus and canarypox, among others.

The viruses used as viral vectors are attenuated so that they cannot cause disease. They are also manipulated, so that in addition to containing their own genes they can carry HIV genes, referred to as antigens, which cannot cause an HIV infection.

The HIV genes that are placed into the viral vector are referred to as the vaccine insert. Once the vaccine candidate is injected into the body, HIV’s genetic material is taken up by cells and converted into protein that hopefully will trigger the immune system to respond to HIV. This sounds simple enough, but viral vector-based vaccine candidates present some unique design and manufacturing challenges. Because the manufacturing process is so complicated, additional effort is required to avoid delays in the clinical testing of viral vector-based vaccine candidates.

Not harmonious

To develop viral vector-based candidates, scientists first need to design and generate the vector with the HIV insert in cells that can support virus growth. The virus vector is then amplified multiple times to produce hundreds of virus particles carrying the HIV genes, which are then subjected to extensive testing.

One of the major challenges in making viral vector-based vaccine candidates comes down to chemistry, or rather, a lack of chemistry between the vector and the insert. Sometimes the vector and the insert are simply incompatible. For instance, if the length of the insert is too long or its configuration is not suitable to the viral vector, the vector may simply reject the insert. In other cases, the virus acting as the vector may introduce mutations into the HIV genes that may prevent production of the complete protein once inside the body. These changes can ultimately impact the generation of a good immune response following vaccination. Sometimes the vector can even clip the insert, rendering it completely useless.

In some cases the vector will tolerate the insert for a while, at other times it will reject it outright. In either case it represents a setback in the production of the vaccine candidate. It is therefore important to analyze the stability of these vectors during the early stages of vaccine development. This is accomplished by subjecting these vector particles to a series of stress tests that assess whether they are stable enough to be tested in a clinical trial. The stress test evaluates the ability of these vectors to express the HIV proteins in cells and in small animals. Even after this vetting process is complete, the vector may still reject the inserts, so it is not uncommon for researchers to have to repeat this cycle several times prior to obtaining a stable vector that expresses the HIV protein and can be advanced into clinical trials.

Mosaic antigens

Most of the inserts used in current viral vector vaccine candidates contain HIV gene sequences from a single virus found in a certain region of the world, or a consensus sequence generated from different viruses that are circulating in that region of the world. Because HIV replicates so rapidly, there is tremendous variation among viruses circulating in a population, and even within a single infected individual. To address this, scientists are also attempting to design HIV inserts known as mosaic antigens that are designed to address the overwhelming diversity of HIV (see VAXMarch 2009 Primer on Understanding How Inserts for Vaccine Candidates are Designed). Mosaic antigens are based on optimized genetic sequences of the many circulating strains of HIV globally and are meant to induce immune responses to a broad range of circulating strains.

To make mosaic antigens, scientists must stitch together different genetic sequences from multiple strains. These gene sequences do not exist in nature but rather are computer-generated. This makes designing and developing novel viral vector-based candidates that can carry these mosaic antigens even more challenging. Before advancing them into clinical trials, researchers will have to ensure that viral vectors carrying mosaic antigens can be obtained and manufactured at large scale, while maintaining their stability. Researchers are hoping to begin clinical trials with these vaccine candidates containing mosaic antigens soon.

This article is from VAX: The Bulletin on AIDS Vaccine Research.  Download the full March bulletin here: [Download not found]

One Patient’s Story Illuminates a Whole
Situation: Information and Commentary

The patient decided to quit his AIDS drugs.

Click HERE to read the full article about this study at http://aidspolicyproject.blogspot.com/

Article courtesy of AIDS Policy Project

By Sruti Srivatsan

Results from a United Kingdom-based study suggest that fewer than one in
1,000 HIV-positive individuals can control HIV/AIDS disease progression
naturally without antiretroviral therapy.

The authors of the study, however, cautioned that this number could be an
underestimation. They noted that some natural HIV controllers, people who can
control HIV without antiretrovirals, may not have gotten themselves checked for
HIV due to the absence of symptoms.

Results also showed that among slow HIV progressors, people whose HIV
progresses to AIDS but more slowly than usual, those with lower amounts of HIV
in the blood were more likely to show minimal immune system loss over time. In
addition, in most cases, controllers and non-progressors did eventually progress
to AIDS.

“Studying these patients could form the basis for the design of novel
strategies to prevent immune deterioration in HIV-infected individuals,” said
Dr. Nesrina Imami, a medical statistician in Immunology at Imperial College,
London and senior author of the study, in correspondence with The AIDS Beacon.
She added that understanding how the immune systems in these individuals control
HIV could lead to therapeutic options that target the virus.

Click HERE to read the full article about this study on http://www.aidsbeacon.com/

For more information, please refer to the study in PLoS One.

Article courtesy of The AIDS Beacon