In the Age of Antiretrovirals for HIV, New Secondary Tumors Have Emerged

MedicalResearch.com Interview with:

Fahad Mukhtar MD MPH Department of Epidemiology and Biostatistics College of Public Health University of South Florida, Tampa

Dr. Mukhtar

Fahad Mukhtar MD MPH
Department of Epidemiology and Biostatistics
College of Public Health
University of South Florida, Tampa

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Studies done in the 80s and 90s showed that patients with Kaposi sarcoma may be at risk of having secondary tumors. As a result of changes that have taken place in the demographics of patients affected with HIV/AIDS as well as Kaposi’s sarcoma, we hypothesized that tumors that follow Kaposi sarcoma might have also changed. We analyzed the incidence of second tumors developing after Kaposi sarcoma using the Surveillance Epidemiology and End Result (SEER) data.

Our result indicated that the incidence of secondary tumors following Kaposi sarcoma have decreased after the emergence of antiretroviral therapy. However, we observed a significantly higher than expected number of cancer of the anus, liver, tongue, penis lymphomas, and acute lymphocytic leukemia developing in patients with Kaposi sarcoma in the era of antiretroviral therapy.

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Single Measurement May Underestimate HIV Viral Suppression

MedicalResearch.com Interview with:
Dr. Nicole Crepaz PhD
Behavioral Scientist
Division of HIV/AIDS Prevention
CDC

MedicalResearch.com: What is the background for this study?

Response: The most common measure of viral suppression in clinical and surveillance studies is the most recent viral load in past 12 months. This single-value measure does not capture the viral load dynamics over time. We examined durable viral suppression, never virally suppressed, and cumulative HIV burden (measured in the viremia copy-year) to help us better understand viral suppression and transmission risk potential.

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Why Is HIV More Common in African American Women?

MedicalResearch.com Interview with:

Dr. Tiffany Aholou Behavioral Scientist Division of HIV/AIDS Prevention CDC

Dr. Aholou

Dr. Tiffany Aholou
Behavioral Scientist
Division of HIV/AIDS Prevention
CDC

MedicalResearch.com: What is the background for this study?

Response: Women accounted for 24% of people living with HIV in the United States at the end of 2013 and 19% of HIV diagnoses in 2014. Of these diagnoses, 78% were among black women and Latinas. HIV diagnoses among women are overwhelmingly attributed to heterosexual contact with a person known to have, or to be at high risk for, HIV infection. Of note, new HIV diagnoses among US women declined 40% over a 10 year period (2005-2014), yet we continue to see significant racial/ethnic disparities due largely to a complex web of demographic, individual, social and contextual factors with the environment that enables HIV risk behaviors to occur.

While the decline in new HIV diagnoses among US women is noteworthy, in our review of the literature, we found research studies that specifically focus on women and HIV from a domestic perspective were scarce. To fill this gap and sharpen our understanding about sexual behaviors that are associated with heterosexual transmission of HIV, this study used data from three cycles of the National Survey of Family Growth (2006-2008, 2008-2010, and 2011-2013) to examine HIV-related sexual risk and protective behaviors – concurrent sex partnerships, non-monogamous sex partners, and condom use at either last vaginal sex  or anal sex  – among sexually active women aged 18-44 years by race/ethnicity and over time.

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Once-Daily, Fixed-Dose Combination Tablet Containing Doravirine Achieved HIV-1 Viral Suppression

MedicalResearch.com Interview with:

Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA 

Dr. Squires

Dr. Kathleen Squires MD
Professor and Director of Infectious Diseases
Thomas Jefferson University
Philadelphia, PA 

MedicalResearch.com: What is the background for this study? What are the main findings?

  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).

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ONCEMRK Study: Once Daily Raltegravir In Combination With Other Antivirals Effective For Some HIV Patients

MedicalResearch.com Interview with:

Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator

Dr. Pedro Cah

Dr. Pedro Cahn
Chief of the infectious disease unit at Juan A. Fernandez Hospital
Buenos Aires, Argentina, and
ONCEMRK lead study investigator

MedicalResearch.com: What is the background for this study? What are the main findings?

The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.

  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).

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Higher HIV Viral Loads Linked to Increased Squamous Cell Cancers of Skin

MedicalResearch.com Interview with:

Maryam M. Asgari, MD, MPH Department of Dermatology, Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland

Dr. Asgari

Maryam M. Asgari, MD, MPH
Department of Dermatology
Massachusetts General Hospital,
Department of Population Medicine
Harvard Medical School, Boston, Massachusetts
Division of Research, Kaiser Permanente
Northern California, Oakland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised.

We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan.

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Opioid Agonist Therapy Found Cost Effective In Preventing HIV in People Who Inject Drugs

MedicalResearch.com Interview with:

Cora Bernard, MS, PhD candidate Pre-doctoral Student in Management Science and Enginnering Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research Stanford Health Policy

Cora Bernard

Cora Bernard, MS, PhD candidate
Pre-doctoral Student in Management Science and Enginnering
Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research
Stanford Health Policy

MedicalResearch.com: What is the background for this study?

Response: The US opioid epidemic is leading to an increase in the US drug-injecting population, which also increases the risks of HIV transmission. It is critical to public health that the US invests in a coherent and cost-effective suite of HIV prevention programs. In our model-based analysis, we considered programs that have the potential both to prevent HIV and to improve long-term health outcomes for people who inject drugs. Specifically, we evaluated opioid agonist therapy, which reduces the frequency of injection; needle and syringe exchange programs, which reduce the frequency of injecting equipment sharing; enhanced HIV screening and antiretroviral therapy programs, which virally suppress individuals and decrease downstream transmission; and oral HIV pre-exposure prophylaxis (PrEP), which is taken by an uninfected individual and lowers the risk of infection.

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Injectable Cabotegravir Holds Promise as HIV Prevention Stategy

MedicalResearch.com Interview with:

Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University

Dr. Markowitz

Martin Markowitz MD
Clinical Director and Staff Investigator
Aaron Diamond AIDS Research Center
Aaron Diamond Professor at The Rockefeller University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model.

These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed.

The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study.

Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals.

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Toward A Real Cure for HIV: Abivax’s ABX464 Reduced HIV Reservoir in Phase 2 Trial

MedicalResearch.com Interview with:
AbivaxJean-Marc Steens, M.D.

Chief Medical Officer of Abivax

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Antiretroviral therapy (ART) has had an enormous impact on the HIV pandemic since its introduction almost 20 years ago. Most patients treated with ART achieve undetectable or near undetectable plasma levels of the virus. This means that although HIV is controlled, it is not completely eliminated. The virus remains in the body, usually contained in dormant cells (known as the HIV reservoir) that are widely distributed, including to the central nervous system, the gut mucosa, the lymph nodes and other sites. If ART is stopped, the virus rebounds. The goal of any curative therapy would be to eliminate the virus or ensure there is sustained remission in the absence of ART, which until now have been unsuccessful.

Abivax’s Phase 2 clinical study with ABX464 demonstrated, for the first time, a reduction in HIV reservoirs in chronically infected HIV patients as measured by total HIV DNA detected in peripheral blood mononuclear cells (PBMCs).

In the ABX464-004 trial, 30 HIV patients received either ABX464 or matching placebo in addition to their current antiretroviral treatment over 28 days. The viral load at the start of the study was well controlled with boosted darunavir. After the 28-day treatment period, all treatments were interrupted until viral load rebound. Baseline and day 28 blood samples were taken to assess the potential effect of ABX464 on the HIV reservoir in PBMCs.

Safety was the primary endpoint in the trial. ABX464 was well tolerated, with no severe adverse events in the treatment group. Amongst evaluable patients (4 placebo and 14 ABX464-treated patients), a reduction in viral DNA copies/mPBMCs was observed in 7/14 treated patients (mean change of -40%, ranging from -27% to -67%) and no responders were observed in the placebo group. Responders were defined as patients who had a decrease greater than 25% in total HIV DNA in PBMCs and a reduction of at least 50 copies.

Total HIV DNA in PBMC has been validated as a widely accepted biomarker for measuring the HIV reservoir. Specifically, in untreated patients, total HIV DNA load influences the course of the infection and is therefore clinically relevant. In addition, a correlation exists between the pool of HIV-1 DNA and the replication-competent reservoir.

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Many Teens Use Less Effective Contraceptives After Pregnancy

MedicalResearch.com Interview with:
Deborah L. Dee, PhD
Division of Reproductive Health
National Center for Chronic Disease Prevention and Health Promotion
CDC

MedicalResearch.com: What is the background for this study?

Response: Although the national teen birth rate has dropped to a historic low (22.3 births per 1,000 females aged 15-19 years in 2015), many teens continue to have repeat births. Because repeat teen births are more likely than first teen births to be preterm and low birth weight, and giving birth more than once as a teenager can significantly limit a mother’s ability to attend school and obtain work experience, it’s important to assess patterns in repeat teen births and better understand contraceptive use within this population. Continue reading