Take a good look, my dear. It's an historic moment you can tell your grandchildren about.
-- Rhett Butler, Gone With the Wind
The 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) will be held next week in Atlanta, Ga., the land of Gone With the Wind and the home of the U.S. Centers for Disease Control and Prevention (CDC). Over the past decades, CROI has been the place to learn about new drugs to treat HIV and its myriad complications.
These decades have seen many significant advances in care: A once untreatable, usually fatal infection is now controllable with medications -- and, in developed countries, the opportunistic infections that gave the conference its name are uncommon. Indeed, the menu of the conference now reflects this good fortune: It has new focus areas on topics other than AIDS and opportunistic infection.
What to expect in this year's running? Here's my short list of to-watch studies and presentations (which will be updated with links as coverage of them becomes available):
Antiretrovirals: New and Experimental Drugs
You may have heard that the HIV drug pipeline is drying up. I don't think so.
- Updates on the recently approved single-tablet regimen elvitegravir/cobicistat/tenofovir/emtricitabine (Stribild), as well as the hotly anticipated and soon-to-be-approved integrase inhibitor dolutegravir -- a drug that was shown last summer to be superior to the long-held (and previously invincible) standard, efavirenz.
- Session on new approaches to drug delivery. Nanoparticles are all the rage. Last summer, we learned about a nanoparticle formulation of S/GSK1265744 that yielded therapeutic drug levels months after an intramuscular injection. In this session, expect much more about nanoparticles, including efavirenz nanoparticles and discussions about the regulatory pathway for long-acting drugs.
- Tenofovir prodrug (tenofovir alafenamide fumarate, TAF) data in comparison with tenofovir DF (when used alongside emtricitabine, elvitegravir and cobicistat) from a phase 3 clinical trial will be presented on March 5. TAF portends to be more potent and concentrated in target cells, but will the drug cause more or less renal toxicity?
- MK-1439, a new NNRTI, appears to have less central nervous system toxicity and is less filling (no dietary restriction). Early-phase clinical trial data will be presented.
- Twenty-four week data on cenicriviroc, a new CCR5 inhibitor, will be presented; the drug was pitted against efavirenz in treatment-naive adults (who also received tenofovir/emtricitabine).
- Full sessions will be dedicated to neurocognitive disease (which will also be highlighted in more than 70 poster presentations) and cardiovascular disease.
- I'm interested in learning more about the microbiome and virome in HIV disease pathogenesis.
- A session on HPV-associated malignancies may yield noteworthy new data.
The cure agenda took big steps in the past few years, from the initial and follow-up reports on Timothy Brown (aka the "Berlin patient") and subsequent reports of a functional cure in two patients following bone marrow transplant. An additional emerging theme was the use of histone deacetylase inhibitor-based strategies to stir resting cells. At CROI 2013, we will see:
- A provocative report on a functional HIV cure in an infant treated with very early antiretorviral therapy.
- A study on the HDAC medication vorinostat from Australia as a strategy for activation of latent HIV-infected cells.
- A plenary session on stem cell-based genetic therapies and the possible road to an HIV cure.
Biomedical interventions can prevent HIV. Period. But a major question remains: How do we engage the patient and provider communities in achieving an AIDS-free generation? CROI will hopefully explore this question with:
- A symposium on HIV prevention and the treatment cascade in the U.S.
- A look at the VOICE study on pre-exposure prophylaxis (PrEP) in women using oral tenofovir, oral tenofovir/emtricitabine or intravaginal tenofovir gel.
- Study data on a very, very long-acting nanoparticle formulation of S/GSK1265744, an investigational integrase inhibitor. Researchers are testing it for prevention of intrarectal challenge of SHIV in monkeys. Could this be an approach for a long-acting integrase inhibitor for PrEP?
- Research on whether a tenofovir intravaginal ring offers protection from SHIV vaginal challenge. A possible once-monthly discrete PrEP for women?
- A session on implementation and cost-effectiveness of male circumcision.
Hepatitis C (HCV) Treatment
The time has come for widespread treatment of HIV/HCV coinfection. But treatment with which agents and for how long? How to deal with nagging drug-drug interactions? CROI will explore these issues in depth with:
- A full symposium and a full late-breaker session on HCV treatment.
- Coinfection studies: TMC435-C212 (simeprevir) taken with peg-interferon and ribavirin in HIV/HCV-coinfected patients, as well as the use of telaprevir for acute HCV in HIV-infected people.
- Results of STARTVerso 4, a study of the HCV protease inhibitor faldaprevir (BI 201335) taken with peg-interferon and ribavirin, which claims high rates of early virological response.
- Results of ELECTRON, a study of the Gilead Sciences' NS5A nucleotide analog inhibitors sofosbuvir (formerly GS-7977) and ledipasivir (GS-5885), taken with ribavirin. Previously released information about this regimen -- which is interferon-free -- showed very promising viral suppression results; a regulatory filing for sofosbuvir is anticipated for later this year.
The Cascade: Improving Engagement in Care
Only 1 in 4 Americans living with HIV have achieved an undetectable viral load. Seems like the same is happening in other countries. What can we do about it? Hopefully some of these CROI presentations will help point a way forward.
- Sessions on epidemiology and engagement in care in the U.S. and Africa. There'll be a whole talk on age and racial disparities in per-coital (I've always wanted to type that) risk of HIV.
- Sessions on the cascade of care, including presentations focusing on men who have sex with men and on family planning.
- A session on adherence and retention in care in resource-limited settings.
- A CDC analysis of baseline HIV drug resistance testing revealed that about 30% of individuals still fail to receive this recommended test.
We've reached a tipping point in the history of the HIV/AIDS pandemic. A once-fatal infection is now largely controlled with effective, well-tolerated treatments, and access to life-saving treatment is improving (though a long way from adequate). New biomedical interventions to prevent HIV infection, treatment-as-prevention approaches and pre-exposure prophylaxis have greater than 90% effectiveness in adherent individuals. Meanwhile, new treatments for HCV may cure the majority of infected individuals, and emerging data demonstrate their effectiveness in HIV-infected patients as well.
People living with HIV who have access to -- and remain adherent to -- care may have normal life expectancy. But many, perhaps a majority, of people living with HIV fail to reach this goal. The medical community must now confront difficult issues of testing, entry to (and retention in) care and an evolving spectrum of non-AIDS, often non-communicable, diseases.
Last year, my revered friend Paul Sax, M.D., opined that the name of the conference should change along with the evolving spectrum of HIV illness. I think a fitting new name, like that of Atlanta's health beacon, might be "Conference on Long Life With Retroviruses, Hepatitis and Prevention."
Benjamin Young, M.D., Ph.D., is the chief medical officer of the International Association of Providers of AIDS Care (IAPAC), one of the world's largest organizations of HIV health care providers.
Copyright © 2013 Remedy Health Media, LLC. All rights reserved.
Comment by: Lucky M
(Johannesburg, South Africa)
Tue., Mar. 5, 2013 at 6:02 am EST
During pregnancy the placenta is jumping with retroviruses.
"Over half of human genome contains retroelements, including retrotransposons, retroviruses, and other elements. Human endogenous retroviruses (HERVs) comprise about 8% of human genome. The products of 2 of 16 identified genes of HERV-W seem to play a pivotal role in the placentation. These 2 genes are HERV-W env glycoprotein (syncytin-1) and HERV-FRD env glycoprotein (syncytin-2). It has been shown previously that syncytin-1 mediates cell-cell fusions of cytotrophoblasts into syncytiotrophoblasts. In addition, HERV-W env contains an immunosuppressive region that may prevent rejection of a semiallogenic fetus from the mother's immune system.
Role of HERV-W syncytin-1 in placentation and maintenance of human pregnancy. 2009
This is why our retroviruses like HERV-W which are involved in placental implantation and nervous system growth are also highest in babies and fetuses, the retroviruses are involved in fusing cells into organs etc.
The danger in using antiretrovirals on children is they poison as well as prevent cell fusion by retroviruses necessary for the nervous system to develop.
"Deep sequencing of brain transcriptomes disclosed the env transcripts to be the most abundant HERV-W transcripts, showing