The 2011 Conference on Retroviruses and Opportunistic Infections (CROI) was held in Boston from February 27 through March 2. Each year, CROI is one of the major venues for reporting advances in the prevention and treatment of HIV, opportunistic infections, and other health conditions affecting persons living with HIV and AIDS. Although CROI is typically held in the United States or Canada, its scope is international: Research teams from around the world present their findings, which include studies conducted both in the wealthier industrialized nations and in developing nations. Approximately 4,000 scientists and physicians from around the world attended this year’s CROI, which featured hundreds of research presentations.
Since it is nearly impossible to report on the full range of research presented at CROI, I’m providing narrative summaries of two major topics at the conference – “HIV Prevention Technologies” and “HIV and Hepatitis C Coinfection” – followed by a series of brief research capsules in a section called “Other Headlines from CROI.”
In writing this summary, I have drawn heavily on articles written by trusted health and science reporters, recordings of CROI sessions, and online interviews with prominent HIV researchers, public officials, and advocates. These highlights are grouped according to the Conference’s main themes and topic areas. For people interested in learning more about particular research, I have provided links to articles, abstracts, and presentations throughout this summary, together with additional resources at the end of this document.
HIV Prevention Technologies: ARV Pills and Gels
One major focus of the 2011 CROI was HIV prevention technologies – in particular, studies evaluating the use of antiretroviral drugs (ARVs) for the prevention of HIV infection. Last summer, researchers in the CAPRISA 004 reported that a vaginal microbicide gel containing the antiretroviral drug (ARV) tenofovir (brand name Viread) reduced HIV transmission by 39% in a group of about 900 African women. The CAPRISA trial was the first strikingly positive result seen after years of microbicide research.
Then in the fall, an international research team reported the results of a study called iPrEx, which showed that taking a daily ARV pill – combined with regular HIV testing, condom use, and other proven prevention methods – reduced the rates of HIV transmission by 44% among nearly 2,500 men who have sex with men (MSM) and transgender women at 11 sites in 6 countries. The pill used in the iPrEx study combines the drugs tenofovir and emtricitabine, and is better known by its brand name, Truvada.
At CROI, several speakers presented additional findings on ARV-based prevention technologies. The iPrEx researchers reported that, with longer follow-up, their Truvada-based PrEP has continued to provide prevention against HIV infection in persons who take the ARV pill consistently. They also noted that adherence to the once-a-day regimen has varied substantially among the different study sites. In particular, participants from the U.S. sites had nearly perfect adherence, while those at other sites had adherence of about 50%. Interestingly, the 76% reported adherence rate seen among persons who would otherwise have the highest risk of becoming infected – those having unprotected receptive anal intercourse – was substantially higher than among persons at lower risk. The iPrEx data also showed that, compared to those taking the placebo (dummy pill), persons taking Truvada had a small decrease in bone density – a side effect that is also seen among HIV-infected persons who take Truvada for HIV treatment. It is worth noting, however, that the decrease in bone density seen in persons taking Truvada as PrEP was substantially less than that seen in HIV-infected persons taking Truvada as ARV treatment. For more information, see 01 , 02 , 03 , 04 , and 05 .
Another study looked at safety and acceptability of using a vaginal tenofovir gel, oral PrEP, or a combination of the two in a group of over 140 women in Africa and the U.S. The microbicide and PrEP pills were generally well tolerated, with nausea reported in about 14% of women taking the pill and 3% of those using the gel. The women had the highest blood levels of the ARV tenofovir when they took the PrEP pill, but had the highest vaginal tenofovir levels when they used the vaginal gel. A majority of study participants said they would willingly use either the PrEP pill or the microbicide gel for HIV prevention. However, while the American women generally preferred the pill over the gel, the African women showed no preference. For more information, see 06 , 07 , and 08 .
An interesting study involving monkeys showed that a microbicide gel containing another ARV – the integrase inhibitor raltegravir – appeared to provide protection against HIV infection when applied 3 hours after the monkeys were exposed to a combination monkey/human HIV virus. If future studies indicate that ARV-based gels can safely and effectively prevent HIV infection after exposure to the virus, then these microbicides might provide an alternative to pill-based post-exposure prophylaxis (PEP). PEP is an approach that involves taking an ARV regimen for a limited period of time to prevent infection after a known or potential exposure to HIV. For more information, see 12 and 13 .
HIV and Hepatitis C Coinfection
About one-third of all HIV-infected persons in the U.S. – including the majority of those who became HIV-infected through injection drug use – are also coinfected with hepatitis C virus (HCV). A Swiss study reported at CROI found that liver disease far outweighs all other causes of death among people coinfected with HIV and HCV. Many coinfected persons have received HCV treatment to reduce their risk of liver complications or slow the progression of existing disease. When successful, HCV treatment can have the added benefit of reducing the progression of HIV disease and the risk of non-liver-related deaths.
At present, the treatment options for HCV are very limited. The only approved treatment combines a weekly injection of a drug called pegylated interferon plus a twice-daily dose of an antiviral pill called ribavirin. HCV-infected persons are typically treated for up to a year with the goal of completely clearing the hepatitis virus from their bodies. When a person remains free of detectable HCV for at least 6 months after they have finished their treatment, they are said to have a “sustained virologic response” (SVR) and are considered cured of their hepatitis infection.
Unfortunately, the current HCV cure rates for interferon-ribavirin treatment are relatively low for persons coinfected with HCV and HIV. For people coinfected with the most common type of HCV (genotype 1), the cure rate is only about 20% (one in five). Cure rates are higher – 50% to 70% – for those infected with less common types of HCV (genotypes 2 and 3). In addition, many people who take HCV drugs suffer from side effects that can include fatigue, achiness, depression, irritability, and low red or white blood cell counts.
The good news for people with HCV coinfection is that some promising new antiviral drugs are under development. Two of these drugs – telaprevir and bocepravir – have been studied extensively in clinical trials and may be approved this year. Studies of persons infected with HCV alone (not HIV) have shown that, when boceprevir or telaprevir are combined with the current interferon-ribavirin combination treatment, they may substantially increase HCV cure rates and may also decrease the length of time needed for a cure.
At CROI, researchers reported on studies of telaprevir plus interferon and ribarivin in HIV-HCV coinfected persons. They found that, after 4 weeks of this treatment, 70% had an undetectable HCV viral load. This is a very promising result, since most people who have such a rapid positive response to HCV treatment later achieve the sustained virologic response associated with a cure for HCV.
Other studies reported at CROI included news on drug interactions between new HCV drugs and the ARVs used for HIV treatment. Both boceprevir and telaprevir were found to interact with some HIV ARVs. For some drugs, the interactions were quite small, while for others, they were more substantial. As these new HCV treatments become available, it will be important to determine whether, and to what extent, it may be necessary to adjust the dosage of these new HCV drugs or HIV antivirals in persons being treated for both conditions.
In the midst of this generally good news about HIV-HCV coinfection was a sobering report showing a high rate of bone fractures among coinfected persons. In this study, researchers reviewed the medical records of a group of about 775,000 Medicaid patients in five states, comparing the rates of hip and spine fractures among persons coinfected with HIV and HCV, those infected with either HIV or HCV alone, and those not infected with either virus. Although both coinfected men and women had higher bone fracture rates than other groups, the greatest increases were seen among coinfected women. Among these women, the hip fracture rate was over twice as high as that seen in women who were not infected with either virus, and 77% higher than the rate seen in women infected with HIV alone. The risk of spinal fractures was also 65% higher among coinfected women than among women who were not infected with either virus or infected only with HIV.
Other Headlines from CROI
New Dosing or Formulations of Existing Drugs
New Version of Tenofovir Is Much More Potent and Hopefully Safer (from aidsmeds). The drug tenofovir is one of the mainstays of HIV treatment, since it is a common component of many ARV regimens. (Tenofovir is often better known by its brand name, Viread, and the combination pills – Truvada and Atripla – that contain it.) Unfortunately, some people who take tenofovir experience kidney problems and are unable to continue taking the drug. At CROI, researchers reported on a new formulation of tenofovir called GS-7340 that increases drug levels in the CD4 cells targeted by HIV without raising tenofovir levels in the blood or kidneys. This finding raises the hope that GS-7340 will be less likely to cause kidney problems than the current formulation of tenofovir. See also: 22 .
New and Experimental HIV Treatments
CCR5 Gene Therapy Shows HIV Treatment Potential (from aidsmeds.com). Researchers from Quest Clinical Research described their use of an experimental gene therapy called zinc finger technology to produce CD4 T-cells that are resistant to being infected by HIV. These genetically modified cells lack the CCR5 co-receptor that HIV often uses to infect cells. Gene therapy to make cells immune to HIV infection is still in the early stages of development. However, this research bears close watching, because it might ultimately yield effective ways to protect the immune system – or even eradicate the virus. See also: 26 , 27 , 28 , and 29 .
Twice-Daily Dolutegravir (”572″) Holds Up in Heavily Raltegravir-Resistant Patients, Phase 2B Study Finds (from The Body Pro). ARVs known as integrase inhibitors disrupt the life cycle of HIV by preventing the virus from integrating its genetic material into the DNA of infected cells. At present, only one integrase inhibitor, raltegravir (brand name Isentress), has been approved to treat HIV infection. GlaxoSmithKline (GSK) has been testing a new integrase inhibitor called dolutegravir (also called S/GSK1349572 or simply “572″). At CROI, researchers reported that dolutegravir can suppress HIV growth in persons with virus that is highly resistant to raltegravir. In tests of different dosing schedules, the research team found that twice-daily doing of the dolutegravir is more effective than once-daily dosing. See also: 30 and 31 .
Could MicroRNA Be the Next Great Frontier in HIV/AIDS Treatment – and Prevention? According to this article from The Body Pro, “A (relatively) recently discovered form of regulatory RNA dubbed microRNA (miRNA for short) has been found to play a critical role in some viral infections (particularly hepatitis C and Epstein-Barr virus), and there are tantalizing signs that our increasing understanding of miRNA may carve an exciting new niche in HIV care.” This article also has an embedded video interview with Duke University researcher Dr. Bryan Cullen who spoke at CROI about miRNA research and its potential application to HIV. See also: 32 .
Drug Resistance and Treatment Failure
Risk of Virologic Failure 40% Higher Among Blacks vs. Whites. (from aidsmeds.com). A key goal of ARV therapy is to shut down HIV replication and thereby reduce a person’s viral load to undetectable levels. Thanks to today’s potent ARV regimens, many people – especially in wealthier nations like the U.S. – have reached this goal. Sadly, all groups have not benefited equally from ARV treatment, according to researchers who have analyzed data from 5 major U.S. clinical trials of treatment-naive persons starting their first ARV regimens. They found that the rate of virological failure – failure of a regimen to maintain an undetectable viral load – was 40% higher among Blacks than Whites. The analysis identified several factors associated with treatment failure, including: higher pre-treatment viral loads, coinfection with hepatitis C virus, poor adherence, and lower education levels. Unfortunately, the clinical trials included in this study collected only limited information on socioeconomic factors, so it is unclear to what extent these factors contributed to the difference seen in treatment failure rates. See also: 37 and 38 .
After 2 Years, Drug Regimen Works Well Among Treatment-Experienced (from aidsmeds.com). When people develop ARV drug resistance while on treatment, it is important to have second- and third-line ARV regimens available that control HIV effectively. At CROI, researchers reported the results of a French study in which people with a high degree of HIV drug resistance were treated with three of the most recently approved drugs – boosted darunavir (Prezista), etravirine (Intelence), and raltegravir (Isentress). On this regimen, nearly 90% of these highly treatment-experienced patients maintained an undetectable after nearly 2 years of treatment. See also: 39 .
Does Using More ARVs Provide Better Control of HIV?
Additional HIV Prevention News
Viral Load and the Risk of Transmission
Treatment as Prevention
Coinfections and Complications of HIV Infection and Treatment
Managing Tuberculosis Coinfection
Immune Activation, Inflammation, and HIV
The Slow Decline: An Update on Neurological Complications Among People With HIV (from The Body Pro). See also: 48 , 49 , 50 , and 51 .
Bone Loss During HIV Treatment: A Possible Side Effect of CD4 Cell Recovery (from aidsmeds.com). See also: 52 and 53 .
Long-term HIV infection and poor inflammation control, not treatment, predicts risk of atherosclerosis (from aidsmap.com). See also: 54 , 55 , 56 , and 57 .
Abacavir and Heart Disease Risk
Cancer and HIV
Predicting Health and Survival in HIV
Decreased limb muscle and increased abdominal fat linked to higher mortality in people with HIV (from aidsmap.com). Changes in body composition related to HIV infection can also affect infected persons’ survival rates, according to new findings from the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study presented at CROI. FRAM researchers found that, compared to other HIV-infected persons, those with lower arm and leg muscle mass and higher amounts of deep belly fat had significantly higher death rates during a five-year follow-up period.
Also at the Conference, researchers from the Multicenter AIDS Cohort Study (MACS) reported that HIV-infected men over 50 are more likely to be frail than noninfected men the same age. The researchers described what they call a “frailty phenotype,” which involves having several symptoms including fatigue, slow walking speed, low grip strength, low physical activity, and unintended weight loss of 10 or more pounds in the previous year. People with this frailty phenotype are more prone to falls, disability, hospitalizations, and death than healthier persons the same age. Although the prevalence of frailty increases with age for all older men, it increases more rapidly among HIV-infected men. According to the study, 20% of the HIV-infected men age 60 to 69 had the frailty phenotype compared to just 10% of the uninfected men. See also: 67 , 68 , 69 , and 70 .
For More Information
If you who would like to learn more about the research findings from CROI, I recommend that you check out the following sites:
CROI 2011 Boston : This is the official website for the conference. Different sections on the site allow you to review the conference program; search the conference abstracts for particular topics, studies, or presenters; and view webcasts and download audio podcasts of specific presentations.
Several HIV/AIDS reporting services have also provided excellent CROI coverage. You can access their conference reports, articles, and videos from the following links: