EACS 2015: TAF Single-Tablet Regimen Shows Good Efficacy, Improved Kidney and Bone Safety

A single-tablet regimen containing the new tenofovir alafenamide (TAF) -- to be marketed as Genvoya -- suppressed HIV as well as a coformulation containing the older tenofovir disoproxil fumarate (TDF), according to a poster presented this week at the 15th European AIDS Conference in Barcelona. A related studyfound that people who switched from an atazanavir (Reyataz)-based regimen to the new combo had superior virological outcomes, and in both clinical trialsparticipants saw improvements in kidney and bone biomarkers.


EACS 2015: Can Dolutegravir Dual Therapy or Monotherapy Keep HIV Suppressed?

The potent integrase inhibitor dolutegravir taken with a single well-tolerated NRTI was able to fully suppress viral load in people initiating antiretroviral treatment for the first time, while dolutegravir alone was able to keep HIV suppressed in most treatment-experienced people who started with undetectable viral load, according to a set of studies presented at the 15th European AIDS Conference this week in Barcelona. After these presentations experts offered evidence in favor of and opposed to simplifying treatment by reducing drug burden, disagreeing about whether this strategy is beneficial or too risky.


EACS 2015: Can Europe Reach the 90-90-90 Target for HIV Treatment by 2020?

The European region needs to step up prevention and treatment activities if it is to reach the UNAIDS target of 90% of people with HIV diagnosed, 90% of those diagnosed on treatment, and 90% of those on treatment with fully suppressed viral load by 2020, the United Nations Secretary-Generals Special Envoy on HIV/AIDS in Eastern Europe and Central Asia told the opening session of the 15th European AIDS Conference today in Barcelona on Wednesday.


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The 90-90-90 target promoted by UNAIDS, if achieved, would result in 73% of people living with HIV having undetectable viral load. Mathematical modeling suggests that achieving this target by 2020 would end the AIDS epidemic by 2030.

"Europe is not done with AIDS and there is no room for complacency," Professor Michel Kazatchkine told delegates.

"There isn’t one Europe," Kazatchkine said at a press conference on the opening day of the conference. The World Health Organization's Europe region covers 53 countries, and "in fact, there are 3 Europes -- Eastern Europe, Central Europe, and Western Europe -- with different epidemics, different responses, and different levels of success."

The Eastern European epidemic continues to grow, driven largely by unchecked epidemics among people who inject drugs, but autonomous epidemics are also emerging among heterosexual men and women through sexual transmission in the region, Kazatchkine warned. These high levels of transmission make it unlikely that Eastern Europe will be in a position to reach the 90-90-90 target by 2020, he said. Prevention services are not accessible at sufficient scale, access to harm reduction remains very limited, and very low levels of cooperation on the part of government towards non-governmental organizations impedes the scale-up of prevention activities.

In Central Europe, despite low prevalence, HIV incidence has been rising gradually in many countries. The epidemic remains highly concentrated among men who have sex with men and people who inject drugs, but there is "limited willingness to pay" for programs aimed at these vulnerable groups among governments in the region, Kazatchkine said. He reminded delegates of the consequences of reducing HIV prevention services in the region: after Global Fund funding for harm reduction was gradually withdrawn from Romania when it joined the European Union in 2007, the country suddenly went from a minimal epidemic to high incidence among people who inject drugs in less than 2 years.

Although Western Europe appears to have everything needed to mount a successful response to HIV, the overall level of new infections has remained stable over the past decade. Despite universal health coverage, excellent HIV care, and high levels of social support, new infections have increased among men who have sex with men over the past 10-15 years. Much more intense efforts are needed in both prevention and treatment, but the 90-90-90 targets should be achievable for both Western and Central Europe, Kazatchkine predicted.

But, he told the conference, "If we do not intensify our efforts in the next 5 years, we will not be on the path to ending AIDS."

"We need to look carefully at the weaknesses in the European response. We are still missing many infections among men who have sex with men and migrants from countries with generalized epidemics," Kazatchkine said. In particular he expressed concern about testing frequency among men who have sex with men: if a large proportion of new infections among men who have sex with men are a consequence of acquiring HIV from partners who are themselves recently infected, yearly testing may be too infrequent to pick up recent infections and start treatment early enough to interrupt a chain of new infections. "Self-testing will be one of the solutions," he suggested.

A focus on the groups of people left behind will also be necessary: people who inject drugs, migrants, sex workers, and men who have sex with men continue to lack access to testing, treatment, and care in many settings in the region, yet are the groups most affected by HIV.

Closing the treatment gap will be necessary in order to reach the 90-90-90 target, Kazatchkine said. At the moment, the number of new HIV diagnoses in many countries in Eastern Europe continues to exceed the number of people who start treatment each year, which means that the treatment gap is growing, not shrinking. The treatment gap is made worse by national guidelines restricting treatment to people with CD4 cell counts below 350 cells/mm3 throughout Eastern Europe and Central Asia, and by alarmingly poor rates of diagnosis and retention in care. The average treatment cascade for the region as a whole shows that only 47% of people living with HIV know that they are infected. In the Russian Federation, the country with the largest number of people living with HIV, only 12% of HIV-positive people are on treatment.

Late diagnosis continues to be a major challenge for achieving high treatment coverage in Western Europe, especially among migrants who often lack good access to health care. In Eastern Europe, treatment coverage is around 35%, compared to a global average approaching 60%, Kazatchkine told the press conference. "People are very reluctant to go to services because of stigma and discrimination, because of a lack of coordination between TB and HIV services, and because of criminalization of people who inject drugs." Less than 10% of people who inject drugs who are living with HIV are currently accessing treatment in Eastern Europe, he said.

Tamás Berezcky of the European AIDS Treatment Group said that stigma and discrimination are the biggest barriers to testing and treatment among men who have sex with men in Central Europe, and stigma within the community is an important barrier to seeking care. "If you look at how men who have sex with men treat other MSM with HIV it’s very depressing," he told the press conference. He said that stigma is being reinforced by a lack of information about HIV, including a lack of awareness regarding recent advances in HIV treatment, the normal life expectancy of people who receive appropriate antiretroviral therapy, and the impact of treatment on transmission.

There is also insufficient focus on partnership with community organizations, Kazatchkine said. Berezcky called on scientists to join in partnership with the community to achieve implementation.

The financial sustainability of the HIV response in Eastern and Central Europe is also a serious concern following the withdrawal of Global Fund support for HIV and tuberculosis programs in the region. Global Fund support has come to an end as a result of a decision to focus future funding on lower-income countries, despite the political difficulties of funding the necessary prevention and treatment services in Eastern Europe.



15th European AIDS Conference. Barcelona, October 21-24, 2015.

EACS 2015: Benefits of Early HIV Treatment Are Clear, But Issues Raised by START and D:A:D Still Unresolved

The long-running controversy over when to start antiretroviral therapy (ART) has been definitively answered, but research is still needed to fully understand the implications of the large START and D:A:D studies, Professor Jens Lundgren from the University of Copenhagen said at a joint plenary session of the 15th European AIDS Conference and the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV.


IDWeek 2015: Post-Treatment Control of HIV Appears Rare, Biomarkers May Help Predict Rebound

Only 4 individuals out of nearly 5000 people receiving care at U.S. military health facilities were found to exhibit immune control of HIV after starting antiretroviral therapy (ART), achieving viral suppression, and interrupting treatment, according to a presentation at IDWeek 2015 this month in San Diego. A recently published related study identified several biomarkers that may help predict who will be post-treatment controllers, a useful tool for HIV cure research.


EACS 2015: Modest Bone Loss Seen in Young Men Taking Truvada for Pre-Exposure Prophylaxis

Young men participating in a pre-exposure prophylaxis (PrEP) demonstration project experienced modest but significant bone loss after starting Truvada, according to findings presented today at a joint session of the 15th European AIDS Conference and the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV.


Presenter Kathleen Mulligan from the University of California at San Francisco reported that bone mineral density (BMD) declines were seen in men who had tenofovir blood levels shown to be highly protective against HIV infection; in contrast, bone density increased in men with undetectable drug levels, as expected for young men of their age.

Tenofovir disoproxil fumarate (Viread, also in several single-tablet regimens) is one of the most widely used antiretrovirals, and the Truvada(tenofovir/emtricitabine) coformulation is increasingly used for HIV prevention. The iPrEx study showed that daily Truvada reduced the risk of HIV infection by 92% among gay men with measurable blood drug levels.

Tenofovir is considered to be generally safe and well-tolerated, but it is known to cause a small amount of bone loss soon after starting therapy. Bone loss has been seen in HIV-positive adults taking tenofovir-containing antiretroviral therapy and in infants exposed to tenofovir during gestation. Tenofovir-related bone loss has not yet been studied extensively in HIV-negative people, or in adolescents and young adults -- the age at which peak bone density occurs.

This analysis looked at bone density changes among participants in ATN 110, an open-label demonstration project investigating the safety and feasibility of PrEP for young gay men age 18-22 years. Results of the main study were presented at the International AIDS Society Conference this summer.

Bone mass generally peaks during early adulthood -- typically around age 20 -- after which it begins to gradually decline. Peak bone mass is an important predictor of fracture risk later in life, Mulligan noted as background.

ATN 110 enrolled 200 at-risk HIV-negative young men who have sex with men in 12 U.S. cities. The median age was 20 years, nearly half were African American, and about a quarter were Latino. Overall body weight was normal, but with a wide variation (median body mass index 23.6; range 17.3-58.9 kg/m2).

All participants were offered PrEP using once-daily Truvada for 48 weeks, along with a full package of HIV prevention services including risk reduction and adherence counseling, testing and treatment for sexually transmitted infections, and free condoms. Drug levels were measured throughout the study and dosing frequency was estimated based on tenofovir concentrations in dried blood spots.

The bone sub-study performed dual X-ray absorptiometry (DXA) scans of the hip, spine, and whole body at baseline and at weeks 24 and 48. The 4 participants who became HIV-positive during the study were excluded from the bone analysis.

Bone mineral density levels were lower than expected at baseline, falling below norms for age and race/ethnicity; 8.1% of participants had spine BMD, 6.1% had hip BMD, and 3.7% had whole body BMD below standard international thresholds for low bone mass. Mulligan noted that low bone mass has previously been reported in other studies of at-risk HIV-negative men.

At week 24 after starting Truvada, bone density decreased at the spine (by about -0.2%), hip (by about -0.4%) and whole body (by about -0.8%), with the latter 2 changes being statistically significant. At 48 weeks, hip BMD continued to decrease steeply (falling by about -1.0%) and whole body BMD further decreased by a small amount, but spine BMD started to increase and in fact rose above the baseline level.

Z-scores -- a measure of deviation from the norm for people of the same age and race/ethnicity -- decreased for the spine, hip, and whole body at both week 24 and week 48; all these changes were significant.

The researchers then looked at the relationship between bone loss and tenofovir concentrations in dried blood spots. More than half of participants had drug levels shown to confer a high level of protection -- indicating that Truvada was taken at least 4 times per week -- for the first 12 weeks. Adherence declined over time, however, and by week 48 only about a third of participants still had highly protective drug levels.

This allowed the researchers to compare bone density changes between men who had highly protective tenofovir levels and those with lower levels, showing that bone loss at the spine and hip through week 48 was correlated with tenofovir exposure.

Men with highly protective tenofovir levels showed spine bone loss of about -0.5% at week 24 and about -1.5% at week 48, while those with undetectable drug levels saw their bone density rise by approximately the same amount. Hip bone density decreased by smaller amounts at weeks 24 and 48 in men with protective drug levels, while remaining unchanged in those with undetectable drug levels.

Mulligan noted that differences in bone loss between men who took Truvada 7 days a week and those who took it 4 times a week were not significant, so it is not clear whether taking PrEP less often -- perhaps using an intermittent or "on demand" dosing schedule like the one used in the Ipergay study -- would be protective against bone loss.

Looking at bone fractures, about a quarter of participants reported that they had sustained fractures prior to the study. During the study period 5 participants experienced 8 fractures, all due to trauma (slamming fingers in a door, a vehicle accident, a fall, and a fight). None of the men with fractures had Z-scores indicating low bone mass.

"Although the BMD losses were generally modest, their occurrence before attainment of peak bone mass in young men who already have low bone mass may increase their risk of fragility in adulthood," the researchers concluded.

In response to an audience question, Mulligan said there was "very little evidence" of kidney toxicity among PrEP recipients, with very few cases of protein or glucose in the urine and little change in serum creatinine.

The study will continue to follow participants for a year to determine whether bone loss is reversible after stopping Truvada.



K Mulligan, B Rutledge, BG Kapogiannis, et al. Bone Changes in Young Men Ages 18-22 Enrolled in a Pre-Exposure Prophylaxis (PrEP) Safety and Demonstration Study Using Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC). 15th European AIDS Conference and 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV. Barcelona, October 21-24, 2015.

PrEP Preferences of Gay Men Are Predicted by Frequency and Predictability of Sex

A survey from the U.S. and Canada recently published in the Journal of Acquired Immune Deficiency Syndromes reveals that, on the whole, HIV-negative gay men would rather take pre-exposure prophylaxis (PrEP) intermittently and only before they anticipate sex, in what has been called "event-driven" or "on-demand" PrEP.