The 19th Conference on Retroviruses and Opportunistic Infections (CROI) was held in Seattle in March. Here are some important highlights.
PrEP effective even with imperfect adherence
Treatment as prevention and discussions around PrEP figured in a number of sessions at CROI.
An analysis of adherence data from the results of the Pre-Exposure Prophylaxis Initiative (iPrEx) was extensively discussed.
iPrEx, is a large ongoing study that uses Truvada (tenofovir and FTC) to prevent the acquisition of HIV by HIV negative gay men. The initial results, released in late 2010, demonstrated that the HIV infection rate in those who took PrEP was reduced by an average of 44%, compared with those given a placeboA dummy medical treatment, designed to have no pharmacological effect, administered to the control group of a clinical trial.. However, the infection rate was reduced by 73% for those participants who, by self-report and pill count, took the drugs more than 90% of the time.
During the study, men were counselled in safer-sex practices and on average they reduced their sexual partners from 18 in the previous three months from the start of the study to two in the previous three months at the end.
So, data suggests that PrEP is not only effective in reducing HIV transmissions in gay men (some of whom had high-risk behaviours) but also in reducing the number of partners they have.
CROI presenters reported on a detailed analysis of drug levels in blood and immune cells from a sub-set of iPrEx participants — some of whom remained HIV negative (including some who reported instances of receptive anal intercourse) and some of whom became HIV positive. The levels suggested that a minority of men (perhaps 18%) actually took their drugs as prescribed (a daily dose throughout the week). So, adherence was far from perfect.
Taking a single dose for at least four out of seven days in the week resulted in metabolised tenofovir drug concentrations within cells sufficient to theoretically reduce the risk of HIV infection by at least 90%. The statistical analysis also indicated that perfect adherence would result in 99% reduction in risk of infection.
There are, however, limitations to this study. It found that in the three months prior to new seroconversions, drug levels were consistently low; however, it was not able to determine what drug levels were at the time of infection. Additionally the actual doses taken by participants would have varied significantly from what they reported as an average.
It may be that adherence was good when men were having sex and not so when they weren’t.
The study did not record that level of detail.
Additionally, the actual levels of drug that are calculated as protective were based on a small study called STRAND which looked at drug levels achieved by taking tenofovir on two, four or seven days in the week over a six week period. The research reported at CROI looked at drug levels in iPrEx and what was protective, and compared those to the levels found in the STRAND trial, and calculated that taking the drugs four days in the week would provide a high level of protection. However, this analysis does not take into account the number or types of sex practices, and whether sexual partners might have been HIV positive.
These new data confirm what is already known about tenofovir-based PrEP. Providing it achieves sufficiently high levels in blood and immune cells, it will confer significant protection, perhaps as high as 95%, for sexually active gay men.
A warning to monitor and treat high blood pressurePersistently high blood pressure, an outwardly symptomless condition which carries an increased risk of serious illnesses such as stroke, heart disease and heart attack.
In a large cohortIn epidemiology, a group of individuals with some characteristics in common. A cohort study is a special kind of clinical trial which looks at a treatment or treatment strategy in a cohort of people. study in the US, the blood pressure of 82,490 people was monitored and PLHIVPerson (or people) Living with HIV. This term is now preferred over the older PLWHA. were identified and matched with similar people in the study without HIV.
Participants were grouped according to their systolic blood pressure (SBP): normal, prehypertensive (SBP 120-139mmHg), controlled hypertension (SBP <140mmHg on blood pressure medicine) or uncontrolled hypertension (SBP≥140mmHg).
All the participants were free of diagnosed cardiovascular disease.
Everyone was followed for an average of 4½ years, during which time 443 people had a heart attackA life-threatening emergency in which the blood supply to the heart is suddenly cut off, causing the heart muscle (myocardium) to die from lack of oxygen..
In every SBP category those who were living with HIV had consistently higher rates of heart attack than those who were HIV negative. Those PLHIV who had mildly elevated blood pressure (prehypertensive) and were not taking any medication to reduce their blood pressure were 1.7 times more likely to suffer a heart attack, compared to people who were HIV negative and had a normal blood pressure.
Normally, people who are prehypertensive (mildly elevated blood pressure) are encouraged to make lifestyle changes to reduce their risk of heart attack.
These findings suggest that PLHIV need to try getting their blood pressure down to normal levels to reduce risk of heart attack. This may not be possible through lifestyle changes alone (losing weight, reducing salt, exercising and quitting smoking).
People with HIV might need to be treated earlier with antihypertension medications. In fact, PLHIV may need to aim for targets similar to those used for renal or diabetic patients, where target blood pressure is below 130/80mm Hg.
The reasons for this were not examined, but may be related to inflammation caused by HIV and not being on effective HIV treatment.
Switching to raltegravir good for bones
Results from the Australian TROP Study looked at the changes in bone mineral density (BMD) after switching from tenofovir to raltegravir in an effective treatment regime that contained a boosted protease inhibitor. The study’s 37 participants had diagnosed bone disease (osteopenia or osteoporosis) in their spine or neck of the femur and had undetectable viral loadA measurement of the quantity of HIV RNA in the blood. Viral load blood test results are expressed as the number of copies (of HIV) per milliliter of blood plasma. for at least three months.
Almost all (97%) were men who averaged 49 years old and 15 years positive. Their average time on tenofovir was three years.
The participants were followed for 48 weeks, at the end of which they had DEXA scans of their spine, hip and femur, and had biochemical markers of bone activity measured. After 48 weeks BMD showed significant increases in all areas.
Levels of biomarkers of bone turnover decreased consistent with increases in BMD, and no participants sustained fractures during the study. These are good results for people who have signs of decline in bone health; however, the study was limited as it only followed people for 48 weeks after the switch.