Higher pill burden is associated with poorer adherence to HIV therapy and reduced chances of achieving an undetectable viral load

AIDSmap

Lower pill burden is associated with higher rates of adherence to HIV treatment and better virological outcomes, according to the results of a meta-analysis published in the online edition ofClinical Infectious Diseases. The research also showed that adherence was better with once-daily regimens compared to twice-daily treatment, but once-daily therapy did not have any advantages in terms of virological suppression.

“Higher pill burden was associated with both lower adherence and worse virologic suppression in both twice-daily and once-daily subgroups,” comment the authors. “Adherence was higher with once-daily ART [antiretroviral therapy] regimens than twice-daily regimens…however, this difference was minimal and did not translate into better treatment outcomes.”

The past decade has witnessed important improvements in antiretroviral treatment. Overall, drugs are now less toxic and better tolerated than in the past. Pill burden has also been reduced and dosing schedules simplified. Two fixed-dose pills (Atripla and Stribild) are now available, providing potent HIV therapy in a single tablet.

A meta-analysis of randomised trials published in 2009 showed that once-daily treatment was associated with higher rates of adherence compared to twice-daily therapy, but that rates of virologic suppression did not differ greatly between the treatment strategies.

More randomised trials have been published since then. An international team of investigators therefore re-visited the questions of whether pill burden and dosing schedule have an impact on adherence and virologic suppression.

Randomised-controlled trials comparing once- and twice-daily therapy published or presented before 31 March 2013 were eligible for inclusion in the analysis. The study populations could include people who had not taken treatment before (treatment naive); treatment-experienced people switching treatment with an undetectable viral load; or treatment-experienced people switching treatment with detectable viraemia.

A total of 19 studies including 6312 people met the inclusion criteria. The studies were conducted between 2004 and 2011. Most (18/19, 95%) were published in peer-reviewed journals. Seven studies (37%) included treatment-naive patients, nine (47%) monitored patients who switched treatment with an undetectable viral load and three (16%) evaluated treatment-experienced individuals who changed treatment when their viral load was detectable.

The median duration of follow-up was 48 weeks, and 17 studies (89%) reported on both adherence and virologic suppression. The majority of studies (eleven, 58%) used MEMS (Medication Event Monitoring System) to assess adherence. The remaining eight studies used pill count.

However, the authors note that none of the studies included fixed-dose single pill therapies.

Higher pill burden was associated with lower rates of adherence (p = 0.004). But when the results were stratified by treatment strategy, the association between adherence and pill burden was only significant for twice-daily combinations (p = 0.001).

There was also a significant association between higher pill burden and reduced chances of achieving virologic suppression (p < 0.0001). This was the case for both once-daily (p = 0.005) and twice-daily (p = 0.0003) regimens.

Turning to dosing schedule, adherence was higher with once-daily regimens compared to twice-daily therapy (weighted mean difference [WMD] = 2.51%; 95% CI, 1.20%-3.83%, p = 0.0002). The adherence advantage of once-daily treatment was apparent in treatment-naive individuals (WMD = 3.94%; 95% CI, 1.42%-6.47%, p = 0.0002), as well as people switching therapy with detectable viraemia (WMD = 5.28%; 95% CI, 0.60%-9.96%, p = 0.03) and also people who changed treatment with an undetectable viral load (WMD = 0.95%; 95% CI, 0.36%-1.54%, p = 0.002). The difference between these sub-groups was significant (p = 0.02).

Virologic outcomes did not differ significantly between once- and twice-daily regimens. The investigators believe there are several possible explanations for this finding. These include the relatively small difference in adherence rates between once-and twice-daily regimens; the short period of follow-up in many studies; and the high levels of adherence support provided in clinical trials. “For all these reasons,” write the investigators, “the difference in virologic suppression that we found between once- and twice-daily ART regimens may be understated.”

They conclude that once-daily treatment is associated with better adherence, and that higher pill burden is associated with poor virologic outcomes.

The authors believe their findings are of significance to health systems which are looking at ways of reducing costs. Single tablet HIV therapy and fixed-dose combinations are marketed at a premium, but the investigators believe “separating out the single-tablet regimens and or/fixed-dose combinations into their constituents is not likely to have a major detrimental impact on virological outcomes (provided that the overall pill burden does not increase dramatically).”

Reference

Nachega JB et al. Lower pill burden and once-daily dosing antiretroviral treatment regimens for HIV infection: a meta-analysis of randomized controlled trials. Clin Infect Dis, published online ahead of print, 22 January 2014.

New HIV Drug Class Shows Promise

Cenicriviroc, an investigational antiretroviral from the new dual CCR5/CCR2 inhibitor class (photo), performed well in a Phase II trial, although with a high drop-out rate because of a complicated dosing. Investigators are currently developing a simplified regimen to mitigate that problem. Presenting their findings at the 14th European AIDS Conference in Brussels, researchers recruited 143 treatment-naive people with HIV for this double-blind/double-dummy study.

The participants were randomly assigned to take Truvada (tenofovir/emtricitabine) plus either 100 milligrams or 200 mg of cenicriviroc or 600 mg of Sustiva (efavirenz). Because cenicriviroc was only available as a 50 mg pill at the time of the study, participants took four pills (which were either cenicriviroc or a placebo) in the morning, one pill (efavirenz or a placebo) at bedtime and one Truvada at a time of their choosing.

This dosing schedule appeared to contribute to the high rate of dropouts: 29 percent in the 100 mg of cenicriviroc group left the study prematurely, compared with 27 percent in the 200 mg cenicriviroc group and 39 percent in the Sustiva group. Twenty-one percent of the Sustiva arm dropped out because of adverse events, compared with none in the 100 mg cenicriviroc arm and 2 percent in the 200 mg arm.

At 24 weeks, 76 percent in the 100 mg arm reached an undetectable viral load, compared with 73 percent in the 200 mg arm and 71 percent in the Sustiva group. By 48 weeks, these numbers had dropped considerably, mostly because of all the dropouts. The respective rates of a fully suppressed viral load considering all those initially assigned to each group was 68, 64 and 50 percent.

The CCR2 receptor latches onto a cytokine called MCP-1, which promotes inflammation. Tests found that those taking cenicriviroc had lower levels of MCP-1, which showed that the drug was successfully blocking the CCR2 receptor.

There was also evidence that levels of soluble CD14, which is an indicator of inflammation, dropped at the 24-week mark among those taking cenicriviroc; meanwhile it rose in those taking Sustiva. By 48 weeks the levels in the cenicriviroc arm rose again and reached a plateau around the level found at the beginning of the study. Meanwhile, the CD14 levels continued on an upward swing among those taking Sustiva.

To read the aidsmap story, click here.

To read the conference abstract, click here.

Same sex marriage is good for gay & lesbian health says study

Scientists have known for decades that married people are healthier and live longer lives than their single counterparts.1However, virtually all of the research conducted to date has focused exclusively on the health benefits associated with heterosexual marriage. Given that more and more countries have extended marriage rights to same-sex couples, has there been any effect on the health of gays and lesbians? Two recent studies have documented some positive health changes among sexual minorities.

First, a 2012 U.S. study found that in the state of Massachusetts, there was a significant decrease in the number of visits made by gay and bisexual men to healthcare providers for both medical and mental health issues in the year after same-sex marriage was legalized.2 This effect was not specific to men in relationships—rather, there seemed to be an across-the-board health benefit for all sexual minority men, perhaps because legalized same-sex marriage reduced stigma and stress for the entire gay and bisexual community (for more details on this study, see here). However, this study did not look at women and only looked at effects over a one-year period.

A brand new study out of Denmark addressed these limitations by tracking mortality rates of 6.5 million adults in that country between the years 1982 and 2011.3 Researchers examined how living arrangements (single, cohabiting, married) and sexuality were associated with death rates over nearly three decades. Denmark is a particularly interesting country for a study of this nature because they have provided at least some legal recognition of same-sex relationships since 1989.

Consistent with previous research, being involved in a heterosexual married or cohabiting relationship was associated with a longer life than being single, widowed, or divorced. Although persons in heterosexual marriages also had longer life expectancies than persons in same-sex marriages, same-sex marriage was linked to some health benefits. First and foremost, as more time has passed since Denmark started recognizing same-sex relationships, death rates for persons in same-sex marriages (both male and female) have dropped. And this was not because death rates were dropping for every group—in fact, death rates increased for certain groups (e.g., single and divorced men).

The researchers also found that among men over age 50, those who were in same-sex marriages lived longer than guys who were single or divorced. So, being in a same-sex marriage seems better for a man’s health than no relationship at all, but the health benefits do not appear to be as strong as they are for men in heterosexual marriages.

What about women? Among women over age 50, those in same-sex marriages actually had shorter lives than women who were single or divorced. This seemed largely attributable to the fact that women in same-sex marriages had elevated rates of breast cancer and suicides. Why was that the case? Unfortunately, we cannot say with any degree of certainty.

The Denmark study tells us that same-sex marriage has been good overall for the health of persons who have taken advantage of it. However, there remains an important health disparity between persons involved in same- and other-sex marriages, and it appears that this disparity is even larger among women. Although more research is needed to understand why this disparity exists, there is now compelling evidence from several sources that same-sex marriage appears to offer a range of health benefits to the gay and lesbian community.

1Ross. C. E., Mirowsky, J., & Goldsteen, K. (1990). The impact of the family on health: The decade in review. Journal of Marriage and the Family, 52, 1059-1078.

2Hatzenbuehler, M. L., O’Cleirigh, C., Grasso, C., Mayer, K., Safren, S., & Bradford, J. (2012). Effect of same-sex marriage laws on health care use and expenditures in sexual minority men: A quasi-natural experiment. American Journal of Public Health, 102, 285-291.

3Frisch, M., & Simonsen, J. (in press). Marriage, cohabitation and mortality in Denmark: National cohort study of 6.5 million persons followed for up to three decades (1982-2011).International Journal of Epidemiology.

Education Minister says he has been harrassed post the HFLE Manual withdrawal

It is difficult to confirm this one clearly but since the Minister of Education's dithering on the Home and Family Life, HFLE curriculum matter that had contained therein some questions that were deemed objectionable and maybe inappropriate for the age cohort intended, grades 7 - 9, so we can surmise 12 to 14 year olds depending on what age they successfully attained GSAT results etc. Erica Virtue of the Gleaner says the paper has confirmed from the horses mouth that he has been fact been receiving inappropriate emails and other correspondences on the matter.

The Minister on his feet in parliament justifying the withdrawal of the manual in October 2012.

In two previous posts (see linked below) while I have been disappointed and very critical of the minister's decision to seemingly capitulate to the religious right as he himself is a man of the cloth due to the questions that explore homosexuality, anal sex, HIV testing and disclosure and a problematic guided imagery exercise that asks the students in a controlled setting I might add (as I understand it) to imagine themselves gay and everyone else straight or hetersexual and the associated stigmas the student may feel in the reverse roles. 

Urgent need to discuss Sex & sexuality nationally part 1

Urgent need to discuss Sex & sexuality nationally part 2

In the absence of an 2012 online copy of the manual here are some of the questions as carried on TVJ when the story broke in November, the hard copies have been pulled from the trained teachers' hands. (no copyright infringement intended) Here is the 2009 version in case:

DOWNLOAD HERE

Here is the article by Miss Virtue:

Lifestyle Text Withdrawal Backlash - Calls And Letters, Attack Ministry, Minister

Erica Virtue, Senior Gleaner Writer

Jamaica's Education Ministry is taking a beating from local and international rights groups who are upset that it pulled the controversial health and family life education (HFLE) text issued to grades 7-9 students.

Education Minister Ronald Thwaites last week confirmed the attacks, but opted not to disclose the names of the groups and individuals leading them.

"We have been inundated by calls and letters because of the position the ministry took. Up to today (Wednesday), I received a broadside from a group of gay, lesbian and transsexual people in New Jersey in the United States, who wanted to know why I was in favour of hate crimes," Thwaites told The Sunday Gleaner.

According to Thwaites, the New Jersey group wanted to know when he could report to it the full information on non-discriminatory material available to all students in Jamaica.

"It has been surprising to me, because our position is that, in principle we support the instruction of children towards healthy, faithful heterosexual relations, with tolerance and with understanding and non-discrimination towards others who adopt a different and alternative lifestyle," the minister said.

According to Thwaites, the position taken by the ministry was consistent with the position taken by Prime Minister Portia Simpson Miller.

"But, apparently, there are many of those who want something much more than that and who feel that we must instruct children in all aspects of sexuality; homosexuality, heterosexuality at the earliest stages, without any caution or restraint, and we reject that," he said.

In September, the education ministry pulled the text after a parent pointed out the controversial content. Angry parents at the time demanded to know who approved the text even after it was withdrawn.

Approval questioned

The firestorm was ignited when it was discovered that the text, among other things, required grades seven to nine students to give responses to questions on their involvement in homosexual and heterosexual activity. Some stakeholders including parents and teachers questioned the process by which the Ministry of Education approved its teaching guides.

Thwaites accepted that officials at the ministry did not offer the rigid scrutiny the text should have undergone before it was signed off.

"We blinked," he admitted.

Faced with questions in Parliament from the opposition spokesperson on education, Marisa Dalrymple-Philibert, Thwaites argued that, "no minister of education of whatever political stripe would have knowingly allowed material as obnoxious as that contained in the HFLE curriculum to have been published, and it does appear that there were previous instances, and there were warnings, and it was a clear intention of some who have very clear predispositions regarding sexual conduct ... who got away on this one."

- erica.virtue@gleanerjm.com

ENDS

While I am strongly in support of some sort of sex and sexuality intervention at the high school level as I like others feel that the very reason we have so much homo-negativity and homophobia and patriarchal related challenges in society is because we have been taught reproductive health more so than S & S with a tolerant infused message. If this report by Miss Virtue is to be believed I cautiously used "harassment" in the eyes of the Minister is NOT my idea of engaging the official and to be fair to him he has met with JFLAG and other stakeholders prior to this uproar about the manual, he was present at the IDAHO conference in May where the J and other civil society groups were in attendance.

Yes we also appreciate the interventions (if you will) supporters overseas but they must be guided by the advocates on the ground, lest we forget in 2009 the Red Stripe Boycott in San Francisco and the attempted tourism boycott in Canada by what seemed to be over-exuberant friends without proper consultations and strategies, these high handed moves only serve to make the struggle extended or problematic as persons already resist the notion that Jamaica is one of the most homophobic places on earth (truth or not) thus the backlash at times towards homosexuality is actually the affront persons feel being supposedly castigated as homophobes. 

Just a word to the wise.

Peace and tolerance

H

Cell Damage Caused by Application of Certain Personal Lubricants Does Not Increase Risk of HIV Infection in Tissues Exposed to HIV in a Laboratory, According to a New Study

The use of certain water-based, over-the-counter personal lubricants can dry out and irritate vaginal and rectal tissue, but does not appear to increase susceptibility to HIV in vaginal tissues exposed to HIV in a laboratory setting, according to a study published today in PLoS ONE. Even so, say study authors affiliated with the National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), more research is needed to fully understand the safety of personal lubricants and their effect on epithelial tissue, the layer of mucosal cells that acts as the body’s first line of defense against sexually transmitted HIV.

“We tested several kinds of personal lubricants [IN THE LABORATORY] and those that did the most damage to cell tissue were hyperosmolar,” said lead study author Charlene S. Dezzutti, Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and principal investigator of the MTN Network Laboratory.

“While we know there is cellular toxicity associated with hyperosmolar lubes, the damage did not appear to make cells more vulnerable to HIV infection,” Dr. Dezzutti explained.

Hyperosmolar lubricants contain more salts, carbohydrates and proteins than are typically found inside cells of the vagina or rectum. This imbalance causes epithelial cells to lose water and, as a result, dry out. They are different from iso-osmolar lubricants, which contain the same amount of salts and other ingredients as do the cells.

Study investigators tested 14 brand-name over-the-counter and mail-order water-, lipid- and silicon-based lubricants. Lubricants selected were identified as those most commonly used during anal sex in a survey, conducted by IRMA, of more than 6,300 respondents. Results indicated that hyperosmolar water-based lubricants caused the most damage to the epithelium taken from the vagina and rectum compared to iso-osmolar water- and silicon-based lubricants.

When the researchers applied the lubricants to tissue taken from the vagina and then exposed the tissue to HIV, they found that the lubricants did not increase the tissue's susceptibility to HIV infection.

Other studies are seeking to address HIV susceptibility with rectal tissue.

Of the lubricants tested in the lab, Good Clean Love and PRÉ, both water-based iso-osmolar lubricants, were shown to be least harmful to epithelial tissue, along with two silicon-based lubricants, Female Condom 2 and Wet Platinum. Lubricants that were most toxic to the epithelial tissue (Gynol II, KY Jelly and Replens) also tended to damage “good” bacteria called lactobacillus, which is needed to maintain a healthy genital tract.

“Much more work needs to be done to explore the safety of lubes,” said Dr. Dezzutti. “This was an early study and the jury is still out as to whether hyperosmolar lubes cause damage to the epithelium that in conjunction with other processes, like inflammation, could increase susceptibility to HIV.”

“The most important point for people to take away from this study is that condoms are still the best way to protect against HIV and that lubes should always be used with compatible condoms.”

In addition to Dr. Dezzutti, authors include Elizabeth R. Brown, Ph.D., Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle; Bernard Moncla, Ph.D., Julie Russo, Marilyn Cost, Lin Wang, Kevin Uranker, Ratiya Kunjara Na Ayudhya, Kara Pryke, Lisa C. Rohan, Ph.D., with the MTN and the University of Pittsburgh; and Jim Pickett and Marc-André LeBlanc, with International Rectal Microbicide Advocates, Chicago.

The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all components of the NIH.

Additonal reading:

Topical strategies to prevent vaginal HIV transmission.