This article by Sean Hosein first appeared on the CATIE website here  

Une version française est disponible ici. 

In high-income countries such as Canada, Australia and the U.S. and in regions such as Western Europe, huge advances have been made in the treatment of HIV disease. Researchers increasingly expect that a young person who is diagnosed today and who initiates potent combination anti-HIV therapy (commonly called ART or HAART) and who has minimal co-existing health conditions should have several additional decades of life expectancy.

The combinations of therapies available for the initial treatment of HIV are plentiful. Furthermore, pill taking has been simplified by the availability of the co-formulation of several drugs into one pill, creating an entire regimen in a single tablet. Such single-tablet regimens need only be taken once daily. However, things were not always this way.

A look at the past

Initial treatment for HIV infection, when it became available in the late 1980s, consisted of a single drug—the nuke (nucleoside reverse transcriptase inhibitor) AZT (zidovudine, Retrovir)—given at high doses and taken every four hours. Such a regimen frequently caused headache, nausea, vomiting and damaged the bone marrow.

In the early 1990s, other anti-HIV drugs in the same class became available, including the following nukes:

• ddC (zalcitabine, Hivid)
• ddI (didanosine, Videx)
• d4T (stavudine, Zerit) 

These three drugs, commonly called d-drugs, initially appeared to be better tolerated but soon showed their own side effects, such as peripheral neuropathy (painful nerves in the hands, feet and legs). ddC is no longer manufactured and treatment guidelines in high-income countries now discourage the use of d4T and ddI.

In 1996, a new class of anti-HIV drugs became available—protease inhibitors (PIs). When used in combination with nukes, the results were dramatic. For the first time in the history of the AIDS pandemic, people showed sustained recovery from AIDS-related infections.

However, shortly after HAART became available, reports emerged of a strange syndrome of changes in body shape sometimes associated with the loss of the fatty layer just under the skin. This loss of fat, called lipoatrophy, affected all parts of the body but its effect on the face could become most distressing.

Initially, because PIs were the latest class of anti-HIV therapy, they were suspected as the culprits. However, a few years later, researchers began to realize that exposure to d4T and, to a lesser extent, AZT, was linked to lipoatrophy. Today, drugs such as d4T and AZT are generally not recommended as first-line therapy in high-income countries.

Nukes today

In the current era, nukes remain the backbone of many regimens. Nukes commonly used today include the following combinations:

• abacavir + 3TC – sold as a fixed-dose formulation called Kivexa (or Epzicom) and also found in Trizivir
• tenofovir + FTC – sold as a fixed-dose formulation called Truvada and also found in other combinations such as Atripla, Complera and Stribild 

A lingering sense of caution

Decisions about starting therapy for HIV infection have always been challenging; both doctors and their patients have weighed the risks and benefits, as well as a person’s ability to take HIV medicines exactly as directed for many years. In the current era, with safer, simpler therapies and more results from clinical trials, the risk–benefit ratio has swung strongly in favour of very early initiation of therapy. The most recent version of the U.S. Department of Health and Human Services’ (DHHS) HIV/AIDS Treatment Guidelines recommends early therapy for all HIV-positive people, for two reasons, as follows:

• At the level of the individual, early treatment can help preserve the immune system and improve health.
• From a public health point of view, treating more HIV-positive people reduces the amount of HIV in their blood, other tissues, and genital fluids. The result is decreased sexual infectiousness. As a result of this reduced infectiousness, at the level of a large urban area or region, widespread use of ART can help to reduce new cases of HIV transmission. This approach of treating people to reduce their infectiousness is called TasP—treatment as prevention. 

Despite the general tolerability and safety of Kivexa and Truvada, some HIV-positive people and their doctors remain somewhat wary of nukes in general, given their checkered history, and wonder about the potential of these drugs for causing new, unknown side effects. This latter concern is increased as HIV-positive people age and need to take multiple medications, heightening the potential for drug interactions and side effects.

Emerging research suggests the possibility that nukes can affect the energy-producing parts of cells (mitochondria). However, nuke combinations commonly used in the initiation of therapy today have not been proven to cause mitochondrial damage that is directly linked to the ill health of ART users.

Aging and HIV

Some researchers have found hints of apparently accelerated aging in some HIV-positive people. Specifically, some organ-systems, such as the brain, heart, blood vessels and bones, appear to have aged more quickly than they should.

The cause of this apparent aging is not clear.

If premature or accelerated aging does exist in HIV infection, there may be several potential causes affecting different people, including the following:

• long-term exposure to specific proteins produced by HIV-infected cells
• higher-than-normal levels of inflammation, which accompanies chronic viral infections such as HIV
• substance use
• tobacco smoking
• co-infection with other germs, such as members of the herpes virus family—CMV (cytomegalovirus) and EBV (Epstein-Barr virus) 

The immune system and aging

Several research teams have found that, if left untreated, HIV infection does prematurely age the immune system. HIV appears to cause this by repeatedly activating the immune system and producing inflammation. This virus also appears to cause complex and poorly understood changes to the immune system shortly after it enters the body.

ART greatly reduces HIV-related inflammation but cannot entirely eliminate it. Prolonged exposure to higher-than-normal levels of inflammation is associated with many chronic illnesses and it is possible that such inflammation over the long-term may play a role in reports of accelerated aging seen in some HIV-positive people in studies. However, it is important to bear in mind that exposure to unhealthy behaviours—particularly tobacco smoking—also causes inflammation. Separating all the possible drivers of accelerated aging in HIV-positive people will not be easy and will require many studies, some of them quite expensive and daunting in their complexity.

Much caution needed

A research team in Australia has been exploring the theory that nukes somehow contribute to the apparent acceleration in aging in HIV-positive people. Their work, conducted in complex laboratory experiments on cells from HIV-negative and HIV-positive people suggests the possibility that the drug tenofovir (Viread) may accelerate the aging of the immune system. However, we urge our readers to treat this finding with a great deal of caution, if only because the results from the Australian experiments are not definitive. Furthermore, due to built-in limitations of their study’s design (it is cross-sectional in nature), questions remain about the significance of their findings. Next up, we will explore some of the issues related to the Australian study.

—Sean R. Hosein

REFERENCES:

 1. Boasso A, Royle CM, Doumazos S, et al. Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood. 2011 Nov 10;118(19):5152-62.

 2. Herbeuval JP, Nilsson J, Boasso A, et al. HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques. AIDS. 2009 Jan 2;23(1):35-40.

 3. Bestilny LJ, Gill MJ, Mody CH, et al. Accelerated replicative senescence of the peripheral immune system induced by HIV infection. AIDS. 2000 May 5;14(7):771-80.

 4. Leeansyah E, Cameron PU, Solomon A, et al. Inhibition of telomerase activity by HIV Nucleos(t)ide Reverse Transcriptase Inhibitors: a potential factor contributing to HIV-associated accelerated ageing. Journal of Infectious Diseases. 2013; in press.

 5. Payne BA, Wilson IJ, Hateley CA, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature Genetics. 2011 Jun 26;43(8):806-10.

 6. Helleberg M, Afzal S, Kronborg G, et al. Mortality Attributable to Smoking Among HIV-1-Infected Individuals: A Nationwide, Population-Based Cohort Study. Clinical Infectious Diseases. 2013; in press.

 7. Rasmussen LD, Kessel L, Molander LD, et al. Risk of cataract surgery in HIV-infected individuals: a Danish nationwide population-based cohort study. Clinical Infectious Diseases. 2011 Dec;53(11):1156-63.

 8. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clinical Infectious Diseases. 2011 Dec;53(11):1120-6.

 9. Pathai S, Lawn SD, Weiss HA, et al. Increased ocular lens density in HIV-infected individuals with low nadir CD4 counts in South Africa: evidence of accelerated aging. Journal of Acquired Immune Deficiency Syndromes. 2013; in press.

 10. Smith RL, de Boer R, Brul S, et al. Premature and accelerated aging: HIV or HAART? Frontiers in Genetics. 2012;3:328.

 11. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998 May 7;12(7):F51-8.

 12. van der Valk M, Gisolf EH, et al. Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection. AIDS. 2001 May 4;15(7):847-55.

 13. Cohen S, Janicki-Deverts D, Turner RB, et al. Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. JAMA. 2013 Feb 20;309(7):699-705.

This article by James Wilton originally appeared on the CATIE http://www.catie.ca/en/home  website here. 

Une version française est disponible ici.

The sexual transmission of HIV occurs after an exposure to fluids that contain HIV, such as semen and fluids from the vagina and rectum. Research shows that a higher amount of HIV (viral load) in these fluids increases the risk of HIV transmission and that a lower viral load decreases the risk.1

Treatment, viral load and HIV transmission

The viral load in the blood of a person living with HIV is measured to monitor the success of antiretroviral therapy (also called ART, HAART or cART). Successful HIV treatment can reduce the viral load in the blood (and other bodily fluids) to undetectable levels and thereby reduce the risk of sexual HIV transmission. In fact, a research study known as HPTN 052 found that the risk of HIV transmission among heterosexual serodiscordant couples was 96% lower when the HIV-positive partner was on treatment.2 (In serodiscordant couples, one partner is HIV-positive and the other is HIV-negative.)

Undetectable viral load does not mean that there is no virus, but rather that the amount of HIV in a bodily fluid is below a level that tests can detect. (Tests used in some places, such as Canada, cannot detect HIV if there are less than 40 copies of HIV per ml of blood, while tests used in other parts of the world have higher limits of detection.)

Also, not all people living with HIV who take HIV treatment and have an undetectable viral load in the blood also have an undetectable viral load in their other bodily fluids. Research suggests that of those people living with HIV who have an undetectable blood viral load, 5 to 48% can have detectable virus in their semen, vaginal fluid and rectal fluid.3,4,5

Although previous research has demonstrated that treatment can reduce the risk of HIV transmission in heterosexual couples, it is unclear exactly what the HIV transmission risk is when a person’s blood viral load is undetectable. A recent systematic review6 of the literature was conducted by Dr. Mona Loutfy, one of Canada’s leading infectious disease specialists, and colleagues to gain a better understanding of this risk.

Systematic review

The authors searched for published studies that followed serodiscordant heterosexual or same-sex couples over time. The main purpose of the review was to find studies that met the following criteria:

• the HIV-positive partner was on antiretroviral treatment
• the number of HIV infections in the HIV-negative partner was recorded
• if HIV transmission occurred, the HIV-positive partner’s blood viral load was measured close to the time of transmission

The authors identified only three studies that fit all of their criteria. These studies followed a total of 222 heterosexual couples from Brazil, Spain and Uganda.

An additional three studies were identified that fit all of their criteria but did not measure the viral load of the HIV-positive partner near the time of HIV transmission, including the HPTN 052 randomized controlled trial. These studies enrolled a total of 1,304 couples on treatment.

Overall, these six studies contained 2,975 person-years follow up of treated couples. This is the equivalent of following 2,975 couples for one year. The vast majority of these couples were heterosexual and only a small number were same-sex couples (3% of the couples in the HPTN 052 study were same-sex).

Number of HIV transmissions and HIV transmission risk

In the three studies where viral load was measured, no HIV transmissions occurred among couples where the HIV-positive partner was on treatment and the viral load was undetectable.

In the additional three studies, for which viral load was not measured, a total of four transmissions occurred. However, it is not known if the viral load of the HIV-positive partner was detectable or undetectable at the time of transmission. All of these HIV transmissions occurred shortly after the HIV-positive partner started treatment; therefore, the viral load was likely declining but still detectable when transmission occurred.

In these six studies, the definition of undetectable viral load ranged from less than 50 copies per ml to less than 500.

The lack of HIV transmissions in these studies does not mean there is no risk of HIV transmission when the viral load is undetectable. Using data from all six studies (but excluding the four HIV transmissions that occurred in the additional three studies), the authors calculated that when the viral load is undetectable, there may be a 1% risk of HIV transmission per 10 years of relationship and sexual activity.

Limitations of the study findings

There are several factors—other than viral load—that can influence the risk of HIV transmission between serodiscordant couples and may partly explain the lack of HIV transmissions observed in this review. As a result, the authors of the systematic review listed several caveats to their findings, including the lack of data on:

1.Extent of condom use 

Condoms are an effective method of preventing the transmission of HIV and many STIs and couples in these studies may have been using condoms often. For example, in the HPTN 052 study, 96% of the couples reported using condoms every time they had sex. Although people often say they use condoms more than they actually do, condom use may have played an important role in keeping the number of HIV transmissions low in these studies.

2. Same-sex couples and type of sexual intercourse

The vast majority of the couples enrolled in the studies were heterosexual and were (likely) having mostly vaginal sex. Therefore, it is unclear how much these findings apply to same-sex couples and other couples who mostly have anal sex. Some researchers think the risk of HIV transmission when undetectable may be higher for anal sex compared to vaginal sex.

3. Rates of sexually transmitted infections (STIs)

STIs are known to increase the risk of HIV-positive people transmitting HIV and HIV-negative partners becoming infected. STIs may increase the risk of HIV transmission even when a person’s viral load is undetectable. However, most of the studies reviewed did not provide data on STIs other than HIV; therefore, the review could not evaluate their impact.

In general, the risk of having STIs is lower among stable heterosexual couples (particularly those who are monogamous) than among people in casual relationships. Also, in some studies, such as the HPTN 052 study, participants were provided with regular STI testing and treatment which can help to further reduce the rate of STIs. A low number of STIs among couples in these studies may have decreased the risk of HIV transmission.

Conclusion

This systematic review supports previous research showing that treatment can significantly reduce the risk of HIV transmission among heterosexual couples. The authors concluded: “Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health.”

Research is ongoing to gain a better understanding of the risk of HIV transmission (a) when the HIV-positive partner’s viral load is undetectable and condoms are not used and (b) in same-sex serodiscordant couples where the HIV-positive partner is taking ART.

RESOURCE:

Understanding Risk: A Conversation

REFERENCES:

 1. Baeten JM, Kahle E, Lingappa JR et al. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Science Translational Medicine. 2011 Apr 6;3(77):77ra29.

 2. Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493–505.

 3. Marcelin A-G, Tubiana R, Lambert-Niclot S et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS. 2008 Aug 20;22(13):1677–9.

 4. Sheth PM, Yi TJ, Kovacs C et al. Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy. Mucosal Immunology. 2012 May;5(3):248–57.

 5. Sheth PM, Kovacs C, Kemal KS et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS. 2009 Sep 24;23(15):2050–4.

 6. Loutfy MR, Wu W, Letchumanan M et al. Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy. PLoS ONE. 2013 Feb 13;8(2):e55747.

This article by Sean Hosein first appeared on the CATIE website here 

Une version française est disponible ici. 

In Canada and in most other high-income countries the cost of HIV treatment is subsidized for permanent residents and citizens. Such treatment, commonly called ART or HAART, helps to stabilize the immune system and reduces the amount of HIV in the blood and genital fluids. ART’s power is so profound that an HIV-positive young adult who initiates therapy and takes his/her medicine every day exactly as directed and who has minimal pre-existing health conditions is expected to live for several decades.

ART also has another effect: Clinical trials in heterosexual couples where one partner has HIV and takes ART have found that effective treatment reduces the sexual spread of HIV. In these clinical trials, screening for and treatment of sexually transmitted infections, safer-sex counselling and condoms are all regularly provided. Clinical trials with same-sex couples are ongoing.

Faced with promising data from clinical trials performed so far, researchers, public health authorities, policy planners, doctors and nurses are increasingly looking toward the expansion of ART to more HIV-positive people as one means of helping to slow the HIV pandemic. This use of ART—to help reduce the spread of HIV—is called Treatment as Prevention (TasP). A key aspect of programs that focus on TasP is testing for HIV.

Traditionally, HIV testing strategies have targeted specific populations who are at high risk for HIV transmission. In addition to diagnosing HIV in those who are unaware of their status and connecting them with care, targeted testing strategies provide opportunities for enhanced prevention counselling in high-risk populations. However, in Canada and other high income countries, a significant proportion of people living with HIV remain undiagnosed despite targeted testing strategies. Often these people access other health services but are not offered an HIV test because they are not identified as high-risk candidates.

In order to help uncover HIV, the U.S. Preventive Services Task Force (USPSTF) is now poised to endorse the routine testing of HIV in people aged 15 to 65 in medical settings, where HIV testing takes place just like any other test. This recommendation is very important because researchers estimate that between 20% and 25% of HIV-positive people in the U.S. do not know that they have this virus. Unaware that HIV is slowly degrading their immune system, such people may ignore warning signs of impending illnesses. This increases their risk of serious AIDS-related infections, which can be difficult to treat, are expensive for hospitals to manage and can lead to death. Furthermore, if someone does not know their HIV status, they may not take steps to help prevent its spread.

In the U.S. there are about 1.1 million HIV-positive people and 56,000 new HIV infections every year. Many public health officials hope that the looming USPSTF recommendations about HIV testing will be a very important step on the road to bringing the HIV epidemic under control.

The USPSTF recommendations will add to the growing consensus from leading public health, medical and scientific organizations in the U.S. that routine HIV testing is an important step forward in helping to reduce the spread of this virus and bring people into care. Such organizations include the following:

• The Centers for Disease Control and Prevention (CDC)
• The American College of Physicians
• The Infectious Disease Society of America
• The American College of Obstetricians and Gynecologists 

Due to changes underway in the American healthcare system, routine HIV testing should increasingly become available at no additional cost to the person seeking it.

Hopefully, the USPSTF recommendations will help to uncover the 20% to 25% of Americans who researchers estimate are HIV positive but unaware of their infection and usher them into care and treatment.

In Canada there are approximately 71,000 HIV-positive people and about 3,200 new HIV infections per year. Public health authorities in British Columbia that have been working to expand opportunities for HIV testing in that province have recently called for the routine offer of an HIV test to be expanded across Canada. As in the U.S., Canada also has a large proportion (about 26%) of HIV-positive people who do not know their infection status.

AIDS was first recognized in 1981, and the cause, a virus we now call HIV, was discovered in 1983. Now, 30 years later, high hopes are being placed on the normalization and expansion of HIV testing and treatment so that the spread of the epidemic can be slowed, particularly in high-income countries such as Canada, France and the U.S. 

Sean R. Hosein

Resources 

Editorial in Canada’s leading medical journal calls for routine HIV testing – CATIE News

High rates of HIV testing among pregnant women in Ontario – CATIE News

The HIV treatment cascade – patching the leaks to improve HIV prevention – Prevention in Focus

This article by David Evans originally appeared on the CATIE website here.

Une version française est disponible ici. 

Before starting HIV medication, flight attendant Terry Wong never had a problem with jet lag or sleeping. “I could sleep just about anywhere anytime,” he recalls. “If I was tired and there was a bed, I would pass out and be snoring in minutes.” Diagnosed with HIV 15 years ago, Terry’s health took a nosedive seven years later—his weight dropped from 175 to 109 pounds and his CD4 count plummeted to zero. He was hospitalized for a week and started HIV treatment immediately. The meds saved his life but when combined with flying, they made getting some shut-eye a thing of the past.

Once on treatment, Terry started to gain weight and his health steadily improved, allowing him to return to work shortly afterwards. That’s when the insomnia hit: “When you’re switching time zones regularly, juggling your sleep and medication schedule without missing a dose becomes very complicated.” At first, he took his meds with lunch when in Vancouver. That meant that from his regular destination, Hong Kong, he had to take them at 3 am. He would call the hotel front desk to order a wakeup call and room service for that time, so he could take his pills with food. This threw his whole sleep schedule into a state of disarray. “My sleep was terrible,” he says. “I couldn’t sleep at all. It was the darkest period of my life.” In addition to the headaches and diarrhea he experienced as side effects from the medication, Terry constantly felt groggy, irritable, weak and depressed. After several years of this, he suffered a nervous breakdown.

Like Terry, many people living with HIV experience sleep problems. These can occur at any stage of HIV infection. Upwards of 75 percent of people report sleep issues on a regular basis. Some have difficulty falling asleep, some have trouble staying asleep (due to poor-quality sleep or frequent nightmares) and others wake up too early. Then there are people, like Jasmine, who have the misfortune of experiencing many or all of the above.

For years, when Jasmine went to bed at night she found herself wide awake, staring at the clock for hours on end. “If I fall asleep now,” she would calculate, “I’ll get only five hours of sleep…now only four hours…”—a vicious circle of insomnia and anxiety. Once she finally nodded off, she had problems staying asleep and achieving a deep sleep. As a result, she awoke each morning feeling sluggish. “It was very frustrating because it took a long time to get my engine up and running, ready to start the day.” When she started working night shifts, the problem only got worse. “When I’m sleep-deprived, I’m not as quick with my thinking or speech. I’m off my game and have to push myself to get stuff done.” 

Key to quality of life

Sleep is vital to our health and well-being: It can help regulate our hormones, reduce stress, manage our weight and improve immune function. As many of us know all too well, a lack of sleep can impair our memory, affect our ability to focus, deprive us of energy and leave us more susceptible to infection. Over time, this can lead to depression and anxiety, which can make it even harder to sleep.

Poor sleep can also make it more challenging to adhere to a pill-taking schedule—something that is crucial for successful HIV treatment. Dr. Julio Montaner, director of the BC Centre for Excellence in HIV/AIDS, stresses the importance of identifying sleep disturbances caused by HIV treatment early: “It is my job to be proactive and monitor for potential side effects. The more I can support people’s HIV treatment and help them be free of side effects, the more they are likely to be able to adhere to their medication regimen. Patients should be encouraged to bring up issues early as opposed to suffering in silence.”

Getting to the root of the problem

Identifying the nature of a sleep problem and figuring out what’s behind it is step number one, best done in conversation with a knowledgeable doctor or nurse. For people with HIV, the root cause tends to be one or some combination of the following:

• HIV itself – HIV-infected cells in the brain, which produce neurotoxins and chemical signals that may impair the sleep of some people.
• medications – such as efavirenz (Sustiva, also found in Atripla) used to treat HIV, interferon used to treat hepatitis C and other drugs prescribed for HIV-related illnesses.
• mental health issues – such as depression and anxiety.
• alcohol and drug use – heavy drinking or using drugs, especially stimulants such as cocaine, speed and ecstasy. 

Other causes of sleep problems can include changing hormone levels (for example, high or low levels of thyroid hormone, changes in estrogen levels during menopause and declining levels of free testosterone), calcium and/or vitamin B12 deficiencies, and infections (including a cold or flu).

After years of tossing and turning, Jasmine was determined to pinpoint the cause of her problems. The efavirenz she was taking as part of her HIV treatment was a possible culprit but not an obvious one because she had been taking the medication for years without side effects. The vivid dreams, nightmares and insomnia that some experience when taking this drug normally occur when people start the medication and tend to diminish or go away with time. But when Jasmine switched HIV drugs, it was confirmed: “My sleep was much better within days. It was definitely one of the things that had been causing me problems.” Working nights was another—but more about that later. 

How sleep works

When we sleep, we alternate between periods of non-rapid eye movement (NREM) and rapid eye movement (REM). One cycle takes about 90 minutes to complete and typically consists of five stages. Stage 1 is a drowsy sleep that usually lasts five to 10 minutes. During stage 2, our muscle activity diminishes and body temperature drops as we lose consciousness. Stages 3 and 4 are characterized by a deep, restorative sleep when the growth hormone responsible for cellular regeneration and muscle development is released. Stage 5 is REM sleep: Our eyes move back and forth rapidly and dreaming occurs as a result of increased brain activity.

People’s sleep needs vary, but most of us need seven to nine hours per night. This is known as “sleep architecture”—the total time asleep and the duration of NREM and REM periods. A good night’s sleep depends on the right balance between these different stages. Various factors, such as light, stimulants and poor sleep hygiene, can disrupt this balance. The goal for insomniacs is to restore this balance.

Strategiezzz…

Finding the solution that’s right for you might not happen overnight, but persistence and trying different strategies with the support of a knowledgeable doctor can go a long way. Here are some suggestions:

Stay away from the light! Light at night is one reason why many people don’t get enough sleep. Our circadian rhythms respond to the light and dark around us. Derived from the Latin words circa and diem, meaning “around a day,” the term describes our sleep/wake pattern, hormone release, body temperature and other bodily functions over a 24-hour period. In the past, people would wake up with the sun and go to bed with the moon, but the lightbulb changed all that. Bathed in artificial light long after the sun has set, many of us find our patterns out of sync with our body’s biological clock. And our sleep suffers from it. (Research suggests that it may also contribute to cancer, diabetes, heart disease and obesity.)

In the absence of light, our bodies release the hormone melatonin, which helps us get to sleep. When we are exposed to light, the release of melatonin is suppressed and makes sleep more difficult. Any kind of light has this effect, but the “blue light” emitted from electronic devices makes it particularly easy to disregard the body’s readiness for sleep. That is why it is important to sleep in total darkness. The best way to achieve this is with a specialized window covering that blocks outside light (a “blackout blind”), but a sleep mask is effective as well. It is also important to eliminate all sources of light in the bedroom, including all blinking lights or display screens, by turning them off, taping over them or removing them altogether.

Cut back on caffeine. Caffeine is the world’s most consumed psychoactive (mind-altering) drug and can be found in coffee, tea, soda, energy drinks and chocolate. Coffee is the most popular choice, with 65% of Canadians drinking an average of 2.8 cups per day. With its ability to boost energy, increase alertness and improve mood, it is a simple solution for a quick pick-me-up. Unfortunately, it can also disrupt sleep patterns. A central nervous system stimulant, caffeine increases the heart rate, core temperature and blood pressure, which, in turn, can increase the time needed to get to sleep, decrease sleep duration and limit your time spent in deep sleep.

Caffeine has a half-life of five hours—that’s how long it takes to metabolize half the amount circulating in your system. So if you drank a 12-oz coffee containing 260 mg of caffeine at 8 am, there would be 33 mg of caffeine left in your system by 11 pm, which is more than enough to disrupt sleep.

Want to sleep better? Here are some caffeine tips:

1. Limit your consumption after 10 am.
2. Reduce your overall intake—withdrawal symptoms like headaches can occur within 48 hours after you stop and can last two to nine days. If this happens, you’re on the right track!
3. Decaf does not mean caffeine-free—that same coffee still has 20 mg of caffeine. 

Check your meds and supplements. Review with your doctor all the medications and supplements you’re taking to determine if any of them could be to blame. Dr. Montaner points out that it’s essential to find the medication regimen best suited for each individual—one that is highly effective and can be taken long-term without disrupting daily activities. “Antiretroviral therapy is a lifelong proposition,” he says. “This is a marriage that has to work.”

Some cough and cold medicines, Gravol, antihistamines and other over-the-counter remedies are used to help people sleep; however, these can exacerbate underlying sleep problems and, when used over time, can lead to anxiety and depression.

Get your vitamins and minerals. If you have a calcium or vitamin B12 deficiency, taking a B-complex vitamin along with calcium and magnesium supplements can help your muscles relax.

Seek peace of mind. If an underlying emotional issue is keeping you awake, seeing a psychologist, counsellor or other health professional can help with depression, anxiety and other issues. A healthy support system and meditation, yoga or acupuncture can also help you rest easier.

Avoid sleeping pills. Sleeping pills offer a short-term solution for some people, but using them over the long-term can create dependency, negatively impact sleep architecture and make you feel drowsy the next day.

You are getting sleepy... A bedtime routine is essential for quality rest. We know its value for children, so why do so few adults have one? A consistent bedtime routine, which ideally starts 60 minutes before hitting the hay, helps you prepare for sleep by giving your day closure, quieting your mind and relaxing your body. A few pointers:

1. Turn off all electronics.
2. Dim the lights to start the release of melatonin.
3. Listen to soft music.
4. Set the temperature in your bedroom between 16°C and 20°C and make sure the room is well ventilated.
5. Have a hot bath. The rapid drop in body temperature that occurs when you get out will help you fall asleep.
6. Spend time reading, stretching or meditating.
7. Try some deep breathing in bed: Inhale for five seconds, hold for two seconds, exhale for five seconds. Repeat until asleep.

When Jasmine gets home from her night shift, around 3 am, she says it’s not as easy for her to “do the whole wind down/relaxation thing, the way a person who works regular hours would.” Instead, she finds that putting on a pair of blue-light-blocking glasses for two to three hours before bed helps; in fact, she swears by it. She starts wearing them toward the end of her shift and doesn’t remove them until she’s in bed with the lights off. She also makes a point of exercising (cross-training, kick-boxing, roller-blading or biking) during the day, which helps with her sleep. Although working nights isn’t easy, her modified regimen of anti-HIV drugs combined with these lifestyle changes has helped.

As for Terry, after years of trial and error, he now has a roster of strategies that have turned his formerly sleepless nights into long, uninterrupted deep sleeps. He tweaked his medication schedule (he now takes his meds at 7 or 8 pm in BC and at 9 or 10 pm in Asia) so that he no longer needs to call for room service in the middle of the night. He consulted with a dietitian who recommended light meals (nothing greasy) before a flight to reduce jet lag. When travelling, he routinely orders hotel turndown service, to make sure his room is completely dark at bedtime (he also tapes the curtains to the wall to make extra sure that no light comes through when day breaks). Regular Chinese acupressure massages and use of the hotel steam rooms or a bath help him relax before bed. Emotionally, he is now faring much better. When asked how he sleeps, he says unequivocally, “Like a baby.”

About the author: For 23 years, David Evans woke up feeling the same way he did when he went to bed. Desperate for answers, he did his own research, met with specialists and completed an overnight sleep study. Blood tests turned up nothing. Meds for sleep, anxiety, depression and daytime drowsiness produced more side effects than benefits. His relationships and finances were a mess and he had difficulty holding down a job. He became isolated and considered suicide as he longed for a state of non-existence.

Fast-forward to today: David’s sleep is under control and he is leading an energetic life. He no longer needs caffeine, naps are a rarity and he takes no sleep medication. Since transforming his own life, he now dedicates his time to helping others sleep soundly. He has delivered the workshop “Better than Counting Sheep” at Positive Living BC and Vancouver Friends for Life Society. For more info, visit www.sleepstudent.com

This important article by James Wilton first appeared in Prevention in Focus on the CATE website here.

Une version française est disponible ici. 

Since the beginning of the HIV epidemic, condoms have been a cornerstone of our HIV prevention efforts—often promoted as the most effective way to prevent the sexual transmission of the virus. However, in the past few years the number of HIV prevention options has increased and some people are interested in, or are already using, newer strategies. As a result, frontline service providers are being asked challenging questions: Are condoms the most effective strategy available? How do they compare to other strategies? This article explores the evidence on how effectively condoms prevent HIV transmission and the implications for our HIV prevention messaging.

Condoms 101

Condoms are physical barriers used during sex to prevent parts of the body that are vulnerable to HIV infection (such as the penis, vagina, rectum and mouth) from coming into contact with fluids that may contain HIV and other infections. We currently have two main types of condoms: the male condom (also known as the external condom) and the female condom (also known as the internal or insertive condom).

What are they made of? Most male and female condoms are made from nitrile, latex, polyisopropene or polyurethane, all of which cannot be penetrated by the viruses and bacteria that cause sexually transmitted infections (STIs), including HIV.1 Lambskin condoms, which are made from sheep intestines, can be penetrated by bacteria and viruses and should therefore never be used to prevent the transmission of HIV.

To lube or not to lube? Sexual lubricants are commonly used in combination with condoms to increase pleasure. The use of lubricant is also recommended to decrease friction that can cause breakage, particularly during anal sex. Water- and silicone-based lubricants are safe to use with all condoms, but oil-based lubricants can compromise the integrity of latex and polyisopropene condoms and increase the risk of the condom breaking.

Using condoms correctly and consistently

Since condoms are impermeable to viruses, shouldn’t we expect them to be 100% protective against HIV? Unfortunately, it’s not that simple. As with any type of prevention strategy, condoms only work if they are used correctly and consistently. Inconsistent use can greatly decrease their ability to prevent HIV transmission.

Incorrect use of condoms can also compromise their effectiveness. For example, some people may use condoms that are too small or too large, damaged or expired; unroll condoms before putting them on; not pinch the tip when putting them on; use sharp objects to open condom packages; not use enough lubrication in combination with condoms or use oil-based lubrication with latex or polyisopropene condoms; or not hold the rim of the condom when pulling out. All of these can potentially increase the risk of HIV transmission by causing a condom to break, slip or leak.

Incorrect condom use can also take the form of putting on a condom late (after intercourse has started), removing the condom early (before ejaculation has occurred) or putting the condom on inside out and then flipping it over to use. If a condom is used incorrectly in these ways, then HIV transmission could occur even though the condom does not break, slip or leak.

A recent literature review of 50 studies revealed that the incorrect use of male condoms is surprisingly common.2 For example:

• Studies found that 17 to 51% of participants reported not putting on a condom until after intercourse had started.
• Some studies also reported high rates of condom problems, such as breakage (0 to 33%), slippage (0 to 78%) and leakage (0 to 7%), which could lead to HIV transmission. Errors in condom use may be partly responsible for these problems. For example, 24 to 46% of participants reported not pinching the tip of the condom and 16 to 26% reported using a condom that was not lubricated.

How often do condoms break, slip or leak when they are used perfectly in every possible way? We don’t know and probably never will. However, when condoms are used correctly, the rates of breakage, slippage, and leakage are likely quite low. Research shows that education and more experience using condoms can help lower rates of condom failure.3,4

So how effective are male condoms?

The best evidence we have on the effectiveness of male condoms comes from an analysis of 14 observational studies that enrolled heterosexual serodiscordant couples (where one partner is HIV-positive and the other is HIV-negative).5 The analysis compared the rate of HIV transmission between couples who said they always used male condoms to the rate among couples who said they never used male condoms. The analysis found that the rate of HIV transmission was 80% lower among couples who reported always using condoms.

For many people working in HIV prevention, an 80% effectiveness rate may be lower than you thought or have previously told clients and patients. However, it is important to consider the limitations of this analysis when interpreting its results. There are three reasons why this analysis may make condoms look less effective than they can be: 

Incorrect use. The couples who said they always used condoms may not have been using condoms correctly. This would have increased their risk of HIV transmission and reduced condom effectiveness.

Inconsistent use. The couples who said they always used condoms, in reality, may not always use them! Some of the couples may have had trouble remembering how often they used condoms or felt uncomfortable saying that they did not use condoms. This would have increased their risk of HIV transmission and made condoms appear less effective.

Differences in behaviour. The risk-taking behaviours of the couples who said that they always used condoms may have been different from those couples who said they never use condoms. For example, couples who reported always using condoms may have engaged in behaviours that increased their risk of HIV transmission, such as having sex more often or engaging in higher-risk types of sex. If this was the case, these behaviours would have increased their risk of HIV transmission, making condoms appear to be less effective. It’s also possible that people who reported never using condoms may have engaged in behaviours that put them at lower risk of HIV transmission, such as having sex less often or only engaging in lower-risk types of sex (such as oral sex). If this was the case, this would make it appear as though there was less of a difference in HIV transmission rate between the two groups and make condoms appear less effective.

Given these limitations, the estimate of 80% likely does not reflect how effective condoms can be in preventing heterosexual HIV transmission. If used consistently and correctly, condom effectiveness is likely much higher.

Is the same true for men who have sex with men?

Are male condoms also effective at reducing HIV transmission when used by gay men or other men who have sex with men? Several studies have explored this question and estimated a similar effectiveness rate of 70 to 80% for consistent condom use during anal sex.6,7,8 However, these studies are affected by the same three limitations as studies of heterosexual couples—incorrect use, inconsistent use and differences in behaviour. So the effectiveness rate for consistent and correct condom use during anal sex is likely higher.

What about female condoms?

No studies have evaluated the effectiveness of female condoms in preventing HIV transmission during vaginal sex or anal sex. However, research shows that they are as effective as male condoms at preventing other STIs.9,10,11

The expanding HIV prevention toolkit

In the past decade the number of HIV prevention options available to reduce the risk of HIV transmission has increased. Some of these strategies are generating a lot of excitement because they may provide an option for people who don’t want to, or are unable to, use condoms. These include the following:

Antiretroviral treatment – which reduced the risk of HIV transmission by 96% among heterosexual serodiscordant couples in a randomized controlled trial (RCT).12

Pre-exposure prophylaxis (PrEP) – which reduced the risk of HIV transmission by 40 to 70% for gay men13 and heterosexual men and women14,15 in RCTs. Further analysis suggested that PrEP may have reduced HIV risk by up to 90% among those who always took their pills.13,14

Post-exposure prophylaxis (PEP) – which reduced the risk of HIV transmission by up to 80% in an observational study of healthcare workers exposed to HIV in the workplace.16

Observational studies suggest that behavioural strategies such as serosorting, strategic positioning and withdrawal may slightly reduce the risk of HIV transmission.17

People who want to use, or are already using, these strategies may want to know how effective they are compared to condoms. These questions can be challenging to answer and it’s important that, in our responses, we don’t compare apples and oranges. For example, comparing results from different types of studies can be problematic. Some of the new prevention strategies were evaluated using an RCT while condoms were evaluated using observational studies. Comparing the results from these two kinds of studies can be problematic for a number of reasons:

• In RCTs the two groups are randomized to ensure that there are no differences between the groups other than whether or not they received the intervention. This is important because we know that each group should have similar risk behaviours and that neither group should be more or less likely to get HIV. However, in observational studies (such as those used to assess condoms), one group could be having sex more often or engaging in riskier sex. This could impact the results and make a strategy, such as condoms, appear to be less effective than they actually are.
• RCTs create “ideal” conditions that can make a strategy appear more effective than it would be in the “real world.” For example, RCT participants are supported to ensure they use the strategy correctly and all participants are provided with a comprehensive package of prevention services, including STI testing and treatment, free condoms, and intensive adherence and risk-reduction counselling. By contrast, observational studies, such as those used to evaluate condoms, generally do not provide participants with additional supports. Therefore, these results may not be directly comparable to the results of RCTs.

When it comes to comparing the effectiveness of two prevention strategies, we need to pay attention to the research design used to measure that effectiveness. Most new prevention strategies, such as PrEP or treatment as prevention, have been evaluated using RCTs, which can tell us about the effectiveness of the strategy under “ideal conditions.” Unfortunately, we don’t know how effective condoms would be under the ideal conditions of an RCT; however, we have good reason to believe that they would be more than 80% effective when used consistently and correctly.

Implications for HIV prevention messaging

Safer sex messaging and prevention counselling need to emphasize that the correct and consistent use of condoms is a very highly effective method of preventing the sexual transmission of HIV.

When answering questions about the effectiveness of condoms, it’s important to emphasize that they have several advantages over other options. Key messages include the following:

• If a condom is used correctly and it doesn’t break, slip or leak, then it is virtually 100% protective. However, there is a still a possibility that condoms will break, slip, or leak even when used correctly. Condoms do not eliminate the risk of HIV transmission.
• Condom effectiveness does not rely on accurate knowledge of a person’s HIV status, as opposed to serosorting, which requires accurate knowledge of the HIV status of both partners—something that is often difficult to know for certain.
• Whereas the goal of some other strategies—such as PEP, PrEP or having an undetectable viral load— is to reduce the risk of an exposure leading to an infection, condoms prevent an exposure to HIV from occurring in the first place.
• Other prevention options may be less effective if either partner has an STI, a higher viral load or other biological factors that affect HIV risk whereas condom effectiveness is not affected by these.
• If they don’t break, slip or leak, condoms can reduce the risk of HIV transmission for both anal and vaginal sex to the same level. However, the risk of HIV transmission while using PrEP or when the viral load is undetectable may be higher for anal sex than for vaginal sex. (This is because anal sex has a higher baseline risk of HIV transmission than vaginal sex.18)
• Condoms also reduce the risk of other STIs, such as gonorrhea, chlamydia, herpes and syphilis.19 Although other strategies may reduce the risk of HIV transmission, they do not reduce the risk of STI transmission. This is important because STIs can increase a person’s risk of HIV transmission.20
• Condoms can reduce the risk of unintended pregnancy.
• Condoms are less expensive, more readily available and less toxic than strategies that involve antiretroviral medications, such as PEP and PrEP.

Despite the advantages of condoms, we can’t ignore the important role that other prevention strategies may play in helping someone reduce their risk of HIV transmission. Condoms are not without their disadvantages and these can make it difficult for people to use them consistently and correctly. For example, condom use can be difficult to negotiate, condoms can decrease sexual pleasure and intimacy, they need to be available at the time of intercourse, they may be difficult to use when under the influence of alcohol or drugs, and they do not allow a woman to conceive. For these reasons, some people may choose to reduce their risk of HIV transmission in other ways.

Conclusion

HIV prevention efforts need to focus on helping people adopt prevention strategies that are appropriate to their circumstances and will be most effective for them. If people are having difficulty using condoms or are having problems with condom breakage, slippage or leakage, counselling may help them use condoms more consistently and correctly.

At the same time, alternative strategies for reducing the risk of HIV transmission may need to be discussed with these clients. When exploring other prevention options, it’s important to clearly explain their limitations, factors that may decrease their effectiveness and how a person can keep their risk of HIV transmission as low as possible while using these strategies. No strategy—including condoms—is 100% effective; all have their limitations and can fail in different ways. Since condoms provide less than 100% protection, using other strategies in combination with condoms will help decrease a person's overall risk of HIV transmission. However, if a client or patient decreases their condom use in favour of a less protective strategy, they may be increasing their overall risk of HIV transmission.

Resources

AIDSMAP – Do condoms work?

CATIE News – High prevalence of condom use errors and problems – implications for HIV prevention messaging

Canadian HIV/AIDS Legal Network – HIV non-disclosure and the criminal law: Implications of recent Supreme Court of Canada decisions for people living with HIV: Questions & Answers

References

1. Lytle CD, Routson LB, Seaborn GB, Dixon LG, Bushar HF, Cyr WH. An in vitro evaluation of condoms as barriers to a small virus. Sex Transm Dis. 1997 Mar;24(3):161–4.

2. Sanders SA, Yarber WL, Kaufman EL, Crosby RA, Graham CA, Milhausen RR. Condom use errors and problems: a global view. Sex. Health. 2012 Feb 17;9(1):81–95.

3. Lindberg L, Sonenstein F, Ku L, Levine G. Young men’s experience with condom breakage. Family Planning Perspectives. 1997 Jun;29(3):128–31.

4. Steiner MJ, Taylor D, Hylton-Kong T, Mehta N, Figueroa JP, Bourne D, et al. Decreased condom breakage and slippage rates after counseling men at a sexually transmitted infection clinic in Jamaica. Contraception. 2007 Apr;75(4):289–93.

5. Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev. 2002;(1):CD003255.

6. Vittinghoff E, Douglas J, Judson F, McKirnan D, MacQueen K, Buchbinder SP. Per-contact risk of human immunodeficiency virus transmission between male sexual partners. Am. J. Epidemiol. 1999 Aug 1;150(3):306–11.

7. Golden M. HIV serosorting among men who have sex with men: implications for prevention. 13th Conference on Retroviruses and Opportunistic Infections. 2006;Abstract 163.

8. Detels R, English P, Visscher BR, Jacobson L, Kingsley LA, Chmiel JS, et al. Seroconversion, sexual activity, and condom use among 2915 HIV seronegative men followed for up to 2 years. J. Acquir. Immune Defic. Syndr. 1989;2(1):77–83.

9. Minnis AM, Padian NS. Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions. Sex Transm Infect. 2005 Jun;81(3):193–200.

10. French PP, Latka M, Gollub EL, Rogers C, Hoover DR, Stein ZA. Use-effectiveness of the female versus male condom in preventing sexually transmitted disease in women. Sex Transm Dis. 2003 May;30(5):433–9.

11. Kelvin EA, Mantell JE, Candelario N, Hoffman S, Exner TM, Stackhouse W, et al. Off-label use of the female condom for anal intercourse among men in New York City. Am J Public Health. 2011 Dec;101(12):2241–4.

12. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 2011 Aug 11;365(6):493–505.

13.a. b. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 2010 Dec 30;363(27):2587–99.

14.a. b. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 2012 Aug 2;367(5):399–410.

15. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N. Engl. J. Med. 2012 Aug 2;367(5):423–34.

16. Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N. Engl. J. Med. 1997 Nov 20;337(21):1485–90.

17. Vallabhaneni S, Li X, Vittinghoff E, Donnell D, Pilcher CD, Buchbinder SP. Seroadaptive Practices: Association with HIV Acquisition among HIV-Negative Men Who Have Sex with Men. PLoS ONE. 2012;7(10):e45718.

18. Boily M-C, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, et al. Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis. 2009 Feb;9(2):118–29.

19. Holmes KK, Levine R, Weaver M. Effectiveness of condoms in preventing sexually transmitted infections. Bull. World Health Organ. 2004 Jun;82(6):454–61.

20. Ward H, Rönn M. Contribution of sexually transmitted infections to the sexual transmission of HIV. Curr Opin HIV AIDS. 2010 Jul;5(4):305–10.

About the author: 

James Wilton is the Coordinator of the Biomedical Science of HIV Prevention Project at CATIE. James is currently completing his master’s degree of Public Health in Epidemiology at the University of Toronto and has completed an undergraduate degree in Microbiology and Immunology at the University of British Columbia.

This article by CATIE’s James Wilton and Logan Broeckaert first appeared on the CATIE  website here.

Une version française est disponible ici.

We have known for years that antiretroviral therapy can significantly improve the health outcomes of people living with HIV. More recently, research has revealed the important role that antiretroviral therapy plays in preventing the transmission of the virus. As HIV treatment and prevention have converged, attention has turned to how well we are engaging people living with HIV in the continuum of services, including testing, care and, ultimately, effective treatment. The concept of an HIV treatment cascade has emerged as a way to identify gaps in the continuum, which are preventing people from realizing the treatment and prevention benefits of antiretroviral therapy.

This article takes a closer look at the cascade, why it’s important for HIV prevention and how it can be improved.

Steps in the HIV treatment cascade

Antiretroviral therapy is normally considered successful when it reduces the viral load of a person living with HIV to undetectable levels. Research shows that people who have an undetectable viral load in their blood are more likely to live a long and healthy life1 and are less likely to pass HIV to others.2

For a person living with HIV to achieve an undetectable viral load, they need access to a continuum of services: HIV testing and diagnosis, linkage to appropriate medical care (and other health services), support while in care, access to antiretroviral treatment if and when they are ready, and support while on treatment. This sequence of steps is commonly referred to as the HIV treatment cascade or the HIV care cascade. Unfortunately, the cascade isn’t seamless and some people “leak” out and are lost at each step, due to barriers to getting tested, staying in care, and starting or adhering to antiretroviral treatment. These barriers include:

• poor access to services;
• stigma and discrimination;
• poverty, food insecurity and homelessness; and
• mental health and addiction issues.3

As a result of these leaks at different points in the continuum, only a small proportion of people living with HIV are engaged in all the steps needed to achieve an undetectable viral load. For example, in the United States it is estimated that only 19% to 28% of people living with HIV have an undetectable viral load (see Figure 1).4,5

Figure 1. Engagement in the HIV treatment cascade in the United States

Source: Adapted from the Centers for Disease Control and Prevention – Morbidity and Mortality Weekly Report, December 2nd, 2011.

There are currently no official estimates for the number of people engaged in the treatment cascade in Canada; however, preliminary data suggest that there are also significant leaks in the cascade in Canada and that the proportion of people with an undetectable viral load may be similar to that in the United States6 (although it likely varies across regions and for different populations).

Patching the cascade to improve treatment and prevention

Poor engagement of people living with HIV with healthcare and social services limits the effectiveness of our HIV programs and our response to the HIV epidemic. Increasing the number of people engaged at all levels of treatment and care may both improve the health of people living with HIV and reduce new HIV transmissions. Increasing engagement in the cascade requires programs that address the multiple barriers.

However, we do not know what the “ideal” cascade should look like and aiming to get everyone living with HIV on successful treatment is not realistic, nor would it be ethical. It’s critical that efforts to better engage people in services do not come at the cost of individual rights and that we make sure clients and patients are ready and willing to take each step. To ensure informed consent, the risks and challenges that come with testing positive for HIV and starting treatment need to be explained to clients and patients before they make these important decisions.

Let’s take a look at each step of the cascade, its importance for treatment and prevention, and how we might be able to better engage people in each step.

HIV testing and diagnosis

An estimated 26% of people living with HIV in Canada do not know they have HIV.7 Reducing the number of people who are unaware of their HIV status requires increased uptake and frequency of HIV testing.

Increasing the frequency and rates of HIV testing will help diagnose people sooner after they have become infected with HIV. Currently, many people in Canada are not learning about their HIV status until late in their HIV disease, when they start to develop symptoms or opportunistic infections.8 At this point, antiretroviral treatment can help improve their health, but not as effectively as when treatment is started earlier.9,10 Furthermore, research suggests that a disproportionate number of HIV transmissions originate from people who are unaware of their HIV status because they are less likely to take measures to prevent transmitting the virus to others 11 and are more likely to have a higher viral load, particularly if they have recently become infected and are in the acute stage of HIV infection.12 Earlier diagnosis is therefore important for both the health of a person living with HIV and for preventing the transmission of the virus.

These are some of the interventions being used in Canada to promote HIV testing and diagnose people earlier:

Campaigns to improve awareness of HIV risk and encourage people to get tested regularly. Campaigns such as Get on it in Ontario, Find out where you stand in Montreal, and What’s your number? and Hottest at the Start in Vancouver encourage gay men and other men who have sex with men to test regularly for HIV. Some of these also aim to improve awareness of acute HIV infection and its role in HIV transmission.

Improving access to more acceptable types of HIV testing, such as point-of-care (POC) antibody testing and peer testing, to increase options for people who want to get tested. For example, POC testing is now more widely available in large Canadian cities. Peer outreach and testing in gay bathhouses is offered by some organizations, such as Toronto’s Hassle Free Clinic. In Montreal, the SPOT Project offers gay men anonymous HIV rapid testing and counselling as well as a full range of tests for sexually transmitted infections (STIs) from a storefront site.

Improving access to tests that have shorter window periods and can detect HIV infection earlier than antibody tests. These tests can help identify people in the acute stage of HIV infection. For example, P24 antigen testing has been used in Ontario since 2010 and a pilot study using nucleic acid amplification (NAAT) testing is currently underway in Vancouver.

Making HIV testing a routine part of healthcare to increase the number of people offered an HIV test. For example, Vancouver is scaling up HIV testing; primary care facilities, acute care hospitals and a few dental clinics in the city are now routinely offering HIV tests to patients.

Integrating HIV testing with testing for other STIs. Some organizations, such as the Hassle Free Clinic, offer an HIV test to anyone seeking STI testing. This greatly increases opportunities for HIV testing since people are more likely to seek testing and treatment for other STIs than for HIV.

Enhanced partner notification services to better identify and diagnose people who may have been exposed to HIV. Some regions, such as Vancouver, are re-examining how they perform partner notification to improve the effectiveness of the service.

Linkage to care and support

Linking people who receive a positive diagnosis to accessible and culturally appropriate care and support services is important to ensure that people living with HIV enter the next step of the treatment cascade. Research shows that delays in linkage to medical care after HIV diagnosis are associated with faster disease progression.4 Interventions that currently improve linkage to care in Canada include the following:

Referral systems that link people diagnosed with HIV into care. For example, the Manitoba HIV program, which provides a wide range of integrated care and support services at two sites in Winnipeg, has a referral line for people who test positive. This line can be used by the healthcare provider who performed the test to refer newly diagnosed individuals to the Manitoba HIV program for care.

Improved outreach interventions. For example, the STOP Outreach Team in Vancouver uses case-management to connect people with complex needs to the most appropriate service or program and ensures strong engagement in care before discharging them from the team’s caseload.

Retention in care and adherence support

Once linked to care, a person needs to be supported and monitored and receive counselling to determine when they are ready and eligible to start treatment. Once a person decides to start treatment, remaining in care is important so a person can be supported with adherence and receive ongoing viral load monitoring to ensure that their treatment is working.

Appropriate care and support for people living with HIV may include a wide range of services in addition to medical care, such as mental health and addiction services, adherence support, affordable housing and prevention counselling. These services can improve the quality of life of people living with HIV, address the underlying reasons people may drop out of care or find it difficult to adhere to treatment, and improve sexual well-being. Research shows that a combination of medical care and additional types of care and support improve the health outcomes of people living with HIV13 and make them less likely to engage in behaviours that can lead to HIV transmission.14

Recently, the International Association of Providers of AIDS Care released guidelines for healthcare providers that contain 37 evidence-based recommendations to improve retention in care and adherence to antiretrovirals.

• Interventions and services are offered across Canada that keep people engaged in care and help them access treatment, adhere to their medications and prevent the transmission of HIV.
• Intensive case management approaches can improve engagement in care by providing tailored support to individuals who need it. For example, the Manitoba HIV program proactively follows up with people who entered the program but have been lost to care and provides highly individualized services to people who have a history of lapses in care.
• Maximally assisted therapy (MAT) programs deliver daily treatment and support services to their clients. For example, the Positive Outlook Program at Vancouver Native Health Services and the MAT program at the Downtown Community Health Centre in Vancouver both provide assistance with daily treatment adherence and comprehensive support to their clients.
• Peer navigator programs train HIV-positive peers to offer services to people living with HIV who face multiple barriers to engagement. For example, Positive Living BC’s peer navigators provide tailored support to people who need it. They do this through community outreach and at the Immunodeficiency Clinic at St. Paul’s Hospital.  
• Programs that offer psychosocial supports, such as housing and food security programs, can reduce structural barriers to engagement in HIV care and treatment. For example, La Corporation Félix Hubert d’Hérelle in Montreal, the SHARP Foundation in Calgary, and many others across the country offer housing and housing supports to people living with HIV. A Loving Spoonful in Vancouver offers 1,200 meals a week to people living with HIV.
• Programs that support people living with HIV to live healthy sexual lives and incorporate prevention as part of their overall health and well-being. For example, the Poz prevention program at Toronto People With AIDS Foundation provides peer consultations, training for service providers and group discussions on sexual health and HIV prevention.

What can you do?

Public health authorities, healthcare providers and frontline service providers all have a role to play in making services more accessible and providing people with ongoing care. 

Patching the leaks in the cascade may require new interventions and new partnerships and/or the re-conceptualization of how services are integrated and linked with other services. It may also involve changing how services are evaluated. 

Key questions to ask yourself and your organization are:

• How can your organization better engage people living with HIV in the treatment cascade?
• What additional services could your organization provide to improve engagement in one or more steps of the cascade? Can you learn from what other agencies have done? Would it work in your region?
• What initiatives or partnerships could you develop to connect people living with HIV to your services? What initiatives or partnerships could you develop to connect your clients with other relevant services in your community?
• How can you evaluate whether your clients are entering the next step of the cascade? 

As we work to improve engagement in the treatment cascade, it is critical that human rights are respected and that people living with HIV and at risk of HIV are empowered through information to make decisions about testing and treatment that are right for them. This includes information about the legal requirement to disclose prior to some sexual activities.

Improving HIV treatment and prevention

Each step in the cascade is important for improving the health of people living with HIV and preventing new transmissions. The idea of a treatment cascade is useful for conceptualizing how services are linked and for identifying gaps that need to be addressed. At the same time, it has several shortcomings. First, it represents care for people living with HIV as a linear process, which we know isn’t always the case. For example, a person living with HIV may fall out of care or stop treatment for various reasons, they may move backwards or forwards at different points along this continuum, or they may receive healthcare for many years without starting treatment. When developing programs and services, we need to take these realities into account. Secondly, the concept of a treatment cascade does not include prevention as a component of an effective response. As a model of care for people living with HIV, it indirectly reinforces the false view that the responsibility for HIV prevention rests solely with people living with HIV. In fact, prevention is a shared responsibility and all people, regardless of serostatus, have an important role to play. Additionally, treatment as a mechanism for prevention is only one of several effective prevention strategies, all of which, when appropriately combined will provide a more effective response to the HIV epidemic than any one strategy alone. We should no longer do prevention work in isolation of those working in HIV testing, treatment, care and support, as they are all reinforcing elements of an effective response to HIV.

While each organization has a role to play in improving care for people living with HIV, we also need to look at the issue from a systemic level. How can we, as policymakers, service providers, healthcare providers and people living with HIV, improve services for people living with and at risk of HIV? We need to identify gaps and ways to improve care in conjunction with the community, to ensure that a person can effectively navigate their way within the healthcare system. Fragmented, stand-alone programs and services need to be linked to ensure that people living with and at risk for HIV have access to services that can support their care. 

In September 2013, CATIE will host a national forum called New Science, New Directions in HIV and Hepatitis C. This forum will provide an opportunity for frontline workers to come together to learn about new directions in service provision, share programming experiences and strategize about developing more integrated approaches to treatment and prevention.

Resources 

TreatmentUpdate – HTPN 052: The trial that changed everything

Prevention in Focus – Detecting HIV earlier: Advances in HIV testing

Prevention in Focus – Recently infected individuals: A priority for HIV prevention

Prevention in Focus – The STOP HIV/AIDS Project: Treatment as prevention in the real world

References

1. Nakagawa F, Lodwick RK, Smith CJ et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS. 2012 Jan;26(3):335–43.

2. Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493–505.

3. Hull MW, Wu Z, Montaner JSG. Optimizing the engagement of care cascade. Current Opinion in HIV and AIDS. 2012 Nov;7(6):579–86.

4.a. b. Gardner EM, McLees MP, Steiner JF et al. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clinical Infectious Diseases. 2011 Mar 1;52(6):793–800.

5. Vital signs: HIV prevention through care and treatment--United States. MMWR Morb. Mortal. Wkly. Rep. 2011 Dec 2;60(47):1618–23.

6. Adam BD. Epistemic fault lines in biomedical and social approaches to HIV prevention. Journal of the International AIDS Society. 2011;14(Suppl 2):S2.

7. Government of Canada Public Health Agency of Canada. HIV/AIDS Epi Updates—July 2010. [Internet]. Available from: www.phac-aspc.gc.ca/aids-sida/publication/epi/2010/2-eng.php

8. Althoff KN, Gange SJ, Klein MB et al. Late presentation for human immunodeficiency virus care in the United States and Canada. Clinical Infectious Diseases. 2010 Jun;50(11):1512–20.

9. Li X, Margolick JB, Jamieson BD, Rinaldo CR et al. CD4+ T-cell counts and plasma HIV-1 RNA levels beyond 5 years of highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes. 2011 Aug 15;57(5):421–8.

10. Siegfried N, Uthman OA, Rutherford GW. Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults. Cochrane Database of Systematic Reviews. 2010 Mar 17;(3):CD008272.

11. Marks G, Crepaz N, Senterfitt JW, Janssen RS. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: implications for HIV prevention programs. Journal of Acquired Immune Deficiency Syndromes. 2005 Aug 1;39(4):446–53.

12. Miller WC, Rosenberg NE, Rutstein SE, Powers KA. Role of acute and early HIV infection in the sexual transmission of HIV. Current Opinion in HIV and AIDS. 2010 Jul;5(4):277–82.

13. Giordano TP, Gifford AL, White AC et al. Retention in care: a challenge to survival with HIV infection. Clinical Infectious Diseases. 2007 Jun 1;44(11):1493–9.

14. Metsch LR, Pereyra M, Messinger S et al. HIV transmission risk behaviors among HIV-infected persons who are successfully linked to care. Clinical Infectious Diseases. 2008 Aug 15;47(4):577–84.

About the author(s)

James Wilton is the coordinator of the Biomedical Science of HIV Prevention Project at CATIE. James is currently completing his master’s degree of Public Health in Epidemiology at the University of Toronto and has completed an undergraduate degree in microbiology and immunology at the University of British Columbia.

Logan Broeckaert holds a Master’s degree in History and is currently a researcher/writer at CATIE. Before joining CATIE, Logan worked on provincial and national research and knowledge exchange projects for the Canadian AIDS Society and the Ontario Public Health Association.