This article by Roger Pebody  first appeared on aidsmap.com here.  

The majority of American gay men in relationships say they establish a ‘sexual agreement’ with their partner, both to minimise HIV risks and to maintain the quality of their relationship, according to research published online ahead of print by the Journal of Sex Research last month.

However, partners do not always agree on whether they have an agreement, on whether it was explicitly discussed, or on what sex is allowed with other people. And the agreement had been broken by one or both partners in just under half the couples studied.

The study has also found that around a quarter of the HIV-negative men who have casual sex attempt to 'serosort' or use 'strategic positioning' when doing so. However, regular HIV testing was far from universal in this group, making such practices potentially unreliable.

“From a public health perspective, we need to encourage gay couples to have more honest and explicit discussions when establishing and honouring sexual agreements,” commented Dr Jason Mitchell of the University of Michigan, who conducted the research. “Sexual agreements are not only advantageous from a prevention standpoint for couples, but the agreement can also help strengthen their relationship.”

A sexual agreement is made between two individuals, and concerns what sexual behaviour may occur within and outside their relationship. Some agreements may simply clarify that sex is not permitted with other people. Other agreements may concern the relationship being ‘open’ to a lesser or greater extent. Many couples use agreements, in part, to limit their risk of HIV infection.

A couples study

Jason Mitchell’s study recruited both partners in couples and compared their responses, rather than relying on just one partner’s perspective. Men were recruited to this cross-sectional online survey via adverts on Facebook in 2011 – the advertising was targeted to reach individuals whose profile information indicated that they might be a man in a relationship with a man. The first participants provided the email address of their partners, who were then contacted and asked to complete the survey.

The study recruited 722 men (361 couples). This was a predominantly white (77%) and relatively well-educated sample, with a mean age of 33, all living in the United States. Couples had been together for an average of an average of five years; three-quarters were living together.

One in eight men had been diagnosed with HIV. Half of them were in a relationship with another man with HIV, and half with an HIV-negative man (i.e. in a 'serodifferent' or ‘serodiscordant’ relationship).

Most men reported that they were HIV negative. (Just 3% of the sample reported that they did not know their HIV status.) However, one in five of the ‘HIV-negative’ men had not tested since the beginning of their relationship, and on average, HIV-negative men had last taken an HIV test two years ago. There was considerable diversity in the men’s HIV testing practices, with a minority testing much more frequently than others.

On average, men said that they had discussed their HIV status 12 days into the relationship, and this occurred before the couple started having unprotected sex (a mean of 81 days into the relationship). However, when the couple made a sexual agreement, this typically occurred much later – 174 days into the relationship. 

Agreements

Although seven in ten men reported having a sexual agreement, this perspective was not always shared by the man’s partner. In 57% of couples both men agreed that they had a sexual agreement, but in 25% of couples, one man thought there was an agreement, while his partner said that there wasn’t.

Amongst those couples who agreed that they had agreed, 58% said that there had been an explicit discussion, while 11% reported that their understanding was more implied or assumed. In a further 31% of cases, one partner had thought they had had an explicit discussion, while his partner thought that it was implicit.

For 56% of men who thought they had an agreement, it was that the relationship was monogamous.

For a further 41%, the agreement was to permit sex with casual partners, but with some rules or guidelines. For the last 3%, there was an open relationship, without any conditions.

Responses detailing what was permitted for those with open relationship guidelines showed that around a quarter actually permitted unprotected anal sex with casual partners. While the data shows that some couples had different rules for receptive and insertive sex, and for withdrawal before ejaculation, respondents were not asked whether there were conditions based on the partner’s HIV status and seroadaptive behaviours.

Far more couples allowed oral sex and masturbation.

Open relationship guidelines were not just about the risk of infections, but also about intimacy and context. Having sex with a casual partner on more than one occasion, physically sleeping together and dating were all permitted by half or less of couples, whereas threesomes or group sex were allowed by 81%.

Men’s motivations for making agreements were not just about minimising the risk of HIV or sexually transmitted infections, although this was the most common primary reason, cited by 23%. Other important reasons included wanting monogamy or exclusivity; fulfilling sexual desires; establishing guidelines so as to manage expectations; and building and maintaining trust.

Jason Mitchell did not analyse motivations by type of agreement, but in a separate study, another group of researchers previously found that the themes of trust, honesty and strengthening the relationship were predominant in the motivations both of men with open agreements and men with monogamy agreements.

Breaking agreements

Looking at couples, including those with an agreement to monogamy, in 46% of cases, either one or both partners had broken the rules at some point during the relationship.

But in the previous three months, 80% of couples had stuck to their rules. In 15% of the couples, one partner had broken the agreement, and in 5% both partners had.

The main reasons for breaking agreements were sexual frustration and the ‘heat of the moment’. Only a minority of men (30%) told their partner that they had broken the agreement. Reasons given for not disclosing included not giving the partner a reason not to trust the respondent and fearing that this could lead to the relationship ending.

Risk reduction strategies

In a separate article, published in AIDS & Behavior in December, Jason Mitchell has also reported on the risk-reduction strategies employed by this group of men, both inside and outside of their primary relationships.

He was interested in strategies such as serosorting, strategic positioning, 100% condom use and taking undetectable viral load into account.

This analysis is especially interesting because Mitchell actually asked respondents whether they had used strategies to reduce their risk of HIV or sexually transmitted infections. In contrast, most other studies on this topic have examined the pattern of men’s sexual practices with partners of different HIV statuses, and attempted to infer whether there was a strategy in place or not.

It therefore hasn’t been clear from previous research whether the conscious and deliberate use of strategies such as strategic positioning is something widely practiced by gay men, or just a minority pursuit.

For this couple-based analysis, those couples in which both partners had diagnosed HIV were excluded. Participants were asked about strategies used in the last previous three months – they could name more than one strategy, either because strategies were combined, or because different strategies were used in different situations.  

Always using condoms for anal sex, or always doing so with an HIV-positive partner, was reported by a minority of men. Within the main relationship, 15% of HIV-negative couples (i.e. in which both partners thought they were negative) always used condoms, rising to 38% of serodifferent couples (i.e. in which one partner had HIV and the other did not).

When having sex outside the relationship, 38% of men always used a condom for anal sex.

Only having oral sex and never anal sex was reported, for the main relationship, by 23% of HIV-negative couples and 31% of serodifferent couples. This strategy was more commonly reported for sex with casual partners – by 51% of men.

'Serosorting' (having unprotected anal intercourse [UAI] with a partner because he was thought to have the same HIV status) was reported by 66% of HIV-negative couples. Moreover, this was also reported for sex with casual partners, by 27% of men.

‘Strategic positioning’ (only having UAI with the HIV-positive partner in the receptive role) was reported, for the main relationship, by 32% of serodifferent couples. During casual sex, it was also reported by 23% of men.

Having unprotected sex because the HIV-positive partner was either taking HIV treatment or had an undetectable viral load was reported by 24% of serodifferent couples.

It was much less commonly employed as a strategy with casual partners – by 1% of men in an HIV-negative couple and 14% of men in a serodifferent couple

Finally, it’s important to note that a significant proportion of men did not have a risk-reduction strategy at all, especially with their main partner. One of the answers men could choose was ‘‘regardless of HIV-status, we never use condoms and ejaculate inside’’.

For their primary relationship, 24% of HIV-negative couples and 22% of serodifferent couples chose this answer. It was also chosen by 9% of men having sex outside the relationship.

Overall, having unprotected sex within the main relationship (in the last three months) was reported by 87% of HIV-negative couples and 69% of serodifferent couples. Moreover, for 16% of couples, there had been unprotected sex both with the main partner and at least one casual partner during the same time frame.

Improving the quality of agreements

Clearly, with a number of couples permitting unprotected anal sex outside of the relationship and with a significant minority of men breaking agreements in one way or another, there are risks that HIV can be brought into relationships.

The research highlights a number of other limitations of some men’s sexual agreements, in terms of the frequency of HIV testing, the discrepancy in partners’ perceptions of whether there is an agreement and what it entails, and the quality of communication following breaks in an agreement.

This suggests that HIV-prevention interventions which support men in strengthening their relationships and in making better agreements would be warranted.

One such approach that is being piloted is couples voluntary counselling and testing, in which couples take an HIV test and receive the results together. The focus of the counselling is not on past sexual history, but on how the couple wish to manage the risk of HIV in the future. Quantitative and qualitative research suggests that this is an intervention that many men in relationships would be interested in.

References

Mitchell JW Characteristics and Allowed Behaviors of Gay Male Couples' Sexual Agreements. Journal of Sex Research, online ahead of print, 2013. (Abstract here)

Mitchell JW, Petroll AE Patterns of HIV and sexually transmitted infection testing among men who have sex with men couples in the United States. Sexually Transmitted Diseases 39: 871-876, 2012. (Abstract here)

Mitchell JW HIV-Negative and HIV-Discordant Gay Male Couples' Use of HIV Risk-Reduction Strategies: Differences by Partner Type and Couples' HIV-Status. AIDS & Behavior, online ahead of print, 2012. (Abstract here) 

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 Michael Carter first appeared on aidsmap.com here.  

Coffee consumption reduces the risk of liver cancer by approximately 50%, the results of a meta-analysis published in the online journal BMC Gastroenterology show. A total of 16 studies published before May 2012 were included in the analysis. Closer examination of the results suggested that the magnitude of the protective effective of drinking coffee was higher among men than women and also differed between patients of Asian and European origin. However, the authors do not believe their results are definitive and call for further research.

Liver cancer is an increasingly important cause of illness and death in both men and women. Infection with hepatitis B or C and excessive alcohol consumption are known risk factors for the malignancy. Factors protective against the development of liver cancer are uncertain, and the impact of coffee consumption is especially controversial.

A team of Chinese investigators therefore performed a meta-analysis of case-controlled and cohort studies examining the impact of coffee consumption and the risk of liver cancer.

Nine case-controlled and seven cohort studies met the investigators’ inclusion criteria. A total of eleven studies were conducted in Asia (nine in Japan) and five in Europe. All the studies provided data on the risk of liver cancer according to coffee consumption. However, there was little heterogeneity between the design of the studies. In particular, the level of coffee consumption against which the risk of liver cancer was assessed varied considerably, from as little as one cup each day to as many as eight or more daily cups.

Overall, the investigators found that a high coffee intake reduced the risk of liver cancer by 50% (OR = 0.50; 95% CI, 0.42-0.59). The protective effect of coffee consumption was similar in the case control studies (OR = 0.50; 95% CI, 0.40-0.63) and the cohort studies (OR = 0.48; 95% CI, 0.398-0.62).

Adjusting the results to take account of liver disease status provided similar results (OR = 0.54; 95% CI, 0.46-0.66).

“The results of the current meta-analysis…suggest that there is an inverse association between coffee consumption and liver cancer among different groups according to consumption level,” comment the investigators. “There were significant reductions of 50% in the risk of liver cancer with the highest consumption of coffee compared with non/almost never consumption.”

Stratifying the results by region suggested that the degree of protection provided by coffee consumption was higher in Asia (OR = 0.45; 95% CI, 0.36-0.56) than Europe (OR = 0.57; 95% CI, 0.44-0.75). 

“The different results may be explained by racial differences,” suggest the authors. “Differences in coffee drinking habits may be a partial explanation for the discrepancy.”

Analysis according to sex showed that drinking coffee reduced the risk of liver cancer by 62% in men (OR = 0.38; 95% CI, 0.25-0.56) and by 40% in women (OR = 0.60; 95% CI, 0.33-1.10).

The authors note that caffeine has antioxidant properties, possibly explaining the protective effect of coffee consumption. However, the meta-analysis was unable to show the level of coffee consumption needed to provide protection against liver cancer.

“The results of this meta-analysis suggested that coffee consumption may be associated with a reduced risk of liver cancer,” the authors conclude. “However, because of potential confounding, this finding should be treated with caution. Further better-controlled studies are needed to confirm this finding.”

Reference

Sang L et al. Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis. BMC Gastroenterology, doi: 10.1186/1471-1230X-13-34, 2013.

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.

PrEP – or Pre-Exposure Prophylaxis – as an HIV prevention tool has been a hot topic within HIV circles for months, particularly since May 2012 when the Food and Drug Administration (FDA) recommended for approval the use of Truvada to seronegative people at high risk of contracting HIV. On July 16th, 2012, the FDA took historic steps in approving Truvada as the first pill used to help prevent transmission of HIV. 

Truvada was approved for PrEP usage based on the findings of the PrEP Initiative (or the iPrEx Study) which was a double-blind study involving 2,499 HIV-negative men or transgender women who have sex with men. 1,251 of them were given Truvada while the remaining 1,248 received a placebo. The study took place in six different countries around the world between July 2007 and December 2009.   

Back in 2011, The Body.com published an article entitled “Six Reasons Why People Skip Their HIV Meds”, which outlined – you guessed it – the myriad barriers that get in the way of sticking to a strict ARV regime. Though this article speaks specifically to people living with HIV, the hurdles that impede some poz folks likely also apply to those taking Truvada preventatively. For some, the task of “simply” remembering to take their meds like clockwork can be burdensome; however, similarly to the birth control pill, Truvada is most effective when taken precisely at the same time daily.

The iPrEx Study found that for those able to adhere to the strident prescription guidelines, the efficacy of PrEP was more than 90%, which is both considerable and noteworthy. While this number – more than 90% effective against the transmission of HIV – sounds appealing, it’s important to stress that this number reflects the ideal scenario in which everyone always takes Truvada as they should; unfettered access, no missed pills, no mistakes. Within the somewhat idyllic (i.e. the environment of a study which focuses on sexual practices, safer sex and HIV prevention with the pills being consumed serving as a daily reminder of this study) conditions of a clinical trial, a number like this isn’t shocking. In fact, it’s to our benefit to see the highest potential of PrEP and how it can thrive in ideal conditions. 

In the real world however, people fuck up. Sometimes a lot. So what does this look like in relation to PrEP? It looks like rates of protection against HIV transmission hovering around 44%, which isn’t quite as sexy as more than 90%, is it?

It is likely for this reason that Gilead Sciences, the manufacturers of Truvada, stress that Truvada, when used for PrEP, must be used in combination with other safer sex practices and shouldn’t be used as the only source of protection against HIV transmission. Oddly, this crucial piece of information hasn’t been highlighted as much as one might expect in various newspaper articles and coverage on Truvada which is concerning as it might inadvertently suggest that Truvada alone would be enough protection against HIV transmission. In the event that Truvada is used as a singular tool against the transmission of HIV, additional issues are raised around the transmission of other STIs and the problems this may cause. 

As outlined in “Six Reasons”, challenges to medication adherence reach beyond just taking the pill daily. Navigating the medical system can be a monster. For many folks within North America, the seemingly simple task of having a GP can be near impossible. In Toronto, for example, it has become exceedingly difficult over the last few years to find a health care clinic or centre that is accepting new patients, let alone to find a doctor who would be familiar with the ins and outs of HIV prevention and open to prescribing off-label usage of Truvada. 

Should you find yourself lucky enough to secure a doctor and garner access to PrEP, another issue you may face is whether or not you have health insurance and if this insurance will cover Truvada. Without health insurance, the cost of PrEP monthly is close to $1,000. With coverage, the price would be reduced; however, it could likely still cost several hundreds or even thousands of dollars annually. For many considering the use of Truvada for PrEP, the cost associated with the drug brings those considerations to an end. For someone who makes a modest $45,000 a year salary, paying for PrEP without coverage would attenuate approximately 25% of your annual wages, which is a position that for many (ironically, those who might benefit from the use of Truvada the most) are not able to afford.

Not surprisingly, upon the FDA’s approval of Truvada for PrEP, Gilead Sciences declared that they would not change (read: lower) the price of the drug. Given the notorious greed and cut-throat mechanisms which Big Pharma utilizes to profit off of people’s health and well-being, it’s far from astonishing that Gilead Sciences didn’t budge on their pricing given the new expansion of their market and potential for profit. 

Outside of the financial barriers which many may face in accessing Truvada, there are a slew of other elements which could impact peoples’ ability to stick to an unyielding pill regime including depression and various other mental health issues, unstable housing, busy schedules and importantly, the side effects which Truvada can cause. For some people, side effects are a non-issue but for others, experiencing severe side effects can be enough to deter them from adhering to their meds.  

Some of the more minor side effects include nausea, headaches, dizziness, diarrhea, rash, vomiting, abdominal distension/pain, and gas. While none of those sound terribly pleasant – particularly bad cases of diarrhea and vomiting which could be debilitating in some cases – they could be tolerated.

Some of the more serious side effects are a bit more worrisome including lactic acidosis, which is the build-up of acid in blood and a condition which could be considered a medical emergency. Symptoms of lactic acidosis include weakness, unusual muscle pain, difficulty breathing, nausea, vomiting, irregular heartbeat and feeling lightheaded.

Another serious side effect of Truvada is hepatotoxicity or chemically-induced liver damage. Some of the symptoms of hepatotoxicity include liver enlargement, jaundiced (yellowed) skin and the whites of your eyes, dark coloured urine, light stools, lack of appetite, nausea, and pain in your lower stomach. 

As noted on Truvada’s website, one of the causes of hepatotoxicity is long-term use of Truvada. What “long-term” means isn’t exactly defined but it does make me consider what other long term side effects may occur especially since Truvada has only been on the market for nine years (approved in 2004).

As with any medication, these are potential side effects that will impact people in different ways, to varying degrees, if at all. Additional serious side effects include new or worsening kidney problems and bone problems such as thinning or softening leading to fractures. 

For those who are taking Truvada preventatively, it hasn’t yet been determined (based on Truvada’s website, the IPrEx Study, and various newspaper article reporting on Truvada) how long people can be on this drug. The potential for long-term side effects coupled with concerns around developing a resistance to Truvada (typically caused by intermittent or inconsistent use) warrants raising additional questions around the safety and use of the drug. 

To be clear, I believe there is a great deal of value in PrEP as a prevention tool and that a battery of preventive options should and must  be available to people in order to adequately meet the needs of the diverse plethora of sexually active folks the world over. My concern lies in how easily we have jumped on the PrEP bandwagon without necessarily examining the multitude of complexities that accompany it.

Images like this don’t exactly showcase the various factors which one might want to consider before committing to taking PrEP. This advertisement, created by The Stigma Project, presents an image of a young man who appears happy and care-free with his Truvada in hand and not a worry in the world. According to this ad, PrEP is more than 90% effective against HIV transmission – apparently prevention is as simple as popping a pill! But that only applies to you if the numerous reasons for not taking your meds outlined in this article don’t apply to you.  

All this being said, there are many who have engaged and thought critically on the numerous complexities which complicate PrEP, one example being Len Tooley in his interview with PositiveLite.com's John McCullagh (see related articles, below). For many, PrEP will and can be an excellent option for HIV prevention. My hope is that the development of PrEP continues in a way that makes it more effective and accessible for anyone who wants to use it. I also hope that critical conversations about PrEP expand and continue in order to challenge the various uncertainties and barriers which currently engulf it.

Report of the 20th Conference on Retroviruses and Opportunistic Infections (CROI) of a presentation by Susan Buchbinder . 

Reports of the HIV ‘cure’ of a baby in the USA have attracted global attention. My guess is that although this provides further support for the concept of cure, and will add momentum to research, it will make no immediate difference to mothers and their babies. Once more information emerges from the conference, I might return to this topic.

Reading other conference presentations, there is information on prevention that is of immediate strategic relevance.

In her presentation on “HIV Prevention Research: What’s Next?” Susan Buchbinder highlights evidence that provides a useful guide for action.

Networks - again

In HIV, size matters. HIV prevention work must address the influence of sexual networks and the numbers of sexual partners on HIV transmission. The point here is that even a small increase in the mean number of partners a person has in a community leads to a massive degree of interconnectedness of networks. The flip side is that if we can reduce that number of sexual partners, the potential for rapid spread is also massively lowered.

The data presented by Buchbinder is taken from Carnegie (2012) which modeled a population of 10,000 in which 44% had one sexual partner in the year, and 56% had two or three partners. In this case, there was only a 2% interconnectedness through networks.

Immediately that percentage with two or three partners increases, so much the greater is the interconnectedness. Relatively small increases of 4% having two or three partners bump the interconnectedness to 10%. If 64% have two or three partners, it rises to 41%. At a 68% of individuals with two or three partners, interconnectedness rises to a massive 64%.

According to McDaid’s (2012) most recent bar-based study, 11.9% of gay men interviewed had more than six sexual partners in the previous 12 months. Of those who had never tested, 24.1% reported a high-risk event of unprotected anal intercourse in the previous 12 months.

Disparate efficacy

It has been reported previously and I have commented on the steadying of rates of increase in new infections globally. After the peak in the mid 1990s, there has been a decrease of 25% in new cases, attributable to a variety of factors including the effect of treatment on infectivity. It might be too early to identify such a trend in the UK, but from what we understand, a plateau overall in rates of diagnosis of HIV conceals a worrying disparity between populations most affected. Whilst new heterosexual infections have reduced, in contrast among men who have sex with men they have increased. The same is true in the USA, Sub-Saharan Africa, and Latin America.

In the USA, more detailed analysis reveals the impact not only upon MSM but also upon black MSM, particularly in the South which represents nine of the ten areas with highest fatality rates, mirroring high rates on HIV incidence. Globally, HIV rates in MSM are 50 times higher than in the population generally. Geography, race and sexuality matter in this context.

Focus of prevention as well as of public interest upon sero-discordant couples reveals an assumption that this is the major source of new infections. In fact, within Sub-Saharan Africa, the majority of men infected acquire their HIV outwith their primary relationship. Women on the other hand are more likely to become infected within their relationship. Risk strategies and messages need to be different. Reaching and influencing men is key to prevention.

The high rates of HIV in MSM and the disparate risks between men and women in heterosexual relationships cannot but be linked. Legal and safety barriers for men who have sex with men are all the greater with the current anti-gay politics and laws being debated and passed in many African nations. This serves to increase infectiousness because African men are less likely to test or to go on treatment. At the same time secrecy and fear drive men’s sexuality underground and out of reach of prevention.

Real life science

The research priority currently is in treatment as prevention. Not only do we know that in specific circumstances an undetectable viral load reduces infectivity, but that statistically the same treatment is as effective as condom use in HIV negative individuals.

The best research results are reported in highly controlled trials. Less promising are the Fem-Prep trials and a trial recently with MSM in Chicago. The differences are not in the drug formulations or the kinetics and dynamics of the drugs, but in adherence to the demands of a strict regimen. Without good adherence, poor concentration of drug reduces its effect on viral load and therefore on infectivity.

The rate of adherence in the Chicago MSM study was found to be only 20%. The most likely explanation is that instead of taking the drug Truvada regularly every day, men were using it occasionally and only when they anticipated having sex. This is difficult to establish without some way of reliably linking time of medication to the time when the men had sex.

Efforts to improve adherence are looking at interventions such as texting, not to remind individuals when to take the medication, but to establish what kind of support might be needed at different times. A comparison with texting to remind people when to apply sunscreen ie when the sun was out, found a better response for the sunscreen than for anti-retrovirals. In other words, getting your shirt off and slapping on factor 25 is less stigmatising than swallowing down Truvada before unprotected sex with a positive partner!

Better cover

The standard and effect of research from the USA is outstanding, related primarily to the power of the dollar and the prestige of its academia. Sequestration of their budgets is likely to knock this primacy, but even more worryingly, it will hit hardest those who are without a good insurance policy in one of the few Western or indeed medium resourced nations with no universal health cover.

For prevention to be effective, it needs to use various drivers. We see clearly that the effectiveness of biomedical interventions such as treatment as prevention and more detailed action such as PEP and PrEP depend on a host of other factors.

If for example, 80% of those diagnosed with HIV are on ARVs and diagnosed at or around a CD4 count of 350, then modeling suggests a major impact on transmission. Treatment of all people with HIV was credited with the promise of the future elimination of HIV at last summer’s Washington 2012 international conference. In the cooler and more reflective Atlanta of March 2013, optimism might be as lively, but hope faded in light of the reality on Capitol Hill. In Scotland, the 80% point is exceeded by our HIV clinics, yet we see rates of HIV continue to rise. Fall in condom use has already been suggested as a major factor. In addition, however, the fact that 50% of new infections are diagnosed below the 350 CD4 count level, and half of them below 200, adds to a tragic Sisyphean effort of never quite getting the boulder to the top of the hill.

Summary

Mainly structural and socially determined factors negatively affect our prevention efforts. Buchbinder summarised in the following five points:

• Understanding and addressing disparities
• Understanding drivers, design and test interventions for largest impact
• Identifying new PrEP agents, delivery and scalable, durable adherence interventions
• Integrate clinical trials, ecological studies and mathematical modeling
• Scale up, measure impact, correct course

This article first appeared on Roy’s own blog scotfreehiv here.