Fwd: CATIE News - Swiss guidelines take a troubling turn

[Guest guest]

From: info@...To: catie-news@...Sent: 3/7/2008 12:47:39 P.M. Central Daylight TimeSubj: CATIE News - Swiss guidelines take a troubling turn

CATIE News - Swiss guidelines take a troubling turn

In February 2008, the Swiss National AIDS Commission published an article about safer-sex practices. Specifically, the Commission stated that HIV-positive people are not at risk for transmitting HIV to their partners if they meet all of the following requirements:

* they are adherent to highly active antiretroviral therapy (HAART)* their viral load in the blood is consistently below the lower level of detection (usually 50 copies in Canada and 40 copies in Switzerland)* they are in a “stable relationshipâ€* they do not have any sexually transmitted infections (STIs)

Readers should note that the Swiss Commission’s statements about unprotected sex are based on opinion and not fact. We urge all sexually active people to continue to practice safer sex and take other precautions so as not to acquire or pass on HIV to their partners and to protect themselves from other STIs, many of which can be symptom-free.

In response to the Swiss Commission’s opinion, the following agencies have recently reinforced the importance of safer sex in preventing HIV infection:

* the Public Health Agency of Canada (PHAC) * the American Centers for Disease Control and Prevention (CDC)* the French Ministry of Health* the World Health Organization (WHO)* UNAIDS (the United Nations program on AIDS)

That the Swiss have issued guidelines that appear to weaken prevention messages against HIV transmission is disheartening, particularly at a time when HIV infections are on the rise in the high-income regions of North America and Western Europe.

What’s up?There are many problems with the opinion of the Swiss Commission. Perhaps most disturbing is that it is based on an apparent belief and not robust scientific data. Moreover, some of the references cited by the Swiss do not appear to support their opinion. The assumptions made by the Swiss Commission are weak, as they appear to have overlooked, forgotten or misunderstood important research.

A key assumption made by the Swiss is that a suppressed viral load in the blood results in a suppressed viral load in other parts of the body, particularly in the genital tract. In this article we summarize evidence showing that this is not the case. We also address other weaknesses that significantly undermine the foundations of the Swiss Commission’s opinion.

The limits of therapyIntroduced in high-income countries in 1996, highly active antiretroviral therapy, or HAART, which consists of potent combinations of anti-HIV drugs, has helped save and extend the lives of many HIV-positive people. The drugs work by impairing HIV’s ability to infect cells and produce new viruses. This gives the immune system a chance to begin to repair the damage caused by HIV.

However, after many years of HAART and good adherence in HIV-positive people, researchers have not been able to cure HIV infection. Attempts at a cure have consisted of intensifying therapy, adding unusual medications to regimens and, later, the cessation of HAART. But once HIV-positive people stop taking HAART, virus levels surge, damaging the immune system and increasing the risk of death.

It is important to bear in mind that HAART can also cause unpleasant and dangerous side effects. Although much progress has been made in the past 25 years against AIDS, HIV remains an incurable and deadly infection.

Viral load—undetectable may be misleadingTo ensure that anti-HIV therapy is working, doctors regularly have blood samples from their patients assessed for viral load, as one of the goals of HAART is to suppress viral load in the blood as low as possible. Commercially available technology can usually assess viral loads as low as 50 copies. When a viral load result returns with an “undetectable†reading—below the 50-copy mark—it does not mean that HIV is not replicating. New copies of HIV could be produced and new infections could be occurring in the body, but the test cannot accurately assess viral loads below the 50-copy mark. Tests that can count viral load below the 50-copy mark are restricted to research laboratories and not used for routine care.

Viral load—focus on 2% It is also worth remembering that only 2% of the body’s immune cells are carried in the blood at any given time. The vast majority (98%) of the immune cells, including CD4+ cells, spend most of their time in the lymph nodes and lymph tissues lining the gastrointestinal tract. Since so little HIV is actually produced in the blood, we cannot be sure that routine viral load testing accurately reflects the amount of HIV present in other parts of the body. Thus an undetectable viral load in the blood does not necessarily indicate a low or a high level of HIV replication in other parts of the body.

A word about blipsIn addition, many people on HAART experience “blips†in their viral loads. These are periods when the amount of HIV temporarily increases into the detectable range, generally anywhere from 51 to 500 copies. Usually the viral load drops back below detectable limits without a change in therapy. What causes these “blips,†how often they occur, and how long they last is not generally well understood. And the fact that blips are relatively common pokes yet another hole in the assumptions made by the Swiss Commission about the stability of viral load.

Timing of viral load testsIt usually takes a few weeks before viral load test results are sent to a doctor’s office. By the time a patient has returned to the doctor’s office for the results, several weeks or even a month may have passed since the test was done. During this time, viral load could rise depending on a number of factors. The viral load at the last test does not necessarily represent the viral load at another point in the future. One factor that can affect viral load is the ability to take medications every day, exactly as prescribed. This behaviour is called adherence.

Adherence and viral loadA recent American clinical trial documented how adherence can change over time, whether HAART is taken once or twice daily. As adherence degraded in the study, viral load rose above the 50-copy mark. When participants were told that their viral load had risen and they needed to submit another blood sample to confirm this result, their adherence improved and viral load fell below the 50-copy mark.

Adherence is a dynamic behaviour: It can go up or down and change yet again—and so can viral load. Therefore, relying on viral load measures to prevent HIV infection is fraught with risk.

Blood vs. semenThe genital tracts of men and women can have a different viral load from that of the blood. Men taking HAART may have a suppressed viral load in the blood, but viral load in the semen may not simultaneously be suppressed. Here is one reason for this:

* HAART may not fully penetrate and suppress HIV in the genital tract.

In one study at the University of Pittsburg, researchers with experience finding HIV in different parts of the body monitored the health of eight men taking HAART for five years. During this time, viral load in their blood was below the 50-copy mark. However, the research team was able to find that HIV had been replicating, at low levels, in both blood and semen samples from the men over the five years of the study. This replication was not due to drug resistance but likely because drugs could not accumulate in all regions of the genitals. The team was also able to find a greater proportion of HIV-infected cells in semen samples than in blood, even though there are more cells to infect in the blood than in semen. This finding occurred throughout the study.

The source of HIV that occurs in semen is not clear. Some researchers have fingered the prostate gland as a possible reservoir of HIV. However, more recent research, focusing on men who do not have STIs, suggests that there may be other parts of the male genital tract that harbour HIV.

Other studies have also assessed HIV levels in semen samples from men whose viral load in the blood was less than 50 copies. Depending on the study, the proportion of these men with detectable HIV in their semen has been between 7% and 40%.

Overall, these studies highlight the risk of exposure to semen, even if viral load in the blood was less than 50 copies.

The Swiss Commission suggests that men with viral loads below the 50-copy mark may have HIV in their semen that might not be capable of causing infection. We argue against that. Researchers who have conducted long-term studies of HIV-positive people on HAART have found HIV in cells from their blood and elsewhere that can replicate. The idea that HIV in semen may have special properties that render it non-infectious seems strange, given that sexual transmission is the most common way that HIV is spread.

Semen—more than HIVResearchers have found that HIV is not the only virus that can be found in semen. Several teams have isolated the following viruses from human semen samples:

* cytomegalovirus* hepatitis B virus* hepatitis C virus* herpes simplex virus* human herpes virus-8* human papilloma virus

Avoiding exposure to semen (and other fluids from the male genital tract) can reduce not only the risk of HIV infection but also other viral infections.

Women and viral loadResearch on HIV in the female genital tract appears to be more limited than in men. However, results similar to those in men have generally been found. Specifically, HIV can be detected in the genital secretions of women, whether or not they are taking HAART and regardless of the viral load level in their blood. Similar to the situation in men, not all anti-HIV medications can enter and reach high levels in the female genital tract.

And don’t forget the rectumResearchers in Seattle, Washington, have assessed HIV not only in the blood but also in semen samples and rectal tissue from 64 men. Twenty-seven, or 42%, of these men were taking anti-HIV medications. The study team found that these medications reduced viral load in the blood and semen. But HIV could still be detected in the semen of these 27 men on medication. Furthermore, HIV could also be found in the rectums of the men, whether or not they took anti-HIV therapy.

Sneaky STIsSTIs in the genital tract can cause inflammation and activate latent HIV hiding inside cells. This activation stimulates HIV out of hiding and turns cells into virus factories. Increased HIV in the genital tract together with inflammation heightens the risk of transmitting HIV.

The Swiss Commission does suggest that HIV-positive people be educated about the symptoms of STI infection. This approach to detecting possible STIs, while well intentioned, is at best problematic. Here is why:

A study by the San Francisco Department of Public Health of men who have sex with men found many cases where men were infected with STIs but were unaware of it because the infections were free of symptoms. Moreover, because the infections were at different places in the body, simply screening the urethra (the tube in the penis through which urine flows) for STIs would have missed detecting these infections elsewhere in the body. Here are some findings from their study:

* 85% of cases of rectal infections with either chlamydia or gonorrhea were symptom-free.

* 53% of chlamydia infections and 64% of gonorrhea were in either the throat or rectum

* 70% of chlamydia infections occurred in men who did not also have gonorrhea.

The San Francisco researchers say that these findings prompt the need for screening different parts of the body for these infections. They also underscore the fact that STIs can occur without causing symptoms.

Another study in Birmingham, Alabama, focusing on men, found that another STI—genital herpes—can occur in the absence of symptoms.

Overall, these findings confirm that self-checks for symptoms of STIs may not be the most reliable way to assess infection with these germs.

Misreading the dataOne of the key studies upon which the Swiss Commission’s assumptions rest, is an observational study from Spain. Observational studies are not the most reliable way to investigate a research question. These studies can find associations but are unable to link cause and effect.

In the Spanish study, researchers recruited heterosexual couples where one partner was HIV positive and the other partner presumed to be HIV negative. This was done between 1991 and 2003. Mostly the men were HIV positive. Researchers interviewed the other partner and collected blood for testing.

The researchers found that the partners of HIV positive people were more likely to be HIV negative if they joined the study in 1999 or after, compared to people who joined the study before this time. From this finding, the Swiss Commission inferred that using HAART reduced the risk of HIV transmission. However, there are several reasons why their inference may not be correct, as follows:

* only a small proportion (about 15%) of the HIV positive people in the study took HAART.

* viral loads were not included in the data analysis so we have no idea how many people were on suppressive HAART.

* importantly, the team performed a statistical analysis that took many factors into account (called a multivariate analysis). This revealed that use of HAART did not have an impact on HIV transmission.

* when asked about the use of condoms in the past six months, roughly half the participants noted that they were consistently practicing protected intercourse.

A factor significantly associated with HIV transmission in this study was having unprotected sex.

Toward the end of the report on their study, the Spanish team cautions that an increase in unsafe sex could “cancel or even reverse†any beneficial effect that HAART might have on transmission on HIV. In closing they make this point:

* “This is why it is important not to forget that the main preventive measure for HIV sexual transmission remains the avoidance of risky sexual practices.â€

It is significant to note that the studies of sero-discordant couples used by the Swiss Commission in developing their guidelines investigated HIV transmission among heterosexual couples where the primary mode of transmission is vaginal intercourse. There is very little data on the impact of HAART on transmission through unprotected anal intercourse which is the most infectious mode of sexual transmission.

Reality checkThere are many factors that can affect the risk of HIV transmission during sex, including type of sexual activity, the presence of sexually transmitted infections, use of condoms, and so on. Furthermore, these factors may change over time and from one situation to another. Because of these and perhaps other factors, calculating the precise risk of HIV transmission during sex is difficult.

Relying on the presence of a low viral load in the blood is not sufficient information to prevent infection, as HIV replication continues to take place in the body despite a low viral load in the blood. New copies of HIV can be produced in many parts of the body, such as the male and female genital tracts as well as the rectum.

STIs can cause infection without triggering symptoms. This means that self-checks for STIs are not a reliable way of assessing if these germs are present. And, even if the Swiss guidelines are restricted to people in stable relationships, in reality people have affairs and do not tell their spouse or partner.

Currently the scientific data do not support the claim that HIV positive people whose viral loads are undetectable cannot transmit HIV. More research is needed to find out the relationship between viral load, HAART and HIV transmission.

Practicing safer sex can help minimize the risk of transmitting and acquiring STIs, HIV and new drug-resistant strains of HIV.

ResourcesThe Canadian AIDS Society developed guidelines to help assess the risk of HIV transmission during sex. These are available from its website:

http://www.cdnaids.ca/web/repguide.nsf/pages/cas-rep-0307

The Public Health Agency of Canada recently issued a statement emphasizing the importance of safer sex to prevent the transmission of HIV. That statement is available at:

http://www.phac-aspc.gc.ca/aids-sida/new-nouv-eng.html

AcknowledgementsWe thank the many doctors and infectious disease specialists across Canada who have given us their analysis of the Swiss Commission’s opinion. We particularly thank Tim , PhD, MacPherson MD, PhD, Curtis MD and Angel MD, for their assistance, helpful discussion, research and review in writing this article.

— R. Hosein

REFERENCES:

Vernazza P, Bernasconi E, Hirschel B and Flepp M. Les personnes séropositives ne souffrant d’aucune autre MST et suivant un traitement antirétroviral efficace ne transmettent pas le VIH par voie sexuelle. Bulletin des Médecins Suisses: 2008;89: 5.

Jaffe HW, Valdisseri RO and De Cock KM. The reemerging HIV/AIDS epidemic in men who have sex with men. Journal of the American Medical Association 2007 Nov 28;298(20):2412-4.

Chun TW, Nickle DC, Justement JS, et al. Persistence of HIV in Gut-Associated Lymphoid Tissue despite Long-Term Antiretroviral Therapy. Journal of Infectious Diseases. 2008 Feb 8; (in press).

Siliciano JD, Lai J, Callender M, et al. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. Journal of Infectious Diseases. 2007 Mar 15;195(6):833-6.

Hopkin M. HIV can never be cured: AIDS virus thwarts even the best drugs by hiding in gut. Nature 14 February, 2008. Available at: http://www.nature.com/news/2008/080214/full/news.2008.595.html

El-Sadr W, Neaton J. Episodic CD4-guided use of ART is inferior to continuous therapy: results of the SMART study. Abstract 106LB. In: Program and abstracts of 13th Conference on Retroviruses and Opportunistic Infections (Denver, CO). andria, VA, 2006.

Podsadecki TJ, Vrijens BC, Tousset EP, et al. Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia. Journal of Infectious Diseases 2007 Dec 15;196(12):1773-8.

Gallant J. Making sense of blips. Journal of Infectious Diseases 2007 Dec 15;196(12):1729-31.

Roan NR, Greene WC. A seminal finding for understanding HIV transmission. Cell. 2007 Dec 14;131(6):1044-6.

Kalichman SC, Di Berto G, Eaton L. Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sexually Transmitted Diseases. 2008 Jan;35(1):55-60.

Roulet V, Satie AP, Ruffault A, et al. Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro. American Journal of Pathology. 2006 Dec;169(6):2094-103.

La Sala GB, Pilotti E, Nicoli A, et al. Dynamics of HIV viral load in blood and semen of patients under HAART: impact of therapy in assisted reproduction procedures. AIDS. 2007 Jan 30;21(3):377-9.

Sheth PM, Danesh A, Shahabi K, et al. HIV-specific CD8+ lymphocytes in semen are not associated with reduced HIV shedding. Journal of Immunology. 2005 Oct 1;175(7):4789-96.

Zuckerman RA, Whittington WL, Celum CL, et al. Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy. Journal of Infectious Diseases. Jul 1 2004;190(1):156-161.

Coombs RW, Lockhart D, Ross SO, et al. Lower genitourinary tract sources of seminal HIV. Journal of Acquired Immune Deficiency Syndromes. 2006 Apr 1;41(4):430-8.

Shehu-Xhilaga M, de Kretser D, Dejucq-Rainsford N, et al. Standing in the way of eradication: HIV-1 infection and treatment in the male genital tract. Current HIV Research. 2005 Oct;3(4):345-59.

Craigo JK, BK, Paranjpe S, et al. Persistent HIV type 1 infection in semen and blood compartments in patients after long-term potent antiretroviral therapy. AIDS Research and Human Retroviruses. 2004 Nov;20(11):1196-209.

Furtado MR, Callaway DS, Phair JP, et al. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. New England Journal of Medicine. 1999 May 27;340(21):1614-22.

Chan DJ, Ray JE. Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis. Journal of Pharmacy and Pharmacology. 2007 Nov;59(11):1451-62.

Sharkey ME, Teo I, Greenough T, et al. Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy. Nature Medicine. 2000 Jan;6(1):76-81.

Nunnari G, Leto D, Sullivan J et al. Seminal reservoirs during an HIV type 1 eradication trial. AIDS Research and Human Retroviruses. 2005 Sep;21(9):768-75.

Sizemore JM Jr, Lakeman F, Whitley R, et al. The spectrum of genital herpes simplex virus infection in men attending a sexually transmitted disease clinic. Journal of Infectious Diseases. 2006 Apr 1;193(7):905-11.

Cu-Uvin S, Snyder B, Harwell JI, et al. Association between paired plasma and cervicovaginal lavage fluid HIV-1 RNA levels during 36 months. Journal of Acquired Immune Deficiency Syndromes. 2006 Aug 15;42(5):584-7.

Eron JJ, Jr., Smeaton LM, Fiscus SA, et al. The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). Journal of Infectious Diseases May 2000;181(5):1622-1628.

Bujan L, Daudin M, Matsuda T, et al. Factors of intermittent HIV-1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes. AIDS. Mar 26 2004;18(5):757-766.

Leruez-Ville M, Dulioust E, Costabliola D, et al. Decrease in HIV-1 seminal shedding in men receiving highly active antiretroviral therapy: an 18 month longitudinal study (ANRS EP012). AIDS. Feb 15 2002;16(3):486-488.

Barroso PF, Schechter M, Gupta P, Bressan C, Bomfim A, on LH. Adherence to antiretroviral therapy and persistence of HIV RNA in semen. Journal of Acquired Immune Deficiency Syndromes. Apr 1 2003;32(4):435-440.

Lafeuillade A, Solas C, Chadapaud S, Hittinger G, Poggi C, Lacarelle B. HIV-1 RNA levels, resistance, and drug diffusion in semen versus blood in patients receiving a lopinavir-containing regimen. Journal of Acquired Immune Deficiency Syndromes Apr 1 2003;32(4):462-464.

Dornadula G, Zhang H, VanUitert B, et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. Journal of the American Medical Association Nov 3 1999;282(17):1627-1632.

DM, Wong JK, Shao H, et al. Long-term persistence of transmitted HIV drug resistance in male genital tract secretions: implications for secondary transmission. Journal of Infectious Diseases. 2007 Aug 1;196(3):356-60. Epub 2007 Jun 19.

van Leeuwen E, Ter Heine R, van der Veen F, et al. Penetration of atazanavir in seminal plasma of men infected with human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy. 2007 Jan;51(1):335-7.

Castilla J, Del Romero J, Hernando V, et al. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. Journal of Acquired Immune Deficiency Syndromes. 2005 Sep 1;40(1):96-101

Sabatté J, Ceballos A, Raiden S, et al. Human seminal plasma abrogates the capture and transmission of human immunodeficiency virus type 1 to CD4+ T cells mediated by DC-SIGN. Journal of Virology. 2007 Dec;81(24):13723-34.

UNAIDS and WHO. Antiretroviral therapy and transmission of HIV. Statement. 1 February, 2008. Available at: http://data.unaids.org/pub/PressStatement/2008/080201_hivtransmission_en.pdf

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

[Guest guest]

From: info@...To: catie-news@...Sent: 3/7/2008 12:47:39 P.M. Central Daylight TimeSubj: CATIE News - Swiss guidelines take a troubling turn

CATIE News - Swiss guidelines take a troubling turn

In February 2008, the Swiss National AIDS Commission published an article about safer-sex practices. Specifically, the Commission stated that HIV-positive people are not at risk for transmitting HIV to their partners if they meet all of the following requirements:

* they are adherent to highly active antiretroviral therapy (HAART)* their viral load in the blood is consistently below the lower level of detection (usually 50 copies in Canada and 40 copies in Switzerland)* they are in a “stable relationshipâ€* they do not have any sexually transmitted infections (STIs)

Readers should note that the Swiss Commission’s statements about unprotected sex are based on opinion and not fact. We urge all sexually active people to continue to practice safer sex and take other precautions so as not to acquire or pass on HIV to their partners and to protect themselves from other STIs, many of which can be symptom-free.

In response to the Swiss Commission’s opinion, the following agencies have recently reinforced the importance of safer sex in preventing HIV infection:

* the Public Health Agency of Canada (PHAC) * the American Centers for Disease Control and Prevention (CDC)* the French Ministry of Health* the World Health Organization (WHO)* UNAIDS (the United Nations program on AIDS)

That the Swiss have issued guidelines that appear to weaken prevention messages against HIV transmission is disheartening, particularly at a time when HIV infections are on the rise in the high-income regions of North America and Western Europe.

What’s up?There are many problems with the opinion of the Swiss Commission. Perhaps most disturbing is that it is based on an apparent belief and not robust scientific data. Moreover, some of the references cited by the Swiss do not appear to support their opinion. The assumptions made by the Swiss Commission are weak, as they appear to have overlooked, forgotten or misunderstood important research.

A key assumption made by the Swiss is that a suppressed viral load in the blood results in a suppressed viral load in other parts of the body, particularly in the genital tract. In this article we summarize evidence showing that this is not the case. We also address other weaknesses that significantly undermine the foundations of the Swiss Commission’s opinion.

The limits of therapyIntroduced in high-income countries in 1996, highly active antiretroviral therapy, or HAART, which consists of potent combinations of anti-HIV drugs, has helped save and extend the lives of many HIV-positive people. The drugs work by impairing HIV’s ability to infect cells and produce new viruses. This gives the immune system a chance to begin to repair the damage caused by HIV.

However, after many years of HAART and good adherence in HIV-positive people, researchers have not been able to cure HIV infection. Attempts at a cure have consisted of intensifying therapy, adding unusual medications to regimens and, later, the cessation of HAART. But once HIV-positive people stop taking HAART, virus levels surge, damaging the immune system and increasing the risk of death.

It is important to bear in mind that HAART can also cause unpleasant and dangerous side effects. Although much progress has been made in the past 25 years against AIDS, HIV remains an incurable and deadly infection.

Viral load—undetectable may be misleadingTo ensure that anti-HIV therapy is working, doctors regularly have blood samples from their patients assessed for viral load, as one of the goals of HAART is to suppress viral load in the blood as low as possible. Commercially available technology can usually assess viral loads as low as 50 copies. When a viral load result returns with an “undetectable†reading—below the 50-copy mark—it does not mean that HIV is not replicating. New copies of HIV could be produced and new infections could be occurring in the body, but the test cannot accurately assess viral loads below the 50-copy mark. Tests that can count viral load below the 50-copy mark are restricted to research laboratories and not used for routine care.

Viral load—focus on 2% It is also worth remembering that only 2% of the body’s immune cells are carried in the blood at any given time. The vast majority (98%) of the immune cells, including CD4+ cells, spend most of their time in the lymph nodes and lymph tissues lining the gastrointestinal tract. Since so little HIV is actually produced in the blood, we cannot be sure that routine viral load testing accurately reflects the amount of HIV present in other parts of the body. Thus an undetectable viral load in the blood does not necessarily indicate a low or a high level of HIV replication in other parts of the body.

A word about blipsIn addition, many people on HAART experience “blips†in their viral loads. These are periods when the amount of HIV temporarily increases into the detectable range, generally anywhere from 51 to 500 copies. Usually the viral load drops back below detectable limits without a change in therapy. What causes these “blips,†how often they occur, and how long they last is not generally well understood. And the fact that blips are relatively common pokes yet another hole in the assumptions made by the Swiss Commission about the stability of viral load.

Timing of viral load testsIt usually takes a few weeks before viral load test results are sent to a doctor’s office. By the time a patient has returned to the doctor’s office for the results, several weeks or even a month may have passed since the test was done. During this time, viral load could rise depending on a number of factors. The viral load at the last test does not necessarily represent the viral load at another point in the future. One factor that can affect viral load is the ability to take medications every day, exactly as prescribed. This behaviour is called adherence.

Adherence and viral loadA recent American clinical trial documented how adherence can change over time, whether HAART is taken once or twice daily. As adherence degraded in the study, viral load rose above the 50-copy mark. When participants were told that their viral load had risen and they needed to submit another blood sample to confirm this result, their adherence improved and viral load fell below the 50-copy mark.

Adherence is a dynamic behaviour: It can go up or down and change yet again—and so can viral load. Therefore, relying on viral load measures to prevent HIV infection is fraught with risk.

Blood vs. semenThe genital tracts of men and women can have a different viral load from that of the blood. Men taking HAART may have a suppressed viral load in the blood, but viral load in the semen may not simultaneously be suppressed. Here is one reason for this:

* HAART may not fully penetrate and suppress HIV in the genital tract.

In one study at the University of Pittsburg, researchers with experience finding HIV in different parts of the body monitored the health of eight men taking HAART for five years. During this time, viral load in their blood was below the 50-copy mark. However, the research team was able to find that HIV had been replicating, at low levels, in both blood and semen samples from the men over the five years of the study. This replication was not due to drug resistance but likely because drugs could not accumulate in all regions of the genitals. The team was also able to find a greater proportion of HIV-infected cells in semen samples than in blood, even though there are more cells to infect in the blood than in semen. This finding occurred throughout the study.

The source of HIV that occurs in semen is not clear. Some researchers have fingered the prostate gland as a possible reservoir of HIV. However, more recent research, focusing on men who do not have STIs, suggests that there may be other parts of the male genital tract that harbour HIV.

Other studies have also assessed HIV levels in semen samples from men whose viral load in the blood was less than 50 copies. Depending on the study, the proportion of these men with detectable HIV in their semen has been between 7% and 40%.

Overall, these studies highlight the risk of exposure to semen, even if viral load in the blood was less than 50 copies.

The Swiss Commission suggests that men with viral loads below the 50-copy mark may have HIV in their semen that might not be capable of causing infection. We argue against that. Researchers who have conducted long-term studies of HIV-positive people on HAART have found HIV in cells from their blood and elsewhere that can replicate. The idea that HIV in semen may have special properties that render it non-infectious seems strange, given that sexual transmission is the most common way that HIV is spread.

Semen—more than HIVResearchers have found that HIV is not the only virus that can be found in semen. Several teams have isolated the following viruses from human semen samples:

* cytomegalovirus* hepatitis B virus* hepatitis C virus* herpes simplex virus* human herpes virus-8* human papilloma virus

Avoiding exposure to semen (and other fluids from the male genital tract) can reduce not only the risk of HIV infection but also other viral infections.

Women and viral loadResearch on HIV in the female genital tract appears to be more limited than in men. However, results similar to those in men have generally been found. Specifically, HIV can be detected in the genital secretions of women, whether or not they are taking HAART and regardless of the viral load level in their blood. Similar to the situation in men, not all anti-HIV medications can enter and reach high levels in the female genital tract.

And don’t forget the rectumResearchers in Seattle, Washington, have assessed HIV not only in the blood but also in semen samples and rectal tissue from 64 men. Twenty-seven, or 42%, of these men were taking anti-HIV medications. The study team found that these medications reduced viral load in the blood and semen. But HIV could still be detected in the semen of these 27 men on medication. Furthermore, HIV could also be found in the rectums of the men, whether or not they took anti-HIV therapy.

Sneaky STIsSTIs in the genital tract can cause inflammation and activate latent HIV hiding inside cells. This activation stimulates HIV out of hiding and turns cells into virus factories. Increased HIV in the genital tract together with inflammation heightens the risk of transmitting HIV.

The Swiss Commission does suggest that HIV-positive people be educated about the symptoms of STI infection. This approach to detecting possible STIs, while well intentioned, is at best problematic. Here is why:

A study by the San Francisco Department of Public Health of men who have sex with men found many cases where men were infected with STIs but were unaware of it because the infections were free of symptoms. Moreover, because the infections were at different places in the body, simply screening the urethra (the tube in the penis through which urine flows) for STIs would have missed detecting these infections elsewhere in the body. Here are some findings from their study:

* 85% of cases of rectal infections with either chlamydia or gonorrhea were symptom-free.

* 53% of chlamydia infections and 64% of gonorrhea were in either the throat or rectum

* 70% of chlamydia infections occurred in men who did not also have gonorrhea.

The San Francisco researchers say that these findings prompt the need for screening different parts of the body for these infections. They also underscore the fact that STIs can occur without causing symptoms.

Another study in Birmingham, Alabama, focusing on men, found that another STI—genital herpes—can occur in the absence of symptoms.

Overall, these findings confirm that self-checks for symptoms of STIs may not be the most reliable way to assess infection with these germs.

Misreading the dataOne of the key studies upon which the Swiss Commission’s assumptions rest, is an observational study from Spain. Observational studies are not the most reliable way to investigate a research question. These studies can find associations but are unable to link cause and effect.

In the Spanish study, researchers recruited heterosexual couples where one partner was HIV positive and the other partner presumed to be HIV negative. This was done between 1991 and 2003. Mostly the men were HIV positive. Researchers interviewed the other partner and collected blood for testing.

The researchers found that the partners of HIV positive people were more likely to be HIV negative if they joined the study in 1999 or after, compared to people who joined the study before this time. From this finding, the Swiss Commission inferred that using HAART reduced the risk of HIV transmission. However, there are several reasons why their inference may not be correct, as follows:

* only a small proportion (about 15%) of the HIV positive people in the study took HAART.

* viral loads were not included in the data analysis so we have no idea how many people were on suppressive HAART.

* importantly, the team performed a statistical analysis that took many factors into account (called a multivariate analysis). This revealed that use of HAART did not have an impact on HIV transmission.

* when asked about the use of condoms in the past six months, roughly half the participants noted that they were consistently practicing protected intercourse.

A factor significantly associated with HIV transmission in this study was having unprotected sex.

Toward the end of the report on their study, the Spanish team cautions that an increase in unsafe sex could “cancel or even reverse†any beneficial effect that HAART might have on transmission on HIV. In closing they make this point:

* “This is why it is important not to forget that the main preventive measure for HIV sexual transmission remains the avoidance of risky sexual practices.â€

It is significant to note that the studies of sero-discordant couples used by the Swiss Commission in developing their guidelines investigated HIV transmission among heterosexual couples where the primary mode of transmission is vaginal intercourse. There is very little data on the impact of HAART on transmission through unprotected anal intercourse which is the most infectious mode of sexual transmission.

Reality checkThere are many factors that can affect the risk of HIV transmission during sex, including type of sexual activity, the presence of sexually transmitted infections, use of condoms, and so on. Furthermore, these factors may change over time and from one situation to another. Because of these and perhaps other factors, calculating the precise risk of HIV transmission during sex is difficult.

Relying on the presence of a low viral load in the blood is not sufficient information to prevent infection, as HIV replication continues to take place in the body despite a low viral load in the blood. New copies of HIV can be produced in many parts of the body, such as the male and female genital tracts as well as the rectum.

STIs can cause infection without triggering symptoms. This means that self-checks for STIs are not a reliable way of assessing if these germs are present. And, even if the Swiss guidelines are restricted to people in stable relationships, in reality people have affairs and do not tell their spouse or partner.

Currently the scientific data do not support the claim that HIV positive people whose viral loads are undetectable cannot transmit HIV. More research is needed to find out the relationship between viral load, HAART and HIV transmission.

Practicing safer sex can help minimize the risk of transmitting and acquiring STIs, HIV and new drug-resistant strains of HIV.

ResourcesThe Canadian AIDS Society developed guidelines to help assess the risk of HIV transmission during sex. These are available from its website:

http://www.cdnaids.ca/web/repguide.nsf/pages/cas-rep-0307

The Public Health Agency of Canada recently issued a statement emphasizing the importance of safer sex to prevent the transmission of HIV. That statement is available at:

http://www.phac-aspc.gc.ca/aids-sida/new-nouv-eng.html

AcknowledgementsWe thank the many doctors and infectious disease specialists across Canada who have given us their analysis of the Swiss Commission’s opinion. We particularly thank Tim , PhD, MacPherson MD, PhD, Curtis MD and Angel MD, for their assistance, helpful discussion, research and review in writing this article.

— R. Hosein

REFERENCES:

Vernazza P, Bernasconi E, Hirschel B and Flepp M. Les personnes séropositives ne souffrant d’aucune autre MST et suivant un traitement antirétroviral efficace ne transmettent pas le VIH par voie sexuelle. Bulletin des Médecins Suisses: 2008;89: 5.

Jaffe HW, Valdisseri RO and De Cock KM. The reemerging HIV/AIDS epidemic in men who have sex with men. Journal of the American Medical Association 2007 Nov 28;298(20):2412-4.

Chun TW, Nickle DC, Justement JS, et al. Persistence of HIV in Gut-Associated Lymphoid Tissue despite Long-Term Antiretroviral Therapy. Journal of Infectious Diseases. 2008 Feb 8; (in press).

Siliciano JD, Lai J, Callender M, et al. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. Journal of Infectious Diseases. 2007 Mar 15;195(6):833-6.

Hopkin M. HIV can never be cured: AIDS virus thwarts even the best drugs by hiding in gut. Nature 14 February, 2008. Available at: http://www.nature.com/news/2008/080214/full/news.2008.595.html

El-Sadr W, Neaton J. Episodic CD4-guided use of ART is inferior to continuous therapy: results of the SMART study. Abstract 106LB. In: Program and abstracts of 13th Conference on Retroviruses and Opportunistic Infections (Denver, CO). andria, VA, 2006.

Podsadecki TJ, Vrijens BC, Tousset EP, et al. Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia. Journal of Infectious Diseases 2007 Dec 15;196(12):1773-8.

Gallant J. Making sense of blips. Journal of Infectious Diseases 2007 Dec 15;196(12):1729-31.

Roan NR, Greene WC. A seminal finding for understanding HIV transmission. Cell. 2007 Dec 14;131(6):1044-6.

Kalichman SC, Di Berto G, Eaton L. Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sexually Transmitted Diseases. 2008 Jan;35(1):55-60.

Roulet V, Satie AP, Ruffault A, et al. Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro. American Journal of Pathology. 2006 Dec;169(6):2094-103.

La Sala GB, Pilotti E, Nicoli A, et al. Dynamics of HIV viral load in blood and semen of patients under HAART: impact of therapy in assisted reproduction procedures. AIDS. 2007 Jan 30;21(3):377-9.

Sheth PM, Danesh A, Shahabi K, et al. HIV-specific CD8+ lymphocytes in semen are not associated with reduced HIV shedding. Journal of Immunology. 2005 Oct 1;175(7):4789-96.

Zuckerman RA, Whittington WL, Celum CL, et al. Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy. Journal of Infectious Diseases. Jul 1 2004;190(1):156-161.

Coombs RW, Lockhart D, Ross SO, et al. Lower genitourinary tract sources of seminal HIV. Journal of Acquired Immune Deficiency Syndromes. 2006 Apr 1;41(4):430-8.

Shehu-Xhilaga M, de Kretser D, Dejucq-Rainsford N, et al. Standing in the way of eradication: HIV-1 infection and treatment in the male genital tract. Current HIV Research. 2005 Oct;3(4):345-59.

Craigo JK, BK, Paranjpe S, et al. Persistent HIV type 1 infection in semen and blood compartments in patients after long-term potent antiretroviral therapy. AIDS Research and Human Retroviruses. 2004 Nov;20(11):1196-209.

Furtado MR, Callaway DS, Phair JP, et al. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. New England Journal of Medicine. 1999 May 27;340(21):1614-22.

Chan DJ, Ray JE. Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis. Journal of Pharmacy and Pharmacology. 2007 Nov;59(11):1451-62.

Sharkey ME, Teo I, Greenough T, et al. Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy. Nature Medicine. 2000 Jan;6(1):76-81.

Nunnari G, Leto D, Sullivan J et al. Seminal reservoirs during an HIV type 1 eradication trial. AIDS Research and Human Retroviruses. 2005 Sep;21(9):768-75.

Sizemore JM Jr, Lakeman F, Whitley R, et al. The spectrum of genital herpes simplex virus infection in men attending a sexually transmitted disease clinic. Journal of Infectious Diseases. 2006 Apr 1;193(7):905-11.

Cu-Uvin S, Snyder B, Harwell JI, et al. Association between paired plasma and cervicovaginal lavage fluid HIV-1 RNA levels during 36 months. Journal of Acquired Immune Deficiency Syndromes. 2006 Aug 15;42(5):584-7.

Eron JJ, Jr., Smeaton LM, Fiscus SA, et al. The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). Journal of Infectious Diseases May 2000;181(5):1622-1628.

Bujan L, Daudin M, Matsuda T, et al. Factors of intermittent HIV-1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes. AIDS. Mar 26 2004;18(5):757-766.

Leruez-Ville M, Dulioust E, Costabliola D, et al. Decrease in HIV-1 seminal shedding in men receiving highly active antiretroviral therapy: an 18 month longitudinal study (ANRS EP012). AIDS. Feb 15 2002;16(3):486-488.

Barroso PF, Schechter M, Gupta P, Bressan C, Bomfim A, on LH. Adherence to antiretroviral therapy and persistence of HIV RNA in semen. Journal of Acquired Immune Deficiency Syndromes. Apr 1 2003;32(4):435-440.

Lafeuillade A, Solas C, Chadapaud S, Hittinger G, Poggi C, Lacarelle B. HIV-1 RNA levels, resistance, and drug diffusion in semen versus blood in patients receiving a lopinavir-containing regimen. Journal of Acquired Immune Deficiency Syndromes Apr 1 2003;32(4):462-464.

Dornadula G, Zhang H, VanUitert B, et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. Journal of the American Medical Association Nov 3 1999;282(17):1627-1632.

DM, Wong JK, Shao H, et al. Long-term persistence of transmitted HIV drug resistance in male genital tract secretions: implications for secondary transmission. Journal of Infectious Diseases. 2007 Aug 1;196(3):356-60. Epub 2007 Jun 19.

van Leeuwen E, Ter Heine R, van der Veen F, et al. Penetration of atazanavir in seminal plasma of men infected with human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy. 2007 Jan;51(1):335-7.

Castilla J, Del Romero J, Hernando V, et al. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. Journal of Acquired Immune Deficiency Syndromes. 2005 Sep 1;40(1):96-101

Sabatté J, Ceballos A, Raiden S, et al. Human seminal plasma abrogates the capture and transmission of human immunodeficiency virus type 1 to CD4+ T cells mediated by DC-SIGN. Journal of Virology. 2007 Dec;81(24):13723-34.

UNAIDS and WHO. Antiretroviral therapy and transmission of HIV. Statement. 1 February, 2008. Available at: http://data.unaids.org/pub/PressStatement/2008/080201_hivtransmission_en.pdf

It's Tax Time! Get tips, forms and advice on AOL Money Finance.