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Swiss HIV Report v SF DPH Rejection Statement
January 30, 2008
Communicated by the Federal Commission for HIV/AIDS.
HIV-infected persons on effective anti-retroviral therapy are sexually non-infectious
P. Vernazza, B. Hirschel, E. Bernasconi
Summary.
The Federal Commission for HIV/AIDS, following the proposal of the Sub-commission on Clinical and Therapeutic Aspects, and after review of the medical literature and extensive discussion, resolves that:
An HIV-infected person on anti-retroviral therapy with completely suppressed viremia („effective ART“) is not sexually infectious, i.e. cannot propagate HIV through sexual contact.
This statement is valid if
· this person is compliant with ART, whose effect must be evaluated regularly by the treating physician, and
· the viral load has been suppressed (non-detectable) since at least six months ago, and
· there are no other sexually transmitted diseases
a) Transmission depends on the viral load.
We define „effective ART“ as fully suppressive, stable treatment, with a viral load below the limits of detection in plasma (< style=""> Treatment is considered "stable" once the viral load has been undetectable for at least six months.
The Commission realizes that medical and biologic data available today do not permit proof that HIV-infection during effective ART is impossible, because the non-occurrence of an improbable event cannot be proven. If no transmission events were observed among 100 couples followed for two years, for instance, there might still be some such events if 10'000 couples are followed for 10 years. The situation is analogous to 1986, when the statement “HIV cannot be transmitted by kissing” was publicized. This statement cannot be proven, but after 20 years’ experience its accuracy appears highly plausible.
Concerning the statement "an HIV-infected person on anti-retroviral therapy with completely suppressed viremia („effective ART“) cannot propagate HIV through sexual contact” however, the evidence is much better than what was available in 1986 regarding kissing.
1) In sero-discordant couples (one person seropositive, the other seronegative), the risk of transmission depends on the viral load of the HIV-infected partner, see Figure 1 from reference (1).
2) In a prospective study of 393 heterosexual sero-discordant couples there were no infections among partners of persons on ART, compared to a rate of transmission of 8.6% among partners of untreated patients (3).
3) In another prospective study of 92 sero-discordant couples, where in 41 cases the HIV-positive partner had started therapy, there were 6 infections. All these occurred in partners of untreated patients (3).
4).Among 62 sero-discordant couples, where the male partner was HIV positive and on ART, with unprotected sex in order to conceive, there was no transmission (4).
5) Transmission from mother to newborn also depends on the maternal viral load, and did not occur in pregnancies where the maternal viral load was below 1000 copies per ml. If the maternal viral load is higher, transmission can be prevented by ART (5-8).
b) Effective ART eliminates virus from genital secretions
HIV-RNA, measured in sperm, declines below the limits of detection during ART (15-17). The viral load (HIV-RNA) in female genital secretions is, as a rule, below the plasma VL and below the limits of detection during effective ART. As a rule, it rises after, not before, an increase in plasma VL (18). Cell-associated viral genomes are present in genital secretions, even during ART (15, 19-21). But these are not functional virions. HIV-containing cells in sperm lack markers of viral proliferations such as circular LTR-DNA (22).
The concentration of HIV RNA in sperm (sperm VL) correlates with the risk of transmission. Transmission risk declines towards 0 with falling sperm VL, see Figure 2. These data indicate that the risk of transmission is greatly decreased by ART.
c) Exceptions and caveats
· After a few days or weeks of discontinuation of ART, plasma viral load rises rapidly. There is at least one case report of transmission during this rebound (14)
· In patients without ART, sexually transmitted diseases (STDs, for instance urethritis or genital ulcer disease) increase the genital VL; it falls again after treatment of STD (24). In a patient with urethritis, sperm VL can rise slightly even while patient is receiving effective ART. This rise is small, however, much smaller that the rise observed in patients without ART.
d) Conclusion
· During effective ART, free virus is absent from blood and genital secretions. Epidemiologic and biologic data indicate that during such treatment, there is no relevant risk of transmission.
· Residual risk can not be scientifically excluded, but is, in the judgment of the Commission, negligibly small
References
1 Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group [see comments]. N Engl J Med 2000; 342: 921-929.
2 Castilla J, del Romero J, Hernando V, Marincovich B, Garcia S, Rodriguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr 2005; 40: 96-101.
3 Melo M, Varella I, Nielsen K, Turella L, Santos B. Demographic characteristics, sexual transmission and CD4 progression among heterosexual HIV-1 serodiscordant couples followed in Porto Alegre, Brazil. 16th International AIDS Conference, Toronto, 13-18.August 2006, TUPE0430. 2006.
4 Barreiro P, del Romero J, Leal M, et al. Natural pregnancies in HIV-serodiscordant couples receiving successful antiretroviral therapy. J Acquir Immune Defic Syndr 2006; 43: 324-326.
5 Garcia PM, Kalish LA, Pitt J, et al. Maternal Levels of Plasma Human Immunodeficiency Virus Type 1 RNA and the Risk of Perinatal Transmission. New England Journal of Medicine 1999; 431: 394-402.
6 Rousseau C, Nduati R, Richardson B, et al. Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis 2003; 187: 741-747.
7 Kilewo C, Karlsson K, Massawe A, et al. Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers prophylactically with triple antiretroviral therapy in Dar es Salaam, Tanzania - the MITRA PLUS study. 4th IAS Conference, Sydney, July 2007 TUAX 101. 2007.
8 Arendt V. AMATA study: effectiveness of antiretroviral therapy in breastfeeding mothers to prevent post-natal vertical transmission in Rwanda. 4th IAS Conference, Sydney, July 2007 Abstract TUAX 102. 2007.
9 Porco TC, Martin JN, Page-Shafer KA, et al. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS 2004; 18: 81-88.
10 Yerly S, Vora S, Rizzardi P, et al. Acute HIV infection: impact on the spread of HIV and transmission of drug resistance. AIDS 2001; 15: 2287-2292.
11 Yerly S, Race E, Vora S, et al: HIV Drug Resistance and Molecular Epidemiology in Patients with Primary HIV Infection. 8th Conference on Retroviruses and Opportunistic Infections, Chicago, 4.-8.Feb.2001 2001; Abstract 754(Abstract)
12 Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 2007; 195: 951-959.
13 Chesson HW, Pinkerton SD. Sexually transmitted diseases and the increased risk for HIV transmission: implications for cost-effectiveness analyses of sexually transmitted disease prevention interventions. J Acquir Immune Defic Syndr 2000; 24: 48-56.
14 Bernasconi E, Vernazza PL, Bernasconi A, Hirschel B. HIV transmission after suspension of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001; 27: 209.
15 Vernazza, P. L., Troiani, L., Flepp, M. J., Cone, R. W., Schock, J., Roth, F., Boggian, K., Cohen, M. S., Fiscus, S. A., Eron, J. J., and and the Swiss HIV Cohort Study. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. AIDS. 2. 2000.
16 Cu-Uvin S, Caliendo AM, Reinert S, et al. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS 2000; 14: 415-421.
17 Vettore MV, Schechter M, Melo MF, Boechat LJ, Barroso PF. Genital HIV-1 viral load is correlated with blood plasma HIV-1 viral load in Brazilian women and is reduced by antiretroviral therapy. J Infect 2006; 52: 290-293.
18 Cu-Uvin S, Snyder B, Harwell JI, et al. Association between paired plasma and cervicovaginal lavage fluid HIV-1 RNA levels during 36 months. J Acquir Immune Defic Syndr 2006; 42: 584-587.
19 Vernazza PL, Kashuba DM, Cohen MS. Biological correlates of sexual transmission of HIV: practical consequences and potential targets for public health. Reviews in Medical Microbiology 2001; 12: 131-142.
20 Neely MN, Benning L, Xu J, et al. Cervical shedding of HIV-1 RNA among women with low levels of viremia while receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2007; 44: 38-42.
21 Kovacs A, Wasserman SS, Burns D, et al. Determinants of HIV-1 shedding in the genital tract of women. Lancet 2001; 358: 1593-1601.
22 Nunnari G, Otero M, Dornadula G, et al. Residual HIV-1 disease in seminal cells of HIV-1-infected men on suppressive HAART: latency without on-going cellular infections. AIDS 2002; 16: 39-45.
23 Chakraborty H, Sen P, Pranab K, et al. Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model. AIDS 2001; 15: 621-627.
24 Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 1997; 349: 1868-1873.
25 Sadiq ST, Taylor S, Kaye S, et al. The effects of antiretroviral therapy on HIV-1 RNA loads in seminal plasma in HIV-positive patients with and without urethritis. AIDS 2002; 16: 219-225.
26 Pilcher CD, Tien HC, Eron JJ, Jr., et al. Brief but Efficient: Acute HIV Infection and the Sexual Transmission of HIV. J Infect Dis 2004; 189: 1785-1792.
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February 7, 2008
SFAF/SFDPH Statement on the Swiss Natl. AIDS Commission's Report on HIV Transmission
The report reviewed data from four studies conducted among heterosexual couples alone. One, involving 393 serodiscordant couples, found that as long as the HIV-positive partner adhered to a treatment regimen, had an undetectable viral load for at least six months, and did not suffer from any other sexually transmitted infections, the HIV-negative partner did not become infected. But another study that was part of the same report found that 6 out of 43 HIV-negative partners did become infected—a rate of nearly 14%—due to the fact that the HIV-positive partner was not always faithful to a treatment regimen.
Neither the San Francisco AIDS Foundation nor the Department of Health endorse the Swiss AIDS Commission statement, because:
- all of the studies involved heterosexual intercourse and may have little bearing on intercourse among men who have sex with men;
- HIV-positive people with apparently undetectable viral loads can experience occasional spikes in viral load;
- HIV-positive people who carefully follow their treatment regimen may develop viral resistance;
- people with other sexually transmitted infections can be asymptomatic yet still capable of transmitting or contracting HIV; and
- the Swiss report, since it did not use randomized, controlled studies, has not yet verified its causal conclusions.
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