HIV Prevention and Testing: Update From the 17th International AIDS Conference

HIV testing and prevention were two important, and sometimes controversial, research themes at the 17th International AIDS Conference (IAC) held from August 3 to 8, 2008, in Mexico City. Both topics, usually low-tech activities, saw a renewed interest in an evidence-based approach and pleas for more data. The HIV prevention debate focused on the role of treatment as a prevention strategy, and presentations on the risk of HIV transmission focused on patients with low viral loads who were receiving treatment. Discussions on HIV testing included the use of newer technologies to calculate the incidence of HIV infections in the United States.

CDC REVISED HIV INCIDENCE ESTIMATES
The CDC's revised estimates of the numbers of new HIV infections in the United States, published before the conference,1 received attention from public health and research communities alike. This new analysis found that there were about 56,300 new HIV infections in 2006, the most recent year for which data are available. This is higher than the CDC's long-standing estimate of 40,000 for the last several years. According to the CDC, the number of new infections was never as low as the previous estimate of 40,000, but it has been relatively stable overall since the late 1990s. The problem is that previous estimates, based on reports from states with HIV reporting, failed to distinguish between recent and long-term infections.

Central to these revised estimates is that early sero­converters have a lower proportion of HIV-specific IgG in their serum/plasma than those with long-term in­fection.^2,3 A recently developed assay-the Aware BED EIA HIV-1 Incidence enzyme immunoassay (EIA) test (Calypte Biomedical Corporation, Portland, Ore)-helped close the gap between the previous and revised estimates. The Aware BED EIA test is an in vitro, quantitative EIA that estimates HIV incidence by determining the ratio of HIV-1–specific IgG to total IgG in a serum, plasma, or whole blood specimen. The assay allows for the testing of both liquid blood and dried samples. However, it is a surveillance and research tool and is not FDA-approved as a diagnostic test. Currently, it is used for pub­­lic health purposes only, such as estimating HIV incidence in populations already known to be HIV-positive.

According to Dr Kevin Fenton, director of the National Center for HIV, STD, and TB Prevention, prevention programs can use data from the test in targeting resources; monitoring and evaluating; and identifying high-risk cohorts for prevention research, including vaccine trials.4 It is not intended to be used as a diagnostic test for individual patients or to guide patient treatment. He stressed that the current methodology requires that specimens have a confirmatory test for HIV infection, such as the Western blot. More information on this HIV incidence test is shown in the Table.

The Aware BED EIA test is a second-generation assay and largely replaces the detuned method of HIV incidence testing. The detuned assay used commercially available EIA test kits for HIV-1, and laboratories performed the standard EIA on a highly diluted specimen. The drawbacks to the detuned method were the high dilution required (up to 1:20,000), its low sensitivity, and its ability to measure only HIV subtype B. The Aware BED EIA test, however, is reliable for all HIV subtypes.

BARRIERS TO HIV TESTING IN THE UNITED STATES
While we are gaining in our understanding of how many HIV infections occur per year, we are still faced with the problem of having more people tested. One of the major barriers to HIV testing is our uneven approach to HIV consent. In the United States, informed consent requirements vary by state. Recently, Illinois and California passed legislation that eliminated special, written informed consent for HIV testing. This approach conforms to the 2006 receommendations from the CDC on opt-out testing⁵ and hopefully can help reduce the stigma associated with HIV testing by "routinizing" it.

New York is one state that requires separate, written informed consent. A poster presentation by Urbina and colleagues⁶ from St Vincent's Hospital in New York City concluded that separate, written consent is a barrier to HIV testing in hospitals. In a simple, straightforward study, the authors summarized an intervention in which house staff were trained to offer HIV screening to inpatients. Six months after the intervention, the HIV screening rate increased from 3% to 6% of admissions.

At the end of the intervention period, focus groups were held to identify organizational, patient, and pro­vider barriers to HIV testing. Organizational barriers included time constraints associated with state-required consent forms and paperwork not being readily available. From the patient perspective, many experienced anxiety when approached about HIV testing, and some patients felt "profiled" and declined testing. Provider barriers included not wanting the patient to react negatively to them and the excess time required by the state proscribed testing process and paperwork. Urbina and colleagues concluded that states should change HIV testing laws to allow HIV screening to be included in the general consent for medical care in hospitals.

Incorporating HIV screening into the general consent form for inpatient admissions may work for hospitals. Other approaches may be better for ambulatory patients, such as eliminating special written consent altogether and using the opt-out method as recommended by the CDC.⁵

ANTIRETROVIRAL THERAPY AS A PREVENTION MEASURE
Does HIV therapy act as a prevention tool? This question probably generated the most discussion during the conference. While the hard evidence is lacking, most experts agreed that antiretroviral therapy is an important tool for reducing rates of forward or ongoing HIV transmission.

Despite important increases in HIV treatment access worldwide, it will be impossible to "treat our way out of the epidemic," according to Dr Myron Cohen, chief of infectious diseases of the University of North Carolina.⁷ He cited the central role clinical and other HIV treatment providers have played in the greatest HIV prevention success story to date, ie, averting mother-to-child transmission using antiretroviral therapy. Dr Cohen issued a call for treatment providers to become full partners in public health campaigns to prevent HIV infection. He urged that, once and for all, the HIV community should "marry" HIV treatment with prevention. He noted that while there was no randomized clinical trial to show that antiretroviral therapy contributes to decreased forward transmission of HIV, it makes sense intuitively.

To support this hypothesis, he cited our knowledge that many antiretrovirals penetrate semen and vaginal fluid. Also, clinical experience in some parts of the world has shown decreases in forward HIV transmission following the introduction of antiretroviral treatment. He referenced the Taiwan experience reported by Fang and colleagues⁸ in which onward transmission of HIV was decreased by 53% after the use of antiretroviral therapy became widespread in 1997. In that study, investigators concluded that their experience "makes a strong case for more widespread use of potent antiretrovirals as a control measure against HIV transmission in countries with low prevalence."

The unknown variable here is the extent to which antiretrovirals will have a durable effect in settings where viral load testing is not available to identify cases of treatment failure early. In these settings, the lack of viral load testing may lead not only to HIV transmission because of undetected viral rebound but also to the transmission of drug-resistant virus, compromising the success of any second-line treatment.

Dr Julio Montaner's group looked at this issue from an economic perspective.⁹ They calculated that more than two-thirds of all projected new HIV infections by 2030 in British Columbia would be averted if all persons eligible for antiretroviral therapy started treatment when their CD4⁺ cell count was in the region of 350/µL, the current recommended threshold for initiating antiretroviral treatment. Faster expansion of antiretroviral treatment would result in faster decreases in the numbers of new infections, according to the British Columbia model. Furthermore, the immediate expansion of access to anti-HIV treatment would save a total of Can$95 million, or Can$368,000 per patient.

HIV TREATMENT AND INFECTIOUSNESS: THE SWISS STATEMENT
As expected, what has come to be known as the "Swiss statement" on the infectiousness of HIV-positive people with undetectable viral loads proved controversial at this year's IAC. In January 2008, senior HIV physicians and researchers in Switzerland issued a statement that persons who were receiving antiretroviral therapy and had an undetectable plasma HIV RNA level for at least 6 months were not infectious to their heterosexual partners, provided they were adherent to treatment and did not have a sexually transmitted infection (STI). This theory was debated in a heated 2-hour meeting at a satellite event held before the conference.¹⁰

Speaking for the group, Professor Pietro Vernazza said that the statement was never intended for worldwide publication. Rather, it was intended for use by Swiss doctors to help them discuss sexual risk taking with their patients who had steady partners. He also stressed that their statement did not mean that an undetectable viral load was a replacement for a condom. (The Swiss statement was originally published in French¹¹; however, there are many balanced translations that provide the background and context for the authors' position.¹²)

But in defense of the Swiss statement, he noted that sex with condoms was not 100% safe either and carried a risk that was "in a comfortable range so that people can live a normal life." Vernazza continued that he and his colleagues consider sex under antiretroviral therapy to be in a similarly safe range. The caveat was that the group considers this safe only under the "special conditions" noted above.

From a global perspective, some felt that the Swiss statement was irrelevant for most HIV-infected persons around the world. The limited access to viral load testing and the high rates of STIs in many of the countries hardest hit by HIV were two of the reasons cited. On the other hand, the Swiss statement was supported by some community activists who noted that it helped reduce stigma and discrimination.

Vernazza conceded that although the statement was based on an expert assessment of current biological, epidemiological, and ecological evidence, the motivation for the statement was primarily political. He said that since it was possible for the Swiss state to prosecute HIV-positive people who had unprotected sex with consenting, fully informed HIV-negative partners under the country's HIV exposure laws, this statement could be used in court to show that if a person was receiving successful antiretroviral treatment, then he or she could not transmit HIV. He added that the statement was also made to help serodiscordant couples who were unwilling or unable to access sperm-washing or other assisted reproduction techniques in order to conceive safely.

Finally, and most important, Vernazza said that the statement was made because there was a discrepancy between what some doctors told their patients in private and what they were prepared to say in public and, consequently, because they wanted to ward off the "risk of uncontrolled diffusion" of information.

Where Is the Evidence?
The assumption that transmission is not possible if a person's viral load is below a certain level is just that; the evidence to support this phenomenon is lacking. A systematic review of the literature failed to confirm or refute the Swiss statement, according to a presentation by Attia and colleagues.¹³ Of the 252 published articles and abstracts reviewed by these researchers, only 14 were found to be eligible for review because of duplication of cases, problems with study design, or lack of complete data. Of the 14 included in the review, 7 were published or were about to be published and 7 were conference abstracts. None of the studies reviewed met the Swiss criteria completely. Based on the study cohorts from the published reports included in their review, Attia and colleagues calculated an estimated HIV transmission rate of 1.06 per 100 person-years when the HIV-positive partner was receiving antiretro­viral treatment and had an HIV RNA level less than 40 copies/mL. Some of the data presented from the included published reports were anecdotal or included a cutoff of viral supression of less than 400 copies/mL but are still worth mentioning. For example, one instance of transmission occurred from a patient with a viral load of 362 copies/mL. The authors concluded that HIV transmission in patients receiving antiretrovirals with viral load supression is rare but measurable.

A clinical trial is under way to provide the evidence needed to support the Swiss statement and the role of treatment as a prevention tool.¹⁴ The HIV Prevention Trials Network (HPTN) study 052 is designed to answer the question of whether treatment reduces onward transmission. The study is randomizing HIV-positive partners representing 1750 serodiscordant couples to start treatment when the HIV-positive partner's CD4⁺ cell count is between 350/µL and 550/µL or to defer treatment until the CD4⁺ cell count declines to 200/µL to 250/µL, the threshold currently recommended by the World Health Organization. The study will observe the rate of HIV transmission in these serodiscordant couples despite prevention counseling and condom provision. The study is being conducted in Malawi, South Africa, India, Brazil, and Thailand and is designed to last 5 years, reporting results by 2013.

SUMMARY
What do we tell our patients about these issues? Regarding the use of the Aware BED EIA HIV-1 Incidence test, the answer is simple. It is not currently available for diagnostic purposes, so we cannot tell patients who are coming into care whether their infection is recent. The issue of transmissibility from patients receiving antiretroviral therapy with undetectable viral loads requires more thought and discussion. The best answer at the moment is to continue to stress condom use. The year 2013 is a long way off, and a lot of intervening variables can change our thinking as the HTPN 052 study is rolled out. In the meantime, the messages for serodiscordant couples are for the HIV-negative partner to be aware of the positive partner's HIV status and a recommendation for HIV testing for the negative partner at least annually. In conclusion, we as HIV care providers need to recognize that HIV medicine is a moving target. As new data become available and are validated, we may need to discard the dogma of the past in order to give our patients the safest and most accurate information possible.

References:

References1. Hall HI, Song R, Rhodes P, et al; HIV Incidence Surveillance Group. Estimation of HIV incidence in the United States. JAMA. 2008;300:520-529.
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3. Rawal BD, Degula A, Lebedeva L, et al. Development of a new less-sensitive enzyme immunoassay for detection of early HIV-1 infection. J Acquir Immune Defic Syndr. 2003;33:349-355.
4. Fenton K. The USA HIV Epidemic in 2008. Oral Abstract Session. 17th International AIDS Conference; August 3-8, 2008; Mexico City. Session WEAC03. www.kaisernetwork.org/health_cast/hcast_index.cfm?display=detail&hc=2920. Accessed August 12, 2008.
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6. Urbina A, Galatatowitsch M, Gabitto R, et al. Integrating HIV testing into inpatient hospital settings in New York State, United States. 17th International AIDS Conference; August 3-8, 2008; Mexico City. Poster TUPE0435.
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11. Vernazza P, Hirschel B, Bernasconi E, Flepp M. Les personnes séropositives ne souffrant d’aucune autre MST et suivant un traitment antirétroviral efficace ne transmettent pas le VIH par voie sexuelle. Bulletin des Médecins Suisses. 2008;89:165-169.
12. Bernard EJ. Swiss experts say individuals with undetectable viral load and no STI cannot transmit HIV during sex. www.aidsmap.com/en/news/4E9D555B-18FB-4D56-B912-2C28AFCCD36B.asp. Accessed August 12, 2008.
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14. The HIV Prevention Trials Network. Study HPTN 052: a randomized trial to evaluate the effectiveness of antiretroviral therapy plus HIV primary care versus HIV primary care alone to prevent the sexual transmission of HIV-1 in serodiscordant couples. www.hptn.org/research_studies/hptn052.asp. Accessed August 12, 2008.