Update on HIV from the IDSA 44th Annual Meeting in Toronto

Hopkins HIV Report 2007 Jan; 19(1):4-6

Kristine Johnson, M.D., and Emily Erbelding M.D., M.P.H.
Johns Hopkins

The sessions with HIV content at the meetings of IDSA tend to be designed to provide broad and timely updates on HIV for the infectious disease practitioner, as well as to allow a forum for the presentation of research findings. This article will summarize some IDSA highlights relevant to acute HIV infection, epidemiology and prevention.

A New Operational Paradigm in HIV Testing

Rochelle Walenksy [Abstract 712] summarized the central tenets and the key features of the Centers for Disease Control’s (CDC) new guidelines for HIV testing released on September 22, 2006 [MMWR Recomm Rep. 2006 Sep 22, 55(RR14);1-17]; for a perspective on the draft version, see Erbelding E, HHR 2006;18(6)]. These recommendations represent a major shift in the standard approach to HIV testing in the United States: They promote routine testing of patients ages 13-64 in all health-care settings. For streamlining the testing process, they emphasize a change from the use of specialized written, informed consent for HIV testing to an “opt-out” HIV testing strategy for adolescents, adults and pregnant women. “Opt-out” testing means that the patient is informed that the test will be performed as part of routine healthcare unless s/he decides to “opt-out” and decline the test. Because knowledge of HIV serostatus represents the first step to engaging in HIV care and accruing health benefits, the guidelines are meant to identify and bring to treatment the estimated 250,000 to 300,000 Americans living with undiagnosed HIV infection (roughly 25% of those living with HIV).

These recommendations replace those emphasizing pre-test counseling and written informed consent that have, in some form, been in effect for two decades. Past guidelines were developed when stigma associated with HIV infection was pervasive and, more importantly, treatment did not offer the same promising outcomes as the HAART regimens of today. Circumstances have changed considerably since then, with new therapeutic options and some lessening of stigma. With this new approach to HIV testing, systems that deliver healthcare are encouraged to use the process of consent for general medical care as the means to obtain consent for HIV testing. Therefore, no separate written, informed consent process would be required. This recommendation may not be compatible with laws in many states in the United States, but the guidelines may serve to catalyze discussions of policy change.

The recommendations also advise that patients identified to be at higher risk for HIV infection (men with same sex contact, injection drug users) be tested annually. For prenatal care, the guidelines also endorse the “opt-out” approach. Repeat screening of pregnant women within high risk populations or in regions of high HIV prevalence is encouraged during the third trimester. HIV testing for individuals pursuing STD care remains the recommended standard.

In a change from prior practice, the need to link counseling by certified counselors to testing is no longer the CDC standard in medical settings. However, the guidelines do emphasize that HIV testing must remain voluntary and that patients should not be tested without their knowledge and assent. For all those testing positive, follow-up care, prevention counseling and social support are vital to manage HIV disease long-term and to prevention transmission. The CDC’s recommendations have generated relatively little controversy within the medical community. This should not be surprising, given the fact that medical providers have reasons to be more confident now than ever before in their ability to treat HIV. They are also the stakeholder group most likely to experience frustration in identifying AIDS-related complications (now nearly entirely preventable) as the first sign of HIV in their patients.

Treatment of Acute HIV Infection

In an oral symposium, Susan Little from UCSD reviewed the balance of factors for and against treating acute HIV infection [Abstract 786]. Despite the collective extensive experience in the treatment of HIV infection garnered over the last 2 and a half decades, the benefits of treating acute HIV infection—defined as the seronegative window period between established HIV infection and formation of antibodies—remains controversial. This remains a challenging area of clinical research for a myriad of reasons: Acute HIV infection is infrequently diagnosed, making it difficult to enroll patients in randomized controlled trials. What we think of as the “gold standard” for evidence based clinical practice guidelines–the controlled trial–is difficult to conduct and will take decades to reach meaningful clinical endpoints. Some have hypothesized, though it remains unproven, that HAART initiated in the stage of acute infection may reverse the massive mucosal CD4 T-cell depletion that occurs early in infection. One small study of three patients treated during with HAART acute infection suggests restoration of gut CD4 cells in jejunal biopsies [Guadalupe M, et al. J Virol. 2006 Aug;80(16):8236-47]. However, Mehandru and colleagues performed rectosigmoid biopsies before and during HAART in 8 of 19 HIV-infected subjects identified during acute (6/19) or early (2/19) infection [J Exp Med. 2004 Sep 20;200(6):761-70]. These subjects were followed and re-biopsied at 6 months to 5 years after HAART initiation. There was no significant gut CD4 repletion, although peripheral immune reconstitution was noted. These data suggest that treatment during acute HIV infection does not result in a robust reconstitution of a high percentage of the body’s total lymphocyte population. As these studies suggest, however, there is no established standard of gut tissue sampling.

During and immediately following acute HIV infection, HIV superinfection remains a concern as well, offering the added possibility of resistant virus transmission and therapy complications due to reduced or inactive drug potency against the predominant viral clone. The high viral loads seen in acute infection probably contribute to greater transmission risk. It may be reasonable to presume that early treatment reduces transmission risk to sexual partners, but the direct and durable benefits to the individual patient remain unclear. Overall, there is evidence to suggest that early treatment is well-tolerated, but there is also an inherent risk of evolution of drug-resistance in non-adherent patients or in patients who acquire a drug-resistant strain and initiate therapy that is only partially active. Large, well-designed prospective controlled trials that use standardized measures to quantify mucosal CD4 cells and that follow treatment outcomes over the long term will be essential before we can formulate guidelines on the management of patients with acute or early HIV infection.

HIV Spread and Methamphetamine

In an oral session, Grant Colfax provided an overview of the growing problem of methamphetamine (“meth”) use, particularly among men having sex with men (MSM), its link to HIV transmission, and the possibilities for effective drug treatment [Abstract 785]. As of 2004, an estimated 1.4 million Americans use meth. Within the MSM population, use of this drug has been linked to greater risk of HIV prevalence and increased STD risk; the use of meth among MSM also appears to be disproportionate to use within other demographic groups. The National HIV Behavioral Surveillance (NHBS) program conducted by the CDC in 17 metropolitan centers show that meth use among HIV-infected MSM in urban centers reflect these trends, though use varied by site. In San Francisco, 21% of the HIV-infected MSM population interviewed admitted to use of meth within the last 12 months, and 6% used weekly or more frequently. In Baltimore, 7% used the drug within the last 12 months, and 3% used it weekly or more often. Casual use of meth among gay men is rare, and the drug is more often associated with abuse and dependence [Shoptaw S, Top HIV Med 2006;84:14].

Meth use appears to elevate risk of HIV acquisition independent of other known behavioral risk factors. For example, in the EXPLORE study (a behavioral intervention enrolling HIV-MSM) meth use significantly elevated the risk of new HIV infection (adjusted HR of 1.9, 95% CI 1.4-2.0). While there may be unknown behavioral risk variables associated with meth use that explain this elevated risk (more traumatic sex, partner selection, or differential recall in meth users within the studied population) it is also possible that meth use modifies the host inflammatory response to increase biologic susceptibility to HIV infection. Meth use also clearly adversely influences HAART adherence which can lead to ARV resistance mutations.

In light of the high risks of HIV transmission by HIV-infected MSM and secondary ARV resistance, promising and creative prevention strategies targeted for the MSM population have been the subject of several clinical trials. These recent studies have explored options for prolonged and effective intervention in meth users. The MATRIX intervention of intensive outpatient cognitive behavioral therapy (CBT) led to reductions in meth use at 6 months of follow-up compared to standard rehabilitation therapy [Rawson RA, et al. Addiction. 2004 Jun;99(6):708-17]. CBT versus standard therapy led to greater reductions in unprotected anal intercourse and other sexual risk behaviors. Other strategies include positive reinforcement with vouchers for negative urine toxicology tests, a form of “contingency management,” which provides prompt positive feedback when the desired behavior is displayed [Shoptaw S, et al. BMC Public Health. 2006 Aug 18;6:214; Shoptaw S, et al. Drug Alcohol Depend. 2005 May 9;78(2):125-34; Higgins ST, et al. Am J Psychiatry. 1993 May;150(5):763-9]. Pharmacologic agents have shown some failures (sertraline and dextromethorphan are two examples), but other candidates for pharmacologic therapy , including modafinil, buproprion, mirtazapine, and apripazole are being studied. Given the urgency of need, combination treatment strategies that incorporate behavioral and pharmacologic interventions within a comprehensive program need to be developed and tested.

A Rising Prevalence of Fluoroquinolone Resistance Among Gonococci

The Gonococcal Isolate Surveillance Project (GISP) is a sentinel surveillance program designed to monitor antimicrobial susceptibility of Neisseria gonorrheae isolates in the United State and to guide treatment recommendations. Weinstock presented data from GISP for 2005 that indicates that the days of easy and low-cost therapy with ciprofloxacin (and other fluoroquinolones) are likely to be very limited [Abstract 698]. In 2000, the overall prevalence of quinalone resistant Neisseria gonorrhea (QRNG) among GISP isolates was 0.35%, with all QRNG isolates coming from either Hawaii or the West Coast. By 2005, QRNG represented 9.4% of all GISP isolates; 29% of all isolates from MSM were QRNG, while only 3.9% of isolates from heterosexual men were QRNG. Being heterosexual, Black, or living in Southeastern US were all associated with lower rates of fluoroquinolone resistance. Given these trends, it is unlikely that fluoroquinolones will be reliably useful in the treatment of gonorrhea much longer, leaving clinicians with only a very limited menu of choices. New antibiotic therapies for the treatment of gonorrhea are needed.

HIV RNA Shedding Among Women on HAART

Very low plasma HIV RNA levels are associated with a low risk of HIV transmission among discordant couples, suggesting that achieving virologic control on HAART may prevent sexual transmission of HIV. Susan Cu-Uvin presented data on genital tract HIV RNA from women on HAART followed over time: 45 women with a median CD4 cell count of 415 cells/mm³ were followed over 346 visits [Abstract 694]. Plasma HIV RNA was undetectable in 81% of these visits; 63% of women had at least 1 episode of HIV shedding. With an undetectable plasma viral load, the probability of HIV shedding was 0.03 from the endocervix, 0.02 from the ectocervix, and 0.03 from the vagina. The authors concluded that most HIV-infected women on HAART continue to shed HIV RNA in their genital tract even with good systemic virologic control, which may have implications for the public health benefits of HAART.

2007-01-10
HHR-2007-01-02

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