Eight strategies to trim transmission risk in people with HIV.
Subject: Sexually transmitted diseases (Risk factors)
Sexually transmitted diseases (Prevention)
Sexually transmitted diseases (Health aspects)
HIV patients (Health aspects)
HIV (Viruses) (Risk factors)
HIV (Viruses) (Prevention)
HIV (Viruses) (Health aspects)
Cancer (Care and treatment)
Cancer (Health aspects)
Author: Mascolini, Mark
Pub Date: 12/22/2011
Publication: Name: Research Initiative/Treatment Action! Publisher: The Center for AIDS: Hope & Remembrance Project Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 The Center for AIDS: Hope & Remembrance Project ISSN: 1520-8745
Issue: Date: Winter, 2011 Source Volume: 16 Source Issue: 2
Product: Product Code: 8000432 Cancer Therapy NAICS Code: 621 Ambulatory Health Care Services
Organization: Government Agency: United States. Centers for Disease Control and Prevention
Accession Number: 289355756
Full Text: Abstract: Working with HIV-positive people to tell their sex and drug-injecting partners they have HIV is the first step in prevention with positives. Step 2 is encouraging positive people to consider starting antiretroviral therapy, with an eye toward reaching and maintaining an undetectable viral load. Clinician experience in the United States suggests that results of HPTN 052 have opened another avenue to discussing starting antiretroviral therapy. Because most sexually transmitted infections (STIs) remain asymptomatic, appropriate screening for STIs is essential to limiting HIV transmission risk from positive people. Despite data confirming low HIV transmission risk in people with an undetectable viral load, providers should continue to stress condom use. Circumcision lowers the risk of HIV transmission from positive heterosexual men. But the CDC and other groups urge caution in considering circumcision for gay men because of limited evidence in this population and because the risks of circumcision remain largely unexplored in them. Serosorting limits HIV transmission in gay men who do not use condoms but cannot be recommended as a primary prevention strategy. Clinicians should remember that most HIV transmissions from injection drug users come during sex, not needle sharing. Plentiful evidence shows that behavioral interventions can help HIV-positive people refrain from transmission-risk behavior. Some of these interventions involve little or no provider time and can be completed by patients using hand-held devices in the waiting room. The CDC plans to stress these time-saving strategies in its 2012 prevention-with-positives guidelines.

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Reasons why clinicians fail to engage HIV-positive patients on transmission risk almost outnumber reasons why clinic-based prevention strategies work. The first article in this issue ponders both lists of reasons. This article probes clinic-based strategies for bridling transmission from positives--with a focus on strategies that take little provider time and won't break the clinic budget.

First step in positive prevention: telling partners

Before providers can lift a finger--or prescription pad--to prevent HIV-positive people from transmitting their virus, they've got to know who's positive. That's why the CDC and others are pushing hard to test as many people as possible, regardless of perceived HIV risk. Once a person gets diagnosed and referred to care, the provider must address another urgent priority--making sure the new patient's partners know.

For an array of reasons easy to imagine, people with HIV often avoid telling sex partners they're infected. One study of 675 HIV-positive men who have sex with men (MSM) in six US cities found that 30% told no sex partners they had HIV in the past 90 days. (1) Another study discussed below recorded a 7% notification rate. (2)

HIV providers must remember that most states and some local governments have laws regulating HIV disclosure to partners; many states also regulate disclosure by clinicians to third parties at high risk of getting infected by already positive patients. (3) Some health departments give HIV-positive people a set time to notify partners. If the partners don't show up for counseling and testing by the end of that "contract period," the health department gives them the news. (3)

CDC guidelines advise providers to ask all positive people at their first visit whether they've told sex and needle-sharing partners they have HIV. (3) And keep asking at follow-up visits, the CDC says, because many patients will have found new partners in the interim. (The CDC is releasing revised and greatly expanded guidance on prevention with positives in 2012. See the interview with the CDC's Kathleen Irwin in this issue.)

A 1992 trial that randomized newly diagnosed people to physician- or self-notification of partners found that physicians successfully notified 78 of 157 sex or needle-sharing partners (50%), while patients themselves notified only 10 of 153 partners (7%). (2) Among notified partners, 23% had HIV.

Second step to positive prevention: undetectable viral load

Long before HPTN 052 offered sumptuous proof that triple antiretroviral therapy slashes the risk of HIV transmission in HIV-discordant couples, plentiful evidence forged a fast link between lower viral loads and slimmer chances of transmission. That principle became clear well before the dawn of triple therapy, when US and French investigators found that zidovudine taken by pregnant women and newborns sliced the risk of mother-to-child transmission 67.5% (95% confidence interval [CI] 18.4 to 32.5, P = 0.00006). (4)

In ensuing decades, one trial after another showed that one drug is better than none, two are better than one, and three are best in cutting chances of vertical HIV transmission, clearly because each stronger regimen lowers viral load more. Testing three triple regimens in 730 women, the Mma Bana study in Botswana found that more than 90% of women across the three groups had a viral load below 400 copies/mL at delivery and through follow-up. (5) Six months after delivery, the HIV transmission rate in this breast-feeding population was 1.1%--equivalent to rates in formula-feeding Western populations.

The same principle applies to sexual or parenteral transmission of HIV. In the seminal study of 415 HIV-discordant Ugandan couples before antiretroviral therapy became available, none of 51 people with a viral load below 1500 copies/mL infected their partner. (6) In a study of 253 antiretroviral-naive HIV-discordant monogamous Ugandan couples, the researchers divided HIV-positive partners into four equal groups reflecting their HIV load: under 3090 copies/mL, 3090 to 14,450 copies/mL, 14,450 to 75,850 copies/mL, and over 75,850 copies/mL. (7) Compared with people in the lowest viral load quartile, those in the next higher quartile had a 3.31 times higher risk of transmitting HIV, those in the quartile above that had a 6.39 times higher risk, and those in the highest quartile had a 7.06 times higher risk. (Figure 1).

Though HIV incidence data from HIV-discordant heterosexual African couples may not apply precisely to gay and straight couples in the United States and similar countries, this research certainly offers keen insights into how viral load may affect transmission. A canny modeling study relied on data prospectively collected from 3381 HIV-discordant African couples from 2004 to 2008, including 108 with genetically linked HIV transmissions. (8) The model predicted that every 0.74 log (about 5.5-fold) lower viral load cut heterosexual transmission risk 50%, regardless of starting viral load in the population and other HIV-related population traits.

Meta-analysis of 11 studies involving 5021 heterosexual couples counted 461 HIV transmissions, only 5 of them from an antiretroviral-treated partner? No one with a viral load below 400 copies/mL passed HIV to a partner. These couples lived in three African countries, Brazil, India, Spain, Thailand, and the United States.

Population-based modeling studies show that, as communities start using robust antiretroviral combinations, "community viral load" drops, followed by HIV incidence (the new infection rate). (10-12) For example, British Columbia's centrally controlled antiretroviral program allowed researchers to figure that individual use of triple therapy soared 547% from 1996 to 2009, reaching only 837 people in 1996 and 5413 in 2009 (P = 0.002). (11) Over the same period, the number of new HIV diagnoses dwindled 52%, from 702 to 338 per year (P = 0.001). On an annual basis, the number of people on combination therapy correlated inversely--and tightly--with the number testing positive (-0.89, P < 0.0001).

With all these findings pointing (insistently) in the same direction, no one could be surprised that antiretroviral therapy stymied sexual HIV transmission in HPTN 052. (13) But the magnitude of that effect was stunning. The trial enrolled 1763 HIV-discordant couples in nine countries, 97% of them heterosexual and 94% of them married. Everyone had a CD4 count between 350 and 550 cells/[mm.sup.3], and no one had taken antiretrovirals. The investigators randomized HIV-positive partners in these couples to start antiretroviral therapy immediately or to wait till their CD4 count dropped to 250 cells/[mm.sup.3] or they had an AIDS disease.

The Data and Safety Monitoring Board pulled the plug on HPTN 052 early when results through February 2011 showed that 28 couples had a genetically confirmed HIV transmission, only I of them in the early-antiretroviral group. Starting antiretrovirals immediately chopped the HIV transmission risk by 96%. Because the 1 genetically linked transmission in the early-antiretroviral group probably occurred before treatment made the positive partner's viral load undetectable, HPTN 052 confirmed earlier nonrandomized studies that found no sexual HIV transmissions from people with an undetectable viral load.

"Drinking the Kool-Aid" on treatment as prevention

Long before HPTN 052 confirmed that antiretrovirals taper HIV transmission rates, the CDC cautioned that undetectable virus in plasma does not necessarily mean virus-free semen, rectal secretions, or genital or pharyngeal fluids. (3,14,15) And an unreadable load in plasma depends on steady adherence and staying free of other sexually transmitted infections. Even certain vaccinations can hike viral load. On top of that, some studies show that doing well on antiretroviral therapy can make people reckless in bed. So even universal treatment of diagnosed people will not tamp down their transmission risk completely.

But it's a big step in that direction. Of the 18 top HIV physicians who responded to RITA!'s survey on positive prevention (see box on page 13), 16 listed reining in HIV with antiretrovirals as a prime strategy, and 7 of those 16 cited HPTN 052. (13)

"The single most important thing clinicians can do to prevent transmission is to treat their HIV-positive patients with antiretroviral therapy, our most effective form of prevention," wrote Joel Gallant (Johns Hopkins University). "That doesn't mean that other forms of prevention don't matter anymore," he added. "It's still important to talk about behavior change and condom use, for example. But if every HIV-positive person had an undetectable viral load, the epidemic would be over."

David Wohl (University of North Carolina) seconded that opinion, noting that HIV incidence in HPTN 052 "was pretty low in the control group not treated with antiretrovirals." That means the "prevention measures in the control [arm]--pretty standard stuff seemed to have an effect. That said, I have really drunk the Kool-Aid when it comes to use of antiretrovirals to prevent transmission."

Others believe HPTN 052 opens an avenue to discussing positive prevention with their patients. "I've been pleasantly surprised how the 'treatment-as-prevention' message from 052 has facilitated discussion about prevention in clinical practice, and how motivating prevention can be for people considering starting therapy," said Paul Sax (Harvard Medical School).

Steven Deeks (University of California, San Francisco) agreed, noting that "in my recent experience, this public health aspect of treatment has been a great motivator for some individuals to seek care and begin therapy, so I am optimistic transmission rates will decline."

Some HIV-positive people who may not want to start treatment for their own health "will opt for treatment to prevent transmission," Ian Frank (University of Pennsylvania) is finding. As a corollary to this emerging attitude, Frank suggested, treatment as prevention "can be particularly motivational for people in discordant couple relationships" and for another patient subset--HIV-positive people looking for a partner but assuming no HIV-negative person would consider a relationship. Now, Frank noted, a positive person with well-controlled infection can tell a potential partner, "I have a low risk for transmission of my infection because my viral load is undetectable," and that "can change someone's outlook" on finding a partner.

Risk screening and STI testing for positive prevention

Besides treating people to make their viral load too low to tote, what else should HIV providers do to help patients avoid dispatching their virus to others? HIV Medicine Association (HIVMA) primary care guidelines prescribe four essentials: (16)

1. Screen people for high-risk behavior at each visit.

2. Ask patients about sexually transmitted infection (STI)-related symptoms at each visit.

3. Give a general message about risk reduction at each visit.

4. Tailor messages for patients who report high-risk behavior.

Do providers have to keep hammering on prevention at every visit? The CDC thinks so. "Clinicians should recognize that [HIV transmission] risk is not static," the 2003 guidelines state. (3) "Patients' lives and circumstances Change, and a patient's risk of transmitting HIV may change from one medical encounter to another."

The HIVMA guidelines, freely available online, (16) boast an ample section on risk screening in people with HIV, including a list of questions most clinicians should feel comfortable asking (Table 3 in Reference 16). HIVMA guidelines also feature pointers on carrying out the four steps listed above.

CDC positive-prevention advice spells out recommendations on screening for transmission risk and STIs (Table 1). (3) The CDC stresses that most STIs are asymptomatic, so these risky infections remain masked unless lab tests uncover them. CDC and HIVMA guidelines outline asymptomatic STI screening advice by (1) initial versus subsequent patient visit, (2) gender, and (3) risk (Table 2).

Patients can even test themselves for gonorrhea and chlamydia in an HIV clinic, according to results of a large London study. (17) In this nurse-led self-screening program, HIV-positive men and women are invited to collect specimens by self-swabbing. Diagrams on rectal, pharyngeal, and vaginal self-swabbing are posted in clinic rest rooms. Staff" screens samples with nucleic acid amplification tests.

The 976 screens completed over 8 months in people without STI symptoms disclosed 143 infections (14.6%), at rates of 17.4% in MSM, 2.1% in heterosexual men, and 1.5% in women. (17) Six people with a self-detected STI had a transient spike in HIV load. Among 78 people taking antiretrovirals at STI diagnosis, 72 had a viral load below 40 copies/mL and 6 had a load between 40 and 70 copies/mL. The researchers recommend STI screening for MSM every 4 months and annual testing for heterosexuals. They suggest this approach "may address some of the barriers to screening in this population."

The Health Resources and Services Administration (HRSA) 2011 Guide for HIV/AIDS Clinical Care includes a useful table (on pages 134 and 135) suggesting questions to ask and assessments for (1) sexual practices, (2) partner notification, (3) STI screening, and (4) drug and alcohol use. (18)

Getting HIV-positive people to don condoms

Condoms are lots easier to make than antiretrovirals, lots cheaper, and lots easier to get to people with HIV. Yet this low-tech latex sheath stops HIV transmission dead if used properly. No one has figured out how much condoms have stunted the epidemic's growth, but they certainly had a hand in Uganda's dramatic drop in HIV prevalence from 18% in 1992 to 6% in 2002. (19) And a recent study from India suggests that a pilot prevention program stressing condom use and other measures may have averted over 100,000 new HIV cases in 5 years. (20)

In a systematic review of five studies, WHO researchers figured that consistent condom use by MSM cuts HIV transmission risk 64% and STI acquisition risk 42%. (21) WHO guidelines for HIV prevention and treatment in MSM strongly recommend condoms for MSM and transgender people, noting that "water- and silicone-based lubricant use is key for the correct functioning of condoms during anal sex." (21)

The first figure in 2003 CDC prevention guidelines suggest how to tailor messages on condom use for HIV-positive people. (3) The opening question might be, "How often do you use condoms when you have sex?" If the person says never or sometimes, the next question could be, "What do you plan to do about using condoms in the future?" And if the person has no plan, an appropriate follow-up may be, "Do you know that you could catch an STI that way, and it could make your HIV infection worse?"

CDC authorities urge physicians to supply condoms to HIV-positive patients, (3) and HRSA guidelines say physicians should hand out condoms and lubricant. (18) HRSA details condom-use pointers providers can give patients, as well as suggestions for people who complain about lack of sensitivity with condoms (Table 3).

Circumcision works ... for some

Three randomized trials established that medical male circumcision cuts the risk of HIV acquisition in heterosexual African men. (22-24) WHO now endorses circumcision for heterosexual men in countries with high HIV prevalence, (25) and some African countries gave circumcision a prominent place in their HIV prevention agenda. But WHO does not recommend circumcision for gay or bisexual men and, in fact, advises against it: "Not offering adult male circumcision to prevent HIV and STI acquisition is suggested over offering it to MSM and transgender people." (21) Although WHO aims these guidelines at MSM in low- and middle-income countries, the agency recommends making this document available to men in high-income countries as well.

What makes WHO take this negative stance? WHO cited a Cochrane Database systematic review decocting 20 studies of male circumcision for HIV prevention in MSM. (26) Three studies of 1792 men determined that circumcision did not protect MSM who primarily practiced receptive anal intercourse (odds ratio [OR] 1.20, 95% confidence interval [CI] 0.63 to 2.29). Seven studies of 3465 men who mostly practiced insertive anal sex yielded evidence that foreskin removal did lower their HIV acquisition risk almost 75% (OR 0.27, 95% CI 0.17 and 0.44). (26)

The Cochrane review found no evidence that circumcision protects gays or bisexuals from syphilis, herpes simplex virus 1, or herpes simplex virus 2. (26) Cochrane rated overall evidence quality low in these studies and stressed that no studies analyzed adverse effects of circumcision.

Surveying all these findings, WHO guideline writers decided "it is not clear if the benefits outweigh the risks [for MSM] at this point in time, as male circumcision, like any other operation, carries some risks." (21) On top of that, WHO cautioned, "there are significant concerns regarding its acceptability and implementation among MSM in different cultural settings." (21) WHO, Cochrane, and the CDC (27) all agree that findings to date do not support circumcision as an HIV prevention strategy for gay or bisexual men and that further research should address the potential role of circumcision among MSM who take the insertive role during anal intercourse.

Caution makes sense when weighing the potential role of circumcision in preventing HIV among gay men, regardless of whether they prefer being insertive "tops" or receptive "bottoms." A retrospective CDC study of 4889 North American and European MSM enrolled in the VAXGen HIV vaccine trial underlines that point. (28) An analysis that controlled for demographics and risk behaviors determined that being uncircumcised did not raise the risk of picking up HIV even a tiny bit (adjusted hazards ratio [AHR] 0.97, CI 0.56 to 1.68). In study visits during which men reported unprotected insertive anal sex with a positive partner, HIV infection was reported in 3.16% of visits by circumcised men and 3.93% of visits by uncircumcised men (relative risk [RR] 0.80, CI 0.46 to 1.39).

Should uncircumcised HIV-negative heterosexual men in the United States and countries with similar HIV epidemics be encouraged to get circumcised to lower their HIV risk? In April 2007, after release of results from the three randomized African trials, (22-24) the CDC held a 2-day pow-wow on circumcision to prevent HIV infection in the United States and summed up with this advice for heterosexuals:

"Sufficient evidence exists to propose that heterosexually active males be informed about the significant but partial efficacy of male circumcision in reducing risk for HIV acquisition and be provided with affordable access to voluntary, high-quality surgical and risk-reduction counseling services." (27)

Whether uncircumcised HIV-positive heterosexuals should be urged to get circumcised to curb chances of transmitting HIV to sex partners is another question entirely. Mathematical modeling suggests that male circumcision trims the risk of male-to-female HIV transmission more than first predicted. (29) Basing their analysis on HIV transmission rates in four randomized trials and in observational studies of already circumcised men in stable partnerships, these investigators calculated that male circumcision eases the risk of male-to-female HIV transmission by 46%.

But it is probably naive to imagine that many uncircumcised HIV-positive men--straight or gay--can be persuaded to shed their foreskin to protect sex partners. A confidential survey of 653 MSM recruited in London gyms found that only 10% of 464 uncircumcised men said they would sign up for a study of circumcision to prevent HIV infection. (30) Only one third of uncircumcised men thought circumcision has benefits, compared with two thirds of circumcised men. Similar proportions of these men (39% uncircumcised and 37% circumcised) reported unprotected anal sex in the past 3 months. One quarter of uncircumcised men had HIV infection.

On the other hand, about half of HIV-negative MSM in a 2006 US study claimed they would get circumcised if research showed the operation would trim their HIV risk. (31) Researchers interviewed 780 men at gay pride events, all of them presumed to be HIV-negative and 133 of them (17%) uncircumcised. The gay pride events took place in Birmingham, Alabama, Anchorage, Alaska, Raleigh-Durham, North Carolina, Springdale, Utah, Charlotte, North Carolina, Chicago, and St. Louis.

Seventy-one of 133 uncircumcised men (53%) claimed they would consider circumcision, pending favorable research results. Black men, men who did not inject drugs, and men who believed circumcision would lower their risk of penile cancer were more likely to consider circumcision. The research summarized above suggests those men are still waiting to see if circumcision will help keep them free of HIV. But physicians who care for HIV-negative gay men should be aware some may consider circumcision.

Does serosorting sort out HIV risk?

HIV clinicians heaved grateful sighs in the middle of the last decade when they learned that gay men had devised their own strategy to limit HIV transmission and that it seemed to work. (32,33) Serosorting--having sex only with men of the same HIV status--appeared to explain why STI incidence rose from 1998 through 2004 in San Francisco MSM while HIV incidence peaked in 1999 then leveled off. (33) But even these early reports noted that HIV incidence remained high and cautioned that "a strategy of risk reduction by HIV serosorting can be severely limited by imperfect knowledge of one's own and one's partners' serostatus." (33)

Analyzing data from 3 studies in developed countries, WHO figured that HIV-negative men who relied on serosorting rather than consistent condom use had a 79% higher risk of HIV acquisition (RR 1.79, 95% CI 1.2 to 2.65) and a 61% higher risk of getting a new STI (RR 1.61, 95% CI 1.43 to 1.81). (21) Compared with no condom use, however, serosorting cut chances of HIV infection 53% (RR 0.47, 95% CI 0.26 to 0.84) and whittled STI risk by 14% (RR 0.86, 95% CI 0.78 to 0.93).

WHO concluded that "serosorting may be a potential harm reduction strategy for [MSM] who choose not to use condoms, but it should not be promoted as an alternative strategy for HIV prevention. Consistent condom use is a more effective method to prevent HIV infection." (21) These experts advise frequent HIV and STI screening for MSM who rely solely on serosorting to shield themselves from sexually transmitted intruders.

CDC positive-prevention guidelines stress that condom-free serosorting does not protect men from picking up new STIs or another HIV. (3) Although the clinical hazards of superinfection with a second HIV remain open to question, a few case reports suggest a second HIV may be much nastier than the first, (34-36) and a superinfecting HIV could bear resistance mutations.

HIV providers should be aware that HIV-negative serosorters may believe they have a lower risk of getting infected, may indulge in unprotected sex as a result, and may get tested for HIV less than once yearly, as the CDC recommends. (37)

Advice on working with IDUs and other drug abusers

Although injection drug users (IDUs) accounted for only 10% of new HIV infections in the United States in recent years, that rate did not budge from 2006 through 2009, the most recent years for CDC calculations. (38) That plateau implies that IDUs continue to infect their partners at a steady pace.

There's no secret about how to cut HIV transmissions in drug injectors--get them to quit shooting up by referring them to opioid-substitution programs? And if that doesn't work, urge them to use clean injection equipment and never to reuse or share that equipment? Providers should not neglect counseling IDUs about sexual transmission of HIV, which accounts for more transmissions in this group than equipment sharing.

The CDC's 2003 positive-prevention guidelines suggest a thoughtful approach to asking IDUs about their needle-sharing habits and encouraging them to stop completely if they haven't already (Figure 2 in CDC guidelines (3)). An HIV provider might get the ball rolling by asking, "How often do you borrow or share a needle or works?" If the patient answers sometimes or always, the provider could ask, "What do you plan to do about sharing needles in the future?" If the person has no plans, possible follow-up questions may be "Have you heard that HIV can survive in the cotton and rinse water?" or "Can you tell me something about sharing needles?" If the person does have a plan, the clinician might ask, "How do you think your friends will deal with you when you don't share needles or works?"

The CDC stresses that giving up injecting "is the only reliable way to eliminate the risk of injection-associated HIV transmission." (3) These guidelines cite more than a dozen studies showing that substance abuse treatment--particularly opioid substitution--can reduce risky injection habits, risky sex, and HIV incidence. For IDUs who can't or won't quit shooting, the CDC favors "once-only use of sterile syringes" because "it is difficult to reliably disinfect syringes" and because studies show disinfecting is not as safe as using a new sterile syringe.

The Midwest AIDS Training + Education Center offers a useful patient-level flier on avoiding needle sharing and keeping needles clean at http://www.uic.edu/depts/matec/Drug/Safer.htm (accessed November 5, 2011). Providers can download the flier and print it on two pages.

As research summarized in the first article in this issue shows, noninjection drug use also inflates the risk of HIV transmission. HIV providers should talk to patients about drug use and should refer those who need help getting a handle on their habit.

Behavioral interventions can trim transmission risk

One might assume that getting people on antiretrovirals, getting their viral load under 50, and screening for and treating other STIs will prevent HIV transmission so effectively that providers needn't bother with costly, time-consuming, hit-or-miss behavioral interventions.

But some new behavioral tactics are inexpensive, require little or no provider time, and proved effective in randomized trials.

So ignoring this option may deprive some HIV-positive people of an approach that fits their needs best. For example, behavioral interventions may be a good bet for healthy people who want to put off antiretroviral therapy, those on treatment who can't reach an undetectable viral load, people with continuing high-risk behavior despite regular counseling, patients who like to take charge of their own health, and people inclined to try group programs or who have an amicable provider relationship that makes one-on-one interventions a natural fit.

In 2006 CDC investigators ran a meta-analysis of interventions designed to quell risk behaviors in HIV-positive people to see what worked and what predicted success. (39) They considered only studies that used randomization or assignment with minimal bias, relied on statistical analysis, and assessed behavioral or biologic outcomes at least 3 months after the intervention. Together the interventions cut the risk of unprotected sex almost 40% (OR 0.57, 95% CI 0.40 to 0.82) and clipped STI incidence 80% (OR 0.20, 95% CI 0.05 to 0.73). Among the traits of successful programs were delivery by providers or counselors, delivery in settings where HIV-positive people receive routine services or medical care, and a design based on behavioral theory. (See the interview with the CDC's Nicole Crepaz in this issue for details of this meta-analysis.)

[ILLUSTRATION OMITTED]

The Cochrane group analyzed 44 studies of behavioral interventions involving 18,585 MSM with or without HIV. (40) These studies, published or presented from 1988 through 2007, included 26 small-group interventions, 21 individual-level interventions, and 11 community-level interventions. Overall, these programs cut the risk of unprotected sex or partner numbers by 15% to 27%, depending upon study type. The Cochrane experts concluded that "HIV prevention for this population can work and should be supported." (40)

Besides conducting the just-cited meta-analysis, (39) the CDC's Prevention Research Synthesis (PRS) team reviews and vets mountains of evidence on HIV prevention interventions and distills it all on Web pages devoted to "promising-evidence interventions" that can rein in sex- or drug-related risk behaviors, curb rates of new HIV and other STIs, or bolster HIV-protective behaviors. (41) The 28 programs identified to date meet PRS efficacy criteria and are judged scientifically sound.

Four of these interventions target HIV-positive people: Options/Opciones Project, Partnership for Health, Together Learning Choices (TLC), and Women Involved in Life Learning With Other Women (WILLOW). Options/Opciones and Partnership for Health are one-on-one interventions delivered by the HIV provider. TLC is a small-group intervention aimed at teens and young adults, and WILLOW is a small-group program for HIV-positive women, Table 4 describes these tour programs and provides links for further information.

Innovative interventions discussed by Stephen Morin in the interview in this issue let patients screen themselves for transmission risk behaviors on laptops or handheld devices while waiting for their appointment. If the patient signals some risk on these self-administered surveys, a red flag waves in the clinic's electronic medical records, alerting the provider before the patient visit and allowing the provider to take appropriate action. The table between the two interviews in this issue describes four patient self-administered programs.

Not content with merely parsing and rating HIV risk-reduction programs, the CDC collaborates with Danya International to train providers, health departments, and community groups in science-based HIV-prevention interventions. (42) A comprehensive Web site offers complete explanations of programs and a city-by-city calendar of free courses: go to the Diffusion of Effective Behavioral Interventions (DEBI) site at http://www.effectiveinterventions.org/en/home.aspx. The top of the home page offers a link to a 20-minute online DEBI overview.

Reviewing findings from trials done largely in high-income countries, WHO recommends behavioral interventions for HIV prevention in MSM, including individual interventions, community-level interventions, targeted Internetbased information, social marketing strategies, and sex venue-based outreach. (21)

WHO analyzed studies of two Internet-based strategies, one that aimed to temper risk behavior in US MSM with HIV (21%) or without HIV (43) and one in Peru to increase HIV testing in seronegative MSM. (44) Among men who practiced unprotected anal intercourse when the US study began, after 3 months those randomized to the Internet program reported a marginally lower number of men with whom they had risky sex than did men in the control arm (risk reduction 15.6%, 95% CI 0.704 to 1.013, P = 0.068 in an adjusted analysis). (43)

WHO observed that "Internet-based HIV prevention interventions make it easier for MSM with Internet access to obtain relevant HIV prevention messages in an anonymous fashion, at a convenient time and in private. (21) Prevention instruction and counseling via the Internet may be particularly appropriate for rural residents, who have to travel far to their HIV clinic or behavioral intervention sites, or for people uncomfortable with group interventions. One study of 475 rural US MSM found that one such program reduced anal sex and increased condom use. (45) But so far the CDC lists no Internet-based prevention programs for HIV-positive people.

Clinicians who don't know how their patients use digital media should start Learning. How many providers who care for gay men know that many of them favor a smart-phone app, GRINDR, that melds social networking with GPS to help men find friends--and sex partners--fast? A study of 375 young gay men who use GRINDR in Los Angles found that 153 men (43%) reported unprotected receptive anal intercourse in the past month, 163 (47%) reported unprotected insertive anal intercourse, and 181 (48%) had sex under the influence of alcohol or drugs. (46) More than half of these men, 56%, found a sex partner via GRINDR. And when using GRINDR, fewer HIV-positive than negative men asked their potential partner's HIV status, a finding suggesting some of these positive men don't bother serosorting.

Limited clinic time and other strictures may sometimes frustrate clinicians who set their mind on one of the 3- to 10-minute positive-prevention exchanges recommended by the CDC (Table 4, Options/Opciones Project and Partnership for Health). But interventions self-administered by patients (summarized between the two interviews in this issue) take little or no provider time. And it takes about 5 seconds to ask office staff to copy the Prevention Pointers sheet that follows this article in RITA! and about 4 seconds to pull it out of a drawer and hand it to an HIV-positive patient at every visit.

Pointers for Providers and Patients

Prevention pointers for people with HIV: How to avoid passing your virus to someone else

* The easiest ways to pass HIV to someone else are in blood or sexual fluids.

* Having sex without a condom or sharing drug-injection works can infect a partner with your HIV.

* If you inject drugs, you can stop with a drug-substitution program (for example, with methadone).

* If you continue to inject drugs, always use clean injecting equipment and never share injecting equipment with partners.

* Always use a condom during anal or vaginal sex.

* Use enough lubrication with a condom to avoid causing minor cuts in your partner's anus or vagina.

* Don't rely on a sex partner to tell you accurately (or truthfully) if he or she has HIV.

* Using drugs or alcohol before sex raises the chance you will forget to use a condom or won't bother to use one.

* If you haven't started antiretroviral therapy, consider starting as a way to limit chances you will infect a partner.

* If you're taking antiretrovirals, take your drugs as directed to make sure you reach and maintain an undetectable viral load.

* If you reach an undetectable viral load, your virus may become detectable again if you miss antiretroviral doses or get another sexually transmitted infection.

* Tell your HIV provider immediately if you have signs of a sexually transmitted infection, such as genital sores.

* Don't donate blood, plasma, tissue, organs, or semen because they can transmit HIV.

* Don't share toothbrushes, razors, douche equipment, or sex toys.

* Pointers based primarily on US Department of Health and Human Services Health Resources and Services Administration. Guide for HI V/AIDS Clinical Care. January 2011. http://hab.hrsa.gov/deliverhivaidscare/cliniealguide11/.

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(15.) Neely MN, Benning L, Xu J, et al. Cervical shedding of HIV-I RNA among women with low levels of viremia while receiving highly active antiretroviral therapy.J Acquir Immune Defic Syndr. 2007;44:38-42.

(16.) Aberg JA, Kaplan JE, Libman H, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2009;49:651-681. http://www.uphs.upenn.edu/bugdrug/antibiotie_manual/idsahivprimaryeare2009. pdf. Accessed October 24, 2011.

(17.) Soni S, White JA. Self-screening for Neisseria gonorrboeae and Chlamydia trochomatis in the human immunodeficiency virus clinic--high yields and high acceptability. Sex Transm Dis. 2011;38:1107-1109.

(18.) US Department of Health and Human Services Health Resources and Services Administration. Guide for HIV/AIDS Clinical Care. January 2011. http://hab.hrsa.gov/deliverhivaidscare/clinicalguide11/. Accessed October I0, 2011.

(19.) Government of Uganda. UNGASS country progress report Uganda. January 2008-December 2009. March 2010. http://www.unaids.org/en/dataanalysis/monitoringcountryprogress/ 2010progressreportssubmittedbycountries/ uganda_2010_country_progress_report_en.pdf. Accessed October 25, 2011.

(20.) Ng M, Gakidou E, Levin-Rector A, et al. Assessment of population-level effect of Avahan, an HIV-prevention initiative in India. Lancet. Early online publication. October 11, 2011.

(21.) World Health Organization. Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender people: recommendations tar a public health approach. 2011. http://whqlibdoc.who.int/publications/2011/9789241501750_eng.pdf. Accessed November 1, 2011.

(22.) Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005;2:e298.

(23.) Bailey RC, Moses S, Parket CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369:643-656.

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(26.) Wiysonge CS, Kongnyuy El, Shey M, et al. Male circumcision for prevention of homosexual acquisition of H IV in men. Cochrane Database Syst Rev. 2011 ;CD007496.

(27.) Smith DK, Taylor A, Kilmarx PH, et al. Male circumcision in the United States for the prevention of HIV infection and other adverse health outcomes: report from a CDC consultation. Public Health Re,.]). 2010; 125(suppl 1):72-82.

(28.) Gust DA, Wiegand RE, Kretsinger K, et al. Circumcision status and HIV infection among MSM: reanalysis of a phase III HIV vaccine clinical trial. AIDS. 2010;24:1135-1143.

(29.) Hallett TB, Alsallaq RA, Baeten JM, et al. Will circumcision provide even more protection from HIV to women and men? New estimates of the population impact of circumcision interventions. Sex Transm Infect. 2011 ;87:88-93.

(30.) Thornton AC, Lattimore S, Delpech V, Weiss HA, Elford J. Circumcision among men who have sex with men in London, United Kingdom: an unlikely strategy for HIV prevention. Sex Transm Dis'. 2011;38:928-931.

(31.) Begley EB, Jafa K, Voetsch AC, Heffelfinger JD, Borkowf CB, Sullivan PS. Willingness of men who have sex with men (MSM) in the United States to be circumcised as adults to reduce the risk of HIV infection. PLoS One. 2008;3:e2731. http://www.plosone.org/article/info%3Adoi%2FlO.1371%2Fjournal.pone.O002731. Accessed November 2, 2011.

(32.) San Francisco serosorting may explain odd HIV data. STDs have risen, but not new HIV infections. AIDS Alert. 2004; 19:55-56.

(33.) Truong HM, Kellogg T, Klausner JD, et al. Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting? Sex Transm Infect. 2006;82:461-466.

(34.) Braibant M, Xie J, Samri A, Agut H, Autran B, Barin E Disease progression due to dual infection in an HLA-B57- positive asymptomatic long-term nonprogressor infected with a nef-defective HIV-1 strain. Virology. 2010;405:81-92.

(35.) Clerc O, Colombo S, Yerly S, Telenti A, Cavassini M. HIV-1 elite controllers: beware of super-infections. J Clin Virol. 2010;47:376-378.

(36.) Gottlieb GS, Nickle DC, Jensen MA, et al. H 1V type 1 superinfection with a dual-tropic virus and rapid progression to AIDS: a case report. Clin Infect Dis. 2007;45:501-509. Erratum in: Clin Infect Dis. 2010;51:638.

(37.) Eaton I,A, Kalichman SC, Cain DN, et al. Serosorting sexual partners and risk for HIV among men who have sex with men. Am J Prev Med. 2007;33:479-485.

(38.) Prejean J, Song R, Hernandez A, Ziebell R, Green l; et al. Estimated HIV incidence in the United States, 20062009. PLoS One. 2011 ;6(8):e17502.

(39.) Crepaz N, Lyles CM, Wolitski RJ, et al; HIV/AIDS Prevention Research Synthesis (PRS) Team. Do prevention interventions reduce HIV risk behaviors among people living with HIV? A meta-analytic review of controlled trials. AIDS. 2006;20:143-157. http://pdf s.journals.lww.com/aidsonline/2006/01090/ Do_prevention_interventions_reduce_HI_risk.2.pdf.

(40.) Johnson WD, Diaz RM, Flanders WD, et al. Behavioral interventions to reduce risk for sexual transmission of HIV among men who have sex with men. Cochrane Database Syst Rev. 2008(3):CD001230.

(41.) CDC. Promising-evidence interventions, http://www.cdc.gov/hiv/topics/research/prs/promising-evidence- interventions.htm. Accessed November 3, 2011.

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(43.) Rosser BR, Oakes JM, Konstan J, et al. Reducing HIV risk behaviour of men who have sex with men through persuasive computing: results of the Men's INTernet Study-II. AIDS. 2010;24:2099-2107.

(44.) Bias MM Alva IE, Carcamo CP, et al. Effect of an online video-based intervention to increase HIV testing in men who have sex with men in Peru. PLoS One. 2010;5:e10448.

(45.) Bowen AM, Williams ML, Daniel CM, Clayton S. Internet based HIV prevention research targeting rural MSM: feasibility, acceptability, and preliminary efficacy. J Behav Med. 2008;31:463-477. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614302/?tool=pubmed. Accessed November 4, 2011.

(46.) Landovitz RJ, Tseng C, Weissman M, et al. Epidemiolog-y and sexual risk behavior of MSM Using GRINDR in Los Angeles, California. 51 st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H 1-1149.
Table 1. CDC advice on screening HIV-positive people for
transmission risk and STIs

Source: Centers for Disease Control and Prevention. Incorporating H
I V prevention into the medical care of persons living with HIV:
recommendations of CDC, the Health Resources and Services
Administration, the National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases Society of America.
MMWR. 2003;52(No. RR-12). (3)

Screen HIV-positive adults for HIV transmission risk behaviors in a
straightforward, nonjudgmental manner. Screening should be done at
the initial visit and subsequent routine visits, at least once a
year.

Any indication of risky behavior should prompt a more thorough
assessment of HIV transmission risks.

Ask HIV-positive adults about STI symptoms at the first and every
following routine visit.

Regardless of reported sexual behavior or other epidemiologic risk
information, such signs or symptoms should always prompt diagnostic
testing and, when appropriate, treatment.

At the first visit screen all HIV-positive adults for laboratory
evidence of syphilis and all HIV-positive women for trichomoniasis.

Screen for cervical chlamydial infection at the first visit in all
sexually active women under 25 years and other women at increased
risk, even if asymptomatic.

At the first visit consider screening all HIV-positive adults for
gonorrhea and chlamydial infection.

Because of the cost of screening and the variability of gonorrhea
and chlamydia prevalence, decisions about routine screening for
these infections should be based on epidemiologic factors. [But see
results of the large British self-screening study discussed in the
text. (17)]

Repeat ST1 screening at least annually if the patient is sexually
active or if earlier screening revealed STIs.

STI screening should be done more frequently (for example, every 3
to 6 months) for asymptomatic people at higher risk.

At the first and each subsequent routine visit, question
HIV-positive women of childbearing age to identify possible current
pregnancy, interest in future pregnancy, or sexual activity without
reliable contraception.

Ask women whether they suspect pregnancy or have missed their
menses and, if so, test them for pregnancy.

STI, sexually transmitted infection.

Source: Centers for Disease Control and Prevention. Incorporating
HIV prevention into the medical care of persons living with HIV:
recommendations of CDC, the Health Resources and Services
Administration, the National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases Society of America.
MMWR. 2003;52(No. RR-12). (3)

Table 2. CDC and HIVMA guidelines for screening to detect asymptomatic
STIs

                              First visit

All patients      Women             Patients          Patients
                                    reporting         reporting
                                    receptive         receptive
                                    anal sex          oral sex

* Serologic       * Examination     * Culture of      * Culture of
  test for          of vaginal        rectal sample     pharyngeal
  syphilis (ie,     secretions        for Neisseiia     sample for N
  nontreponemal     for               gonorrhoeae       gariorrhoeae
  test, such as     Trichomonas
  RPR or VDRL)      species         * Culture of
                                      rectal sample
                  * Cervical          for Chlamydia
                    specimen for      species
                    NAAT for
* Consider          Chlamydia
  urine-based       species for
  (first-void       all sexually
  specimen)         active women
  NAAT for          aged <25
  gonorrhea         years and
                    other women
* Consider          at increased
  urine-based       risk
  (first-void
  specimen)
  NAAT for
  Chlamydia
  species

* Serologic
  tests for
  hepatitis B
  and C (if
  hepatitis B
  negative,
  vaccinate)

Table 3. HRSA condom use advice for HIV-positive people

General advice

* Use a new latex or polyurethane condom with each sex act (oral,
anal, or vaginal).

* Make sure that the condom is undamaged and that its expiration
date has not passed.

* Carefully handle the condom to avoid damage (for example, from
fingernails or teeth).

* Being sure the condom roll faces out, unroll the condom onto the
erect penis before any genital contact with a partner.

* Ensure that the tip of the condom is pinched when applying it to
the top of the penis to eliminate air in the tip that could cause
breakage during ejaculation.

* Use only water-based lubricants with latex condoms. Oil-based
lubricants (such as mineral oil, cooking oil, massage oil, body
lotion, and petroleum jelly) can weaken latex or cause it to break,
although they are fine with polyurethane condoms.

* Adequate lubrication during intercourse helps reduce the risk of
condom breakage.

Advice for people who complain about lack of sensitivity with
condoms

* Apply a drop of lubricant inside the condom (not more, because
it increases the risk that the condom will come off).

* Use polyurethane condoms instead of latex because they conduct
heat and may feel more natural.

* Use insertive (female) condoms, which are not as restrictive to
the penis.

* Use specially designed condoms that do not restrict the top of
the penis (for example, Inspiral, Xtra Pleasure).

Source: US Department of Health and Human Services Health Resources
and Services Administration. Guide for HIV/AIDS Clinical
Care. January 2011.
http://kab.hrsa.gov/deliverhivaidscare/clinicalguide11/.

Table 4. Four effective risk-reducing behavioral programs for
people with HIV

Options/Opciones Project

Options/Opciones is an individual-level, clinician-delivered HIV
risk reduction intervention for HIV-positive persons during their
routine clinical care visits and repeated at each visit. The
intervention consists of a brief, patient-centered discussion (5-10
minutes) between clinician and patient at each clinic visit. Based
on motivational interviewing techniques, clinicians evaluate sexual
and drug-use behaviors of HIV-positive patients, assess the
patient's readiness to change risky (or maintain safer) behaviors,
and elicit various methods from patients for moving toward change
or maintaining safer behaviors. Clinician and patient then
negotiate an individually tailored behavior change goal or plan of
action, which is written on a prescription pad, for the participant
to achieve by the next visit.

For more information:

http://www.cdc.gov/hiv/topics/research/prs/resources/factsheets/
options.htm

Partnership for Health

The Partnership for Health (PfH) loss-frame intervention is a
one-on-one, brief provider-administered safer sex intervention for
HIV-positive persons in care. The intervention emphasizes the
importance of the patient-provider relationship to promote
patients' healthful behavior. At each clinic visit, the provider
delivers a brief counseling session (3-5 minutes) with messages
that focus on self-protection, partner protection, and disclosure.
Loss-framed messages are framed in a way that emphasizes the risks
or negative consequences of risky behavior. The provider also uses
brochures, informational flyers, and posters with the loss-framed
messages to facilitate counseling and works with the patient to
identify goals for the patient to work on.

For more information:

http://www.cdc.gov/hiv/topics/research/prs/resources/factsheets/
PfH.htm

TLC (Together Learning Choices, previously referred to as Teens
Linked to Care) is a small-group intervention designed for youth
and young adults living with HIV. TLC consists of 2 modules: Stay
Healthy and Act Safe. The Stay Healthy module consists of 12
sessions to promote positive health behaviors. Intervention
sessions are focused on coping with learning one's seropositive
status, addressing issues of disclosure, and helping youth to
implement new daily routines to stay healthy and actively
participate in health care decisions. The Act Safe module consists
of 11 sessions to increase self-protection and other-protection
motivation to change behavior and to reduce substance use and
unprotected sex acts.... Group discussions, role-play, video,
exercises, and goal setting encourage the ability to effectively
reach goals, solve problems, and effectively respond to stressful
situations.

For more information:

http://www.cdc.gov/hiv/topics/research/prs/resources/factsheets/
TLC.htm

Women Involved in Life Learning With Other Women (WILLOW)

The WILLOW intervention is a small group, skill-training
intervention for women living with HIV. Through interactive
discussions within groups of 8 to 10 women, the intervention
emphasizes gender pride and informs women how to identify and
maintain supportive people in their social networks. The
intervention enhances awareness of HIV transmission risk behaviors,
discredits myths regarding HIV prevention for people living with
HIV, teaches communication skills for negotiating safer sex, and
reinforces the benefits of consistent condom use. WILLOW also
teaches women how to distinguish between healthy and unhealthy
relationships, discusses the impact of abusive partners on safer
sex, and provides information about local shelters for women in
abusive relationships.

For more information:

http://www.cdc.gov/hiv/topics/research/prs/resources/factsheets/
WiLLOW.htm.

Source: CDC Promising-Evidence Interventions. (41)

http://www.cdc.gov/hiv/topics/research/prs/promising-evidence-
interventions.htm.

Subsequent visits

                                    Asymptomatic persons at higher
All sexually active patients        risk

* Screening tests for STIs          More frequent periodic
  should be repeated at least       screening (eg, every 3 to 6
  annually                          months) if any of the
                                    following factors are present:

                                    * Multiple or anonymous sex
                                      partners
                                    * History of any STI
                                    * Identification of other
                                      behaviors associated with
                                      transmission of HIV and other
                                      STIs
                                    * Sex or needle-sharing
                                      partner(s) with any of the
                                      above-mentioned risks
                                    * Developmental changes in
                                      life that may lead to
                                      behavioral change with
                                      increased risky behavior (eg,
                                      end of a relationship)
                                    * High prevalence of STIs in
                                      the area or in the patient
                                      population

NAA1, nucleic acid amplification test; RPR, rapid plasma reagin; STI,
sexually transmitted infection; VDRI , venereal disease research
laboratory test for syphilis.

Sources: Centers for Disease Control and Prevention. Incorporating
HIV prevention into the medical care of persons living with HIV:
recommendations of CDC, the Health Resources and Services
Administration, the National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases Society of America.
MMWR. 2003;52(No. RR- 12). (3) Aberg JA, Kaplan JL, Libman H, et
al. Primary care guidelines for the management of persons infected
with human immunodeficiency virus: 2009 update by the HIV Medicine
Association of the Infectious Diseases Society of America. Clin Infect
Dis. 2009;49:651-631. (16)

Figure 1. Higher viral load in the HIV-positive partner of
HIV-discordant couples independently raised the risk of HIV
transmission by the indicated rate ratios. Transmission risk
rose with each higher viral load quartile (Q) in this study
of 253 antiretroviral-naive monogamous Ugandan couples. (7)

HIV transmission risk by viral load in infecting partner

                             Compared with lowest quartile
                                 (under 3090 copies/mL)

2nd Q (3090 to 14,450)                    3.31
3rd Q (14,450 to 75,850)                  6.39
4th Q (over 75,850)                       7.06

Note: Table made from bar graph.
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