Thanks to busy CDC number summers, the United States has well-estimated and routinely updated counts of HIV prevalence, incidence, and (less often) transmission. But discerning precisely what these tallies say about positive prevention takes an extra army of experts.
In 2008 the CDC heralded a 1977-2006 estimate of HIV transmission with the headline "Dramatic Declines [in HIV transmission] Indicate Success in U.S. HIV Prevention."21 The CDC summary explained work by Johns Hopkins researchers who used CDC data to reckon HIV infections transmitted per 100 HIV-positive people by dividing HIV incidence (the number of new infections) for a given year by HIV prevalence (the overall number of people with HIV) for the same year.22
Three years after clinicians identified AIDS, in 1984, the Hopkins team figured a transmission rate of 44.4%, meaning 44 out of every 100 HIV-positive people passed the virus to someone else.22 That rate plunged to 11.7% in 1990, to 7.5% in 1997 (a year or 2 after triple therapy arrived), and to 5.0% in 2006, the final year of the analysis (Figure 4). The nosedive from 44 to 5 transmissions per 100 positive people represents an 89% decline. So something -- probably many things -- were going right.
Figure 4. Using CDC data, independent researchers calculated that the US HIV transmission rate swooned from 44 per 100 HIV-positive people in 1984 to 5 per 100 in 2006.21,22 But HIV incidence, the numerator in the transmission rate equation (incidence/prevalence), did not keep dwindling after 2006. (Reproduced from CDC HIV/AIDS Facts. HIV transmission rates in the United States. December 2008.21)
The Hopkins formula for calculating transmission rate (incidence/prevalence in a given year22) means transmission would drop if incidence fell and/or if prevalence rose. Indeed, US HIV incidence did tumble from its estimated peak of 130,400 new infections in 1984 and 1985 to about 84,000 from 1986 to 1990, then to about 48,000 in 1991 to 1996.22 From 1997 through 2006, the last year of this analysis, HIV incidence fell no farther.
Over the same years, HIV prevalence climbed steadfastly from about 400,000 cases in 1985, to about 800,000 in 1998, and up to 1.2 million in 2008, the last year for which the CDC made an estimate.23 These estimates include people with undiagnosed HIV. US HIV prevalence rose so doggedly after combination therapy arrived not because lots more people were getting infected (incidence was flat), but because already infected people were living longer. Much longer. Together, falling (or flat) incidence plus rising prevalence would make the transmission rate (incidence/prevalence) sink.
Despite the dwindling estimated transmission rate through 2006, HIV incidence among people 13 and older bottomed out that same year at around 48,000 new infections per year, according to a 2011 CDC study.24 From 2006 through 2009, incidence stayed stuck at that level -- 48,600 new infections in 2006, 56,000 in 2007, 47,800 in 2008, and 48,100 in 2009. But because HIV prevalence continued to climb, at least through 2008,23 the CDC's Kathleen Irwin believes transmission rates were falling in those years (see the interview in this issue): If there are more and more people with HIV from one year to the next but incidence (new infections) stays flat, the transmission rate must be dropping.
What these numbers don't explain is why HIV transmission rates appeared to keep dipping in the 15 years since triple therapy arrived. Almost certainly, pushing viral loads to uncountable levels in more and more people stanched transmission considerably.25-27 Whether prevention counseling or risk reduction has much to do with waning transmission seems dubious, since these studies also found rising rates of sans-condom receptive anal intercourse,25 vaulting prevalence of infectious syphilis, genital gonorrhea, and genital chlamydia,26 and climbing rates of rectal gonorrhea.27
The CDC incidence study had no trouble pinpointing groups whose new HIV infection rate marooned incidence on a high plateau:24 "The only population with a change in HIV incidence over the entire four-year [2006-2009] period was 13-29 year olds, and within that age group, the only risk group experiencing increases was MSM," the CDC reported. "Among young MSM the estimated number of new infections increased significantly from 2006 to 2009; the increase in incidence in this group was largely driven by a statistically significant increase in new HIV infections of 48% (12.2% annually) in young, black/African American MSM."24
HIV-positive people unaware of their viral stowaways constitute a deep and covert pool of potential transmitters. In 2006 the CDC figured that HIV-positive but undiagnosed people have a 3.5 times higher risk of passing HIV to a sex partner than people who know they carry the virus.28 Wider HIV screening and earlier diagnosis can curtail HIV transmission, and clinicians can promote HIV testing through their positive patients and in their community -- topics examined in the preceding issue of RITA!.29 But this review focuses on how providers can limit transmission from people who know they have HIV.
The list of likely transmitters is no secret to HIV providers:
But some studies identify transmission-risk groups one might not readily suspect.
Ugandan studies of heterosexual couples (discussed above under "How often does HIV get transmitted?") framed a tight link between viral load and sexual transmission risk.18,19 Almost a decade earlier, US researchers found sky-high levels of infectious virus (up to 1000 tissue culture-infective doses per milliliter of plasma) 6 to 15 days after the onset of primary infection symptoms.30 Those loads "fell precipitously" by day 27.
Modeling blood and semen HIV loads in 30 men with known dates of infection or onset of acute HIV symptoms, another US team estimated that -- depending on how often they have sex -- men with average seminal loads during primary infection would infect 7% to 24% of female sex partners during the first 2 months of infection.31 If either partner has a sexually transmitted disease, those proportions would grow. In Quebec phylogenetic analysis of HIV from 591 people with primary infection and 795 with chronic infection yielded numbers suggesting that early
HIV infection accounted for half of HIV transmissions in the whole group.32 HIV providers understand the higher transmission risk conferred by lofty viral loads, but many people with early infection don't. In-depth interviews with 34 newly infected people in 6 US cities showed that "most participants knew little about the meaning and/or consequences of acute HIV infection, particularly that it is a period of elevated infectiousness."33 Health workers who see acutely or recently infected adults should make sure they understand the link between high viral load and HIV transmission.
The CDC's latest HIV incidence study left no doubt that MSM still comprise the premier risk group in the United States.24 HIV incidence among all people 13 and older remained flat at 48,000 new infections yearly from 2006 through 2009, but the new case rate did grow in one group: boys and men between 13 and 29 years old. Among young blacks, HIV incidence rose 12% annually over those 4 years (Figure 5). MSM accounted for 61% of new HIV infections in 2009, and MSM who injected drugs made up another 3%. A versatile few of these newly infected gays and bisexuals may be picking up HIV from women, but most are netting the retrovirus from other MSM.
Figure 5. From 2006 through 2009, HIV incidence per 100,000 population rose steadily among black boys and men between 13 to 29, while remaining essentially flat among Hispanic and white boys and men that age.24 HIV incidence in blacks this age was about 3 times higher than in Hispanics and more than 7 times higher in whites.
Studies of HIV-positive people in primary care bear out this torqued-up transmission risk in MSM. In a 15-city US study, 2109 HIV-positive MSM, 1104 women, and 803 men who have sex with women (MSW) completed a computer-assisted survey asking how often they had unprotected anal or vaginal sex with an HIV-negative partner or a partner with an unknown HIV status.34 Compared with MSW, MSM had more than a doubled risk of condom-free sex (OR 2.35, 95% CI 1.84 to 3.00, P < 0.001).
In a result that may surprise some, women in this study reported more than a 50% higher rate of risky sex than MSW (OR 1.56, 95% CI 1.19 to 2.05, P < 0.001).34 An earlier study of 3723 HIV-positive people in Los Angeles, Milwaukee, New York City, and San Francisco found that 19% of women, 15.6% of MSM, and 13.1% of MSW had unprotected vaginal or anal intercourse with HIV-negative or status-unknown partners.35 But this study of 1918 MSM, 978 women, and 827 MSW found that fewer than one quarter of women and MSW had 2 or more sex partners, compared with 59% of MSM. Researchers estimated that 30 sex partners of these HIV-positive people would get infected during the 3-month study, and 24 of them (80%) would pick up HIV from MSM.
Modeling HIV transmission data on the basis of partner information provided by 3652 MSM in five US cities, Emory University researchers figured that two thirds of transmissions in these men (68%) involve their main sex partner, not casual partners.36 Sensitivity analyses plugging in different variables indicated that transmission from main sex partners may account for 52% to 74% of new HIV infections. Modeling also calculated that 69% of HIV infections resulted from receptive anal intercourse, 28% from insertive anal intercourse, and 2% from oral sex. Model-based estimated HIV incidence in this population was 2.2% per year.
The high transmission rate from main partners reflected more frequent sex with main partners, more frequent receptive anal intercourse with main partners, and lower condom use during anal sex with main partners.36 These findings led the investigators to propose that "couples-based HIV prevention interventions for MSM should be given high priority in the US HIV prevention research portfolio." Not to mention the HIV clinical care portfolio.
Nearly everyone who follows the US HIV epidemic understands the high and abiding risk of viral transmission from gay and bisexual men. But as noted earlier in this article (see "Prevention Counseling Takes Back Seat"), that understanding has not spurred many HIV providers to talk to MSM frankly and frequently about protecting their partners from HIV.
Several studies confirm that using stimulants like crystal meth heightens the risk of HIV transmission. The already-discussed 15-city study of 4016 HIV-positive people in primary care found that stimulant use swelled transmission risk in gay men, straight men, and women (P < 0.05).34
A four-city study of 1910 HIV-positive MSM (36% African American) who completed computer-assisted interviews about their 5 most recent partners traced significant links between three types of drug use and unprotected sex partners:37 Stimulant use doubled the risk of unprotected sex with steady partners (adjusted OR 2.10, reference 1.00 to 4.39, P = 0.050), and both crystal meth (adjusted OR 1.76, reference 1.16 to 2.68, P = 0.009) and other drugs (adjusted OR 1.82, reference 1.16 to 2.86, P = 0.009) almost doubled the risk with casual partners. Neither education level nor race/ethnicity affected unprotected sex risk in these analyses. Men who did not disclose their HIV status to partners -- including steady partners -- had risky sex more often than serostatus disclosers.
A study of 90 HIV-positive MSM found that binge meth users reported more risky sexual behaviors -- as well as more social difficulties and physical and mental health problems -- than MSM who used meth but did not binge.38 Forty-one of these 90 men (46%) said they binged for periods ranging from 2 to 33 days. Bingers were significantly more likely to be ethnic minorities and to have less education than non-bingers.
A study of 303 HIV-positive male and female African-American crack cocaine users defined binging as using as much crack cocaine as you can, until you run out of crack or can't use any more, in the last 30 days.39 Half of these people (51%) reported binging for an average 3.7 days, during which they smoked 40 rocks of crack. Almost three quarters of bingers (72%) had sex during their last binge with an average of 3.1 partners. Recent male bingers were more likely than non-bingers to report lifetime and recent exchange of money for sex and drugs for sex. Recent female bingers were more likely to report lifetime trading of sex for drugs. Multivariate analysis determined that recent bingers were more likely than non-bingers to have high transmission risk scores, to have more sex partners in the last 1 month or 6 months, and never to use a condom during sex in the last 30 days.
Of course injection drug use poses a prodigious risk of HIV transmission, not only because HIV passes from person to person more readily through needle sharing than during sex (Figure 2), but also because of the social and psychological factors that boost HIV transmission risk among IDUs. And sharing injection works is not the only way IDUs transmit HIV, as indicated by a case-control comparison of 58 San Francisco IDUs who picked up HIV during follow-up and 1134 controls (matched for gender and date) who did not.40 Compared with controls, the IDUs who became infected were almost 9 times more likely to be MSM (OR 8.8, 95% CI 3.7 to 20.5) and 5 times more likely to have traded sex for money in the past year (OR 5.1, 95% CI 1.9 to 13.7). Women with a steady sex partner who injected drugs were almost 70% less likely to become infected (OR 0.32, 95% CI 0.11 to 0.92).
The CDC figures that drug injectors accounted for 36% of AIDS cases since the US epidemic began through 2000.41 The 2006-2009 CDC study of HIV incidence found that IDUs made up about 10% of new HIV cases in each of those years.24
Changing mental health in HIV-positive people has complex interactions with HIV transmission risk, as illustrated in a 936-person longitudinal study of positive people enrolled in a transmission-prevention trial.42 This four-city study recruited HIV-positive people from community agencies, AIDS service organizations, and medical clinics for a trial of an individually administered cognitive-behavioral intervention; 851 people had at least one follow-up visit. All study participants had signs of severe neuropsychological impairment or psychosis and reported unprotected vaginal or anal intercourse in the past 3 months with a sex partner whose HIV serostatus was negative or unknown. Participants were randomized to start the Healthy Living Program cognitive-behavioral intervention immediately or after 25 months of follow-up.
Ages ranged from 19 to 66. Most participants (79%) were men, 46% were black, 32% white, and 14% Hispanic.42 Almost three quarters of these people (72%) reported having sex with other men, and 43% had less than a high school education. When the study began, 40% of participants had clinically significant depression, 36% had clinically significant anxiety, and 25% had both.
Upon study entry, lower levels of depressive symptoms in the entire study group and higher scores in the Positive States of Mind (PSOM) scale were associated with having more HIV-negative partners in bivariate analysis.42 In the intervention group, worse anxiety symptoms were related to lower numbers of HIV-negative partners at baseline, and lower PSOM scores were related to increasing numbers of HIV-negative partners over time. In the delayed-intervention group, increasing depressive symptoms were related to decreasing numbers of HIV-negative partners over time. For the entire study group, lower PSOM scores from assessment to assessment were "modestly" associated with more risky sex acts, and more anxiety symptoms were associated with more HIV-negative partners. Stephen Morin (University of California, San Francisco), one of the investigators, discusses this study in an interview in this issue of RITA!
A Women's Interagency HIV Study (WIHS) analysis found evidence that poor antiretroviral adherence ups the risk of low condom use in women with HIV.43 This study involved 766 antiretroviral-treated women, 66% of whom reported at least 95% adherence. Among sexually active women, less than 95% adherence doubled the risk of inconsistent condom use (OR 2.17). In the entire study group, poor adherence independently doubled chances of active drug use (OR 2.27, 95% CI 1.39 to 3.33). The WIHS team believes their results "highlight the importance of discussing [sexual behavior and adherence] in relation to one another, particularly with regard to patients experiencing virologic failure."
Even being hungry may boost the risk of unsafe sex, at least among IDUs taking antiretrovirals. Researchers in British Columbia reached that conclusion in a longitudinal study of 420 IDUs enrolled in the AIDS Care Cohort to Evaluate Exposure to Survival Services from 2005 through 2009.44 Almost three quarters of this group (71%) suffered from food insecurity, marked by hunger due to lack of access or means to acquire food. People with food insecurity were marginally less likely to have an undetectable viral load (31% versus 39%, P = 0.099). Multivariate analysis that controlled for age, gender, marriage or cohabitation, binge drug use, homelessness, and antiretroviral use determined that food insecurity almost tripled the risk of unprotected sex (adjusted OR 2.68, 95% CI 1.49 to 4.82).
The second review article in this issue of RITA! scrutinizes diverse strategies for helping HIV-positive people avoid transmitting their virus. One of the clinician/researchers we polled for their opinions on this question, Babafemi Taiwo (Northwestern University, Chicago), offered this admirably succinct advice: "1. Test as many people as possible. 2. Treat as many infected patients as possible." But the next article will ask readers in endure considerably more detail.
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