Page 215 - HIV/AIDS Guidelines

prevalence, transmission risk, risk behaviors, transmission rates, and potential for pharmacologic
intervention all vary according to the type of substance used. 19-21 Risk-reduction strategies for injection drug
users (IDUs), in addition to condom use, include needle exchange and instructions on cleaning drug
paraphernalia. Evidence supporting the efficacy of interventions to reduce injection drug use risk behavior
also exists. Interventions include both behavioral strategies 14-15, 22 and opiate substitution treatment with
methadone or buprenorphine. 23-24 No successful pharmacologic interventions have been found for cocaine
and methamphetamine users; cognitive and behavioral interventions demonstrate the greatest effect on
reducing the risk behaviors of these users. 25-27 Given the significant impact of cocaine and methamphetamine
on sexual risk behavior, reinforcement of sexual risk-reduction strategies is important. 14-18, 28

Antiretroviral Therapy as Prevention
ART can play an important role in preventing HIV transmission. Lower levels of plasma HIV RNA have
been associated with decreases in the concentration of virus in genital secretions. 29-32 Observational studies
have demonstrated the association between low serum or genital HIV RNA and a decreased rate of HIV
transmission among serodiscordant heterosexual couples. 29, 33-34 Ecological studies of communities with
relatively high concentrations of men who have sex with men (MSM) and IDUs suggest increased use of
ART is associated with decreased community viral load and reduced rates of new HIV diagnoses. 35-37 These
data suggest that the risk of HIV transmission is low when an individual’s viral load is below 400
copies/mL, 35, 38 but the threshold below which transmission of the virus becomes impossible is unknown.
Furthermore, to be effective at preventing transmission it is assumed that: (1) ART is capable of durably and
continuously suppressing viremia; (2) adherence to an effective ARV regimen is high; and (3) there is an
absence of a concomitant STD. Importantly, detection of HIV RNA in genital secretions has been
documented in individuals with controlled plasma HIV RNA and data describing a differential in
concentration of most ARV drugs in the blood and genital compartments exist. 30, 39 At least one case of HIV
transmission from a patient with suppressed plasma viral load to a monogamous uninfected sexual partner
has been reported. 40

In the HPTN 052 trial in HIV-discordant couples, the HIV-infected partners who were ART naive and had
3
CD4 counts between 350 and 550 cells/mm were randomized to initiate or delay ART. In this study, those
3
who initiated ART had a 96% reduction in HIV transmission to the uninfected partners. Almost all of the
participants were in heterosexual relationships, all participants received risk-reduction counseling, and the
absolute number of transmission events was low: 1 among ART initiators and 27 among ART delayers. Over
the course of the study virologic failure rates were less than 5%, a value much lower than generally seen in
individuals taking ART for their own health. These low virologic failure rates suggest high levels of
adherence to ART in the study, which may have been facilitated by the frequency of study follow-up (study
visits were monthly) and by participants’ sense of obligation to protect their uninfected partners. Therefore,
caution is indicated when interpreting the extent to which ART for the HIV-infected partner protects
seronegative partners in contexts where adherence and, thus, rates of continuous viral suppression, may be
lower. Furthermore, for HIV-infected MSM and IDUs, biological and observational data suggest suppressive
ART also should protect against transmission, but the actual extent of protection has not been established.
Rates of HIV risk behaviors can increase coincidently with the availability of potent combination ART, in
some cases almost doubling compared with rates in the era prior to highly effective therapy. A meta-analysis
9
demonstrated that the prevalence of unprotected sex acts was increased in HIV-infected individuals who
believed that receiving ART or having a suppressed viral load protected against transmitting HIV. 41
Attitudinal shifts away from safer sexual practices since the availability of potent ART underscore the role of
provider-initiated HIV prevention counseling. With wider recognition that effective treatment decreases the
risk of HIV transmission, it is particularly important for providers to help patients understand that a sustained
viral load below the limits of detection will dramatically reduce but does not absolutely assure the absence of

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents L-2

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