Page 49 - HIV/AIDS Guidelines

progression, independent of other factors such as plasma HIV RNA levels and peripheral CD4 T-cell
count. 103-104 ART results in a rapid, but often incomplete, decrease in most markers of HIV-associated
immune activation. 105-109 Persistent T-cell activation and/or T-cell dysfunction is particularly evident in
3 106, 109-110
patients who delay therapy until later stage disease (CD4 count <350 cells/mm ). The degree of
persistent inflammation during treatment, as represented by the levels of IL-6, may be independently
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associated with risk of death. Collectively, these observations support earlier use of ART for at least two
reasons. First, treatment decreases the level of inflammation and T-cell activation, which may be associated
with reduced short-term risk of AIDS- and non-AIDS-related morbidity and mortality. 58, 111-112 Second,
because the degree of residual inflammation and/or T-cell dysfunction during ART appears to be higher in
patients with lower CD4 cell nadirs, 106, 109-110 earlier treatment may result in less residual immunological
perturbations on therapy and, hence, less risk for AIDS- and non-AIDS-related complications (CIII).

Antiretroviral Therapy for Prevention of HIV Transmission
Prevention of perinatal transmission
Effective ART reduces transmission of HIV. The most dramatic and well-established example of this effect is
the use of ART in pregnant women to prevent perinatal transmission of HIV. Effective suppression of HIV
replication, as reflected in plasma HIV RNA, is a key determinant in reducing perinatal transmission. In the
setting of ART initiation prior to 28 weeks’ gestation and an HIV RNA level <50 copies/mL near delivery, use
of combination ART during pregnancy has reduced the rate of perinatal transmission of HIV from
approximately 20% to 30% to <0.5%. 113 Thus, use of combination ART drug regimens is recommended for all
HIV-infected pregnant women (AI). Following delivery, in the absence of breastfeeding, considerations
regarding continuation of the ARV regimen for maternal therapeutic indications are the same as those regarding
ART for other non-pregnant individuals. For detailed recommendations, see the perinatal guidelines. 114

Prevention of sexual transmission
Recent study results provide strong support for the premise that treatment of the HIV-infected individual can
significantly reduce sexual transmission of HIV. Lower plasma HIV RNA levels are associated with
decreases in the concentration of the virus in genital secretions. 115-116 Studies of HIV-serodiscordant
heterosexual couples have demonstrated a relationship between level of plasma viremia and risk of
transmission of HIV: when plasma HIV RNA levels are lower, transmission events are less common. 117-121

HPTN 052 was a multicontinental trial that enrolled 1,763 HIV-serodiscordant couples, in which the HIV-
3
infected partner was ART naive and had a CD4 count of 350 to 550 cells/mm at enrollment. The study
compared immediate ART with delayed therapy (not started until CD4 count <250 cells/mm ) for the HIV-
3
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infected partner. At study entry, 98% of the participants were in heterosexual monogamous relationships.
All study participants were counseled on behavioral modification and condom use. Twenty-eight linked HIV
transmission events were identified during the study period but only 1 event occurred in the early therapy
arm. This 96% reduction in transmission associated with early ART was statistically significant (HR 0.04,
95% CI: 0.01–0.27, P <0.001). These results show that early ART is more effective at preventing
transmission of HIV than all other behavioral and biomedical prevention interventions studied to date,
including condom use, male circumcision, vaginal microbicides, HIV vaccination, and pre-exposure
prophylaxis. This study, as well as other observational studies, and modeling analyses showing a decreased
rate of HIV transmission among serodiscordant heterosexual couples following the introduction of ART,
demonstrate that suppression of viremia in ART-adherent patients with no concomitant sexually transmitted
diseases (STDs) substantially reduces the risk of transmission of HIV. 120-125 HPTN 052 was conducted in
heterosexual couples and not in populations at risk of transmission via homosexual exposure or needle
sharing. However, the prevention benefits of effective ART probably will apply to these populations as well.
Therefore, the Panel recommends that ART be offered to patients who are at risk of transmitting HIV to
sexual partners. (The strength of this recommendation varies according to mode of sexual transmission: AI
for heterosexual transmission and AIII for male-to-male and other modes of sexual transmission.) Clinicians
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents E-8

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