Page 580 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 39 HIV and Acquired Immunodeficiency Syndrome 557

include male circumcision and expanded use of ART in infected
Immune Reconstitution Inflammatory Syndrome individuals to prevent ongoing infection (treatment as prevention)
Immune reconstitution inflammatory syndrome (IRIS) is a or prophylactically in uninfected individuals either before or after
well-known, if incompletely understood, response in patients potential exposure to HIV to prevent acquisition of infection
29
with AIDS after initiating ART. IRIS is characterized by an (preexposure prophylaxis [PrEP] and postexposure prophylaxis).
acute paradoxical worsening of inflammatory symptoms of treated
opportunistic infections or the unmasking of previously subclini- Male Medical Circumcision
cal, untreated infections related to the recovery of immune The penile foreskin contains HIV-susceptible cells and is a
responses to opportunistic pathogens. IRIS occurs within weeks potential portal of viral entry. Randomized controlled trials in
of ART initiation as the memory and effector antigen-activated several African countries have indicated that male medical cir-
CD4 T-cell population recovers. A recent systematic review found cumcision reduces the risk of heterosexually acquiring HIV
37
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that IRIS developed in 13% of patients after initiation of ART. infection by 50–60%. The WHO recommends male circumcision
The most predictive risk factor for the development of IRIS was as part of a comprehensive HIV prevention package; however,
a low CD4 T-cell count at the start of ART, with the incidence condom use and other prevention modalities remain important
of IRIS increasing exponentially as the CD4 T-cell count declined. in HIV prevention. There was only a modest benefit for the
IRIS develops more commonly in patients with cytomegalovirus female partners of the circumcised men. In fact, in some cir-
(CMV) retinitis, cryptococcal meningitis, progressive multifocal cumstances, the risk of transmission to women from men with
leukoencephalopathy, and tuberculosis. Studies reported that as HIV infection who have undergone circumcision may be
many as 4% of patients with IRIS died, but the proportion was increased, perhaps through exposure to infected blood attributed
much higher if the syndrome was associated with cryptococcal to resumption of sexual activity before the circumcision site has
meningitis. 29 fully healed. 37
Hyperallergenic State Associated With Preexposure Prophylaxis
Immunoreconstitution Recently, two different modalities of ART have been found to
Another complication possibly associated to IRIS is the appearance decrease acquisition of HIV when used by uninfected individuals
of asthma in children who were perinatally infected with HIV before their exposure to the virus as PrEP: topically applied ARV
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and received combination ART since infancy. This condition medications and systemic ART. Topically applied ARVs have been
may be mediated by CD4 T-cell activation, release of Th2-type shown to block the acquisition of HIV in women from their
cytokines, and loss of Tregs and tolerance. In support of this partners with HIV infection by 35–54%. The Centre for the
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concept, Gingo et al. reported at least a 20% prevalence of AIDS Program of Research in South Africa (CAPRISA 004) trial
asthma in adults with HIV infection compared with that of was the first double-blind randomized controlled trial demonstrat-
8.8% in the general population. In a subsequent pediatric study ing the efficacy of vaginally inserted gel containing the ARV
in which pulmonary function testing was objectively measured medication tenofovir disoproxil fumarate, compared with a
by spirometry, the following findings emerged: Nonreversible placebo gel, in preventing HIV transmission from men with
obstructive pulmonary disease was present in youth who had HIV infection to their uninfected partners. Vaginal PrEP represents
been perinatally infected with HIV and possibly in those exposed a promising intervention for preventing heterosexual transmission
to HIV but were uninfected. This pulmonary disorder contains of HIV to women. This method may be particularly effective
elements of asthma and chronic obstructive pulmonary disease because women are able to initiate and control its use to protect
(COPD) and closely resembles the asthma–COPD overlap syn- themselves from infection.
drome. Chronic infections and immune dysregulation appears
to play a significant role in this complication of HIV infection. 32 Prophylactic Antiretroviral Therapy
ARVs taken prophylactically have also been shown to be effective
PREVENTION in reducing the transmission of HIV both in MSM and in
heterosexual individuals and couples. The multinational Preex-
Prevention of Mother-to-Child Transmission posure Prophylaxis Initiative trial demonstrated that daily oral
More than 90% of children living with HIV worldwide were combination therapy with emtricitabine and tenofovir disoproxil
infected through mother-to-child transmission during pregnancy, fumarate (FTC-TDF) reduced the incidence of HIV among MSM
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around the time of birth, or through breastfeeding. Efforts to by 44% compared with placebo. Daily oral FTC-TDF was also
prevent this transmission hold the most promise in reducing the shown to reduce HIV incidence among heterosexual individuals
number of children infected with HIV, and these efforts include (i) by 63–78% and by 73% among heterosexual discordant couples.
early identification of HIV infection in pregnant women through Despite these successful trials, preliminary results of one PrEP
routine antenatal testing; (ii) provision of ARV medications to trial have failed to show similar efficacy for preventing HIV
both the pregnant woman and her infant 34,35 ; (iii) delivery by elec- acquisition among heterosexual women.
tive cesarean section, when indicated; (iv) complete avoidance of
breastfeeding when safe and sustainable alternatives are available; Expanded Treatment With Antiretroviral Therapy
(v) widespread availability of educational programs addressing The expanded use of ART in infected individuals has been shown
HIV infection; (vi) prevention of HIV perinatal transmission; to reduce HIV transmission to uninfected partners. Both “Treat-
and (vii) HIV counseling and testing services. 35,36 ment as Prevention” and “Test and Treat” strategies involve the
use of ART in individuals who do not otherwise meet the criteria
Prevention of Sexual Transmission for ART initiation with the express purpose of reducing transmis-
Several biomedical interventions have the potential for radically sion to others. In both approaches, ART is initiated regardless
changing the patterns and rates of HIV transmission. These of CD4 count or viral load to reduce the viral load in the genital