(Υπάρχει ερωτηματικό;
Εδώ κοντέψαμε να πάρουμε όλοι και όλες
χάπια γνωστής Φαρμακευτικής Εταιρείας, για πρόληψη,
πριν βγούμε βόλτα μήπως και κάνουμε σεξ,
μήπως ο/η σύντροφος τύχει νάναι οροθετικός/ή.
χάπια γνωστής Φαρμακευτικής Εταιρείας, για πρόληψη,
πριν βγούμε βόλτα μήπως και κάνουμε σεξ,
μήπως ο/η σύντροφος τύχει νάναι οροθετικός/ή.
Αντί της πρόληψης μας πρότειναν προληπτική φαρμακευτική
αγωγή...
Πολλά τα λεφτα...)
Πολλά τα λεφτα...)
Σ.Σ.: Τα πλάγια γράμματα είναι δικά μας σχόλια..
...---...---...---...---...---...
Abstract and Introduction
Abstract
Objective: To review the evidence for antiretroviral 'treatment as prevention' for HIV transmission
among MSM.
ΣΤΟΧΟΣ: η μελέτη στόχευσε στο να επανεξετάσει τις ενδείξεις
για τη χορήγηση της αντιρετροϊκής θεραπείας ως τρόπου πρόληψης της μετάδοσης
της HIV μεταξύ των ομο/αμφιφυλόφιλων ανδρών.
Methods: We reviewed
studies that assess the biological plausibility that virally suppressive
antiretroviral therapy (ART) reduces HIV infectiousness via anal intercourse
and the epidemiologic evidence of whether ART has played a role in attenuating
HIV incidence among MSM.
Results: Although
ART treatment among MSM is likely to provide some preventive benefit, it is
unknown whether it will reduce HIV infectiousness via anal intercourse to the
same extent as via penile–vaginal intercourse. Additional research is needed on
the pharmacokinetic properties of specific antiretroviral agents in the
gastrointestinal tract. Estimates of risk behaviors and the incidence of HIV
among MSM before and after the introduction and expansion of ART suggest that
the population-level protective benefits of ART may be attenuated by a number
of factors, most notably, continuing or increasing frequency of condomless anal
intercourse and incidence of other sexually transmitted infections (STIs).
Additional studies are needed on the impact of ART on HIV sexual risk behaviors
and transmission among MSM outside of developed countries in North America,
western Europe, and Australia.
ΑΠΟΤΕΛΕΣΜΑΤΑ:
παρόλο που η χορήγηση αντιρετροϊκής θεραπείας στους ομο/αμφιφυλόφιλους άνδρες φαίνεται να
προσφέρει κάποιο πλεονέκτημα στην πρόληψη της μετάδοσης, είναι άγνωστο εαν
μειώνει τη μολυσματικότητα του HIV κατά την πρωκτική επαφή τόσο όσο κατά την κολπική
επαφή. ΑΠΑΙΤΟΥΝΤΑΙ ΠΕΡΑΙΤΕΡΩ ΜΕΛΕΤΕΣ ΓΙΑ ΤΙΣ ΦΑΡΜΑΚΟΚΙΝΗΤΙΚΕΣ ΙΔΙΟΤΗΤΕΣ ΕΙΔΙΚΩΝ
ΑΝΤΙΡΕΤΡΟΪΚΩΝ ΣΤΟ ΓΑΣΤΡΕΝΤΕΡΙΚΟ ΣΩΛΗΝΑ.
Εκτιμήσεις των επικινδυνων συμπεριφορών
και της επίπτωσης του HIV μεταξύ των ομο/αμφιφυλόφιλων ανδρών, πριν και μετά
την χρήση και επέκτασή της χρήσης της αντιρετροϊκής θεραπείας υποδεικνύει οτι
το προστατευτικό αποτέλεσμα της αντιρετροϊκής θεραπείας μπορεί να αλλοιωθεί από
σειρά παραγόντων, κυρίως από τη συνεχιζόμενη και κλιμακούμενη απροφύλακτη
πρωκτική επαφή αλλά και την επίπτωση άλλων ΣΜΝ.
ΧΡΕΙΑΖΟΝΤΑΙ ΚΑΙ ΑΛΛΕΣ ΜΕΛΕΤΕΣ
για τη σημασία της αντιρετροϊκής θεραπείας στις επικίνδυνες σεξουαλικές
συμπεριφορές και τη μετάδοαη του ΗΙV μεταξύ των ομο/αμφιφυλόφιλων
ανδρών πλην των αναπτυγμένων χωρών της
Β. Αμερικής, Δ. Ευρώπης και Αυστραλίας..
Τι φοβερό!
Είναι άλλο το γαστρεντερικό σύστημα κι άλλο το γεννητικό!
Οτι δουλεύει στο ένα
δεν είναι υποχρεωτικό να δουλεύει με τον ίδιο τρόπο και στο άλλο! Κοινώς:
άλλο το πέος...άλλο ο πρωκτός...!
Conclusion: The benefits of treatment as
prevention for MSM are highly plausible, but not certain. In the face of these
unknowns, treatment guidelines for earlier ART initiation should be considered
within a combination prevention strategy that includes earlier diagnosis,
expanded STI treatment, and structural and behavioral interventions.
ΣΥΜΠΕΡΑΣΜΑΤΑ:
τα οφέλη
της χορήγησης της θεραπείας ως πρόληψης της μετάδοσης στους ομο/αμφιφυλόφιλους άνδρες είναι σημαντικά ΑΛΛΑ ΔΕΝ ΕΛΙΝΑΙ ΒΕΒΑΙΑ.
Μπροστά
στα άγνωστα αυτά σημεία, οι κατευθυντήριες οδηγίες για την πρώϊμη έναρξη
αντιρετροϊκής θεραπείας θα έπρεπε να συνδυαστούν με μια στρατηγική πρόληψης που
περιλαμβάνει πρώϊμη διάγνωση, θεραπεία των ΣΜΝ και συμπεριφορικές παρεμβάσεις..
Κατάντησε πληκτικό!
Πρόληψη, είναι η προσπάθεια αλλαγής
συμπεριφορών..
Δεν μπόρεσε να τα καταργήσει το χάπι.
Είναι κι αυτοί οι περίεργοι
επιστήμονες που κάνουν ανασκοπήσεις στις δημοσιεύσεις..
Ξεφεύγει και κανένας..
Ξεφεύγει και κανένας..
Introduction
One
randomized controlled trial [1] and
numerous observational studies [2–6] provide
strong evidence that antiretroviral therapy (ART) can reduce or prevent the
sexual transmission of HIV-1 within serodiscordant heterosexual couples. A key
question remains: does ART reduce HIV transmission among men who have sex with
men (MSM), in which case the primary mode of transmission is via condomless
anal intercourse? New WHO guidelines for earlier initiation of ART among
serodiscordant couples were released in April 2012, [7] and some
countries, such as China, have already embraced treatment as prevention (TasP)
for heterosexual couples. In the process of re-evaluating current ART
guidelines, we anticipate that for some countries, the issue of whether to
recommend TasP for MSM will be under debate. The evidence supporting TasP for
MSM is promising, but major gaps in our knowledge remain. To identify priority
areas for research, in this study, we synthesize evidence from studies of MSM
of the biological plausibility that virally suppressive ART reduces HIV
infectiousness via anal intercourse and epidemiologic evidence of whether ART
has played a role in attenuating HIV incidence.
Some
biological and epidemiological evidence suggests that ART for preventing
transmission via anal intercourse may have more limited efficacy than via
vaginal intercourse. Without ART, the probability of HIV transmission is
estimated as 1 infection for every 20–300 acts of condomless anal intercourse,
as compared to one in 200 to one in 2000 for penile–vaginal exposure. [8–13]
Additionally, a higher median number of HIV variants are transmitted in MSM
couples as compared to heterosexual couples, [14,15] potentially
posing greater challenges for drug resistance. [16]
The pharmacology of
antiretroviral agents also differs between the urogenital tract (vaginal
intercourse) and the gastrointestinal tract (anal intercourse). Antiretroviral
drugs can reduce – but not eliminate – the amount of HIV recovered from the
genital tract [17–19] and gastrointestinal tract. [20–22] Higher levels of HIV DNA and
RNA have been found in the gastrointestinal tract (duodenum, ileum, ascending
colon, and rectum) as compared to the blood [23,24] and semen, [22] irrespective of ART use,
although these levels may be positively correlated. [20,25,26] Some
antiretrovirals such as tenofovir, tenofovir diphosphate, and maraviroc have
been shown to penetrate rectal tissue with greater efficiency than blood or
seminal plasma, [27,28] but the
durability of this penetration and required levels for prevention are not yet
established. Furthermore, paired blood and rectal biopsy samples tested for
resistance to antiretrovirals have shown different mutation profiles in the
virus recovered from each site. [29] This would
suggest that replication can persist in the rectum even if a patient appears
otherwise virally suppressed. Although the results of the HIV Prevention Trials
Network 052 randomized trial among serodiscordant couples (HPTN 052)
demonstrated the capacity of antiretroviral drugs to markedly reduce the risk
of penile–vaginal transmission [1] despite
similar biological and pharmacokinetic uncertainties, we cannot be certain that
this will be the case for anal intercourse given the much higher transmission
probability in the absence of ART.
In addition,
we do not know the extent to which sexual risk behaviors might offset the
potential prevention benefits of ART. Increases in bacterial sexually
transmitted infections (STIs) are compelling evidence of ongoing high-risk
behaviors among MSM, [30–34] and these
co-infections amplify HIV transmission. [35–40] Globally,
there is evidence of increases in STIs among MSM including rectal gonorrhea, [30,32,33,41] urethral
gonorrhea, [42] and
syphilis. [32,33,43–45] Other behaviors such as
serosorting (limiting sexual partners to those thought to be of the same HIV
serostatus) [46] and rectal
douching [47] also alter the risk of HIV transmission among MSM.
We do not
know the extent to which sexual risk behaviors among MSM are changing due to
the increasing availability of ART. Positive beliefs about the protective
ability of ART (treatment optimism) [48–51] and being
on ART itself, [50,52,53]
irrespective of actual viral suppression, have been associated with increased
condomless anal intercourse. A meta-analytic review of studies published
between 1996 and 2003 found a nonsignificant association between taking ART and
increased condomless anal intercourse among MSM [odds ratio (OR) 1.38, 95%
confidence interval (CI) 0.62–3.07]; however, the belief that being on ART
protects against transmission was associated with an almost two-fold increase
in condomless anal intercourse (OR 1.84, 95% CI 1.53–2.20). [54] The number
of studies on these impacts of ART on behavior has more than doubled since this
review, and an updated meta-analysis has been commissioned by the WHO with
results anticipated in 2012. Changes in transmission risk behaviors are also
being assessed as a secondary outcome in the randomized controlled START trial
(Strategic Timing of Antiretroviral Treatment), a study among treatment-naive,
HIV-positive persons recruited from over 200 sites worldwide comparing
initiation of ART at CD4 cell count greater than 500 cells/μl to
initiation at less than 350 cells/μl. [55]
Observational studies of
whether ART reduces HIV transmission among MSM produce mixed findings.
Surveillance data and longitudinal cohort studies suggest that HIV incidence
among MSM has fluctuated, in some cases increasing, in spite of widespread ART
availability. [41–43,56–62] To estimate
how ART has affected HIV transmission among MSM, some studies have calculated a
per-partner or per-act transmission risk and compared these rates pre and post
highly active antiretroviral therapy (HAART). [13,63] For
example, the Health in Men Australian cohort (2001–2007) used behavioral risk
data and annual HIV-incident infections to estimate per-contact HIV
transmission risk. In Sydney – with overall stable incidence of HIV and
increasing uptake of ART – the authors conclude that the overall per-contact
risk of transmission has not changed in spite of increased ART coverage and
more effective regimens. [13]
Other
studies have combined HIV surveillance and/or cohort data from communities with
high ART coverage to compare trends in ART use and transmission (). [42,56,64–66] For
instance, one older study in San Francisco (1995–1999) using community
surveillance and clinic data concluded that any decrease in HIV infectivity
gained by widespread use of ART may have been offset by increases in condomless
anal intercourse and/or STIs. [56] A more
recent San Francisco study using HIV surveillance data (2004–2008) described a
significant correlation between decreased annual mean community viral load
(CVL, an aggregate measure of the total known viral load among a particular
population) and decreases in newly diagnosed cases of HIV; however, the
association with HIV incidence measured with the BED capture enzyme immunoassay
was not statistically significant. [64] A similar
study using surveillance data (2004–2008) from Washington, DC, found a decrease
in mean CVL and an increase in the proportion of known HIV-positive persons
virally suppressed, but a statistically significant increase in newly diagnosed
cases of HIV. [66] In these
data, MSM had the highest proportion of individuals with undetectable viral
load compared with other risk groups; however, black MSM were less likely to
have undetectable viral load compared to white MSM. [66] A study
conducted in Vancouver reported similar associations between decreases in CVL
and new HIV diagnoses [42] however,
the role of injection drug use in driving these trends is unclear, [67,68] and
government surveillance reports show fluctuations in new HIV diagnoses among
MSM in British Columbia with no overall change compared to 2003. [62] Among
Vancouver MSM specifically, HIV prevalence is steady and slightly rising,
likely reflecting increases in survival as well as new diagnoses. [69] In
contrast, a study from Denmark using national HIV surveillance and clinic data
showed that rising proportions of HIV-infected MSM on suppressive treatment
were correlated with stable rates of new HIV diagnoses in spite of increasing
proportions of MSM reporting condomless anal intercourse. [65]
Table 1. Ecological
studies of antiretroviral therapy and new diagnoses of HIV.
Citation
location
|
Data
source
|
Estimation
of suppressive ART
|
Estimation
of HIV incidence
|
Interpretation
of results
|
Castel et al. (2012); Washington, DC, USA [66]
|
District health department HIV/AIDS case surveillance system
|
Annual mean and total of most recent viral load test, proportion of
virally suppressed
|
Number of new HIV diagnoses as reported through the District HIV/AIDS
surveillance system
|
No association was found between trends in the mean CVL and newly
diagnosed HIV/AIDS cases. MSM had a higher proportion of virally suppressed cases
|
Das et al. (2010); San Francisco, USA [64]
|
City health department HIV/AIDS case surveillance system
|
Annual measures of mean and total CVL
|
Newly reported HIV diagnoses and HIV incidence estimated using the STARHS
method
|
Reductions in CVL were significantly associated with fewer annual HIV
diagnoses, though not with estimated HIV incidence using the STARHS method
|
Katz et al. (2002); San Francisco, USA [56]
|
City health department AIDS registry, stored samples from VCT and STI
clinics, and behavioral surveys of MSM
|
Numbers of HIV-infected individuals receiving HAART, reported sexual risk
behaviors
|
Trends in HIV incidence as determined by STARHS method
|
Any decrease in per contact risk of HIV transmission due to HAART use appears
to have been countered or overwhelmed by increases UAI
|
Montaner et al. (2010); British Columbia, Canada [42]
|
Provincial disease surveillance database; provincial treatment center
database
|
Numbers of HIV infected individuals receiving HAART
|
New HIV positive tests per 100 population
|
Rising numbers of individuals receiving HAART and rising proportions of
treated individuals with VL <500 copies/ml were strongly associated with
decreased number of HIV diagnoses per year
|
Cowan et al. (2010); Denmark (national) [65]
|
National HIV surveillance data and behavioral studies of MSM
|
Estimated prevalence of HIVpositive MSM receiving HAART, sexual risk
behaviors
|
Annual numbers of MSM notified as HIV infected via serologic testing,
used as proxy for incidence
|
Increasing numbers of treated MSM coincides with stable numbers of newly
notified HIV positive MSM and increasing STI diagnoses, suggesting reduced
infectiousness among HIV infected MSM
|
ART,
antiretroviral therapy; CVL, community viral load; STARHS, serologic testing
algorithm for recent HIV seroconversion; STI, sexually transmitted infection;
UAI, unprotected (condomless) anal intercourse.
Due to their
reliance on aggregate data and on new diagnosis reports rather than on new
incident infections, these ecological studies are unable to draw causal
inferences about the individual-level processes driving transmission. Their
mixed results suggest that characteristics of specific geographic epidemics as
well as behavioral patterns likely contribute to the population-level impact of
ART on HIV transmission among MSM.
The majority of data available
for the impact of ART among MSM are from developed countries in North America,
Western Europe, and Australia. As a result, what we know about ART's effect on
HIV transmission comes from a small subset of MSM, limiting the
generalizability of these results within other social, cultural, and epidemic
settings. While recognizing the barriers of stigma, discrimination, and legal
repercussions, it is clear that more research is needed in this regard among
MSM populations in South America, Africa, Central Europe, and Asia. In order to
inform optimal ART recommendations, we also need to better understand the
social and cultural environments in which new sexual behavioral trends are
evolving.
Going
forward, there are great opportunities to further our understanding of the
individual and population-level transmission dynamics of HIV and ART among MSM.
For example, applying the tools of phylogenetic analysis, researchers may be
able to identify the most likely source of an individual's HIV infection,
describe the size and distribution of clusters of new cases in the population
and assess the relative contributions to new transmissions by persons at
various stages of infection.
For example, a study utilizing phylogenetic
methods among MSM in the UK identified the following characteristics as likely
to contribute disproportionately to onward HIV transmission: recent infection,
not receiving ART, and concomitant STI. [70] Whereas an
individual-level randomized clinical trial to directly evaluate the efficacy of
ART for prevention in MSM may not be feasible or ethical, [71] well
designed observational studies of seroconcordant and discordant couples – as
reported with heterosexual individuals [3,4] – allow
researchers to measure the risk of acquiring and transmitting HIV. Two such
studies involving MSM couples in Europe and Australia are currently enrolling
or planned. [72,73]
The benefits
of TasP for MSM are highly plausible, but not certain. The results of HPTN 052
have generated great urgency for maximizing the prevention benefit of ART.
However, the impact of ART on HIV transmission via anal intercourse requires
further evaluation due to the inconclusive observational data currently
available for MSM and the challenging biological and behavioral risk factors
that may be present. If TasP becomes part of prevention policy for MSM, it will
be critical to earlier treatment in combination with HIV diagnosis, continued
structural and behavioral interventions, and expanded STI treatment and
prevention.
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