A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy

Bezemer, Daniela; Wolf, Frank de; Boerlijst, Maarten C.; Sighem, Ard van; Hollingsworth, T. Déirdre; Prins, Maria; Geskus, Ronald B.; Gras, Luuk; Coutinho, Roel A.; Fraser, Christophe

doi:10.1097/qad.0b013e3282fd167c

Cited by 157 publications

(133 citation statements)

References 33 publications

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“…2 Antiretroviral therapy (ART) is now highly successful in reversing the effects of HIV and has led to death rates in successfully treated people that are not much greater than those of the general population. 3,4 Given that there are reductions in infectivity of people on ART, 5 there is widespread interest in the potential effect of ART in controlling the HIV epidemic, 6 but there are a number of areas, including the UK, in which ART use is high among MSM, and yet incidence has not declined [7][8][9][10] and its potential impact in epidemics in MSM has been questioned. 9,11 In the Comprehensive Assessment of the Prevention Role of Antiretroviral therapy (CAPRA) programme of research that started in 2010 we set out to address what would be the population-level clinical effectiveness, and cost-effectiveness, of introduction of a policy of initiating ART in all people with a diagnosed HIV infection.…”

Section: Synopsismentioning

confidence: 99%

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Miltz

Phillips

Speakman

et al. 2017

Programme Grants Appl Res

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BackgroundMore than 100,000 people in the UK are living with a human immunodeficiency virus (HIV) infection. There are currently estimated to be around 4000 people newly infected in the UK per year, mostly men who have sex with men (MSM). It has become increasingly clear that antiretroviral therapy (ART) used to treat people infected with HIV also has a profound effect on infectivity. At the initiation of the programme, it was the policy in the UK to initiate ART in people when their cluster of differentiation 4 (CD4) count was approaching 350/µl.ObjectivesTo assess what would be the effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis among MSM, taking into account the potential reductions in new infections.DesignWe calibrated an individual-based model of HIV transmission, progression and the effect of ART in MSM, informed by a series of studies on sexual behaviour in relation to ART use and the transmission risk in people with viral suppression on ART, and by surveillance data collected by Public Health England.Setting, participants and interventionsThe series of studies used to inform the model included (1) the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study, a cross-sectional self-administered questionnaire study of people diagnosed with HIV attending eight HIV outpatient clinics in the UK (2011–12); (2) the Cognitive Impairment in People with HIV in the European Region (CIPHER) study, a study of levels of neurocognitive impairment in HIV-positive ASTRA participants and people from HIV clinics in Rome, Copenhagen and Minsk; (3) the Attitudes to, and Understanding of, Risk of Acquisition of HIV (AURAH) study, a cross-sectional self-administered questionnaire study of individuals who have not been diagnosed as HIV-positive attending 20 genitourinary medicine clinics across the UK (2013–14); (4) a substudy of sexual behaviour among individuals enrolled in an open-label multicentre international randomised trial (from 2013) of immediate versus deferred ART (to CD4 cell counts of 350/µl) in people with CD4 cell counts of > 500/µl [the Strategic Timing of Antiretroviral Therapy (START) trial]; and (5) Partners of People on ART: a new Evaluation of the Risks (PARTNER), an observational multicentre longitudinal study of HIV serodifferent heterosexual and MSM couples, in which the HIV-positive partner is on ART (2010–14).Main outcome measuresThe main outcome measures were the clinical effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis.ResultsBased on data from studies (i)–(v), we estimated from our modelling work that increases in condomless sex (CLS) among MSM as a whole may explain the increase in HIV infection incidence in MSM epidemics over a time when ART coverage and viral suppression increased, demonstrating the limiting effects of non-condom use on the HIV epidemic among MSM. Accordingly, an increase in the overall proportion of MSM living with HIV who are virally suppressed on ART from the current level of < 60% to 90% without increases in CLS was required to achieve a reduction in the incidence of HIV among MSM to < 1 per 1000 person-years. The incremental cost-effectiveness ratio associated with the fourfold increase in levels of HIV testing and ART at diagnosis required to provide this increase from < 60% to 90% was £20,000 if we assumed continuation of current ART prices. However, this value falls to £3500 if we assume that ART prices will fall to 20% of their current cost as a result of the introduction of generic drugs. Therefore, our evaluation suggests that ART initiation at diagnosis is likely to be highly cost-effective in MSM at a population level, particularly accounting for future lower ART costs as generic drugs are used. The impact will be much greater if levels of HIV testing can be enhanced.LimitationsIt was necessary to make some assumptions beyond the available data in order to extrapolate cost-effectiveness through modelling.ConclusionsOur findings suggest that ART initiation at diagnosis is likely to be cost-effective in MSM. Of note, after this programme of work was completed, results from the main START trial demonstrated benefit in ART initiation even in people with CD4 cell counts of > 500/µl, supporting ART initiation in people diagnosed with a HIV infection.Future workThere is a need for future research into the means of increasing the frequency with which MSM test for HIV.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

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Section: Synopsismentioning

confidence: 99%

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Miltz

Phillips

Speakman

et al. 2017

Programme Grants Appl Res

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“…The risk of HIV transmission in MSM despite HAART in the infected partner has never been assessed in large cohorts and is currently under study (35). As a matter of fact, cases of sexual transmission from men under suppressive HAART have been reported (36,37), and a resurgence of the HIV-1 epidemic among MSM is occurring in countries where potent HAART is available (38).…”

mentioning

confidence: 99%

Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

Matusali

Dereuddre-Bosquet

Tortorec

et al. 2015

J Virol

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A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCEA substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated with HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis, and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA ؉ macrophages were observed despite HAART. Importantly, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.A pproximately 35.3 million people worldwide are living with human immunodeficiency virus (HIV)/AIDS, and 2.3 million new infections occur annually (1). Over 80% of these new infections are caused by unprotected sexual intercourse. The risk of sexual transmission of HIV is strongly correlated with HIV RNA levels in genital secretions (2). Because semen is the most common vector of HIV dissemination worldwide (3-5), preventing HIV transmission by...

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“…Specifically, in North America, western Europe and Australia, notwithstanding high levels of HIV-status awareness and increasing coverage for antiretroviral therapy, HIV incidence among MSM has been increasing. [14][15][16][17][18] In British Columbia, where researchers have stated that treatment as prevention has led to a decrease in total HIV transmissions, 1 HIV incidence among MSM reportedly "increased by 13% from 2005 to 2008." 4 Confounding factors affecting HIV transmission, such as Vancouver's safe injection site, needle exchange and peer-based prevention strategies, may have played a role in reducing overall HIV incidence in British Columbia, thus limiting conclusions about the extent to which treatment as prevention can prevent HIV transmission at the population level.…”

Section: Does All Evidence Support Treatment As Prevention?mentioning

confidence: 99%

HIV treatment as prevention in men who have sex with men: examining the evidence

O’Byrne

MacPherson

2015

CMAJ

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A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy

Abstract: We provide the first detailed quantitative analysis of the HIV epidemic in a well defined population and find a resurgent epidemic in the era of highly active antiretroviral therapy, most likely predominantly caused by increasing sexual risk behaviour.

Cited by 157 publications

References 33 publications

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

HIV treatment as prevention in men who have sex with men: examining the evidence

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