USPSTF guidelines on HIV testing and pre-esposure prophylaxis

The US Preventative Services Task Force (USPSTF) just released two recommendations concerning HIV infection, one on testing and one on the use of preexposure prophylaxis for the prevention of HIV Infections (PrEP).

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HIV screening (see hiv screening uspstf jama2019 in dropbox, or doi:10.1001/jama.2019.2592):

Recommendations:

--"The USPSTF recommends that clinicians screen for HIV infections in adolescents and adults aged 15 to 65. Younger adolescents and older adults who are at increased risk of infection should also be screened”, Grade A recommendation

--“The USPSTF recommends that clinicians screen for HIV infection in all pregnant persons, including those who present in labor or at delivery whose HIV status is unknown”, Grade A recommendation

Details (will not go into much detail here):

-- 1.1 million individuals in the US are currently living with HIV, more than 700,000 have died of AIDS

-- in 2017 there were 38,281 new HIV diagnoses, 81% in males/19% in females

-- approximately 15% of people living with HIV are unaware of the their infection

-- 87,000 women living with HIV give birth each year in the US, with potential HIV transmission prenatally, perinatally, and through breast-feeding if not identified/treated

-- 67% of new diagnoses of HIV are attributed to male-to-male sexual contact, the estimated prevalence of HIV infection in MSM is around 12%

-- injection drug users: estimated prevalence of HIV is 1.9%

-- currently recommended testing for HIV is extremely accurate, with sensitivities and specificities very close to 100%

-- the earlier the diagnosis of HIV infection, the better the response to therapy

-- and, the most effective HIV transmission prevention is through effective treatment/HIV suppression in infected people(“ treatment has prevention”)

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PrEP for HIV transmission prevention (see hiv pre-exp prophylaxis recs uspstf jama2019 in dropbox, or doi:10.1001/jama.2019.6390; or go to for the full report):

Recommendation:  “The USPSTF recommends that clinicians offer preexposure prophylaxis (PrEP) with effective antiretroviral therapy to persons who are at high risk of HIV acquisition”, Grade A recommendation

Details:

-- consistent use of condoms decreases HIV acquisition by about 80%, as well as preventing acquisition of other STI’s. PrEP should be considered for those who use condoms inconsistently despite being encouraged to use condoms regularly

-- risk of HIV acquisition is highest with needle-sharing for injection drugs and condomless receptive anal intercourse; condomless insertive anal sex as well as condomless receptive and insertive penile-vaginal sex have a risk of transmission 10 to 15 times lower than receptive anal intercourse

-- also, HIV transmissionrisk assessment should be interpreted in the context of the local HIV prevalence rates, though the exact threshold for that rate is unclear in terms of a risk/benefit analysis

-- though there is inadequate evidence for a specific risk assessment tool to identify those at high risk, the USPSTF accepts the following as “high risk” based on epidemiologic data:

    -- MSM who are sexually active, and have one of the following characteristics:

        -- A serodiscordant sex partner (i.e., the partner has HIV and the patient does not)

        -- inconsistent use of condoms during receptive or insertive anal intercourse

        -- an STI with syphilis, gonorrhea, or chlamydia within the past 6 months

    -- heterosexually active women and men having one of the following characteristics:

        -- a serodiscordant sex partner

        -- inconsistent use of condoms during sex with a partner whose HIV status is unknown and is at high risk (i.e. someone who injects drugs or a man who has had sex with men and women)

        -- an STI with syphilis or gonorrhea within the past 6 months

    -- people who inject drugs and have one of the following characteristics:

        -- shared use of drug injection equipment

        -- risk of sexual acquisition of HIV (as above)

    -- people who engage in transactional sex (i.e. sex for money, drugs, housing), and men who have sex with men and women

    --transgender women and men who are sexually active can be at high risk and should be considered for PrEP [transgender women are considered to be at especially high risk for HIV acquisition: one fourth of transgender women are living with HIV and 56% of black/African-American transgender women are living with HIV

Medications:

-- once daily TDF (tenofovir disoproxil fumarate) and FTC (emtricitabine) is the only formulation approved by the FDA, though some studies have found that TDF by itself works. The CDC guidelines indicate that TDF alone can be considered as an alternative regimen for high risk heterosexually active men and women and persons who inject drugs

--TDF/FTC can be used as PrEP during pregnancy; pregnancy is associated with an increased risk of HIV acquisition. CDC recommends shared decision-making with women, since there been no trials of PrEP that included pregnant women

-- adolescents who weigh at least 35kg are approved for PrEP, though there is concern of long-term use of TDF for decreased bone mineral density as well as adverse renal events (these apply to all persons on TDF). Of note no trial enrolled people younger than 18 years old

-- all of this should still be in the context of intensive behavioral counseling to reduce risk of acquiring STIs and HIV, and to increase condoms

-- all people considered for PrEP need to have prior HIV testing, since PrEP is inadequate therapy for HIV infection and might therefore lead to resistance

-- and the studies confirm that reduced adherence to PrEP leads to decreased effectiveness

-- the overall estimates of PrEP effectiveness are mostly around the 50% range, though adherence to PrEP varied from the 30% to 100% range in the studies (in those trials with adherence >70%, there was a 73% reduced risk of HIV acquisition)

-- It is likely that PrEP needs to be started early: maximum levels of TDF are achieved in 7 days in rectal tissue and 20 days in blood and vaginal tissue

-- those on PrEP should be monitored every 3 months for HIV infection

-- and, postexposure prophylaxis started as soon as possible after a potential exposure also decreases the risk of HIV transmission

Commentary:

-- This guideline goes hand-in-hand with the one on increasing HIV testing, as described above, since HIV diagnosis and treatment is the best prevention (“treatment as prevention”)

-- and, it is extremely important to have a setting where people feel comfortable both in getting tested as well as being open to discussing potential HIV exposure/PrEP, a setting which minimizes any stigma or discrimination against the high risk patients

    -- providers also need to be more proactive in offering PrEP when indicated, with studies suggesting that we need to do a lot better: for example one study showed that only 10% of those who initiated PrEP from 2012-15 were black/African-American, though 44% of all new infections in the US occur in this group. Black women, who are also disproportionately affected by HIV, are more than 4 times less likely to have initiated PrEP than white women

-- there are other structural obstacles to prescribing PrEP, including the remarkably high cost of these medications (which come formulated as the combination pill Truvada), though TDF alone does appear to be equally effective as the combination in the groups tested.  In a really public-health-oriented health care system, PrEP would be freely available to all who need it to minimize the risks of a severe chronic infection (medicalization, med adverse effects, psychological effects of having a chronic disease,...). And chronic HIV is still associated with residual immune dysfunction even in those with suppressed viral load, leading to higher incidence of non-HIV morbidity/mortality (to be reviewed in a blog in the near future). and, offering free PrEP may well be significantly cheaper in the long run than having inaccessible PrEP because of cost etc.

-- there have been trials using PrEP as intermittent or event-driven. It is not clear how do generalize this information. one large trial found an 86% risk reduction in men who averaged 4 doses of PrEP per week, 15 doses per month in MSM. But, these results may not be applicable to people who have sex less frequently for example or other high risk groups (see http://gmodestmedblogs.blogspot.com/2015/12/on-demand-hiv-pre-exposure-prophylaxis.html )

-- one concern with PrEP is that there might be an increased incidence of unprotected high-risk sex, but studies have shown no increase in risk of syphilis, gonorrhea, or chlamydia, suggesting this was not happening

-- another concern is the risk of acquisition of drug-resistant HIV, but of 282 patients who did develop HIV while on PrEP, only 3 (1.1%) had tenofovir resistance mutations

Other blogs on related issues:

-- http://gmodestmedblogs.blogspot.com/2015/06/tenofovir-nephrotoxicity.html reviews the mechanism and appropriate testing for TDF nephrotoxicity

-- http://gmodestmedblogs.blogspot.com/2018/10/prep-mostly-given-to-white-men-and.html reviews the CDC report of the underrepresentation of women and minorities in PrEP

-- http://gmodestmedblogs.blogspot.com/2015/09/hiv-pre-exposure-prophylaxis.htmlreviews the British  PROUD trial

So, none of this is really so surprising, given the large accrual of data showing the benefit of HIV detection and early treatment, as well as the use of PrEP in interrupting HIV transmission in high risk individuals. The issue is that we clinicians need to be systematic in testing for HIV (which i believe we do a pretty good job on now overall), and especially to openly inquire about high-risk exposures and the potentially large benefits of PrEP (which seems to be much less good)...

geoff

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