In 2014, the Spanish System for Information on New Diagnoses of HIV Infection (Sistema de Información sobre Nuevos Diagnósticos de VIH [SINIVIH]) was notified of 3366 new cases of HIV infection in Spain; of these 85% were men, and the mean age was 35 years. Men who have sex with men (MSM) accounted for 54% of all new diagnoses, heterosexual men and women for 26%, and injection drug users (IDU) for 3.4%.1 The EPIVIH study provides the soundest national estimations of incidence, which stands at 1 case per 100 person-years (95%CI, 0.9–1.1) among the 30679 first-time testers with at least one follow-up test between 2000 and 2009.2 The highest risk of infection was recorded among male commercial sex workers (3.0 per 100 person-years; 95%CI, 2.2–4.1), MSM (2.5 per 100 person-years; 95%CI, 2.3–2.7), and IDU (1.6 per 100 person-years; 95%CI, 1.1–2.2). The incidence was 0.1 cases per 100 person-years in heterosexual men and women and female commercial sex workers.

In 2014, it was estimated that approximately 150000 people were infected with HIV, that is, a prevalence in the general population of 0.4% (95%CI, 0.4%–0.5%). Furthermore, the prevalence of occult HIV infection was estimated to be 0.1%.1 The prevalence of infection varies considerably between the different collectives who engage in risk practices. The EPIVIH study revealed a prevalence of HIV infection of 2.5% (95%CI, 2.4%–2.6%) in 145337 first-time testers during the period 2000–2009.2 By category of transmission and risk situations, the highest prevalence was recorded in transgender women (24.5%; 95%CI, 20.4%–29.0%), male sex workers (19%; 95%CI, 10.5%–24.5%), and IDU (17%; 95%CI, 13.3%–21.2%). Prevalence was 7.6% (95%CI, 7.2%–7.9%) in MSM, 0.9% in heterosexual men and women, and 0.8% (95%CI, 0.5%–1.2%) in female commercial sex workers.2

PrEP should be evaluated in individuals who request or agree to the intervention and who fulfill the following criteria:

• 1.

  HIV infection must be ruled out. In cases where it is not clear whether or not the patient is infected, PrEP should not be recommended until HIV infection can reasonably ruled out.

• 2.

  The patient should be prepared to adhere to recommendations and undergo follow-up.

• 3.

  No clinical or laboratory contraindications for TDF or emtricitabine (FTC).

• 4.

  Inclusion in one of the target populations for PrEP

  • A.

    PrEP should be recommended to people with a high risk of HIV infection. A high risk is understood to be inclusion in a group in which the risk is greater than 2 cases per 100 person-years (AI):

    • •

      MSM and transgender women who have had sexual relations without a condom during the previous 6 months and 1 of the following:

      • ∘

        Sexual relations with more than 2 partners

      • ∘

        Diagnosis of ≥1 sexually transmitted infection (STI)

      • ∘

        Administration of postexposure prophylaxis

      • ∘

        Use of psychoactive substances during sexual relations

  • B.

    PrEP should be considered in individuals with a high risk or in whom there is some evidence of a benefit, as follows:

    • •

      Individuals whose partner(s) is infected with HIV and is not undergoing clinical or virological follow-up and who do not use a condom (BI)

    • •

      Individuals who engage in unprotected and transactional sexual relations (money, drugs, accommodation) (BIII)

    • •

      IDU who share syringes (BI)

    • •

      Individuals in situations of social vulnerability who are exposed to unprotected sexual contact with a high risk of HIV infection (CIII)

PrEP is a medical intervention that should be prescribed and monitored by a physician. The physician must have experience in the care of HIV-infected patients and use of antiretroviral drugs and be an expert in STIs19(AIII).

• 1.

  Centers where PrEP is prescribed should fulfill a series of conditions to ensure that they can appropriately implement PrEP programs: presence of an experienced physician (see above), capacity to rule out HIV and other STIs during the initial workup and during follow-up, and capacity to perform the necessary examinations to evaluate drug toxicity and resistance in the case of infection.

• 2.

  The medication used for PrEP can only be dispensed in a hospital; therefore, only hospital units that provide care for HIV-infected patients will be able to prescribe it. It is unlikely that all hospital units have sufficient resources or that all potential users will be able to attend a hospital. Therefore, additional care structures for prescription and dispensing will be necessary.

• 3.

  Centers where PrEP is prescribed must follow uniform criteria for correct prescription and follow-up. In this sense, centers intending to provide the service should be evaluated and accredited.

• 1.

  PrEP programs should be developed in centers (either in a single center or between several centers) that guarantee appropriate fulfillment of all phases of the strategy, including the initial evaluation and follow-up, as well as dispensing. All centers must have the following (AIII):

  • -

    Physician with experience in the management of HIV infection, antiretroviral drugs, and STIs

  • -

    Standardized clinical histories

  • -

    Pharmacy service that stores, supervises, and dispenses medication and provides information on correct follow-up of the regimen prescribed

  • -

    A laboratory to diagnose HIV infection, measure viral load, and study resistance

  • -

    A laboratory for evaluation of blood parameters and biochemistry (necessary for follow-up of drug toxicity)

  • -

    Capacity to evaluate the presence and diagnosis of STIs

  • -

    Capacity to provide counseling on adherence and sexual health

• 2.

  Centers participating in PrEP programs are varied and can adapt to various situations. They include hospital HIV infection units, centers providing care for STIs, sexual and reproductive health centers, harm reduction centers for IDU, and community centers. Specific centers for the development of this strategy could be created for as long as they are necessary (AIII).

• 3.

  Protocols or methods should be defined to enable easy and effective access to medication for individuals who have been prescribed PrEP in a nonhospital center (AIII).

• 1.

  Daily regimens (preferred option). Daily administration of a tablet combining TDF 300mg and FTC 200mg. Monotherapy with TDF can be prescribed in exceptional cases of intolerance or FTC-induced toxicity11,16(AI).

• 2.

  Intermittent regimen (alternative option). The combination of TDF/FTC should be prescribed according to the following regimen: 2 tablets taken together between 24 and 2h before exposure, 1 tablet taken 24h after the first dose, another tablet taken daily for as long as the patient is exposed to risk practices, and a tablet taken 24h after the most recent sexual relationship. This regimen is not indicated if follow-up requires more than 7 tablets per week. The efficacy of this dosing regimen has only been demonstrated in MSM and cannot therefore be recommended in other clinical situations (AI).

The objective is to provide integral care for individuals who are going to receive PrEP. This includes the following:

• -

  Complete blood count

• -

  Serology testing for hepatitis A virus

• -

  Pregnancy should be ruled out and the woman questioned about her desire to become pregnant

• -

  Evaluation of the patient's commitment to taking PrEP correctly and insistence on the importance of adherence, so that PrEP is successful. Information on possible associated adverse effects18,20

Individuals who are going to receive PrEP should receive clear information on key aspects of this approach:

• -

  PrEP is an intervention designed to prevent HIV infection. It should be placed in context with other preventive interventions, such as use of condoms

• -

  PrEP does not protect against other STIs

• -

  PrEP does not work if adherence is poor and could lead to toxicity if it is not monitored appropriately

Patients should also be counseled on sexual health and adherence should be reinforced. Once it has been decided that PrEP is indicated, and before initiation, the patient should be informed about the visits and analyses that are necessary when taking PrEP.

Objective To confirm that the user is not HIV-infected, that he/she fulfills the criteria for PrEP, and that there are no limitations with respect to prescription of PrEP.

Steps:

• •

  Evaluation of baseline laboratory results

• •

  Counseling

• •

  New HIV test in the case of recent infection

• •

  Prescription of medication

• •

  Arrange an appointment at 4–8 weeks, with a request for a laboratory workup

• •

  Vaccination against hepatitis C infection, if necessary

Objective evaluate tolerance, toxicity, and adherence.

Steps

• •

  Evaluation of adverse effects, consumption of other medications, and use of recreational substances and drugs

• •

  Evaluation of adherence

• •

  Arrange appointment at 3 months, with request for laboratory workup

Objective: Evaluate tolerance, toxicity, adherence, HIV infection, and other STIs

Steps

• •

  Evaluation of adverse effects, consumption of other medications, and use of recreational drugs or substances

• •

  Evaluation of adherence

• •

  Analysis with evaluation of renal function

• •

  Serology testing for HIV/qualitative PCR assay for HIV

• •

  Rule out other STIs

• •

  Pregnancy test

• •

  Counseling

• •

  Prescription of medication

• •

  Arrange appointment at 3 months, with request for laboratory workup

PrEP is a promising approach for preventing sexual transmission of HIV infection in women of childbearing age, whether pregnant or not, in areas with a high prevalence of HIV infection.22,23 Acute HIV infection during pregnancy and postpartum in mothers who breastfeed increases the risk of vertical transmission.24,25

Exposure to TDF or TDF/FTC as part of antiretroviral therapy in pregnant women and their newborns has not been associated with malformations or other relevant defects in exposed newborns.26–28

Current therapy guidelines recommend initiating antiretroviral therapy in all HIV-infected individuals. In the case of serodiscordant couples, treatment of the infected person is recommended. Based on available information, unprotected sexual relations at the time of conception when the infected person is receiving antiretroviral therapy and has an undetectable viral load are reasonably safe.29 Therefore, in Spain, PrEP offers no clear advantage to noninfected women whose infected partner is receiving antiretroviral therapy and has a suppressed viral load.

In the case of HBV-infected individuals for whom PrEP is indicated, TDF or TDF/FTC should be administered initially according to the indications and regimens established for treatment of HBV infection.30 Given that treatment of HIV-infected patients with entecavir can lead to resistance to lamivudine or FTC,31 it should not be started in candidates for PrEP with chronic HBV infection.

In patients with chronic HBV infection for whom treatment of HBV infection is not indicated, PrEP can be considered. In these patients, HBV infection should be monitored specifically according to established guidelines.30

Discontinuing TDF in patients with chronic HBV infection can lead to increased replication of HBV, which, in turn, may be accompanied by severe clinical manifestations.32

• •

  In patients with chronic HBV infection who are candidates for PrEP, the indication for treatment of HBV infection should be evaluated and, ideally, TDF/FTC should be administered (AI).

• •

  Patients with chronic HBV infection for whom treatment is not indicated can start PrEP. HBV infection should continue to be monitored, especially if PrEP is suspended (AIII).

• •

  Regimens based on intermittent PrEP should not be administered to patients with chronic HBV infection (AIII).

Chronic HCV infection does not contraindicate administration of PrEP, although the possibility of interactions between PrEP and the medication used to treat HCV infection should be taken into account. At present, the only significant interaction is the increase in TDF levels in patients who simultaneously receive sofosbuvir and ledipasvir, which can increase the risk of TDF-induced nephrotoxicity in these patients.

Diagnosis and treatment of STIs do not contraindicate administration of PrEP. Its presence is a criterion for the administration of PrEP. Acute HIV infection and infection by Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum can progress without symptoms; therefore, when a patient is diagnosed with an STI, acute HIV infection and other STIs should be ruled out.

In HIV-infected patients, continued long-term therapy with TDF can lead to renal toxicity, which usually manifests as proximal tubular dysfunction and, less frequently, as reduced glomerular filtration rate.33

Clinical trials with PrEP performed to date have not revealed differences in the onset of renal adverse effects between individuals who received TDF-based PrEP and those who received placebo; however, follow-up of participants was limited in time and in some studies, a significant—but not clinically relevant—decrease in estimated glomerular filtration rate was observed in participants who received TDF.6,10,15,34

No evidence is currently available on TDF-based PrEP in individuals with eGFR <60ml/min.

In 2015, GeSIDA published a consensus document that addressed the use of nonoccupational postexposure prophylaxis in adults and children.35 The document reviewed evidence supporting the use of postexposure prophylaxis and provided clear guidelines on whether it should be started or not. When initiation of postexposure prophylaxis is being evaluated, it is important to take into account the possible indication of PrEP as part of an integral approach for the prevention of STIs.

HIV infection should be ruled out before starting PrEP. Although the efficacy of PrEP is very high, it is not 100% safe; therefore, HIV infection must be ruled out every 3 months at follow-up visits. A clinical history aimed at recording symptoms and signs of acute retroviral syndrome must be taken, and HIV serology testing with fourth-generation ELISA must be performed.21

If HIV infection is detected, the patient must be sent to specialist centers for evaluation of initiation of treatment and follow-up.

• •

  PrEP should be interrupted in any of the following cases:

  • -

    Patient withdrawal from follow-up (A-III)

  • -

    HIV infection (A-I)

  • -

    Onset of limiting toxicity (A-II)

  • -

    Poor adherence (A-III)