Implications of Antiretroviral Drug Use for HIV Prevention Interventions on Elevated Risk for STIs: Critical Questions for Implementation Effectiveness and Evaluation

Implications of Antiretroviral Drug Use for HIV Prevention Interventions on Elevated Risk for STIs

Part I: Problem Statement

PrEP is a biomedical interventional strategy in which healthy people routinely take one or more antiretroviral (ARV) drugs to reduce their risk of getting HIV through sex. Three RCTs have studied the effects of PrEP on the acquisition of HIV infection***. The first landmark study, the Pre-exposure Prophylaxis Initiative (iPrEX) looked at the effect of daily use of tenofovir-emtricitabine in 2499 MSM from six countries (Peru, Ecuador, South Africa, Brazil, Thailand, and the USA) and was published in 2010. The PRe-exposure Option for reducing HIV in the UK, immediate or Deferred (PROUD) trial enrolled 544 MSM in the UK and randomly assigned them to immediate or a 1 year delayed start of daily oral tenofoviremtricitabine. In the Intervention Préventive de l’Exposition aux Risques avec et pour les Gays (Ipergay) trial, ** **MSM were randomly assigned to either tenofovir-emtricitabine or placebo for intermittent use in France and Canada. In all PrEP trials, adherence was a strong determinant of PrEP effectiveness. **

The currently validated PrEP method involves interventional use of ARVs, tenofovir and emtricitabine, taken daily in a single pill marketed as Truvada, and Descovy. PrEP is a powerful intervention for HIV prevention, but it has the potential to reduce commitment to primary prevention strategies, result in risk compensation and increase proportions of at-risk populations with STIs. For example, new data about PrEP uptake confirms that of approximately 500,000 Black people who could potentially benefit from PrEP, only 7,000 prescriptions have been filled. This data underscores the need to ensure that a policy shift to prophylactic treatment is not producing inequities. The role of PrEP in relation to STI incidence is somewhat easier to assess than with TasP, because PrEP is an individual intervention rather than a population-based one. PrEP is, however, only in the early stages of implementation. Individuals who receive PrEP will need to be followed up carefully over time with the use of quantitative and qualitative research methods to establish whether and how risk compensation and changing patterns of sexual partnerships and practices are affecting STIs.

The long-term effect of PrEP for risk, incidence and prevalence of STIs are not yet known. Widening of PrEP use, together with other behavioral changes could affect sexual networks and proportions and patterns of STI. For example, if non-condom sex partnerships between individuals using PrEP who are not infected with HIV and individuals using TasP who are HIV infected become more common, outbreaks of syphilis, lymphogranuloma venereum, hepatitis, and shigellosis that have occurred mostly in those infected with HIV could spread to networks of individuals without HIV infection. STIs that increase HIV infectiousness through inflammatory mechanisms could then reduce the effect of biomedical HIV prevention methods.

TasP methods are designed to reduce HIV infectiousness and involve starting ARV drug therapy as soon as HIV infection is diagnosed to prevent sexual transmission to uninfected partners. The success of TasP depends on people with HIV having the needed access to health care and taking their medications as prescribed every day of their lives. So, strict adherence to ARV drug treatment over the long term is absolutely essential. The concept of U=U means that people living with HIV who achieve and maintain an undetectable viral load- the amount of HIV in the blood- by taking and adhering to the pharmaceutical regime as prescribed cannot sexually transmit the virus to others. To extrapolate these benefits to a whole population, a sufficiently high proportion of all individuals infected with HIV would need to receive and adhere to effective ARV drug treatment from very early in the course of infection.

The landmark NIH-funded HPTN 052 clinical trial showed that no linked HIV transmissions occurred among HIV serodifferent heterosexual couples when the partner living with HIV had a durably suppressed viral load. Subsequently, the PARTNER and Opposites Attract studies confirmed these findings and extended them to male-male couples. Validation of the TasP strategy and acceptance of the U=U concept has numerous behavioral, social and clinical implications. There is a consensus that knowledge about the effects of ARV treatment on reduced infectiousness of HIV is contributing to risk, incidence, and prevalence of STIs 3.

The shift from condoms to medication as the primary form of prevention does not eliminate human behavior as a limit to effective prevention. The success of these strategies is dependent upon strict adherence to the pharmaceutical regime. Recent studies investigating the interventional use of ARVs suggest a relationship between PrEP uptake and TasP strategies like U=U to increasing STI prevalence. These findings have experts questioning the possible unintended negative consequences of using ARV drug treatment for HIV prevention. A disadvantage inherent to TasP is that its success depends on the behavior of others.** The uninfected individual has to trust that their sexual partners infected with HIV are adherent to ARV treatment, and that this treatment is sufficiently effective to mitigate transmission risk. By contrast, with PrEP, the at-risk individual takes the preventive treatment. Biomedical solutions may be an important tool to “treat our way out of this epidemic,” but increasing rates of HIV and STIs raise questions about the influence of PrEP and TasP strategies on STI epidemiology once implemented more broadly.

Summary points

·         Persons living with HIV who achieve sustained viral suppression with antiretroviral therapy can avoid sexual transmission of HIV without using condoms.

·         Similarly, pre-exposure prophylaxis with tenofovir-emtricitabine in HIV-uninfected persons is highly effective.

·         With this background, rates of sexually transmitted infections are increasing in some HIV-infected populations, and in some at risk for HIV acquisition.

·         The implications require reassessment of the alignment and prioritization of HIV research funding, public health policy, and community engagement.