The COVID-19 pandemic disrupted our ability to provide comprehensive HIV primary care, including sexual health care, to those persons in greatest need. Prior to the COVID-19 pandemic, the HIV epidemic in the United States was experiencing modest downtrends due in part to successful harm reduction strategies, such as HIV pre-exposure prophylaxis (PrEP), as well as increasing testing to identify new cases, improving linkage to care, and more convenient and tolerable dosing of antiretroviral (ART) therapy. Early COVID-19 mitigation strategies affected our ability to provide prompt, in-person care, leading to a tremendous shift to virtual medicine platforms, including telephone and video telemedicine. This transition allowed care to continue for many, highlighting a new avenue for ongoing care. It also accentuated the inequities and may have worsened disparities due to lack of means to participate in virtual care, such as a capable device, internet access, or technology literacy. Many HIV and sexual health clinics halted their in-person visits, interrupting the care continuum for HIV as well as limiting access to in-person sexual health services for STI screening and management. The abrupt shift to telemedicine allowed care to continue, but there were declines in linkage and retention in HIV care, antiretroviral starts, and viral suppression rates at HIV clinics in the USA and globally. Equally important, reagents needed for STI diagnostic testing were diverted to SARS-CoV-2 assays in this public health crisis, undermining availability to offer basic diagnostic tests for chlamydia and gonorrhea. While it remains to be seen how these measures affect the HIV and STI epidemics, it is quite possible, and even likely, that the COVID-19 pandemic will reduce recent progress made.
Most data to date show that persons living with HIV (PLWH) do not have significantly increased susceptibility to COVID-19. Early case series and case-control studies did not show a significant difference in mortality among PLWH, but more recent data from larger population-based cohorts in the USA and Europe has shown trends towards higher COVID-19 mortality among PLWH. These trends are especially notable among PLWH who also have co-morbidities that increase the risk for severe COVID-19 and among racial and ethnic minorities. At this time, data are mixed to truly associate HIV status with adverse outcomes due to COVID-19; rather, it is much more evident that disparate COVID-19 outcomes are more strongly associated with cardiovascular and metabolic co-morbidities and being of racial or ethnic minority status, which are more common among PLWH.
Harm Reduction in Principle
Harm reduction, broadly defined, prioritizes minimizing the harm caused by an action or a behavior over stopping the action or behavior. Critically, harm reduction recognizes the contribution of stigma related to a behavior and aims to reduce this stigma as a barrier to improving health. This approach has been applied most commonly to substance use, such as tobacco use, alcohol use, and injection drug use. Recognizing that substance abuse behaviors lead to adverse health outcomes, the primary goal of harm reduction is to prevent or slow the social and physical harms associated. Harm reductionists often apply these principles to halting the spread of a pathogen. Indeed, HIV and other STI management have also benefited from harm reduction strategies.
If SARS-CoV-2 acquisition and subsequent COVID-19 disease is the adverse outcome to avoid, then what is the behavior or action to minimize to reduce this harm? Undoubtedly, this a difficult question. Merely being near other persons can lead to virus transmission through respiratory droplets and even possibly airborne particles, but complete social isolation is not only impractical but almost impossible. Identifying the harms to minimize must be considered in the broader context that recognizes individual physical and mental health.
Harm Reduction Strategies
Harm reduction strategies for infectious diseases are relatively similar and can correlate from pathogen to pathogen. Indeed, in the case of COVID-19, HIV, and STIs, many of the same principles for harm reduction can be transposed, although with different details.
Prevention
Intuitively, preventing an adverse outcome is ideal. Multiple biomedical and behavioral strategies exist to reduce harm by either stopping exposures, modifying exposures, or preventing acquisition after exposure.
Barrier Protection
Condoms reduce transmission of HIV and bacterial STIs effectively, if used adequately and consistently, but lack of access to condoms or perhaps even personal preference limits their utility. As a correlate to barrier protection, masking has proven effective to reduce the expulsion of SARS-CoV-2 and other respiratory virus droplets. Early in the pandemic, the role of masking was not certain, and the lack of available personal protective equipment (PPE) reinforced tendencies towards inadequate or no masking. Consistent masking remains one of the most effective ways of reducing transmission, especially in close contact, such as hair salons and airplane flights. Multiple concentrated outbreaks have been linked to activities without mask use, such as choir practice, playing close contact sports, and children's summer camp without masks, highlighting the relative ease of transmission without enforced masking or distancing. Although a nationwide mask mandate in the United States has been implemented only for certain circumstances, several US states have adopted broader measures, which have been associated with decreased spread of SARS-CoV-2 and declines in hospitalization rates among persons aged 18–64. Among healthcare workers (HCWs) in one US healthcare system, a mask mandate significantly reduced new virus acquisition after its implementation. Additionally, concurrent social distancing recommendations to stay at least 6 ft. or 1 m apart as well as "shelter-in-place" orders, also referred to as lockdowns or shutdowns, have drastically altered the course of the pandemic in states and countries that have employed these measures. These types of "shelter-in-place" restrictions do not align with harm reduction truly, as the defined harm in COVID-19 is exposure to the virus via contact with other persons. Nevertheless, it remains effective, just as abstinence is effective at preventing HIV and STIs, but permanent abstinence, or long-lasting shutdowns in the case of COVID-19, is not practical, despite their clear short-term effectiveness.
Chemoprophylaxis
Established biomedical HIV prevention strategies, such as PrEP and post-exposure prophylaxis (PEP), have shown incredible ability to reduce HIV acquisition at the individual level as well as some protection at the population level to reduce HIV acquisition. PrEP with combination oral tablets, emtricitabine combined with either tenofovir disoproxil fumarate (F/TDF) or tenofovir alafenamide (F/TAF), as well as newer agents such as long-acting cabotegravir injections effectively reduce sexual HIV acquisition by nearly 100% if taken adequately. For SARS-CoV-2, multiple observational studies and randomized, controlled clinical trials have shown no benefit to hydroxychloroquine (HCQ) as PrEP or PEP. Further, no data support the use of vitamin C, vitamin D, or zinc as PrEP for SARS-CoV-2 infection.
Vaccination
While an effective HIV vaccine remains elusive, multiple phase 3 clinical trials are ongoing to evaluate SARS-CoV-2 vaccines. Similarly, vaccine development against Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum is also proceeding. Vaccination for preventing HIV and STIs has yet to demonstrate robust protection against infection, but vaccination against SARS-CoV-2 to prevent COVID-19 looks to be the most promising route for prevention. Several vaccine candidates have demonstrated considerable efficacy. The first two vaccine candidates, BNT162b2 and mRNA-1273, use innovative messenger ribonucleic acid (mRNA) platforms. These mRNA vaccines employ lipid nanoparticles to introduce mRNA into host cells for the host ribosomes to then create the spike protein which is the antigen target for the adaptive immune response. These have demonstrated remarkable efficacy at preventing severe COVID-19 and good tolerability. Administered in a two-dose regimen 21 days apart, Pfizer/BioNTech's BNT162b2 vaccine showed 95% efficacy to protect against COVID-19 among 36,523 participants with no prior COVID-19 in a large, multinational clinical trial. The primary endpoint was symptomatic COVID-19 confirmed by polymerase chain reaction (PCR). No severe COVID-19 cases were identified in the vaccine arm. The BNT162b2b vaccine was very safe and fairly well tolerated. Among the BNT162b2 recipients, 83% reported a local, injection site reaction after their first dose, and 78% reported a reaction after the second dose; most were mild to moderate and resolved within 1–2 days. There were few serious adverse events in either arm, and there were no deaths related to the vaccine. The BNT162b2 vaccine requires −80 °C storage. While large medical facilities may have the resources to store this vaccine, cold chain transport and need for expensive, −80 °C freezers significantly limits its ability to be rolled out broadly. The other mRNA vaccine, mRNA-1273 produced by Moderna, similarly showed considerable efficacy and safety. Also administered in a two-dose regimen, although 28 days apart, the mRNA-1273 vaccine showed 94.1% efficacy at preventing COVID-19 among 30,420 participants in a large, randomized clinical trial in the USA. Also, there were no severe COVID-19 in the vaccine intervention arm. Similarly, mild to moderate local and systemic reactogenic symptoms were much frequent in the mRNA-1273 participants, but the serious adverse events were rare. Unlike the BNT162b2 vaccine, the mRNA-1273 vaccine does not require such low temperatures for freezing yet still requires cold chain transport and subzero freezers for storage. At the time of this writing, these two mRNA vaccines have been granted Emergency Use Authorization (EUA) by the US Federal Drug Administration (FDA). Other vaccine candidates, which are employing more traditional, although potent, viral vectors, are currently undergoing phase 3 clinical trials. Interim results for three candidates appear promising to offer fairly good efficacy and tolerability. In phase 1–2a trials, Janssen's Ad26.COV2.S vaccine (or JNJ-78436735) against SARS-CoV-2 demonstrated high production of neutralizing antibody in over 90% of participants on day 29 after the first dose and approached 100% by day 57. Early results from the phase 3 ENSEMBLE trial report 72% efficacy in the USA and 66% efficacy overall in preventing moderate to severe COVID-19 28 days after a single dose of the vaccine as well as 85% efficacy in preventing severe disease across all multinational study sites. Perhaps the most promising aspect of this vaccine candidate is that it is administered as a single dose and can be transported through standard vaccine distribution channels. The As26.COV2.S may not be as effective as the mRNA vaccine, but it still offers protection from severe COVID-19 while improving ease of implementation and roll-out. In early, interim analysis, Astra Zeneca's ChAdOx1 nCoV-19 (AZ1222), another two-dose regimen dosed at least 4 weeks apart (although up to 12 weeks), showed efficacy in protecting against symptomatic COVID-19 by 66.7% with no severe COVID-19 cases in the vaccine arm among participants in Brazil, South Africa, and the United Kingdom. "Sputnik V" is the nicknamed adenovirus vector vaccine, Gam-COVID-Vac. Interim results from a large phase 3 trial showed 91.6% efficacy in reducing PCR-confirmed COVID-19 after two doses 21 days apart in among 21,977 participants in Russia.
As vaccination efforts increase in the community, the need to reach communities of color, especially Black/African American, Hispanic/Latinx, and Native and Indigenous communities, demands equitable implementation. Analogous to HIV PrEP, systemic and structural barriers such as few vaccination sites, requirement for online registration, and vaccine hesitancy may prevent at-risk persons from being vaccinated. These barriers must be addressed in all implementation plans to ensure that vaccine access is fair and equitable to all communities.
Detection
Another major tenet of harm reduction in infectious diseases is early detection. While early intervention is actually the key in reducing adverse outcomes, detection early in the course is necessary in order to then perform the intervening treatment. Laboratory methods for detecting HIV, STIs, and SARS-CoV-2 infection are similar, but there are key differences in understanding the utility of diagnostic methods due to the different syndromes, and different timelines, that each of these causes.
Nucleic Acid Amplification Test
Nucleic acid amplification testing (NAAT), most often performed by reverse transcriptase polymerase chain reaction (RT-PCR), detects a pathogen's presence by identifying and amplifying unique nucleic acid sequences or genes of a particular pathogen. Often, NAATs are the most sensitive and specific tests for identifying a pathogen. HIV RNA detection in blood, termed viral load, is not the sole means of identifying infection, but it is the most sensitive and specific. In fact, the viral load is used to monitor response to ART. Similarly, most STIs can be diagnosed by performing a NAAT on a specimen obtained from the site of exposure (oropharynx, urethra, cervix, vagina, or anus) to identify pathogens such as C. trachomatis, N. gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and herpes simplex virus (HSV).