Presently, there is not much research data concerning monkeypox and HIV. Due to the novelty of the recent monkeypox outbreak, there has not been enough time or volume of subjects to complete many studies. Monkeypox is a type of virus known as orthopoxviral. Smallpox is also an orthopox virus which is why the smallpox vaccine is used to protect against monkeypox. However, smallpox was eradicated in 1980 before the HIV/AIDS epidemic.[1] Additionally, monkeypox has existed for years in areas where it has been endemic, yet research has been neglected and underfunded.[2] Many questions need to be investigated. Medical science has already proven that T-cell deficiencies due to HIV render HIV-positive people more susceptible to viral and fungal infections.[1] Two main questions are: does HIV infection increase the risk of contracting monkeypox, and is HIV an aggravating factor in monkeypox infection/progression/severity?

There is some medical evidence that having underlying immune deficiencies increases the risk of infection if exposed and the possibility of severe illness if infected.[5] People living with HIV are immunocompromised. However, the increased risk and negative outcomes of infection is more likely for those with untreated HIV. Untreated HIV means a much weaker immune system than those in treatment. Those inconsistent medical treatments usually have well-controlled HIV with many reaching viral suppression. Being undetectable results in a characteristically immunocompetent immune system more like those who are not living with HIV.[5]

The U.S. Centers for Disease Control & Prevention (CDC) last month updated its Clinical Considerations for Treatment and Prophylaxis of Monkeypox Virus Infection in People with HIV. The CDC contends that people with advanced HIV or who are not virologically suppressed with antiretroviral therapy can be at increased risk of severe disease with monkeypox, but they also note  that these considerations are based upon limited evidence available.

Two recently published studies give some developing insight into the relationship between HIV and monkeypox. One such study is a multinational study published in the New England Journal of Medicine. The study was performed by a collaborative international group of clinicians that spanned 43 sites in 16 countries.[2] Together they compiled a case series of 528 infections. In this sample set, 98% were gay or bisexual men, 2% were heterosexual men, 75% were white, 41% were HIV positive (the majority was well controlled), and the median age was 38.[2] The clinical presentation of those living with HIV and those not HIV positive were very similar, with no significant differences.

This study confirmed sexual activity, among gay and bisexual men, as a significant transmission route. Tracking of infection indicated reports of infection clusters associated with sex parties or saunas. International travel and attendance of large gatherings linked to sex-on-site activities by some subjects support the developing theory of enhanced infection rates through sexual networks.[2] Notably, the study did not conclude that monkeypox was transmitted through semen. The genital, anal, and oral mucosal lesions were found to result from close skin-to-skin contact during sexual activity. However, testing 32 semen samples indicated results are inconclusive as to if the amounts and kinds of viral DNA found in the seminal fluid are replication-competent.[2] More research is needed.

The second study was conducted in Spain. It was an observational prospective cohort study of 181 subjects from 3 sexual health clinics in Madrid and Barcelona.[3] A prospective cohort study means that the subjects are followed and observed over time to monitor the development of their outcomes. Of the 181 subjects, 166 identified as gay men or bisexual men, 15 as heterosexual men or women (6 were female), and 72 (40%) were HIV positive.[3] All of the subjects had skin lesions. Seventy-eight percent had anogenital lesions, and 43% had them in the oral and perioral regions. Additionally, other complications were observed. Proctitis was seen in 45 subjects; 19 had tonsilitis, 15 had penile swelling, and 8 had a widely spread-out rash. Notably, systemic symptoms (fever, headache, flu-like sickness, sore throat) before the appearance of rash occurred more often in those who had participated in anal-receptive intercourse than those who did not.[3]

The important takeaway from both studies is that clinicians need to expand the symptoms of what they look for in monkeypox infection. The current outbreak is not behaving like the outbreaks in the endemic area of Africa, which typically had hundreds of rashes with some as pustules. These studies showed cases where people have only had one lesion on the surface skin. Clinicians should be extra cautious and suspicious of monkeypox disease in at-risk populations. The virus can be present in atypical ways that may appear as other STIs, such as chlamydia or syphilis. Moreover, both studies showed the incubation period was, on average, about 7 to 8 days; thus, focusing energies on pre-exposure intervention is essential.

It is currently unknown how long people can spread disease after lesions have crusted over and healed. Condom use is suggested for eight weeks after healing. HIV subjects are overrepresented in the populations of the studies due to the way subjects were obtained. Subjects were picked from places like sexual health clinics where many HIV-positive patients receive treatment. Additionally, HIV-positive people with the well-controlled diseases are more likely to seek testing. The overrepresentation in the studies does not indicate that an HIV diagnosis necessarily equates to an increased likelihood of infection. However, more research is needed to investigate that. A recent study has also shown that a person can be simultaneously infected with HIV, Covid, and monkeypox.[4] Exploring the interaction with HIV is imperative.

Getting ahead of the current monkeypox infection wave with prevention is the most effective way to stop the current trajectory. Prevention includes behavior modification as well as testing and vaccination. Targeted messaging to vulnerable groups will encourage behavior modification as well as testing. Widespread adoption of expanded protocols of symptom investigation by clinicians will also increase the identification of monkeypox infection in those presenting with atypical symptoms. Halting the spread is paramount before it has the chance to reach pandemic levels.

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