Neisseria gonorrhoeae and chlamydia trachomatis (hereafter, NG/CT) are highly prevalent sexually transmitted infections (STI) among men who have sex with men (MSM) in the United States.¹ NG/CT and HIV share common modes of transmission, and NG/CT infection increases susceptibility to and transmissability of HIV in HIV serodiscordant sexual partnerships.^2,3 Among men living with HIV, NG/CT co-infection can increase the probability of onward transmission of HIV by increasing viral shedding.⁴ Among men at risk of HIV, NG/CT infection can increase susceptibility to HIV by compromising the rectal or urethral epithelium and by increasing the concentration of HIV target cells in the genital or urethral tract.⁴ Among men, from 2015–2019, rates of chlamydia diagnoses increased 32% and gonorrhea diagnoses increased 61%.¹ A recent report found that gonorrhea diagnoses among men living with diagnosed HIV increased 61% from 2010 to 2019.⁵ Urogenital gonorrhea is more prevalent among MSM with HIV compared to MSM without HIV; no differences were observed in urogenital chlamydia prevalence based on HIV status.¹

Screening programs designed to detect and treat NG/CT are a critical component of the public health response to these infections. Currently, the U.S. Centers for Disease Control and Prevention (CDC) recommends that sexually active MSM receive NG/CT screening at all anatomic sites of sexual activity at least annually.⁶ Estimates of how well these guidelines are followed in clinical settings are difficult to obtain because there is not a central data repository describing all STI screenings. In a large national survey of sexually active MSM, only 42% reported receiving any STI test and only 16% had received any extragenital STI test in the past 12 months.⁷ Of those reporting extragenital screening, 87% received throat swabs and 82% received rectal swabs. Screening is particularly important because the vast majority of rectal NG/CT infections are asymptomatic^8,9 and will not be detected based on syndromic management alone.

The overlapping modes of transmission and biological synergy between HIV and STIs led to several trials to test the effectiveness of STI screening programs to reduce HIV incidence, the results of which have been summarized previously.^2,10,11 Briefly, only one trial¹² has demonstrated reductions in HIV incidence following community-level intervention to detect and treat STIs. A number of hypotheses have been put forward for the lack of effect in these trials^10(p), including enhanced STI prevention in control groups that likely diluted any intervention effect. Differences in stage of the HIV epidemic might have also played a role in these disparate trial results. Notably, all of these trials were conducted among the general population; the effectiveness of STI screening and treatment to reduce HIV incidence among MSM remains unclear. HIV is transmitted more efficiently via anal sex compared to vaginal sex^13,14, so the effect of increased STI screening might have a more pronounced effect on HIV incidence among MSM.

Previously, we estimated the population attributable fraction (PAF) of urethral and rectal NG/CT on HIV incidence among MSM to be approximately 10%¹⁵; another study has estimated this value to be 15% among young MSM.¹⁶ The PAF is the proportion of HIV incidence that could be averted if NG/CT were to be eliminated from the population. Although useful, it does not provide a direct estimate of the proportion of new infections of HIV that might be averted due to realistic screening and treatment programs that reduce, but do not eliminate, NG/CT. The goal of this analysis is to estimate the effect of realistic increases in NG/CT screening overall, focusing increases by HIV serostatus and risk group, and increasing rectal screening on HIV incidence among MSM.

We used an open-source, network-based model of HIV, NG, and CT transmission dynamics for a population of MSM in Atlanta, Georgia, built with the EpiModel software platform¹⁷, to assess the effect of NG/CT screening on HIV incidence. We modeled the transmission of HIV, NG, and CT among sexually active Black, Hispanic, and White MSM aged 15–64 years old. Dynamic contact networks were fit using temporal exponential random graph models (TERGMs)¹⁸ to data from the ARTnet Study, an egocentric network study of MSM partnerships in the US.¹⁹ The model has previously been adapted to estimate the contribution of NG/CT on HIV incidence among this population¹⁵ and the effect of different levels of NG/CT screening on NG/CT incidence.²⁰ This model accounts for partnership formation and dissolution; sexual activity within partnerships; transmission and disease progression of HIV, NG, and CT; and screening and treatment of HIV, NG, and CT. Key parameters are described below and presented in Table 1; additional details describing each of these processes are included in the technical appendix.

In the base scenario, HIV incidence was 1.27 (IQR: 1.20, 1.33) per 100 PY (Table 2). Increasing coverage of NG/CT screening among all sexually active MSM had a modest effect on HIV incidence. A 60% relative increase in the percentage of MSM screened for NG/CT at least once per year would avert 4.9% (IQR: 2.8%, 6.8%) of HIV infections over 10 years compared to current estimated screening coverage in the base scenario. Implementing biannual NG/CT screening among MSM with multiple recent partners had a larger impact; when 60% of MSM with multiple recent partners screened for NG/CT biannually, 9.8% (IQR: 8.1%, 11.6%) of HIV infections were averted compared to the base scenario. In all scenarios of increased screening among men with multiple partners in the past six months, more than 99% of simulations resulted in the number of HIV infections averted being greater than zero.

We conducted scenarios to isolate the relative effects of increasing urethral versus rectal NG/CT screening. Increasing urethral screening among MSM without HIV resulted in successively larger percentages of HIV infections averted (Table 3). Within each level of increased urethral screening coverage, increases in the proportion of screening events that included rectal screening resulted in larger percentages of HIV infections averted. With no change in the baseline proportion of screening events that included a rectal screen, a 60% increase in urethral screening among MSM without HIV would avert 2.5% (IQR: 0.5%, 4.3%) of HIV infections; if all urethral screening events included a rectal screen, the same increase in urethral screening would avert 3.9% (IQR: 1.6%, 5.9%) of HIV infections. If rectal screening remained at current coverage levels, one HIV infection would be averted for every 2,117 (IQR: 1,297, 3,512) additional NG/CT tests conducted among MSM without HIV. If all urethral screening events included a rectal screen, one HIV infection would be averted for every 2,310 (IQR: 1,625, 4,221) additional NG/CT tests conducted among MSM without HIV. In these scenarios with a 60% increase in screening among men without HIV, between 80.2% and 90.7% of simulations resulted in averting HIV infections compared to the base scenario, depending on the proportion of screening events that included rectal screening.

Smaller effects on HIV incidence resulted from increases in NG/CT screening among MSM with HIV (Table 4). A 60% increase in NG/CT screening among MSM with HIV with no increase in the proportion of screening events that include a rectal screen would avert 0.8% (IQR: −1.3%, 2.7%) of HIV infections over 10 years; if all screening events included a rectal screen, the same increase in urethral screening would avert 1.3% (IQR: −0.6, 3.3) of HIV infections. In scenarios with a 60% increase in NG/CT screening among MSM with HIV, when rectal screening coverage remained at baseline levels, 745 additional NG/CT tests conducted among MSM with HIV (IQR: 433, 1,472) would avert one new HIV infection. If rectal screens occurred at all NG/CT screening events, 1,031 additional NG/CT tests conducted among MSM with HIV (IQR: 614, 2,163) would avert one new HIV infection. Across the scenarios assuming a 60% increase in NG/CT screening among MSM with HIV, between 61.0% and 67.6% of scenarios resulted in averting HIV infections compared to the base scenario depending on the proportion of screening events that included rectal STI screening.

Using a mathematical modeling framework, we sought to estimate the effect of increasing screening for NG/CT on downstream HIV incidence by HIV serostatus and anatomical site of screening. We found that the most substantial decreases in HIV incidence occurred following increases of screening for NG/CT among MSM who had 2 or more partners in a 6-month period and among sexually active MSM without HIV generally. Smaller reductions in downstream HIV incidence were observed when screening was increased among men with HIV, likely due, at least in part, to the relatively smaller population of MSM with HIV compared to MSM without HIV. At all levels of screening coverage among MSM without HIV, increased coverage of rectal screening resulted in a greater proportion of HIV infections averted; increasing rectal screening among MSM with HIV had smaller and less consistent effects. However, increased screening of MSM with HIV was more efficient at all levels we assessed, as indicated by the lower number of additional NG/CT tests per HIV infection averted for MSM with HIV compared to MSM without HIV. It is important to note that far fewer of the simulations based on scenarios of increased screening among MSM with HIV resulted in averting any HIV infections compared to scenarios of increased screening of MSM without HIV, reflecting the much smaller overall effects on HIV incidence in the former scenarios.

Because we used a modeling approach, our results estimate the total effect of NG/CT screening on HIV incidence. The ideal outcome of a positive screening test, treatment of NG/CT infection, has a direct effect on HIV incidence by decreasing the risk of HIV transmission or acquisition in subsequent sexual encounters. By modeling the effect of screening in a simulated network with a 10-year time horizon, we also capture reduced incidence based on the prevention of earlier HIV cases via NG/CT accelerated treatment.

Previous analyses have demonstrated the expected effects of increased NG/CT screening on NG/CT incidence²⁰; our analysis expands on those results to understand the effects of NG/CT screening on HIV incidence. There is strong evidence for the synergy between the HIV and STI epidemics among MSM, including shared transmission mechanisms and risk factors.^3,4,31s Although most community-based trials that have examined the effect of STI screening on HIV incidence have been negative³, they were also conducted among heterosexual populations. The effect of STI screening on HIV incidence among MSM remains an open question. We previously estimated that 10% of new HIV infections among MSM in the United States were attributable to NG/CT infection¹⁵ and the same proportion has been estimated to be 15% among young MSM.¹⁶ The proportion of HIV incidence attributable to NG/CT infection provides a ceiling for the possible effect of increasing NG/CT screening and treatment on subsequent HIV infections. Thus, based on our previous estimate, one might expect that a screening program that resulted in the elimination of NG/CT among MSM would avert 10% of new HIV infections annually. In some scenarios we modeled in which screening was increased among men with 2 or more sex partners in the previous 6 months, we observed near elimination of NG and CT by the end of the 10-year follow-up period, indicating that NG/CT screening programs may achieve their maximum effect on HIV incidence within 10 years in those scenarios.

Notably, the proportion of HIV incidence attributable to NG/CT is inextricably linked to the overall prevalence of NG/CT in the population. That is, a population with a higher prevalence of NG/CT would have a larger proportion of HIV incidence attributable to NG/CT. Indeed, the initial prevalence of NG/CT in the current model is greater than in our previous work¹⁵, reflecting the increasing prevalence of NG/CT among MSM in recent years.¹ Thus, jurisdictions with higher prevalence of NG/CT among MSM would expect to see a greater reduction in HIV incidence following increased screening and treatment for NG/CT than our model estimates.

An important strength of our analysis is that estimates of the effect of NG/CT on HIV transmission and acquisition were anatomic site-specific. That is, increased risk of HIV acquisition or transmission only occurred in the context of a NG/CT infection at the site of sexual activity. Because NG/CT infection is anatomic site-specific, the CDC recommends screening at all anatomic sites of sexual contact. The vast majority of rectal NG/CT infections are associated with a negative urogenital screen at the same clinic visit^32s, highlighting the need for extragenital screening. Although rectal screening is an important tool for preventing onward transmission of NG/CT and reducing risk of HIV acquisition and transmission, it is much less common than urogenital screening.^7,32s Most rectal NG/CT infections are asymptomatic⁸ and will remain undetected in the absence of a screening test. Our results demonstrate that, beyond the direct benefit of reducing NG/CT incidence, increased rectal screening, particularly among MSM without HIV, will also have downstream effects to reduce HIV incidence.

We observed much larger declines in HIV incidence following increased NG/CT screening among MSM without HIV and MSM who had at least 2 sex partners in the preceding six months. Of note, PrEP-eligible MSM were assumed to initiate PrEP at a rate that resulted in approximately 15% of MSM without HIV using PrEP at any given time. These men were assumed to adhere to the recommended STI screening schedule for PrEP users; thus, the observed effects of increasing NG/CT screening were a result of increasing STI screening among MSM not on PrEP. The smaller effects of increased screening among MSM with HIV are likely a reflection of the smaller population size of MSM with HIV compared to MSM without HIV and the smaller modeled effect of prevalent NG/CT on HIV transmission compared to HIV acquisition.

Our model does not estimate the effect of other STIs (e.g., syphilis) on HIV risk, thus these results are likely an underestimate of the possible effect of STI screening in general on HIV incidence among MSM. Additionally, we only estimate the effect of anal sex on HIV transmission. NG/CT infection can also occur in the pharynx and pharyngeal NG/CT screening is recommended for MSM who engage in receptive oral sex. Oral sex is not a major risk factor for HIV; however, it does play an important role in the NG/CT epidemics.^33s Thus, pharyngeal screening might result in the prevention of transmission of an NG/CT infection that would later be involved in an HIV transmission event. This would also indicate that our results underestimate the possible total effect of increased NG/CT screening on HIV incidence among MSM.

These data demonstrate that increasing screening for NG/CT is expected to have meaningful downstream effects on HIV incidence. The biggest impact was observed when increasing NG/CT screening among MSM without HIV and MSM who had at least 2 sexual partners in the previous six months; however, increasing NG/CT screening among MSM with HIV was more efficient.