Incidence rate of sexually transmitted infections among HIV infected patients on long-term ART in an urban and a rural clinic in Uganda

HIV-related immunosuppression increases susceptibility to other sexually transmitted Infections (STIs) [1, 2]. Co-infection with STIs facilitates HIV acquisition and transmission by disrupting the integrity of genital mucosa, generating inflammatory responses which recruits HIV target cells, inducing cytokine responses which regulate HIV replication and increase HIV shedding [3, 5, 6, 27, 28]. Genital ulcers in women increases male to female HIV transmission 10 to 50-fold [4]. Although, this data is for people living with HIV not on ART, incident STIs in people on ART may thus reduce the preventive benefits of ART [1]. STI incidence can also serve as a marker of risky sexual behavior [7, 8, 14].

STIs are caused by viral, bacterial, protozoa, fungal and parasitic agents and present as abnormal vaginal or urethral discharges and ulcerative or non-ulcerative genital lesions. Because laboratory diagnosis is complex, expensive, and results in a delayed initiation of treatment, WHO recommended a syndromic and case management approach for developing countries [15, 16]. The Uganda Ministry of Health also recommends a syndromic and case management approaches to STIs among people infected with HIV in public health care facilities. STI related history taking, a physical examination, and clinical algorithms are used to diagnose and management the commonest biological causes of STIs. Where possible, syphilis serologic screening is performed [16–18].

A limited number of studies have evaluated the incidence of STIs among people on ART in sub-Saharan Africa. A South African study found a 14% six-month incidence of STIs measured as treatment seeking for a new STI after initiating ART and observed that individuals diagnosed with an incident STI using a syndromic approach were more likely to have a detectable viral load [12]. Another South African study observed a seven-fold higher rate of STIs after starting ART compared to before ART [9]. In Uganda, a study using STIs syndromic screening algorithms with high cervical swabs for women eligible for intra-uterine contraception where DNA was extracted from the swabs and PCR assay done to detect Neisseria gonorrhea, Trichomonas vaginalis and Chlamydia trachomatis infections found STIs incidence of 11.1% (95% CI: 7.8–14.4) among women on ART [10]. In China, among the 4510 market vendors evaluated for STIs using a syndromic approach by the physician, compared with laboratory tests as a gold standard found a sensitivity of 36.7% among participants reporting STI symptoms and 5.1% among those without an STI symptom [31]. In India, among patients who attended an STI clinic found a sensitivity of genital discharge syndrome for Neisseria gonorrhea at 96% and Chlamydia at 91% while the specificity was low (76 and 72%, respectively). The sensitivity of genital ulcers syndrome for herpes simplex virus-2 and Treponema palladium was 83 and 81% respectively while its specificity was at 99% [32].

While there is some information on STI in the first year(s) of ART, there is a dearth of information on STI incidence in patients on long-term ART in resource-limited settings. Using a syndromic and case management approach, we evaluated the STI incidence rate and assessed factors associated with STIs incidence in patients on long-term ART in an urban and a rural cohort in Uganda.

In this cohort study of patients on long-term (≥ 4 years) ART, we found an STI incidence rate of 2.8 per 1000 person-years. The lower incidence rate observed in our study could be because we assessed STIs among patients who were already experienced on ART, thus, they received STIs prevention messages during ART initiation and subsequent clinic follow-up. Rural residence, female gender, and younger age were independently associated with a higher STI incidence.

Data on the incidence of STIs in people on ART in sub-Saharan Africa are scarce. In South Africa, one study also found a low incidence rate of STI of 1.29 per 1000 person-years (95% CI 1.24–1.34) in a cohort of 1465 patients followed for 3 years after initiating ART [12] using syndromic diagnoses of STIs. In the South African study, the rate of treatment seeking for new STIs was seven-fold higher (aRR 7.01, 95% CI 4.64 to 10.59) while on ART compared to prior to initiating ART. Due to lack of published data on the STI incidence rate among people on long-term ART, we could not compare our data to other studies in sub-Saharan Africa.

Our findings that rural residence was associated with higher incidence of STIs was also observed in a nationally representative Uganda survey that assessed STI as self-reported STIs and/or associated symptoms in the past 12 months of the general population aged 18–49 [19]. The lower STIs rates observed among the urban participants could be because they continuously received condom promotion messaging and counseling as evidenced by lower condom use (69.5%,146/210) in the rural participants compared to (30.5%, 64/210) in the urban participants at baseline visit) and urban population had greater exposure to HIV prevention messaging.

In the survey of the general Ugandan adult population, having multiple sexual partners was found to be a significant risk factor for STI [9]. In our cohort, participants reporting risky sexual behavior were 50% more likely to have an STI (aHR 1.51), but the association was not statistically significant (95% CI: 0.91, 2.51). Risky sexual behavior has been shown to persist among people on long-term ART [11–14, 29] and may thus place people on long-term ART at continued risk for STIs and HIV transmission to sexual partners.

The association between female gender and younger age and a high incidence of STIs is consistent with other studies in Uganda and South Africa [11, 19–22]. In a South African cohort study of 1465 patients followed for 3 years after initiating ART, being female and younger were associated with higher incidence of clinic visits for STI treatment [12]. Our findings are not surprising as younger people are a sexually active group, tend to have multiple sexual partners, and their knowledge and awareness of safer sexual behavior and practices may be lower compared to older adults. Additionally, females tend to have a better health-seeking behavior in issues relating to STIs than men and many vaginal discharge may not be an STI [30].

Our study had several strengths, including its prospective data collection design, the inclusion of a cohort in both a rural and an urban setting, and a relatively large sample size with long follow up. An important limitation of our study is that biological samples were not collected to confirm an STI diagnosis. As per Uganda Ministry of Health guidelines (adapted from WHO STI’s guidelines), and similar to the situation in most developing countries, majority of the STI diagnoses were made through a “syndromic and case management approach” [16, 21]. The failure of the syndromic approach to detect STI among asymptomatic patients [31] was a limitation to the study. Another limitation is that some participants may have received an STI diagnosis and treatment in a primary care clinic in between the three monthly visits at the HIV care and treatment center. This could have resulted in an underestimation of the STI incidence.

In this cohort study of patients on long-term (≥ 4 years) ART, we found STIs incidence rate of approximately 3 per 1000 person-years after 3.5 years of follow-up. Rural and younger persons on ART should be prioritized for routine STIs testing in HIV care clinics to enable early diagnosis and management because if diagnosed late and poorly managed lead to serious complications of their own. Furthermore, they enhance sexual transmission of HIV, therefore, making timely and proper STI diagnosis is of paramount importance.