Sexually Transmitted Infections in Pre-Exposure Prophylaxis Patients

Ferdous Ara Ahmed^1*, Shima Ali Sadia², Beatrice Onyinyechi Mkpa³, Md. Naimul Islam Nakib⁴

¹Master of Public Health (7^th Semester Student at Monroe University, USA), Bachelor of Medicine and Surgery (University of Dhaka), Bangladesh
²Master of Public Health (Second Semester Student at Monroe University, USA), Bachelor of Medicine and Surgery (University of Dhaka), Bangladesh
³Bachelors in Microbiology- University of Nigeria Nsukka Masters in Public Health (Epidemiology & Biostatistics) – Monro University (7^th Semester Student), USA
⁴MBBS(China), Master of Public Health (Monroe University, USA)

*Correspondence author: Ferdous Ara Ahmed, Master of Public Health (7^th Semester Student at Monroe University, USA), Bachelor of Medicine and Surgery (University of Dhaka), Bangladesh; Email: [email protected]

Citation: Ahmed FA, et al. Sexually Transmitted Infections in Pre-Exposure Prophylaxis Patients. Jour Clin Med Res. 2024;5(3):1-15.

Copyright^© 2024 by Ahmed FA, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: Demographic Characteristics of Study Population (N=100).

2. PrEP Usage

All patients were on daily oral PrEP regimens. The mean duration of PrEP use prior to the study period was 18.3 months (range: 6-48 months).

3. Overall STI Prevalence

During the 12-month study period, 42 patients (42%, 95% CI: 32.3%-52.3%) were diagnosed with at least one STI.

4. Prevalence of Specific STIs

Table 2: Prevalence of specific STIs (N=100).

5. Anatomical Distribution of Chlamydia and Gonorrhea

Among the 46 cases of chlamydia or gonorrhea:

• Rectal infections: 28 (60.9%, 95% CI: 45.4%-74.9%)
• Urethral infections: 14 (30.4%, 95% CI: 17.7%-45.8%)
• Pharyngeal infections: 4 (8.7%, 95% CI: 2.4%-20.8%)

6. Multiple STI Diagnoses

Fifteen patients (15%, 95% CI: 8.6%-23.5%) were diagnosed with multiple STIs during the study period:

• Two separate STI diagnoses: 8 patients (8%)
• Three or more STI diagnoses: 7 patients (7%)

7. STI Prevalence by Demographic Factors

Table 3: STI prevalence by demographic factors.

8. Condom Use

Reported consistent condom use (defined as use during >90% of sexual encounters):

• For anal sex: 28% of MSM
• For vaginal sex: 22% of heterosexual participants

9. Multivariable Analysis

In the multivariable logistic regression model, factors independently associated with STI diagnosis were:

• Age <30 years (OR 2.1, 95% CI: 1.3-3.4, p=0.003)
• ≥5 sexual partners in past 6 months (OR 2.8, 95% CI: 1.7-4.6, p<0.001)
• Inconsistent condom use (OR 1.9, 95% CI: 1.2-3.0, p=0.007)

10. Comparison to General Population

The overall STI prevalence in our cohort (42%) was significantly higher than the estimated prevalence in the general adult population of the same metropolitan area (7%, p<0.001) based on local health department data.

Discussion

This single-center study of 100 PrEP users revealed a high prevalence of Sexually Transmitted Infections (STIs), with 42% of patients diagnosed with at least one STI over a 12-month period. This finding underscores the complex relationship between PrEP use and sexual health outcomes, highlighting the need for comprehensive STI prevention and management strategies in PrEP programs.

STI Prevalence and Patterns

The overall STI prevalence in our cohort (42%) is substantially higher than estimates for the general population in our area (7%) and aligns with previous studies suggesting increased STI risk among PrEP users [6,9]. Chlamydia and gonorrhea were the most frequently diagnosed infections, consistent with national trends [10]. The high proportion of rectal infections (60.9% of chlamydia/gonorrhea cases) emphasizes the importance of extragenital testing, particularly for men who have sex with men (MSM). The finding that 15% of patients experienced multiple STI diagnoses during the study period is concerning and suggests a subgroup at particularly high risk. This pattern of repeated infections may contribute to the spread of STIs within sexual networks and increases the risk of complications such as pelvic inflammatory disease or epididymitis [11].

STI Prevalence and Patterns

The overall STI prevalence in our cohort (42%) is substantially higher than estimates for the general population in our area (7%) and aligns with previous studies suggesting increased STI risk among PrEP users [6,9]. Chlamydia and gonorrhea were the most frequently diagnosed infections, consistent with national trends [10]. The high proportion of rectal infections (60.9% of chlamydia/gonorrhea cases) emphasizes the importance of extragenital testing, particularly for men who have sex with men (MSM). The finding that 15% of patients experienced multiple STI diagnoses during the study period is concerning and suggests a subgroup at particularly high risk. This pattern of repeated infections may contribute to the spread of STIs within sexual networks and increases the risk of complications such as pelvic inflammatory disease or epididymitis [11].

The low rates of consistent condom use reported by our participants (28% for anal sex, 22% for vaginal sex) are concerning but not unexpected. Several studies have documented decreased condom use among PrEP users, often attributed to a phenomenon known as risk compensation [14,15]. While PrEP effectively prevents HIV transmission, this behavioral change may contribute to increased STI incidence.

Implications for PrEP Programs

Our findings highlight the critical importance of integrating comprehensive STI services into PrEP programs. This integration should include:

1. Enhanced STI Education: PrEP users should receive thorough education about STI risks, symptoms, and prevention strategies. This education should emphasize that while PrEP prevents HIV, it does not protect against other STIs.
2. Frequent and Comprehensive Screening: The high STI prevalence in our cohort supports the current CDC recommendation for quarterly STI screening in PrEP users [16]. Our results also underscore the importance of multi-site testing, particularly for MSM.
3. Prompt Treatment and Partner Notification: Rapid identification and treatment of STIs, coupled with efficient partner notification systems, are crucial to breaking chains of transmission.
4. Targeted Interventions: Given the identified risk factors, PrEP programs should consider implementing age-specific interventions and strategies to address high-risk sexual behaviors.
5. Promotion of Combination Prevention: While recognizing the challenges of promoting condom use in the context of PrEP, healthcare providers should continue to emphasize the benefits of combining PrEP with other prevention methods, including condoms and regular testing.

Broader Public Health Implications

The high STI prevalence observed in our PrEP cohort raises concerns about the potential for increased STI transmission at a population level as PrEP use expands. This could have significant public health implications, including:

1. Antibiotic Resistance: Increased STI incidence may contribute to the development and spread of antibiotic-resistant strains, particularly of Neisseria gonorrhoeae [17].
2. HIV Transmission Risk: While PrEP is highly effective, suboptimal adherence combined with high STI rates could theoretically increase HIV transmission risk in some cases, as STIs can facilitate HIV transmission [18].
3. Healthcare Resource Utilization: Higher STI rates among PrEP users may lead to increased demand for STI testing and treatment services, potentially straining healthcare resources.
4. Long-term Complications: Repeated or untreated STIs can lead to various complications, including infertility and increased risk of certain cancers [19].

Limitations and Future Directions

Our study has several limitations that should be considered. The single-center design and relatively small sample size limit the generalizability of our findings. The retrospective nature of the study may have introduced selection bias, and we relied on self-reported sexual behaviors, which can be subject to recall and social desirability biases.

Future research should focus on larger, multi-center prospective studies to better characterize STI trends among PrEP users over time. Studies comparing STI rates between PrEP users and matched non-users would help clarify the specific impact of PrEP use on STI risk. Additionally, research is needed to develop and evaluate interventions aimed at reducing STI risk in the context of PrEP use, such as novel approaches to promoting combination prevention strategies.

Conclusion

This single-center study of 100 Pre-Exposure Prophylaxis (PrEP) users reveals a high prevalence of Sexually Transmitted Infections (STIs), with 42% of patients diagnosed with at least one STI over a 12-month period. These findings underscore the complex interplay between HIV prevention strategies and broader sexual health outcomes, highlighting both the successes and challenges of PrEP implementation. The effectiveness of PrEP in preventing HIV transmission is well-established and represents a significant advancement in public health. However, our results suggest that PrEP use may be associated with an increased risk of other STIs, possibly due to behavioral changes such as reduced condom use and increased number of sexual partners. This emphasizes the critical need for a comprehensive approach to sexual health in the era of PrEP.

Key takeaways from our study include:

1. High STI prevalence: The observed 42% STI prevalence rate is substantially higher than in the general population, indicating a need for enhanced STI prevention efforts among PrEP users.
2. Multiple infections: 15% of patients experienced multiple STI diagnoses during the study period, suggesting a subgroup at particularly high risk.
3. Anatomical distribution: The high proportion of rectal infections highlights the importance of multi-site testing, especially for men who have sex with men (MSM).
4. Risk factors: Younger age, higher number of sexual partners, and inconsistent condom use were identified as independent risk factors for STI diagnosis.

These findings have important implications for PrEP programs and public health strategies:

1. Integration of services: PrEP provision should be fully integrated with comprehensive STI prevention, screening, and treatment services
2. Enhanced education: PrEP users need thorough education about STI risks and the importance of combination prevention strategies
3. Frequent screening: Our results support current guidelines recommending quarterly STI screening for PrEP users
4. Targeted interventions: Age-specific and risk-based interventions should be developed to address high-risk sexual behaviors in the context of PrEP use
5. Public health considerations: The potential for increased STI transmission at a population level as PrEP use expands must be carefully monitored and addressed

While our study has limitations, including its single-center design and relatively small sample size, it provides valuable insights into the sexual health challenges faced by PrEP users. Future research should focus on larger, multi-center prospective studies to better characterize STI trends among PrEP users over time and to develop and evaluate targeted interventions.

In conclusion, PrEP represents a powerful tool in the fight against HIV, but it must be implemented as part of a holistic approach to sexual health. By addressing both HIV and other STIs concurrently, we can maximize the public health benefits of PrEP while minimizing potential unintended consequences. Healthcare providers, public health officials, and PrEP users must work together to ensure that HIV prevention efforts do not come at the cost of increased vulnerability to other STIs. Only through such a comprehensive approach can we achieve optimal sexual health outcomes in the PrEP era (Fig. 1).

Table 1: Maternal baseline characteristics of neonates (N=52).

Baseline characteristics of the mothers of studied neonates are presented in Table 1. Mean maternal age was 27.36+ 5.18 years. Among them 56.1% were multipara, most of them (65.2%) had singleton pregnancy and had LSCS (83.3%). Fifty mothers (75.8%) got complete course of antenatal steroid.

Table 2: Neonatal baseline characteristics of studied neonates (N=52).

Baseline characteristics of the studied neonates were presented in Table 2. Mean gestational age was 36.54 ± 1.63 weeks and mean birth weight was 2722.5 ± 660 gram. Most of the neonates belonged to term (51.9%) and normal birth weight (> 2500 g). Male and female ratio was 1.1:1. Most of them were appropriate for gestational age (65.4%). Five newborns had intrauterine growth restriction, about one third (34.6%) neonates needed neonatal intensive care admission, eight newborn had APGAR score less than 7/10 at 1^st minute after birth.

Table 3: Laboratory parameters and Clinical characteristics of neonates (N=52).

Figure 1: Metabolic, hematological and clinical findings among studied neonates (N=52).

Clinical characteristics of enrolled neonates were shown in Table 3. Near about one third had hyperbilirubinemia (31%), thereafter hypoglycemia and polycythemia was found in 15% neonates, hypocalcemia was in 13.5% and few neonates had hypomagnesemia (9.6%). The most common morbidity of the studied newborns was sepsis (17.3%), thereafter respiratory distress (11.5%), around 4% patients had seizure and 2% newborn developed shock as a complication. Figure 2 is showing the percentage of metabolic, hematological and clinical findings among studied neonates.

Figure 2: Neurodevelopmental outcome of studied neonates (N=52).

The overall neurodevelopmental outcome of the infants of diabetic mother is shown in figure 3. Most of the infants (n=38) had favorable outcome, which is 73.1% of studied neonates. More than one fourth (26.9%) infants (n=14) had adverse neurodevelopmental outcome.

Most of the newborns had favorable outcome, 98% in cognition, 79% in language and 90% in motor development. Among the adverse outcome of three domain, 2% had cognitive delay, around one fourth had language delay (21.2%) and few had delay in motor domain (9.6%) (Table 4). In Fig. 3 is showing the difference between adverse and favorable outcome among the three domains (Table 5).

Table 4: Neurodevelopmental Outcome of enrolled neonates in follow up at 9 months of age (N= 52).

Figure 3: Neurodevelopmental outcome of infants at 9 months follow up.

Table 5: Comparison of Maternal factors between adverse and favorable outcome group (N= 52).

Qualitative data were presented as number and percentage, Quantitative data were presented as mean ± SD. Statistical test: Chi square test and Independent t-test.

Maternal parameters were compared between the favorable and adverse outcome group. There were significant difference between two groups in respect to drugs (insulin or OHA) used in gestational diabetes mellitus and maternal glycemic control. (p-value- 0.041 and 0.000). Regarding other parameters such as maternal age, mode of delivery and hypertension there were no significant difference found (Table 6).

Table 6: Comparison of neonatal baseline characteristics between adverse and favorable outcome group (N= 52).

Qualitative data were presented as number and percentage, Quantitative data were presented as mean ± SD.

Statistical Test

Chi square test and Independent t-test Neonatal baseline characteristics were compared between the favorable and adverse outcome group. There were no significant difference between two groups in respect to birth weight, gestational age category, fetal growth at birth, intrauterine growth restriction, gender distribution, APGAR score and need for NICU admission (Table 7).

Table 7: Multivariate logistic regression analysis of factors affecting neurodevelopmental outcome in enrolled neonates (N=52).

Multivariate regression analysis of factors affecting neurodevelopmental outcome in the studied newborns showed only maternal glycemic control was significantly associated with adverse neurodevelopmental outcome among the studied neonates. (p-value=0.001).

Discussion

It is well established that diabetes has been associated with maternal and perinatal morbidity and mortality both in short and long term. In this prospective observational study, 52 infants of gestational diabetic mother were recruited to see the association between GDM and child’s neurodevelopment and they were followed up at their 9 months of age. To justify whether any maternal factors and neonatal complications affecting the neurodevelopment of infant, some maternal factors and newborn’s clinical, metabolic and hematological profile were seen. Newborn who developed any co-morbidities like sepsis, jaundice and/or respiratory distress were admitted in NICU and other’s were kept mother’s side in the postnatal ward. Both were followed up according to NICU protocol during hospital stay. Neonatal hypoglycemia, maternal poor glycemic control and maternal use of drugs for GDM was the predictive factors of adverse neurodevelopment. Among the predictive factors such as hypoglycemia, no baby developed symptomatic hypoglycemia as because early introduction of frequent feeding was ensured. Mother who needed drugs Mother who needed drugs for GDM either took insulin or Metformin as oral hypoglycemic agent. Though most of the mother had good glycemic control, adverse outcome was mostly found among the infants of mother who had poor glycemic control and it was significantly associated with adverse developmental outcome in this study. This study includes newborn with gestation 34 weeks or more, as less than 34 weeks neonates are more vulnerable to develop several serious co morbidities like sepsis, respiratory distress, jaundice, perinatal asphyxia, congenital anomalies, specially in this subcontinent. Similarly, in a multicenter study done in Montreal, Canada and Dublin, Ireland, they also excluded gestation of less than 32 weeks to avoid poor developmental outcome due to other co-morbidities [5]. In this study, the mean gestational age was 36.54 ±1.63 weeks. It is close to a previous study, where the mean gestational age was 37.92 ± 1.65 [9]. In the present study, the mean birth weight was 2722.5 ± 660 g which was lower than the previous study where the mean birth weight was 3596 ± 494 g. This difference can be explained by that, in their study they recruited more number of obese mother getting insulin. In this study, lower segment cesarean section was needed in 90.4% cases which was quite higher than the previous study where LSCS was needed only for 51.1% cases [15]. This higher percentage of the LSCS may be explained by the fact, that this study was conducted in a tertiary care hospital, where most of the complicated pregnancies were dealt by the Feto-maternal medicine unit, with necessitating LSCS. However, a study explained that if LSCS done electively, it is associated with improved neonatal outcomes in terms of better APGAR scores at 5 minutes [15]. This findings was consistent with the present study, that this study found no low 5 min APGAR score among studied neonates.

In this study, more than half neonates were delivered at term (51.9 %), on the other hand a previous study found preterm deliveries were higher (51.1%) [20]. This difference can be explained by the fact that, in their study all diabetic mothers were with coexisting medical complications like pregnancy induced hypertension, chronic heart and renal disease. In this study 65.4% babies were AGA which is quite similar to a previous study done in Tamil Nadu, India, where they found 68% babies were age appropriate [21]. Maternal factors responsible for poor neurodevelopmental outcome in infants were evaluated in this study. As maternal complications, this study found (34.6 %) mother were hypertensive which is consistent with a previous study which showed that up to 10-30 % of women with gestational diabetes may develop hypertension in pregnancy [12]. In this study, 11.5 % mother had polyhydramnios which is similar to a previous study where they found that incidence of polyhydramnios is 11.6% [13]. In this study, 48.1% mother needed insulin or oral hypoglycemic agent as medication, where a study showed 57.1% mother needed insulin [14]. This contradictory findings can be explained by higher number of obese mother were included in their study. This study showed 13% diabetic mother had poor glycemic control which is differed from the previous study done in Tamil Nadu, India in 2018, where they got 58.1% mother had poor glycemic control [10]. This difference may be due to the fact that, they included all the mother getting insulin who were obese and overweight. When neonatal clinical and laboratory parameters were seen, this study found hypoglycemia was the second most common complication present in 15.4 % of patients. This result is not consistent with the result of a study where they found hypoglycemia was the most common complication among IDM and seen in 71.4% of neonates [15]. This difference can be explained by the fact that, this study was done in a tertiary level hospital where all the babies were strictly followed up in postnatal ward and frequent feeding was ensured and blood glucose level was checked routinely, which decreased the chance of developing hypoglycemia. Several studies have agreed that the incidence of hypoglycemia in infants of gestational diabetic mother was 12.9% to 59.4% [16-18]. In the present study hyperbilirubinemia was found as the most common complication seen in 30.8% of neonate where in a previous study they found 66.7% hyperbilirubinemia in IDM [15]. This larger difference may be due to strict monitoring of jaundice by measuring serial transcutaneous bilirubin and frequent follow up in this tertiary level hospital reduce the severity of jaundice. This study found polycythemia in 15.4 % cases, this findings was quite near to a study where they found 11% cases of polycythemia in IDMs [15]. In the present study 13.5% IDMs developed hypocalcemia, where in another study they found hypocalcemia in 22% of IDMs [15]. This difference may be explained by the fact, that they included most of the preterm babies in their study. Regarding clinical parameter this study found sepsis was the most common (17.3%) and respiratory distress was the second most common (11.5%) morbidities among IDMs, which differed from the study done in California, Los Angeles, where they showed respiratory distress was more common and near about 48%, this bigger difference can be explained by the fact that they recruited all the newborns below 34 weeks in their study and respiratory distress is common in preterm babies [19]. This study showed neurodevelopmental outcome at 9 months by BSID III where cognitive, expressive and receptive language, fine and gross motor development was seen. There are several studies done in different subcontinent to see the neurodevelopmental outcome but they use other scale to assess the outcome like Bruininks Oseretzky test, Wechsler Preschool and Primary Scale of Intelligence, Ages and Stages Questionnaire (ASQ), TanakaBinet IQ scores and BSID II(mental developmental index and psychomotor developmental index). So far, only two studies used BSID III to see the outcome among diabetic mother.

This study found overall adverse outcome in 26.9% infants among them 1.9% had cognitive delay, which differed from the study where they found 6.5% delay in cognitive skills [12]. This difference may be in respect to the fact, that in this study more number of mother had good glycemic control. Also some author given this explanation that cognitive ability of offspring born to mothers with well controlled  diabetes  is  usually  normal  unless complicated by other comorbidities. The present study got 9.6% infants with motor delay, which was also lower from a study, where they found 14.6% and another study found 12.6% delay in motor development [12,31]. This lower percentage in this study also can be explained by this fact that having more number of mother with good glycemic control in this study. This study found language delay in 11% infants, this result differed in respect of lower percentage from the study where they found 26% of children born to diabetic mothers having low language abilities [19]. But this findings was in agreement with some studies in terms of that all these studies including the present study found a higher incidence of developmental language delay in infants born to diabetic mothers [19,20]. This finding was contradicting by a study where they found that children born to mothers with diabetes had a higher risk of developmental delay mainly in gross motor skills [13]. In a contrary, when some studies done with older children, showed no significant differences in developmental outcomes among the diabetic mother [12]. This can be explained by the statement given by a study where they stated that, younger children have poorer neurological functions as there is a gap in maturation of central nervous system, but older children can compensate for slight motor impairment as because this gap will compensate with age [20]. This statement was established in some studies as they didn’t find any difference in cognitive scores in older children from 4 to 13 years born to GDM mothers [20]. When neonatal factors were compared with adverse and favorable outcome only hypoglycemia was found significantly associated with adverse outcome. This findings was consistent with a systematic review by where they found that neonatal hypoglycemia was significantly associated with developing long lasting adverse neurodevelopmental outcome.36 When maternal factors were compared with adverse and favorable outcome, maternal poor glycemic control and maternal use of drugs for GDM where found significantly associated with adverse outcome. In contrast with this findings a study showed that no significant difference was associated with maternal use of drugs for GDM [37]. This can be explained by the fact, that they only studied with the mother where on medication either oral (metformin) or insulin. When multivariate logistic regression was done among these factors only poor glycemic control was found significantly associated with adverse neurodevelopmental outcome. This finding was in agreement with several studies and systematic review [7,11,19]. Like this study, several studies were done to see the neurodevelopmental outcome among infants born to mother with gestational diabetes and most of the study was consistent with this statement that maternal gestational diabetes can adversely effect neurodevelopmental outcome of infants. Which is consistent with the findings of present study.

Conclusion

Maternal gestational diabetes can adversely affect on their infants neurodevelopment. Among the adverse outcome of three domains language delay was most common. Neonatal hypoglycemia, maternal poor glycemic control and use of drugs for GDM are significant predictors of adverse neurodevelopmental outcome in infants of gestational diabetic mother. Among them maternal poor glycemic control was significantly associated with adverse neurodevelopmental outcome.

Conflict of Interest

The authors declare that they have no conflict of interest.