HIV-1 Infection Trends in Lower Silesia (2010–2020): A Comparative Analysis of Women and Men and the Urgent Need for Enhanced Screening

Introduction

The human immunodeficiency virus (HIV) continues to represent a substantial global health concern, affecting an estimated 37.7 million individuals across the globe.¹ By the end of 2023, 65% of people living with HIV were in Africa, with the highest concentration in sub-Saharan region.^2,3 Women and girls account for over half of the cases globally, largely due to the significant proportion of infected women in Africa.⁴ The underlying causes include, unequal access to healthcare services, early initiation of sexual activity, physiological and immunological factors that increase women’s susceptibility to HIV.^5–8

The epidemiology of HIV exhibits considerable regional variation. In the European Economic Region, the majority of new HIV infections are among men, primarily due to sexual transmission between men who have sex with men (MSM).⁹ In Poland, as of 2021, 79% of individuals infected with HIV were male.¹⁰ Notwithstanding this predominance, there has been a gradual increase in the prevalence of women diagnosed with HIV, rising from 16% in 2016 to 20% in 2021.¹⁰

In Poland, as in Europe, the most common route of infection among women is heterosexual contact.¹¹ Despite the fact that women are in the minority¹¹ among newly diagnosed patients in Poland, their health status at diagnosis is significantly worse than men’s, meaning that women are much more often diagnosed as late presenters.^12–14 Unfortunately, late diagnosis contributes to a higher risk of AIDS and death,^15,16 indicating that women should become a key population for HIV prevention and detection in the forthcoming years.

The Lower Silesian Voivodeship represents a significant region for epidemiological studies related to HIV in Poland. In 2021, 44% of individuals diagnosed with HIV in Poland were residents of the Masovia, Silesia, and Lower Silesian voivodeships.¹⁰ Furthermore, in 2021, the rate of new HIV diagnoses per 100,000 inhabitants in the Lower Silesian Voivodeship was the second highest in the country, at 6.28.¹⁷

The objective of this study is to undertake a comparative analysis of the clinical condition of women and men newly diagnosed with HIV-1 at three critical time points: 2010, 2016, and 2020, in the Lower Silesian Voivodeship. One of the specific objective, among others, is to determine the size of the odds ratio (effect of gender on late presenters (denoting individuals diagnosed with either a CD4+ T lymphocyte count <350 or with present opportunistic diseases)¹⁸ with its 95% CI. This will facilitate a deeper understanding of the dynamics of HIV-1 infection in Lower Silesia, and inform strategies to enhance screening and prevention efforts across the region.

Materials and Methods

A retrospective analysis was conducted using medical records from the largest HIV clinic in Wroclaw, Poland. The study included patients newly diagnosed with HIV-1 in 2010, 2016 and 2020. These specific years were chosen to allow a comparison of the clinical status of patients at the time of diagnosis over a decade at similar intervals (Table 1).

Table 1 Demographic, Clinical, and Serological Characteristics of People Living with HIV (PLWH), by Year (2010–2020)

The study group consisted of all patients with newly diagnosed HIV-1 infection who attended their first specialist appointment at the clinic in 2010, 2016 and 2020. Patients were included regardless of age, gender, or other sociodemographic factors, resulting in a sample size of 202. Exclusion criteria were previous or current antiretroviral treatment and previous treatment at another institution.

The data collected during the first visit, which was the only one included in this database, encompassed the following: demographic information (age and gender), the route of HIV-1 infection, baseline HIV-1 viral load, CD4+ T cell count, and the presence of acute retroviral syndrome (ARS). ARS was identified by the presence of specific symptoms, including fever, lymphadenopathy, headache, fatigue, myalgia, arthralgia, pharyngitis, nausea/vomiting, and diarrhea. Furthermore, data on AIDS-defining illnesses, as well as coexisting infections including Hepatitis B Virus (HBV), defined as Hepatitis B surface antigen (HBsAg) positive, Hepatitis C Virus (HCV), defined as anti-HCV antibodies positive and syphilis, defined as positive Venereal Disease Research Laboratory (VDRL) test, were collected.

The route of HIV-1 infection was categorized based on patient's medical history. Each patient was assigned one of the three routes of infection: heterosexual transmission (HTX), sexual transmission among men who have sex with men (MSM) and intravenous drug use (IDU).

The diagnosis of HIV-1 was confirmed through a two-step process: initial screening with an enzyme-linked immunosorbent assay (ELISA test) and confirmation with the Western Blot test. The ELISA test was also used to detect Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies.

The HIV-1 viral load was determined by means of a real-time PCR assay (COBAS TaqMan HIV-1 Test v. 2.0, Roche Diagnostics, Basel, Switzerland) and the CD4+ T cell count was determined by flow cytometry using a FACSCount system (Becton Dickinson, Franklin Lakes, NJ, USA).

The study was based on archived medical records, which were kept in connection with standard medical care and stored in accordance with the relevant regulations. Any data collected for the purposes of the study were processed in an anonymized form, and the principles of medical confidentiality were observed. The study has been conducted according to the Declaration of Helsinki and was approved by the Bioethical Committee of Wroclaw Medical University, Wroclaw, Poland, 36/2022.

Statistical Analysis

The assumption of normality of distribution (checked using the Shapiro–Wilk test) was not met, so the Mann–Whitney U-test (test performed using Statistica software, version 13.3.7521.1) was used to test for differences between groups for quantitative data. The median (Q1-Q3) was reported. To test for relationships between qualitative variables, the Pearson Chi-square test of independence was used when the expectancy assumption was met (n < 5 in ≤ 20% of cells) or the Fisher's exact test or Fisher-Freeman-Halton test. For tables larger than 2 × 2, a post hoc analysis was performed by counting the expected value for each cell and checking, which actual cell values differed from the expected values, without specifying which cells (using the R version 4.3.1, package “chisq.posthoc.test”). Qualitative data are presented by number of observations and percentages. Descriptive statistics for continuous data and for qualitative data were calculated in Statistica. Trend was examined with the Cochran–Armitage test (using the command “prop_trend_test(tab_count)”. The abbreviation C-A is used in the paper. The odds ratio (OR) on the contingency table and its confidence interval (lower 95% CI–upper 95% CI) last presenters (LP) between sexes were checked. A significance level α = 0.05 was adopted. Due to the multiple comparisons, a Bonferroni correction of the α for the Mann–Whitney U-test (and a Benjamini–Hochberg correction of the α for the Spearman correlation) were applied: α=0.017 and α=0.013.

Results

Characteristics of the Study Group

A total of 202 patients (27 (13.37%) women and 175 (86,63%) men) were included in the analysis: 43 (9 (20.93%) women and 34 (79.07%) men) in 2010, 80 (7 (8.75%) women and 73 (91.25%) men) in 2016 and 79 (11 (13.92%) women and 68 (86.08%) men) in 2020. One hundred twenty-eight (63.37%) of them acquired HIV-1 through male-to-male sexual contact, 34 (16.83%) through heterosexual contact, 20 (9.90%) through intravenous drug use and for 20 (9.90%) patients the route of infection remained unknown. Acute retroviral disease was diagnosed in 52 (25.74%) patients and AIDS in 39 (19.31%). In the analyzed group 26 (12.87%) patients were infected with HCV and 4 (1.98%) with HBV. Positive VDRL results were seen in 31 (15.35%) patients. Among the entire group of women, 6 (2.97%) were diagnosed with HIV-1 during pregnancy. In 2010, the median age of women was: 37.1 (30.1–41.1), in 2016: 28.6 (25.7–37.4), and in 2020: 34.5 (25.4–42.0). The median age for men was 33.6 (28.6–37.5), 31.4 (26.9–37.1), 32.9 (27.0–38.4), respectively. The median age for women of all 3 years is 34.51 (27.42–41.09) and for men 32.29 (26.96–37.53) (Table 1).

Route of Infection

Within the female population, HTX stands out as the primary mode of transmission, accounting for 44.44%, 57.14% and 90.91% of infections in 2010, 2016, and 2020, respectively. The differences are not statistically significant (Fisher’s test: p=0.342). It was noted that there was no trend (C-A test: C = 2.42, df = 1, p = 0.862). The number of women infected with HIV-1 through intravenous drug use (IDU) in the following years was: 33.33%, 28.57% and 0.00%, respectively. This difference is statistically insignificant (Fisher’s test: p=0.060). With the subsequent year of visit, the number of IDUs among women decreases (C-A test: C = 4.72, df = 1, p = 0.030).

In contrast, among males, homosexual contact (MSM) emerges as the predominant route of infection, constituting 52.94%, 80.82%, and 75.00% of cases in 2010, 2016 and 2020, respectively. The number of MSM is statistically significantly different with the year of the first visit for men (Chi-square test: Chi² = 10.59, df = 2, p = 0.005). A weak increasing trend was noted (C-A test: C = 3.90, df = 1, p = 0.048). The difference in the number of men infected through heterosexual contacts between years is statistically insignificant (5.88%, 8.22%, and 11.76% over the same years) (Chi² = 1.03, df = 2, p = 0.600). It was noted that there was no trend (C-A test: Chi² = 0.030, df = 1, p = 0.862). The difference in the number of men infected through intravenous drug use between years is statistically significant (Chi² = 24.85, df = 2, p < 0.001), declining from 29.41% in 2010 to 2.74% in 2016 and 4.41% in 2020.

Baseline Viral Load

The baseline viral load of men and women differed statistically significantly in 2010, where women had significantly higher viral load values. In 2016 and 2020, the median viral load in women was lower than in men, but no statistical significance was observed (Table 1, Supplementary Figure 1 A-F).

CD4+ T Cell Count by Year and by Gender

Over the years, women consistently had lower median CD4+ T cell counts compared to men (Table 1). For women, the median CD4+ T lymphocyte count over the 3 years was 250.00 (108.00–288.00), significantly lower than that for men - 431.00 (280.00–550.00) (Mann–Whitney U-test: z = 4.23, p < 0.001). This is due to the fact that the predominant route of infection in the study group was sexual transmission between MSM. Homosexual men were diagnosed at earlier stages of infection (defined as higher CD4+ T cell count values).

The CD4+ T cell count in women has increased in 2020 compared to 2010 and 2016. The CD4+ T cell count in women is least different from the CD4+ T cell count in men in 2020, with little difference between 2020 and 2010.

Approximately 77.78% of women and 36.57% of men were categorized as late presenters (LP), denoting individuals diagnosed with either a CD4+ T cell count <350 or with present opportunistic diseases.¹⁸ Women were 6 times more likely to be diagnosed as LP (OR: 6.07, 95% CI (2.34–15.82). Despite examining each year individually and aggregating data for the 3 years combined, no statistically significant disparity was observed between the incidence of late presenters and gender (Mann–Whitney U-test: z = 1.26, p = 0.210).

In addition, an analysis comparing CD4+ T lymphocytes levels among heterosexual men and women was performed. The difference is statistically insignificant overall and separately in 2010, 2016 and 2020 (Table 2).

Table 2 CD4+ T Cell Count Women and Men Infected by the HTX Infection Route

Acute Retroviral Disease (ARD)

ARD was diagnosed in 2010 in 1 woman (11.11%) and 6 men (17.65%), in 2016 in 2 women (28.57%) and 19 men (26.03%) and in 2020 in 1 woman (9.09%) and 23 men (33.82%).

Differences in the incidence of ARD in women and all men (Chi² = 0.00, df = 0, p = 1.000; Fisher’s test: p = 0.645) between years were not statistically significant. No trend was found in women and all men (C-A test: C = 0.04, df = 1, p = 0.852; C-A test: C = 3.10, df = 1, p = 0.078).

An increase in the incidence of ARD among only MSM was observed. In 2010, 11.11% among MSM reported during the interview the presence of ARD symptoms (such as fever, adenopathy, headache, fatigue, myalgia, arthralgia, pharyngitis, nausea/vomiting, diarrhea) in the past or demonstrated symptoms at the time of diagnosis. In 2016, the figure was 30.51% and in 2020 39.22%. The difference is statistically insignificant (Chi² = 4.18, df = 2, p = 0.124). A growing trend was found (C-A test: C = 30.8, df = 1, p < 0.001).

AIDS

Although a significant proportion of women (77.78%), compared to all men (36.57%), reported a lower CD4+ T cell count at baseline, this did not translate into a significant higher incidence of AIDS (29.63% vs 17.71%).

AIDS was diagnosed in 2010 in 1 woman (11.11%) and 5 men (14.70%), in 2016 in 4 women (57.10%) and 12 men (16.44%) and in 2020 in 3 women (27.27%) and 14 men (20.59%). The difference in AIDS prevalence between years in women (Fisher’s test p = 0.202) and men (Chi² = 0.68, df = 2, p = 0.713) is not statistically significant. No trend was found in women (C-A test: C = 0.48, df = 1, p = 0.489) and men (C-A test: C = 0.64, df = 1, p = 0.637).

Pregnancy

Among the analyzed group, there were cases involving pregnant patients as well. Specifically, there was one woman in 2010 (11%) and five women in 2020 (45%), all were infected through HTX contact. Notably, all these cases were detected during routine pregnancy screenings. The data underscores a critical observation: all pregnant patients were unaware of their HIV-1-positive status prior to conception.

HBV, HCV and Syphilis

In 2010–22.22% of women were co-infected with HCV, in 2016–42.86%, and in 2020, no infection was reported among women. The difference in HCV presence in women between years is statistically significant (Fisher’s test: p=0.012). The trend is downward and statistically significant (C-A test: C = 5.98, df = 1, p = 0.015).

In contrast, a marked decrease in HCV co-infection was observed in men. In 2010–35.29% were co-infected, in 2016–9.59% and in 2020–2.94%. The differences were statistically significant (Chi² = 2, df = 2, p < 0.001). The trend is downward and statistically significant (C-A test: C = 1.90, df = 1, p < 0.001).

HBV infection and syphilis were not detected in women in any of the years in question. Among men, no one was diagnosed with HBV infection in 2010 either, 1 (1.40%) man was diagnosed in 2016 and 3 (4.41%) in 2020. Among men, syphilis was diagnosed in 20.59% in 2010, 13.70% in 2016 and 20.59% in 2020.

Discussion

In the analyzed cohort, the proportion of women was 21% in 2010, decreased to 9% in 2016 and then increased to 14% in 2020. There was therefore no significant increase in their share of the total number of clinic patients. These figures reflect the trends observed nationwide.¹⁰ According to data from the National Health Fund in Poland, between 2012 and 2017, the share of women among people newly diagnosed with HIV infection fell from 19% to 15% and then gradually increased in subsequent years until it reached 21% in 2020.¹⁰ However, confirming whether this is a sustained change requires observation over a longer period of time.

In the total number of patients included in this study, there are far fewer women than men. In Poland in 2020, the ratio of men to women among new diagnoses was 5.5:1¹¹ while in the study population it was more than 6:1, similar to the Polish population. This relationship is due to the fact that the predominant route of infection both in Poland and across Europe is sex between men.¹¹

Among women, the primary mode of infection appeared to be HTX, whereas among men – MSM. We saw a decline in IDU as a mode of transmission for both genders. Concurrently, there was a rise in the proportion of infections acquired by women through heterosexual contact. These data are in line with European data.¹¹ The decrease in HIV incident infections among drug users is attributed to methadone substitution and needle exchange programs.¹⁹ It is worth noting that the cohort was located in a clinic with methadone substitution program for heroin users²⁰ and no barriers in access to it.

Despite the small number of infected female patients, their health condition at the time of diagnosis was worse than among males. While the statistical analysis did not reveal a significant relationship between delayed diagnosis and gender (due to the large number of women and men having CD4+ T cell counts close to 350), a noticeable disparity persists in the clinical conditions between female and male patients. This phenomenon has remained consistently observed over the analyzed years. Each year, the majority of women were late presenters (LP) (77.78% of all women), in contrast to all men, among whom LPs were a minority (36.57% of all men). Women were 6 times more likely to be diagnosed as LP. This is a result of the high proportion of MSM among all men, who were generally diagnosed quickly, which translates into higher CD4+ T cell counts. Late diagnosis is associated with worse prognosis, increased risk of further virus spread and high healthcare costs.^15,16 Nevertheless, in 2020, CD4+ T cell count among women exhibited an increase compared to previous years, with the smallest difference observed between women and men. This may suggest an improvement in the clinical situation of women. However, further research is required to establish the existence of a trend.

In an analysis based on data from 14 Polish Voluntary Counselling and Testing centers (VCTs) covering nearly 4,000 patients from 2000 to 2015, it was noticed that among women, the majority – 64.5% were diagnosed late. For comparison, among men, 56.3% of diagnoses were LPs. The risk of being diagnosed in a very advanced stage (ie, CD4+ <200/µL or AIDS stage) was also significantly higher for women (42.5% for women and 34.5% for men).¹²

In the subsequent Polish study analyzing data from 13 VCTs from 2016 to 2017, a statistically significant difference was seen between gender and the stage of the disease at the time of diagnosis. Women had a 1.5 times higher risk of delayed diagnosis than men.¹³ A Polish study from 2017, compiling data from 8 VCTs from 2006 to 2008, listed female gender among the factors for very late diagnosis (ie, CD4+ <200/µL or AIDS stage). Women had a 1.49 times greater risk than men of being diagnosed at a very advanced stage of infection.¹⁴

Notwithstanding, in a study from 2018 analyzing data from 2010 to 2014 from 31 European countries, risk factors for delayed diagnosis were identified and they included IDU and HTX transmission routes and being diagnosed in the Central or Eastern European region. Gender had no impact on late diagnosis.²¹ According to the ECDC report from 2020, in Europe, women accounted for 52% of late diagnoses. Among the factors associated with late diagnosis IDU and HTX transmission routes were also mentioned together with increasing age. As in the previous study, gender was not significant for delayed diagnosis.¹¹ Therefore, although European sources do not mention female gender among the risk factors for late diagnosis, studies done in Polish population prove the opposite.

Only in 2010 did the median viral load among women exceed that of men. However, for the remaining years, we observe the opposite trend. This reversal could be attributed to the lower number of men, particularly men who have sex with men (MSM), diagnosed in 2010. Subsequently, there is a notable surge in MSM seeking clinic services due to symptoms of Acute Retroviral Disease (ARD), resulting in higher viral loads among men in the following years. These data demonstrate the increasing awareness among MSM and the resulting rapid diagnosis. It is crucial to emphasize the findings of this analysis, which indicate a significant gender gap in ARD prevalence. The data unequivocally illustrate that ARD is substantially more prevalent among men. This suggests that men are more likely to be diagnosed early, enabling prompt treatment and thus yielding better outcomes and reduction in onward transmission. Unfortunately, women demonstrate a markedly lower incidence of ARD, potentially leading to delayed diagnosis and a worse clinical state upon seeking medical attention as well as onward transmission. This delay may stem from a lack of awareness of symptoms of ARD or a failure to acknowledge their sexual behaviors as the cause for HIV infection.²²

Nearly half of the women newly diagnosed with HIV at the clinic in 2020 were pregnant and referred by gynecologists. This underscores the critical importance of screening during pregnancy. According to the Recommendations of the Expert Team of the Polish Gynecological Society, pregnant women should be tested for HIV twice – up to the 10th week and between the 33rd and 37th week of pregnancy.²³ Based on data from 2018, only 25–30% of pregnant women receive the recommended tests.²⁴ This work serves as a plea to gynecologists to prioritize ordering screening tests for pregnant women, highlighting its immense importance from an epidemiological standpoint. Detecting infection in the mother allows for the rapid initiation of antiretroviral treatment, securing childbirth, and providing prophylactic treatment for the newborn, significantly reducing the risk of infection in children (<1%).²⁵

HBV infection and syphilis were undetected in female participants in all the years examined. The presence of these infections in men suggests additional, unexplored risk factors in this study. The absence of syphilis and HBV in women underscores the need for better education and improved detection methods in this group to achieve a more accurate understanding of the situation.

Women require attention from healthcare and government authorities. For years, they have been presenting to doctors at a more advanced stage than men. Research shows that individuals who are diagnosed late (and thus start antiretroviral treatment late) are at greater risk of AIDS and/or death.²⁶ Therefore, it is paramount to counteract this by raising awareness and promoting screening tests among women especially. In Poland, as well as globally, campaigns promoting screening, safer sex or pre-exposure prophylaxis (PrEP) mainly target MSM as a key population.²⁷ These actions are certainly justified and extremely important, unfortunately they create a sense among women that the HIV epidemic does not concern them. So, in effect they rarely consider getting tested for HIV or using appropriate prophylaxis.²⁸ We believe that women should now be the additional key population to be targeted. Doing so would make it possible to achieve a decline in HIV infections among women and improve their health, as has been achieved among MSM populations in recent years.^29–31

Conclusions

This study reveals significant gender disparities in HIV-1 diagnosis in the Lower Silesian Voivodeship, with women being six times more likely to be diagnosed as late presenters, compared to men. The worse clinical conditions at diagnosis observed in women highlight the need for targeted interventions. Enhanced screening, particularly in antenatal care, is essential to address these disparities. It is therefore recommended that public health initiatives expand their focus to include women in HIV prevention and screening efforts to improve outcomes and reduce incidence.