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PLOS One logoLink to PLOS One
. 2021 Oct 7;16(10):e0258383. doi: 10.1371/journal.pone.0258383

Characteristics of new HIV diagnoses over 1995–2019: A clinic-based study in Montréal, Canada

Katia Giguère 1,*, Maliheh Vaziri 2, Clément Olivier 2, Louise Charest 2, Jason Szabo 2, Réjean Thomas 2, Mathieu Maheu-Giroux 3
Editor: Shui Shan Lee4
PMCID: PMC8496787  PMID: 34618875

Abstract

Background

Characterization of populations at risk of acquiring HIV is required to inform the public health response to HIV. To identify potential changing needs in HIV prevention and care cascade, we aim to describe how the demographic profiles and exposure categories of newly diagnosed HIV positive individuals attending a large sexual health clinic in Montréal (Canada) evolved since the beginning of the antiretroviral therapy era in the mid-1990s.

Methods

Using diagnosis data from participants of the Clinique médicale l’Actuel cohort of HIV-positive patients, we examined the distribution of exposure categories (sexual orientation, sexual behaviours, injection drug use, being born in an HIV-endemic country) by gender and year of diagnosis. Time trends in mean age and in the proportion of patients with late (CD4 <350 cells/μL) or advanced stage (CD4 <200 cells/μL) of HIV infection at diagnosis were assessed through meta-regressions.

Results

A total of 2,612 patients diagnosed with HIV between January 1st, 1995 and December 31st, 2019 were included. Overall, mean age was 35 years (standard deviation: 10 years) and remained stable over time. The proportion of patients with advanced stage of HIV infection decreased from 16% in 1995 to 4% in 2019. Although men who have sex with men (MSM) consistently accounted for the highest proportion of new diagnoses (77%, 2,022/2,612 overall), their proportion decreased since 2013. There was also a concomitant decrease in the proportion of people who inject drugs, with none of the newly diagnosed participants reporting injection drug use since 2017, and an important increase in the proportion of patients born in an HIV-endemic country (24%, 7/29 in 2019), especially among women. Compared to patients from non-endemic countries, those from HIV-endemic countries were characterized by higher proportions of heterosexuals (88% vs 17%) and of women (52% vs 7%), and were twice likely to get diagnosed at an advanced stage of HIV infection (32% vs 15%).

Conclusions

In absolute numbers, MSM continue to account for the largest exposure category. However, patients from HIV-endemic countries, who tend to be diagnosed at later stages of HIV infection, constitute an increasing proportion of newly diagnosed individuals. These persons could face distinct barriers to rapid diagnosis. Tailoring HIV testing strategies and other prevention interventions to the specific unmet prevention needs of these individuals is warranted.

Introduction

Forty years after the first reported case of acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV) remains a global public health issue [1]. In 2019, a total of 2,122 new HIV diagnoses were reported in Canada, of which 646 (30%) were located in the province of Québec [2, 3]. In Québec, the burden is concentrated in Montréal with 9.1 new HIV diagnoses per 100,000 person-year in 2019 [3].

HIV diagnosis is the necessary first step in the HIV care cascade. Early diagnosis and treatment drastically reduce morbidities and improve survival among people living with HIV (PLHIV) [4]. Viral load suppression among treated PLHIV also prevents onwards transmission at population level [5]. Achievement of early diagnosis requires effective HIV testing services. Program data on the number of new HIV diagnoses also form the bedrock of quality HIV surveillance programs [6].

In Québec, HIV prevention is integrated into a comprehensive strategy for preventing sexually transmitted and blood-borne infections (STBBI) [7]. Over 1992–1997, the number of anonymous HIV testing centers was also gradually increased to cover all regions of the province in order to improve access to HIV testing and public health awareness [8, 9]. Most of HIV testing services, including HIV testing, pre- and post-test counselling, and linkage to appropriate HIV prevention, treatment and care services, were provided in free local community service centers and clinics that were run and maintained by the provincial government [9]. In 2004, the Québec Ministry of Health and Social Services called for more targeted screening approaches to increase HIV testing among the most vulnerable groups. These groups include: gay, bisexual, and other men who have sex with men (MSM), people who inject drugs (PWID), individuals born in an HIV-endemic country (e.g. Haïti), incarcerated individuals, youth in difficulty, female sex workers, and indigenous individuals [10].

In 2013, the World Health Organization recommended earlier initiation of antiretroviral therapy at a CD4 count ≤500 cells/μL for all adults and children above 5 years [11]. The same year, the Quebec Ministry of Health published its first interim guidance on pre-exposure prophylaxis (PrEP), stating that tenofovir/emtricitabine use could be beneficial to prevent HIV infection among seronegative MSM and serodiscordant couples [12], and in Montréal, the Clinique médicale l’Actuel (hereafter, l’Actuel), a large health center dedicated to the screening and treatment of STBBI since 1987, opened the first PrEP clinic in Canada, fostering access to and PrEP uptake, especially among MSM [1315].

In 2017, Montréal became the first Canadian Fast-Track City by signing the Paris Declaration, on fast-track to end AIDS by 2030 [16]. This ambitious commitment implies that the HIV care cascade be strengthened to ensure that 90% of PLHIV be diagnosed, 90% of diagnosed PLHIV be on treatment, and 90% of treated PLHIV be virally suppressed [16]. With different vulnerable populations facing diverse HIV prevention challenges, it is imperative to properly characterize the most affected populations in order to inform the public health response to HIV. Using 25 years of clinical data from l’Actuel, we aim to describe how the demographic profiles and exposure categories of newly diagnosed evolved over time since the beginning of the antiretroviral therapy (ART) era in mid-1990s. As the city contemplates how best to achieve HIV elimination, understanding shifts in the epidemiology of new diagnoses is warranted and will help identify unmet HIV prevention needs.

Methods

Setting

In 1999, l’Actuel established an open cohort that prospectively enrolled newly diagnosed HIV-positive individuals and retrospectively enrolled HIV-positive patients who had been diagnosed before 1999 (either at the clinic or outside the clinic) to study their demographic, behavioural, and clinical characteristics. In-person recruitment of participants is ongoing since 1999. All newly diagnosed HIV-positive adults (≥18 years) at l’Actuel are invited by a healthcare provider, in a second visit, to participate to the cohort. HIV-positive adults seeking care for the first time at l’Actuel since having been previously diagnosed somewhere else are also invited to participate. At the cohort’s inception, HIV-positive patients who were already followed at the clinic were invited to participate to the cohort at their first visit following its establishment. All participants provided a free and informed written consent before recruitment.

Participants

All HIV-positive patients who provided consent to participate to the cohort and had a known HIV-diagnosis date were eligible for inclusion in this study.

Variables and measurements

Self-reported date of birth, gender (men, women, transgender), ethno-cultural background, sexual orientation (heterosexual, homosexual, bisexual), and HIV exposure categories were assessed through face-to-face interview by a healthcare provider at enrolment. Exposure categories are not mutually exclusive and include sexual orientation (among men), sexual behaviours (condomless sex, having a partner at risk of HIV, having an HIV-positive partner, having multiple sexual partners, and having ever engaged in sex work), an history of injection drug use, being born in an HIV-endemic country (including Haïti, and sub-Saharan African and Caribbean countries), mother-to-child transmission, and accidental exposure (i.e., injury with a contaminated object).

For patients diagnosed at l’Actuel, the HIV-diagnosis date corresponds to the compiled date of the first HIV-positive test to the patient’s medical record at the clinic. For patients who were diagnosed before their first visit to l’Actuel, the date of the first HIV-positive test (diagnosis date) was self-reported. These patients were confirmed positive for HIV at the clinic before being enrolled in the cohort.

Age at diagnosis was calculated by subtracting the date of birth from the date of HIV diagnosis. CD4 count at HIV diagnosis was not available for patients diagnosed outside of l’Actuel clinic and, because this laboratory test was not widely used before the 1990s, for some patients diagnosed at the clinic. For diagnoses without a CD4 count measurement, we used the first CD4 count performed at the clinic–if measured within one year of diagnosis–to limit the number of missing observations.

Statistical analyses

Authors had full access to the de-identified and anonymized database population. Related variables were cross-validated in order to identify potential data misclassification and, if warranted, corrected by verifying the patients’ medical records.

Because we included both patients diagnosed at l’Actuel and patients initiating care at the clinic but diagnosed elsewhere, we expected that the last few years of data would be affected by right truncation, especially in 2020 due to the COVID-19 global pandemic. In addition, because patients diagnosed before the beginning of ART era, in mid-1990’s, could have passed away before recruitment to the cohort in 1999, left truncation could be an issue. To avoid these, analyses were restricted to patients diagnosed between 1995 and 2019.

We used descriptive analyses to characterize HIV-positive patients at diagnosis, overall and stratifying by gender (men, women) and origin (being born in an HIV-endemic country or not). We examined gender- and age-specific temporal trends along with the distribution of exposure categories (sexual orientation, sexual behaviours, history of injection drug use, origin). Time trends in the mean age and in the proportion of patients with late (CD4 cells count <350 cells/μL) or advanced stage of HIV infection (CD4 cells count <200 cells/μL) at diagnosis were assessed through meta-regressions, using calendar year as a continuous independent variable (linear). We used t-tests to evaluate the statistical significance, and the coefficient of determination (R2) to quantify the proportion of the variance explained by the independent variable. To assess the potential selection bias due to missing data for the CD4 count at diagnosis, we compared the characteristics at diagnosis between participants with and without CD4 count at diagnosis in a post-hoc sensitivity analysis. We used R 4.0.2 for all analyses and the R meta package for meta-regressions. This study was reported according to the REporting of studies Conducted user Observational Routinely-collected health Data (RECORD) statement guidelines (S1 Table).

Ethics approval

All analyses were performed on de-identified and anonymized data from participants who consented participation in the study. This study was approved by the Veritas Institutional and McGill University’s Faculty of Medicine Institutional Review Boards (A12-E84-18A).

Results

A total of 5,554 HIV-positive patients were invited to participate to the l’Actuel’s HIV-positive cohort between January 1999 and March 2020 (Fig 1). Of these patients, 3,502 (63%) consented to participate and were recruited to the cohort. Forty two patients with an unknown date of diagnosis, 845 patients diagnosed before 1995, and 3 patients diagnosed in 2020 were excluded from analyses. A total of 2,612 participants diagnosed between January 1st, 1995 and December 31, 2019 were analysed in this study. The distribution of new diagnoses is presented in Fig 2.

Fig 1. Flow diagram of participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal, Canada.

Fig 1

Fig 2. Distribution of new HIV diagnoses by gender and year, 1995–2019 (n = 2,612).

Fig 2

Characteristics of participants are presented by gender in Table 1. One participant who reported being transwoman, homosexual, and to have sex with men was included among women in all tables. Newly diagnosed participants were mostly MSM (homosexual or bisexual men, 77%, 2,022/2,612). Overall, exposure routes through sexual behaviours were highly prevalent (88%, 2,293/2,612). Among men and women, the most common exposures were condomless sex (59%, 1,384/2,342) and having a partner at risk of HIV (40%, 107/270), respectively. The proportions of women reporting an history of injection drug use (19%, 52/270) and being born in an HIV-endemic country (42%, 113/270) were, respectively, over two and eight times that observed among men. We observed no differences between the median CD4 count at diagnosis among men (440 cells/μL, interquartile range [IQR] = 280–620 cells/μL, n = 1,737) and women (420 cells/μL, IQR = 225–580 cells/μL, n = 153). However, higher proportions of women than men were diagnosed at a CD4 count <350 cells/μL (39% vs 35%) or at a CD4 count <200 cells/μL (20% vs 15%).

Table 1. Characteristics of patients at HIV diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal (Canada), stratified by gender (n = 2,612), 1995–2019.

Overall Men Women a
Characteristics n = 2,612 n = 2,342 n = 270
n (%) n (%) n (%)
Mean age, years (SD) 35 (10) 36 (10) 33 (10)
Ethno-cultural background
    Caucasian 960 (37) 909 (39) 51 (19)
    Black 244 (9) 129 (6) 115 (43)
    Hispanic 183 (7) 175 (8) 8 (3)
    Asian 66 (3) 65 (3) 1 (0.4)
    Native 9 (0.3) 8 (0.3) 1 (0.4)
    Other 51 (2) 48 (2) 3 (1)
    Unknown 1,099 (42) 1,008 (43) 91 (34)
Sexual orientation
    Homosexual 1,876 (72) 1,874 (80) 2 (1)
    Heterosexual 590 (23) 328 (14) 262 (97)
    Bisexual 146 (6) 140 (6) 6 (2)
Exposure category b
    Sexual behaviours 2,293 (88) 2,129 (91) 164 (61)
        Condomless sex 1,449 (56) 1,384 (59) 65 (24)
        Having a partner at risk of HIV c 784 (30) 677 (29) 107 (40)
        Having an HIV-positive partner 506 (19) 438 (19) 68 (25)
        Having multiple sexual partners (>1) 680 (26) 663 (28) 17 (6)
        Having ever engaged in sex work 73 (3) 50 (2) 23 (9)
    Injection drug use 271 (10) 219 (9) 52 (19)
    Born in an HIV-endemic country 219 (8) 106 (5) 113 (42)
    Contaminated blood transfusion 6 (0.2) 4 (0.2) 2 (1)
    Other d 10 (0.4) 8 (0.3) 2 (1)
CD4 count, cells/μL (n = 1,890)
    Median (IQR) 440 (280–620) 440 (280–620) 420 (225–580)
    ≥500 779 (41) 722 (42) 57 (37)
    350–499 447 (24) 411 (24) 36 (24)
    200–349 369 (20) 340 (20) 29 (19)
    50–199 223 (12) 198 (11) 25 (16)
    <50 72 (4) 66 (4) 6 (4)

SD: Standard deviation, IQR: interquartile range.

a Women include one transwoman who reported being homosexual and to have sex with men.

b Categories are not mutually exclusive.

c Partners at risk of HIV include people who inject drugs, HIV-positive individuals, individuals born in an HIV-endemic country, bisexuals, sex workers, and hemophiliacs.

d Other includes accidental exposure and mother-to-child transmission.

From 1995 to 2019, the overall mean age at diagnosis was 35 years (standard deviation [SD]: 10 years) and remained stable over time (p-trend = 0.44, R2 = 5%). Statistically significant positive trends in mean age at diagnosis were observed among women (Fig 3A, p-trend = 0.04, R2 = 25%), heterosexual men (p-trend<0.001, R2 = 100%), and PWID (p-trend = <0.001, R2 = 100%) (S1 Fig). The proportion of newly diagnosed individuals aged ≥45 years increased over time, whereas this age group accounted for 15% of new diagnoses before 2009, but for more than 20% of yearly new diagnoses from 2009 onwards (Fig 3B).

Fig 3. Evolution of age at HIV diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal (Canada) over 1995–2019 (n = 2,612).

Fig 3

Panel A displays the mean age at diagnosis stratified by gender for each calendar year. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Linear time trends (p-values) were assessed by the mean of t-tests within univariate meta-regressions where the year of diagnosis was input as a continuous predictor variable. Panel B shows the underlying age distributions, categorized in ten groups, for both genders combined.

The relative distribution of exposure categories shifted since 1995 (Fig 4). Among men, although MSM always accounted for the highest proportion of new diagnoses, the proportion of heterosexual men increased since 2013, reaching 18% (4/22) in 2019 (Fig 4A). While exposure through sexual behaviours remained highly prevalent (>75%) over time among men (Fig 4B left), their prevalence tended to vary among women, but have remained under 50% since 2016 (Fig 4B right). Among both men and women, there was a decrease in the proportion of PWID and, since 2017, none of the newly diagnosed participants reported injection drug use (Fig 4C). Although the yearly absolute number of newly diagnosed participants born in an HIV-endemic country did not seem to increase since late 1990’s and remained under 15, there was an important increase in their proportion, especially among women (Fig 4D). Of the 32 women diagnosed from 2015 to 2019, 63% were born in an HIV-endemic country.

Fig 4. Prevalence of exposure categories at HIV diagnosis among participants to the HIV-positive cohort at the Clinique médicale L’Actuel in Montréal, Canada, over 1995–2019.

Fig 4

For panels A to D, the left and right figures present proportions among all men (n = 2,342) and among all women (n = 270), respectively. Sexual behaviours include condomless sex, having a partner at risk of HIV, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work.

The proportion of patients diagnosed with a CD4 count <350 cells/μL could be decreasing over time for different exposure categories (S2 Fig) and gender (Fig 5A) but linear trends were not statistically significant. Overall, the proportion of patients with a CD4 count <200 cells/μL decreased from 16% in 1995 to 4% in 2019 (p-trend = 0.004, R2 = 75%). Negative linear trends in late diagnosis (<200 cells/μL) were also observed among all men (p-trend = 0.004, R2 = 70%, Fig 5B), homosexual men (p-trend = 0.005, R2 = 100%), patients having risky sexual behaviours (p-trend = 0.006, R2 = 100%), patients not using injection drugs (p-trend = 0.007, R2 = 100%), and patients born in an non-endemic country (p-trend = 0.002, R2 = 100%; S3 Fig).

Fig 5. Trends in the proportion of patients with late or advanced stage of HIV infection at diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal, Canada, stratified by sex (n = 1,890), 1995–2019.

Fig 5

Late stage of HIV infection (A) is defined as a CD4 count <350 cells/μL, and an advanced stage (B), as a CD4 count <200 cells/μL. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate meta-regressions where the year of diagnosis was input as a continuous predictor variable.

As we observed a shift in new HIV diagnoses towards individuals born in HIV-endemic countries, we compared the characteristics of participants at HIV diagnosis by origin and gender (Table 2). Among all newly diagnosed participants since 1995, a total of 219 (8%) were born in an HIV-endemic country, of whom 179 reported the name of their country. Of those 179 participants, the great majority were born in a sub-Saharan African country (59%) or in Haïti (30%). Men from HIV-endemic countries were mostly heterosexual (75%, 80/106) contrary to men from non-endemic countries who mostly reported being homosexual (83%, 1,852/2,236). While a third (33%, 52/157) of women from a non-endemic country reported injection drug use, none did so among women born in an HIV-endemic country. Both men and women born in HIV-endemic countries tended to have lower CD4 counts at diagnosis than their counterparts from non-endemic countries (Table 2). However, men born in HIV-endemic countries had the lowest median CD4 count of all (285 cells/μL; IQR = 158–463 cells/μL, n = 72) and the higher proportions of late diagnoses with 59% and 37% of them being diagnosed with CD4 counts <350 cells/μL and <200 cells/μL, respectively.

Table 2. Characteristics of patients at HIV diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal (Canada), stratified by origin and gender (n = 2,612), 1995–2019.

Born in a non-endemic country Born in an HIV-endemic country
Overall Men Women Overall Men Women a
n = 2,393 n = 2,236 n = 157 n = 219 n = 106 n = 113
n (%) n (%) n (%) n (%) n (%) n (%)
Mean age, years (SD) 36 (10) 36 (10) 34 (11) 34 (10) 35 (10) 33 (10)
Ethno-cultural background
    Caucasian 956 (40) 907 (41) 49 (31) 4 (2) 2 (2) 2 (2)
    Black 46 (2) 36 (2) 10 (6) 198 (90) 93 (88) 105 (93)
    Hispanic 175 (7) 168 (8) 7 (5) 8 (4) 7 (7) 1 (1)
    Asian 65 (3) 64 (3) 1 (0.6) 1 (0.5) 1 (1) 0 (0)
    Native 9 (0.4) 8 (0.4) 1 (0.6) 0 (0) 0 (0.0) 0 (0)
    Other 48 (2) 48 (2) 0 (0) 3 (1) 0 (0.0) 3 (3)
    Unknown 1,094 (46) 1,105 (47) 89 (57) 5 (2) 3 (3) 2 (2)
Sexual orientation
    Homosexual 1,853 (77) 1,852 (83) 1 (0.6) 23 (11) 22 (21) 1 (1)
    Heterosexual 398 (17) 248 (11) 150 (96) 192 (88) 80 (75) 112 (99)
    Bisexual 142 (6) 136 (6) 6 (4) 4 (2) 4 (4) 0 (0)
Exposure category b
    Sexual behaviours 2,214 (93) 2,085 (93) 129 (82) 79 (36) 44 (42) 35 (31)
        Condomless sex 1,415 (59) 1,364 (61) 51 (33) 34 (16) 20 (19) 14 (12)
        Having a partner at risk of HIV c 735 (31) 653 (29) 82 (52) 49 (22) 24 (23) 25 (22)
        Having an HIV-positive partner 477 (20) 425 (19) 52 (33) 29 (13) 13 (12) 16 (14)
        Having multiple sexual partners (>1) 671 (28) 654 (29) 17 (11) 9 (4) 9 (9) 0 (0)
        Having ever engaged in sex work 72 (3) 49 (2) 23 (15) 1 (0.5) 1 (1) 0 (0)
    Injection drug use 270 (11) 218 (10) 52 (33) 1 (0.5) 1 (1) 0 (0)
    Contaminated blood transfusion 4 (0.2) 3 (0.1) 1 (0.6) 2 (1) 1 (1) 1 (1)
    Other d 8 (0.3) 6 (0.3) 2 (1) 2 (1) 2 (2) 0 (0)
CD4 count, cells/μL (n = 1,890)
    Median (IQR) 445 (290–620) 447 (290–620) 430 (280–600) 315 (168–502) 285 (158–463) 392 (198–545)
    ≥500 745 (42) 706 (42) 39 (42) 34 (26) 16 (22) 18 (30)
    350–499 419 (24) 398 (24) 21 (23) 28 (21) 13 (18) 15 (25)
    200–349 341 (19) 324 (19) 17 (18) 28 (21) 16 (22) 12 (20)
    50–199 191 (11) 177 (11) 14 (15) 32 (24) 21 (29) 11 (18)
    <50 62 (4) 60 (4) 2 (2) 10 (8) 6 (8) 4 (7)

SD: Standard deviation, IQR: Interquartile range.

a Women include one transwoman who reported being homosexual and to have sex with men.

b Categories are not mutually exclusive.

c Partner at risk of HIV includes people who inject drugs, HIV-positive individuals, individuals born in an HIV-endemic country, bisexuals, sex workers, and hemophiliacs.

d Other includes accidental exposure and vertical acquisition.

We compared the characteristics of participants with and without CD4 count at diagnosis in a post-hoc sensitivity analysis (S2 Table). Compared to the group of participants with missing data for the CD4 count at diagnosis, the group without missing data tended to be older, had slightly higher proportions of men, MSM, and exposure through sexual behaviours, and lower proportions of Black patients, PWID, and patients born in an HIV-endemic country.

Discussion

HIV elimination efforts should be based on a granular understanding of shifts in epidemiology of this virus. Using clinical data spanning 25 years, this study highlights the changing portrait of the epidemic. First, the proportion of individuals belonging to the MSM exposure category, along with those with an history of injection drug use, decreased through time. Second, people born in HIV-endemic countries now constitute an increasing share of all new diagnoses, especially among women. Third, they tend to be diagnosed at later stages of HIV infection.

In Canada, MSM have been historically disproportionally affected by HIV. Our results suggest that, although MSM always accounted for the highest proportion of new diagnoses, their absolute number and proportion are decreasing since 2013. This trend is consistent with the decrease in the number of new diagnoses among MSM reported at the provincial level, and the decrease observed in the proportion of gay, bisexual and other MSM among newly diagnosed individuals in the rest of Canada [3, 6]. Such decrease could potentially be explained at least in part by the scale-up of antiretroviral therapy following the World Health Organization’s recommendation towards earlier treatment initiation, and by the introduction of PrEP in Montréal [12], fostering access to and uptake of PrEP, especially among MSM [1315].

We also observed a decline in the proportion of newly diagnosed PWID in our study, especially since the early 2000s. A previous longitudinal study among PWID in Montréal has shown an annual HIV incidence decline of 0.06 cases/100 person-years prior to 2000 followed by a 4-fold more rapid annual decline from 2000 onward [17]. These reductions in proportion of PWID and in HIV incidence may be largely related to changes and enhancements in HIV prevention in the late 1990’s. Montréal was one of the firsts North American cities to implement needle and syringe exchange programs to prevent sharing of injection materials, an important factor in HIV transmission among PWID [17]. Its yearly distribution of syringes greatly increased from 340,000 syringes in 1996 to 950,000 syringes in 1999 [17]. According to the SurvUDI, a provincial bio-behavioral surveillance network for HIV infection among PWID, the proportion of PWID reporting sharing needles decreased by 27 percentage-points between 1995 and 2016, while diagnosis and antiretroviral therapy coverage increased substantially between 2003 and 2016 within this population [18].

The decrease in the proportion of MSM and PWID was accompanied by an important increase in the proportion of newly diagnosed individuals from HIV-endemic countries. This exposure group was characterized mostly by heterosexual transmission and a higher representation of women compared to people born in non-endemic countries. Noticeably, people born in HIV-endemic countries had lower CD4 count at diagnosis and were more likely to get diagnosed with a CD4 count <350 cells/μL or <200 cells/μL. The last two metrics seemed to decrease over time among both patients from endemic and from non-endemic countries, suggesting more rapid diagnosis. However, patients from endemic countries had consistently higher proportions of new diagnoses at late or advanced stages of HIV infection, suggesting persistent longer delays to diagnosis or poor linkage to antiretroviral therapy among this group as compared to others. A recent study has shown that, among newly diagnosed asylum seekers in a primary HIV referral centre in Montréal between 2017 and 2018, the median time from entry into Canada to HIV testing was estimated at 27 days, almost two-thirds of patients were late presenters (CD4 <350 cells/μL), almost a quarter presented with an advanced stage of HIV infection (CD4 <200 cells/μL), and only 45% of patients were linked to care within 30 days [19, 20]. In Canada, people born in HIV-endemic countries are disproportionately affected by social and economic factors that increase their vulnerability to HIV infection and act as barriers to prevention, diagnosis and treatment programs [21]. Attention should be paid to adapt programs for people from HIV-endemic countries who faces distinct barriers to rapid diagnosis [19, 22]. Improving provision of information at the time of entry into Canada about the availability of free HIV-testing services and medical care, and about the absence of denial of entry or residency in Canada based on a positive HIV diagnosis could help in increasing and accelerating access to HIV screening and treatment among migrants from HIV-endemic countries [19]. To better inform public health, additional studies are required to describe if patients from endemic countries are more likely to have been infected before their entry to Canada or to acquire the infection in Canada due to unfavorable socioeconomic factors.

Our findings must be interpreted in light of inherent limitations. First, we used data from a single but large clinic in Montréal that represented a convenience sample of patients. However, the shift we observed in exposure categories are consistent with those observed in Québec and in Canada [3, 6]. Second, some of our subgroup analyses relied on small number of HIV diagnoses that could have led to imprecise estimates. Third, we retrospectively included patients diagnosed before 1999 and this could have resulted in a selection bias if patients with poorer prognosis had died before consenting participation. To alleviate this, we restricted our analyses to the ART era. Fourth, there was a high amount of missing data for the CD4 count at diagnosis leading to high variability of estimates. Fifth, we cannot distinguish the country where HIV was acquired for people born in an endemic country–important information for prevention programs. Finally, most of the variables were self-reported. Potential misreporting, especially if differential between the subgroups being compared, could have biased our inferences (e.g. reporting of sexual orientation among men born in HIV-endemic vs non-endemic countries).

Strengths of this study include the analysis of cohort data from a large sexual health clinic specialized in the diagnosis and treatment of STBBI–cohort spanning 25 years. This cohort provides a unique opportunity to understand how the characteristics of diagnosed PLHIV evolved during the ART era and to identify changing needs in HIV prevention and treatment and care cascade.

Conclusions

In conclusion, MSM continue to account for the largest exposure category in absolute numbers. However, patients born in HIV-endemic countries constitute an increasing proportion of newly diagnosed individuals. Tailoring HIV testing strategies and other prevention interventions to these individuals is warranted.

Supporting information

S1 Fig. Trends in mean age at diagnosis by exposure category, 1995–2019 (n = 2,621).

Panel A presents trends by sexual orientation group among men only (n = 2,342). Panels B to D present trends among combined men and women by sexual risk behaviours (including condomless sex, having a partner at risk, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work), injection drug use, and origin (being born in an HIV-endemic country or not), respectively. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate meta-regressions where the year of diagnosis was input as a continuous predictor variable.

(TIF)

S2 Fig. Trends in the proportion of patients with late stage of HIV infection (<350 CD4 cells/μL) at diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal, Canada, stratified by exposure category (n = 1,890), 1995–2019.

Panel A presents trends by sexual orientation group among men only (n = 1,737). Panels B to D present trends among combined men and women by sexual risk behaviours (including condomless sex, having a partner at risk, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work), injection drug use, and origin (being born in an HIV-endemic country or not), respectively. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate metaregressions where the year of diagnosis was input as a continuous predictor variable.

(TIF)

S3 Fig. Trends in the proportion of patients with advanced stage of HIV infection (<200 CD4 cells/μL) at diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal, Canada, stratified by exposure category (n = 1,890), 1995–2019.

Panel A presents trends by sexual orientation group among men only (n = 1,737). Panels B to D present trends among combined men and women by sexual risk behaviours (including condomless sex, having a partner at risk, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work), injection drug use, and origin (being born in an HIV-endemic country or not), respectively. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate metaregressions where the year of diagnosis was input as a continuous predictor variable.

(TIF)

S1 Table. Checklist of items, extended from the STROBE statement, that should be reported in observational studies using routinely collected health data (RECORD).

(PDF)

S2 Table. Characteristics of patients at HIV diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal (Canada), stratified by availability of CD4 count at diagnosis (n = 2,612), 1995–2019.

(PDF)

Acknowledgments

We thank all participants to the cohort of HIV-positive patients from the Clinique médicale l’Actuel, as well as all the clinicians who practiced at the clinic since its opening in 1987, without whom this study could not have taken place. Special thanks also to the clinic’s Director of Development and Strategic Planification, Anne-Fanny Vassal, for her logistical support and coordination with clinicians.

Data Availability

Data cannot be shared publicly because they contain potentially identifying or sensitive patient information. The data underlying the results presented in the study are available from Clinique médicale l'Actuel at: info@lactuel.ca (https://cliniquelactuel.com/).

Funding Statement

This work was supported by a postdoctoral award through Fonds de recherche du Québec - Santé (FRQS: http://www.frqs.gouv.qc.ca/en/) to KG, and through a Canada Research Chair in Population Health Modeling and grants from the Canadian Foundation for AIDS Research (CANFAR: https://canfar.com/) and the Canadian Institutes of Health Research (CIHR: https://cihr-irsc.gc.ca/e/193.html) to MMG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Shui Shan Lee

11 Jun 2021

PONE-D-21-13938

Characteristics of new HIV diagnoses over 1983-2019: a clinic-based study in Montréal, Canada

PLOS ONE

Dear Dr. Giguère,

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PLOS ONE

Additional Editor Comments (if provided):

This is an epidemiologic study founded on the analyses of routinely collected surveillance data over a long period of 40 years. The manuscript contains data and information which could be of useful reference to epidemiologists, and could strengthen the knowledgebase of HIV epidemiology in North America. There are however some methodological flaws which have been raised by one of the reviewers. Major revisions are needed before this manuscript could be considered for publication.

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competing interests: KG reports a postdoctoral award from the Fonds de recherche du

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outside the submitted work; MMG’s research program is supported by a Canada

Research Chair (Tier 2) in Population Health Modeling, and grants from the Canadian

Foundation for AIDS Research and the Canadian Institutes of Health Research, and

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Reviewer #1: Yes

Reviewer #2: No

**********

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Reviewer #1: Yes

Reviewer #2: No

**********

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Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #2: Yes

**********

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Reviewer #1: - The authors mentioned there are some restrictions on data availability but details are not specified.

- The authors provided a comprehensive analysis on the characteristics of newly diagnosed HIV patients in their center over nearly 4 decades and identified the changes in their trends including the exposure risk. This information is important to inform the health authority to tailor the testing and prevention strategies for the control of HIV transmission.

- The authors reported the decreasing trend of mean CD4 at diagnosis from 1381 to 590 cells/uL over the study period though not statistically significant. This may imply the patients presented later to the service over the years. Any reasons observed to explain this finding?

- Is there any reason why the baseline HIV viral load data is not included in the analysis? The change in the baseline HIV viral load over the study period may have implications on the disease transmission in the city.

- The authors found an important increase in the proportion of patients born in an HIV endemic country. As pointed out by the authors, it would be important to know if they are infected before their entry to Canada or acquire the infection in Canada due to the unfavorable socioeconomic factors rendering them at higher risk of infection. This should be further studied to improve the diagnosis and prevention programs.

Reviewer #2: Giguère and colleagues have performed a statistical analysis on new HIV diagnosis in a clinical setting in Montréal, Canada. The authors had access to data from 1999 onwards including individuals that had been diagnosed with HIV as early as 1983. The authors conclude that although men-who-have-sex-with-men (MSM) remain the predominant route of transmission, the proportion of individuals from HIV endemic countries is increasing. The authors suggest that individuals from HIV endemic countries could face distinct barriers to

rapid diagnosis. The paper also presents data showing that from 1983 to 2019, the mean age at diagnosis increased from 26 to 31 years (p-trend <0.0001) and the mean CD4 count at diagnosis decreased from 1,381 to 590 cells/μL (not significantly). I have several concerns about the paper.

Major comments

1. The authors show an impact of calendar time (1983 to 2019) on age at diagnosis and CD4 cell count. Data used in the paper were collected starting in 1999. Patients that were diagnosed before combination antiretroviral therapy became available in the mid-1990s had a very high risk of mortality (especially the ones diagnosed in the 1980s). As the authors acknowledge in the discussion, inclusion of these patients diagnosed well before effective treatment became available, are likely to have passed away and not have been available for inclusion by 1999. Also, the number of new HIV diagnoses was lower in the early years of the pandemic. Inclusion of data before 1999 will therefore result in a bias in the statistical analysis, as the ones who survived in the period before effective treatment became available are likely to have had a better immune response to HIV (in my view this is also illustrated by the high CD4 cell count at diagnosis found in 1983 and maybe even the younger age at diagnosis in 1983). The paper should therefore be restricted to patients diagnosed from 1999 onwards. Prevention gaps required to meet WHO’s 90-90-90 goals also depend on patients diagnosed in more recent years and not in the time before treatment became available.

2. The CD4 cell count is presented using a mean and standard-deviation assuming a normal distribution. The CD4 cell count is, however, not normally distributed (see for instance this paper: https://aidsrestherapy.biomedcentral.com/articles/10.1186/1742-6405-8-35) . The CD4 cell count should therefore be represented as a median and a type of range. The mean CD4 cell count should not be considered in the statistical analysis.

3. The CD4 cell count is highly variable within and between individuals. In the literature, there is a lot of emphasis on diagnosis in a late stage (CD4<350) or an advanced stage of infection (CD4<200). Unfortunately, the paper does not present the proportion of patients diagnosed in a more advanced stage of infection. The statement in the abstract that people from non-endemic countries are diagnosed at a mean CD4 cell count of 484 and from endemic countries at a CD4 of 374 is therefore not so relevant if all these individuals were diagnosed at a CD4 > 350. I recommend that the authors present the proportion of people diagnosed late and in an advanced stage of infection. A change over time in these proportions would be very relevant information, especially in the most recent years.

4. The introduction covers three pages which in my view is very long. The introduction also includes a lot of historical information about HIV in Quebec that is not very relevant. I recommend to strongly shorten the introduction.

5. Figure 3 shows the fit of regression on the mean age at diagnosis by gender since 1983. Did the authors investigate if the fit improved by using a more complex regression equation as compared to a simpler model?

Minor

1. Please improve the resolution of figure 4.

**********

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Reviewer #2: No

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PLoS One. 2021 Oct 7;16(10):e0258383. doi: 10.1371/journal.pone.0258383.r002

Author response to Decision Letter 0


4 Aug 2021

Editor's Comments

1) Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response. We have carefully reviewed the manuscript, tables and figures to ensure that they meet PLOS ONE's style requirements. Changes and corrections include the use of Level 2 heading (bold type, 16 pt font) for sub-sections of major sections and use of double-space paragraph format for the entire manuscript, including the captions.

2) Thank you for stating the following in the Competing Interests section:

[I have read the journal's policy and the authors of this manuscript have the following competing interests: KG reports a postdoctoral award from the Fonds de recherche du Québec - Santé, during the conduct of the study, and personal fees from UNAIDS, outside the submitted work; MMG’s research program is supported by a Canada Research Chair (Tier 2) in Population Health Modeling, and grants from the Canadian Foundation for AIDS Research and the Canadian Institutes of Health Research, and funding from UNAIDS and WHO, outside the submitted work.].

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Response. We have updated the Competing Interests as follows:

"I have read the journal's policy and the authors of this manuscript have the following competing interests: KG reports postdoctoral awards from the Fonds de recherche du Québec - Santé, the Canadian Institutes of Health Research (176645), and the CIHR Canadian HIV Trials Network during the conduct of the study, and personal fees from UNAIDS, outside the submitted work; MMG’s research program is supported by a Canada Research Chair (Tier 2) in Population Health Modeling, and grants from the Canadian Foundation for AIDS Research and the Canadian Institutes of Health Research, and funding from UNAIDS and WHO, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and material."

There are restrictions on sharing of data and/or materials and we have stated them as follows with the initial submission of our manuscript to PLOS ONE:

"Data cannot be shared publicly because they contain potentially identifying or sensitive patient information. The data underlying the results presented in the study are available from the Clinique médicale l'Actuel (https://cliniquelactuel.com/)."

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Response. We have included our updated Competing Interests statement to our cover letter.

3) We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#locunacceptable- data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

Response. As mentioned above, there are indeed restrictions on sharing of data and we have explained them:

"Data cannot be shared publicly because they contain potentially identifying or sensitive patient information. The data underlying the results presented in the study are available from the Clinique médicale l'Actuel (https://cliniquelactuel.com/)."

If anything is still missing or not properly reported, kindly let us know exactly what and we will be pleased to update this declaration accordingly.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to deidentify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide.

Response. Not applicable as there are ethical restrictions that prohibits us to share the data.

Reviewer #1

1. The authors mentioned there are some restrictions on data availability but details are not specified.

Response. As mentioned by the reviewer, we indeed reported restrictions on data availability. However, contrary to what is mentioned by the reviewer, we had also reported details on these restrictions as follows:

"Data cannot be shared publicly because they contain potentially identifying or sensitive patient information. The data underlying the results presented in the study are available from the Clinique médicale l'Actuel (https://cliniquelactuel.com/)."

2. The authors provided a comprehensive analysis on the characteristics of newly diagnosed HIV patients in their center over nearly 4 decades and identified the changes in their trends including the exposure risk. This information is important to inform the health authority to tailor the testing and prevention strategies for the control of HIV transmission.

Response. We are pleased that the reviewer found that our study results are important to inform the public health response to HIV.

3. The authors reported the decreasing trend of mean CD4 at diagnosis from 1381 to 590 cells/uL over the study period though not statistically significant. This may imply the patients presented later to the service over the years. Any reasons observed to explain this finding?

Response. As per a request of reviewer #2, we do not present trends in mean CD4 count at diagnosis anymore (see response to comments 2 and 3 of reviewer #2 for details). We rather present trends in the proportion of patients with CD4 <350 cells/µL or CD4 <200 cells/µL as proxies for late or advanced stages of HIV infection at diagnosis, respectively. Moreover, we restricted analyses to the ART era (also as requested by reviewer #2 in their first comment) and now present time trends from 1995 to 2019 instead of from 1983 to 2019. We do not observe results suggesting that patients would present later to HIV testing services over the years. Moreover, the trends in proportion of patients with late or advanced stages of HIV infection rather suggest that patients were diagnosed sooner over the years. Unfortunately, available data do not allow us to further investigate the reasons that could explain this finding.

4. Is there any reason why the baseline HIV viral load data is not included in the analysis? The change in the baseline HIV viral load over the study period may have implications on the disease transmission in the city.

Response. HIV viral loads were not routinely collected at diagnosis. That is, only a minority of included patients (13%) had a viral load at diagnosis. Among patients who had a first viral load within a year of HIV diagnosis (72% of analysed patients), time to viral load varied a lot and went from 0 to 365 days, with a median of 26 days and a mean of 53 days. As such, we believe that for many patients, the first viral load was performed after initiation of HIV treatment. Since HIV treatment rapidly decreases viral load, we believe that the first HIV viral load performed within participants would not be a good proxy for viral load at diagnosis and decided not to include this metric in the analyses.

5. The authors found an important increase in the proportion of patients born in an HIV endemic country. As pointed out by the authors, it would be important to know if they are infected before their entry to Canada or acquire the infection in Canada due to the unfavorable socioeconomic factors rendering them at higher risk of infection. This should be further studied to improve the diagnosis and prevention programs.

Response. We agree with the reviewer that understanding if patients from endemic countries were either infected before their entry to Canada or acquired the infection after is important. However, the exact date of infection is rarely known and was not available/reported in our study. We thus added a sentence in the Discussion section to emphasize the reviewer’s point:

"To better inform public health, additional studies are required to describe if patients from endemic countries are more likely to have been infected before their entry to Canada or to acquire the infection in Canada due to unfavorable socioeconomic factors."

Reviewer #2

Giguère and colleagues have performed a statistical analysis on new HIV diagnosis in a clinical setting in Montréal, Canada. The authors had access to data from 1999 onwards including individuals that had been diagnosed with HIV as early as 1983. The authors conclude that although men-who-have-sex-with-men (MSM) remain the predominant route of transmission, the proportion of individuals from HIV endemic countries is increasing. The authors suggest that individuals from HIV endemic countries could face distinct barriers to rapid diagnosis. The paper also presents data showing that from 1983 to 2019, the mean age at diagnosis increased from 26 to 31 years (p-trend <0.0001) and the mean CD4 count at diagnosis decreased from 1,381 to 590 cells/μL (not significantly). I have several concerns about the paper.

Major comments

1. The authors show an impact of calendar time (1983 to 2019) on age at diagnosis and CD4 cell count. Data used in the paper were collected starting in 1999. Patients that were diagnosed before combination antiretroviral therapy became available in the mid-1990s had a very high risk of mortality (especially the ones diagnosed in the 1980s). As the authors acknowledge in the discussion, inclusion of these patients diagnosed well before effective treatment became available, are likely to have passed away and not have been available for inclusion by 1999. Also, the number of new HIV diagnoses was lower in the early years of the pandemic. Inclusion of data before 1999 will therefore result in a bias in the statistical analysis, as the ones who survived in the period before effective treatment became available are likely to have had a better immune response to HIV (in my view this is also illustrated by the high CD4 cell count at diagnosis found in 1983 and maybe even the younger age at diagnosis in 1983). The paper should therefore be restricted to patients diagnosed from 1999 onwards. Prevention gaps required to meet WHO’s 90-90-90 goals also depend on patients diagnosed in more recent years and not in the time before treatment became available.

Response. We agree with the reviewer that patients who were diagnosed before ART era in the mid-1990s may have experienced higher rates of mortality, preventing them to be recruited to the study from 1999 onwards, and potentially leading to selection bias. We thus restricted analyses to the ART era, i.e. to patients diagnosed from 1995 onwards (and still excluding patients diagnosed in 2020 to alleviate the right truncation). All results, as well as all sections of the manuscript have been updated to take this change into account. In the Methods sections, we have added the underlined sentence below to justify this restriction:

"Because we included both patients diagnosed at l'Actuel and patients initiating care at the clinic but diagnosed elsewhere, we expected that the last few years of data would be affected by right truncation, especially in 2020 due to the COVID-19 global pandemic. In addition, because patients diagnosed before the beginning of ART era, in mid-1990's, could have passed away before recruitment to the cohort in 1999, left truncation could be an issue. To avoid these, analyses were restricted to patients diagnosed between 1995 and 2019."

2. The CD4 cell count is presented using a mean and standard-deviation assuming a normal distribution. The CD4 cell count is, however, not normally distributed (see for instance this paper: https://aidsrestherapy. biomedcentral.com/articles/10.1186/1742-6405-8-35) . The CD4 cell count should therefore be represented as a median and a type of range. The mean CD4 cell count should not be considered in the statistical analysis.

Response. We have replaced mean CD4 counts and SD with median CD4 counts and interquartile ranges, respectively, everywhere in the manuscript. To avoid methodological challenges with the meta-regression of medians, we assessed trends in the proportion of patients with late (CD4 cells count <350 cells/µL) or advanced stage of HIV infection (CD4 cells count <200 cells/µL) at diagnosis. These changes did not alter our conclusions, however. We still do not observe differences in CD4 count at diagnosis between men and women overall, both men and women born in HIV-endemic countries tended to have lower CD4 counts at diagnosis than their counterparts from non-endemic countries, and men born in HIV-endemic countries had the lowest CD4 count of all.

3. The CD4 cell count is highly variable within and between individuals. In the literature, there is a lot of emphasis on diagnosis in a late stage (CD4<350) or an advanced stage of infection (CD4<200). Unfortunately, the paper does not present the proportion of patients diagnosed in a more advanced stage of infection. The statement in the abstract that people from non-endemic countries are diagnosed at a mean CD4 cell count of 484 and from endemic countries at a CD4 of 374 is therefore not so relevant if all these individuals were diagnosed at a CD4 > 350. I recommend that the authors present the proportion of people diagnosed late and in an advanced stage of infection. A change over time in these proportions would be very relevant information, especially in the most recent years.

Response. We thank the reviewer for these relevant suggestions. We added the counts and proportions of patients by CD4 cells count categories at diagnosis (≥500, 350-499, 200-349, 50-199, and <50 cells/µL) within tables. We also present trends in the proportion of patients with late (CD4 cells count <350 cells/µL) or advanced stage of HIV infection (CD4 cells count <200 cells/µL). Interestingly, although not statistically significant for gender and exposure category strata, the results suggest overall decreases over time in the proportion of patients diagnosed at later stages of HIV infection, suggesting earlier diagnosis over the years.

4. The introduction covers three pages which in my view is very long. The introduction also includes a lot of historical information about HIV in Quebec that is not very relevant. I recommend to strongly shorten the introduction.

Response. Our study being descriptive and spanning over 25 years, we believe that contextualizing the results is warranted for readers of other jurisdiction. Nonetheless, we have shortened the introduction by removing some secondary information.

5. Figure 3 shows the fit of regression on the mean age at diagnosis by gender since 1983. Did the authors investigate if the fit improved by using a more complex regression equation as compared to a simpler model?

Response. We avoided complex regression models as we worried about overfitting the data. Inspection of model fits suggested that linear time trend models were appropriate to describe patterns and that polynomials or logarithmic were unwarranted.

Minor

1. Please improve the resolution of figure 4.

Response. We have increased the resolution of Figure 4 from 300 dpi to 398 dpi.

Attachment

Submitted filename: Response_to_Reviewers.pdf

Decision Letter 1

Shui Shan Lee

27 Sep 2021

Characteristics of new HIV diagnoses over 1995-2019: a clinic-based study in Montréal, Canada

PONE-D-21-13938R1

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Reviewer #1: - My comments in the previous review have been appropriately addressed

- The authors changed the analysis period to 1995-2019 to avoid the selection bias. Based on the reasons discussed in the article, I suppose cART was widely used in the clinic since 1995.

Reviewer #2: The authors have correctly addressed my concerns.

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Acceptance letter

Shui Shan Lee

29 Sep 2021

PONE-D-21-13938R1

Characteristics of new HIV diagnoses over 1995-2019: a clinic-based study in Montréal, Canada

Dear Dr. Giguère:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Fig. Trends in mean age at diagnosis by exposure category, 1995–2019 (n = 2,621).

    Panel A presents trends by sexual orientation group among men only (n = 2,342). Panels B to D present trends among combined men and women by sexual risk behaviours (including condomless sex, having a partner at risk, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work), injection drug use, and origin (being born in an HIV-endemic country or not), respectively. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate meta-regressions where the year of diagnosis was input as a continuous predictor variable.

    (TIF)

    S2 Fig. Trends in the proportion of patients with late stage of HIV infection (<350 CD4 cells/μL) at diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal, Canada, stratified by exposure category (n = 1,890), 1995–2019.

    Panel A presents trends by sexual orientation group among men only (n = 1,737). Panels B to D present trends among combined men and women by sexual risk behaviours (including condomless sex, having a partner at risk, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work), injection drug use, and origin (being born in an HIV-endemic country or not), respectively. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate metaregressions where the year of diagnosis was input as a continuous predictor variable.

    (TIF)

    S3 Fig. Trends in the proportion of patients with advanced stage of HIV infection (<200 CD4 cells/μL) at diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal, Canada, stratified by exposure category (n = 1,890), 1995–2019.

    Panel A presents trends by sexual orientation group among men only (n = 1,737). Panels B to D present trends among combined men and women by sexual risk behaviours (including condomless sex, having a partner at risk, having an HIV-positive partner, having multiple sexual partners and/or having ever engaged in sex work), injection drug use, and origin (being born in an HIV-endemic country or not), respectively. Trends are displayed using local linear fitting and a degree of smoothing of 0.75. Time trends (p-values) were assessed by the mean of t-tests within univariate metaregressions where the year of diagnosis was input as a continuous predictor variable.

    (TIF)

    S1 Table. Checklist of items, extended from the STROBE statement, that should be reported in observational studies using routinely collected health data (RECORD).

    (PDF)

    S2 Table. Characteristics of patients at HIV diagnosis among participants to the HIV-positive cohort at the Clinique médicale l’Actuel in Montréal (Canada), stratified by availability of CD4 count at diagnosis (n = 2,612), 1995–2019.

    (PDF)

    Attachment

    Submitted filename: Response_to_Reviewers.pdf

    Data Availability Statement

    Data cannot be shared publicly because they contain potentially identifying or sensitive patient information. The data underlying the results presented in the study are available from Clinique médicale l'Actuel at: info@lactuel.ca (https://cliniquelactuel.com/).


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