key: cord-332396-nattdect
authors: Ejima, K.; Koizumi, Y.; Yamamoto, N.; Rosenberg, M.; Ludema, C.; Bento, A. I.; Yoneoka, D.; Ichikawa, S.; Mizushima, D.; Iwami, S.
title: HIV testing by public health centers and municipalities, and new HIV cases during the COVID-19 pandemic in Japan
date: 2020-10-18
journal: nan
DOI: 10.1101/2020.10.16.20213959
sha: 
doc_id: 332396
cord_uid: nattdect

Background: During the COVID-19 outbreak, medical resources were primarily allocated to COVID-19, which might have reduced facility capacity for HIV testing. Further, people may have opted against HIV testing during this period to avoid COVID-19 exposure. We investigate the influence of the COVID-19 pandemic on HIV testing and its consequences in Japan. Methods: We analysed quarterly HIV/AIDS-related data from 2015 to the second quarter of 2020 using an anomaly detection approach. The data included the number of consultations that public health centers received, the number of HIV tests performed by public health centers or municipalities, and the number of newly reported HIV cases with and without AIDS diagnosis. As sensitivity analyses, we performed the same analysis for two subgroups: men who have sex with men (MSM) and non-Japanese. Findings: The number of HIV tests (9,584 vs. 35,908 in the year-before period) and consultations (11,689 vs. 32,565) performed by public health centers significantly declined in the second quarter of 2020, while the proportion of HIV cases with AIDS diagnosis among all HIV cases (36.2% vs. 26.4%) significantly increased after removing the trend and seasonality effects. The number of HIV cases without AIDS diagnosis numerically decreased (166 vs. 217), although the reduction was not significant. We confirmed similar trend for the MSM and non-Japanese groups. Interpretation: The current HIV testing system including public health centers misses more HIV cases at the early phase of the infection during the pandemic. Given that the clear epidemiological picture of HIV incidence during the pandemic is still uncertain, continuously monitoring the situation as well as securing sufficient test resources using self-test is essential.

Evidence before this study 25

Before this study, we searched PubMed, Medline, and Google Scholar on Oct 12, 2020, for articles 26 investigated the number of HIV test and HIV cases during the COVID-19 pandemic in Japan, using the 27 search terms "novel coronavirus" or "SARS-CoV-2", and "HIV" or "AIDS", and "Japan", with no time 28 restrictions. We found no published work relevant to our study. 29

During the COVID-19 pandemic in Japan, the public health centers and municipalities temporarily 31 suspended facility-based HIV testing to concentrate their limited resources to COVID-19 testing. We 32 investigated the impact of the COVID-19 pandemic on the number of HIV tests in public health centers and 33 municipalities, and on the number of HIV cases with and without AIDS diagnosis. We confirmed that the 34 number of the test declined in the second quarter (April to June) of 2020, and the proportion of HIV with 35 AIDS diagnosis among all HIV cases increased during the same period. 36

Providing sufficient HIV testing opportunities even during the pandemic, when facility-based testing is 38 challenging, is necessary for better clinical and public health outcomes. Self-testing and home specimen 39 collection (e.g. dried blood spot or oral fluid test) could be a key to fill the gap between the need for HIV 40 testing and the constraints related to the COVID-19 outbreak. 41 42 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020 . . https://doi.org/10.1101 /2020 testing and its consequences in Japan. 48

We analysed quarterly HIV/AIDS-related data from 2015 to the second quarter of 2020 using an anomaly 50 detection approach. The data included the number of consultations that public health centers received, the 51 number of HIV tests performed by public health centers or municipalities, and the number of newly reported 52

HIV cases with and without AIDS diagnosis. As sensitivity analyses, we performed the same analysis for 53 two subgroups: men who have sex with men (MSM) and non-Japanese. 54

The number of HIV tests (9,584 vs. 35,908 in the year-before period) and consultations (11,689 vs. 32,565) 56 performed by public health centers significantly declined in the second quarter of 2020, while the proportion 57 of HIV cases with AIDS diagnosis among all HIV cases (36·2% vs. 26·4%) significantly increased after 58 removing the trend and seasonality effects. The number of HIV cases without AIDS diagnosis numerically 59 decreased (166 vs. 217), although the reduction was not significant. We confirmed similar trend for the 60 MSM and non-Japanese groups. 61

The current HIV testing system including public health centers misses more HIV cases at the early phase of 63 the infection during the pandemic. Given that the clear epidemiological picture of HIV incidence during the 64 pandemic is still uncertain, continuously monitoring the situation as well as securing sufficient test resources 65 using self-test is essential. 66

Japan Society for the Promotion of Science, Japan Science and Technology Agency, Japan Agency for 68

Medical Research and Development. 69 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 18, 2020 . . https://doi.org/10.1101 /2020 Introduction 72

The ongoing COVID-19 pandemic has had broad influences on lifestyle and health issues beyond COVID-73 19. There have been positive impacts, such as a curtailed 2019/2020 influenza season in Japan (1), which 74 could be partially explained by measures taken to constrain the COVID-19 outbreak. Due to reduced 75 economic activity and human mobility during lockdown, air pollution, which is a risk factor of pulmonary 76 diseases, was temporally improved in China (2). However, there are many problems caused by risk 77 mitigating interventions for COVID-19, many of which are under investigation. Fear and anxiety about this 78 new disease and changed lifestyle have been stressful for many people, which has worsened mental health 79 (3) (4) (5) . 80

Further, during this pandemic period, non-COVID-19 diseases have been at a lower priority for treatment 81 because medical resources have been disproportionately allocated to treat COVID-19 patients in many 82 health care facilities and the capacity to care for non-COVID-19 disease has been limited. Moreover, health 83 care facilities need to balance the benefits of providing care for non-critical conditions with minimizing the 84 risk of COVID-19 infections for both health care professionals and patients (6). 85

People living with HIV infections have better outcomes with early diagnosis and connection to antiretroviral 86 treatment. Early diagnosis is also key to preventing onward transmission because early infection is 87 characterized by high viral load and receiving an HIV diagnosis facilitates behavioural change. However, 88

Lagat et al. reported a decline in HIV test volume in Kenya due to many barriers related to COVID-19, such 89 as lack of funds to visit clinics and fear of COVID-19 infection at clinics (7). 90

To increase HIV testing opportunities, in the United States the CDC is recommending self-testing of HIV or 91 home specimen collection (e.g. dried blood spot or oral fluid test) to avoid COVID-19 infection risk 92 associated with face-to-face testing service (8). In Japan, the number of self-collection-based HIV tests has 93 increased, though the majority of tests are still conducted at public health centers and clinics (i.e., facility-94 based testing). However, during the pandemic, public health centers and clinics have been overwhelmed by 95 COVID-19 PCR testing and administrative work and many have temporally suspended or limited HIV 96 testing. 97 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020. . https://doi.org/10.1101/2020.10.16.20213959 doi: medRxiv preprint 6 AIDS is usually diagnosed by the specific symptoms and the average incubation period is 10 years (9, 10). 98 Therefore, the impact of the pandemic on the number of reported HIV cases with AIDS diagnosis will not be 99 substantial in a short-term period (< 1 year). In contrast, the median time interval between HIV infection to 100 the diagnosis without AIDS symptoms is 1 ·0 years in Tokyo, Japan (11) without AIDS diagnosis in Japan. We further extracted the data of HIV cases with and without AIDS 116 diagnosis for the following two subgroups: men who have sex with men (MSM) and non-Japanese, because 117 MSM accounts for about 70% of the newly reported HIV cases (12), and foreigners are considered 118 vulnerable during disasters due to language barriers (13). The data on the number of tests and consultations 119 for these subgroups were not available. 120

Note that HIV cases with AIDS diagnosis here represent new cases of HIV identified at late-stages, 121 compatible with an AIDS diagnosis. Thus, this number does not include HIV cases with AIDS diagnosis that 122 were previously diagnosed and progressed to AIDS. To rephrase, the new HIV cases here are divided into 123 two categories: early diagnosis (HIV cases without AIDS diagnoses) and late diagnosis (HIV cases with 124 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020. . https://doi.org/10.1101/2020.10.16.20213959 doi: medRxiv preprint 7 AIDS diagnoses). HIV tests at clinics/hospitals and self-testing are also available in Japan. Thus, the number 125 of HIV testing performed by public health centers or municipalities was used to examine the trend of 126 facility-based tests, rather than capturing the total number of HIV tests or examining the proportion of HIV 127 positive cases among all the HIV tests. 128

We applied an anomaly detection approach to those longitudinal data to identify the period when the number Figure 1 shows the observed data points and the computed normal range (the shaded area). We observed a 144 significant downward trend in HIV cases with or without AIDS diagnosis (Figure 1AB) , all the HIV cases 145 (Figure 1C) , and the number of consultations (Figure 1E ) over the period examined (from the first quarter 146 of 2015 to the second quarter of 2020). The trend in number of tests was not significant during the period 147 ( Figure 1D) . The proportion of HIV cases with AIDS diagnosis among all the HIV cases showed a 148 significant downward trend during the period (Figure 1F) , suggesting that more HIV cases have been 149 diagnosed in the early phase of infection recently. Regarding anomaly by the last quarter of 2019 (i.e., 150 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020. . https://doi.org/10.1101/2020.10.16.20213959 doi: medRxiv preprint 8 before the COVID-19 pandemic), there are a couple of data points that significantly deviated from the 151 normal range. However, the magnitude of the deviation of those numbers was modest. 152

We did not observe deviation in any numbers in the first quarter of 2020. However, in the second quarter, 153 the numbers of HIV tests and HIV consultations significantly declined (Figure 1DE) , which is compatible 154 with a public health infrastructure overwhelmed by COVID-19 related work. In contrast, the proportion of 155 HIV cases with AIDS diagnosis among all HIV cases significantly increased ( Figure 1F) . Intriguingly, the 156 number of HIV cases with AIDS diagnosis in the second quarter of 2020 showed the same trend as before 157 ( Figure 1B) . The number of HIV cases without AIDS diagnosis numerically decreased in the second quarter 158 of 2020 (Figure 1A) , however it was not significant. It is worth noting that the number of HIV cases without 159 AIDS diagnosis did not decline as much as the number of tests (the former dropped 23.5%, whereas the 160 latter dropped 73.3% compared with the year-before period). This might be because more HIV cases with 161 acute symptoms (i.e., fever) visited clinics for viral test for SARS-CoV-2 and HIV infection was 162 subsequently diagnosed. 163

As a sensitivity analysis, we examined the longitudinal data of HIV cases with and without AIDS diagnosis 164 of two subgroups: men who have sex with men (MSM) and non-Japanese. We confirmed the same 165 downward trend for the MSM population as for the total population (Figure 2A-C) in terms of newly 166 reported HIV cases with and without AIDS diagnosis. On contrary, the HIV cases without AIDS diagnosis 167 and all HIV cases among non-Japanese were in upward trend ( Figure 3AC ). The number of HIV cases 168 without AIDS diagnosis numerically decreased, whereas HIV cases with AIDS diagnosis numerically 169 increased or were in the same trend as before in these two populations in the second quarter of 2020 ( Figure  170 2AB and 3AB). As a result, the proportion of HIV cases with AIDS diagnosis among all positive cases also 171 numerically increased in the second quarter of 2020 in these two subgroups (Figure 2D and 3D) ; however, 172 they were not significant, which might be due to the small sample size. The proportion of HIV cases among 173 MSM and non-Japanese populations relative to total HIV cases was consistent over time including the 174 second quarter of 2020 (Figure 2E and 3E) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020. We need to interpret the results carefully. First, we have analyzed the number of tests performed by public 188 health centers and municipalities. However, this type of test accounts for less than half of the tests 189 performed in Japan. For example, self-collection-based tests (mostly using dried blood spot) are increasing, 190 and tests are available in clinics and hospitals; however, the count of those tests was not available. It is 191 probable that the number of different types of HIV test has increased during the same period as 192 compensation for the reduction in the number of tests performed by public health centers and municipalities. 193 Second, we do not know the full picture of the impact of the pandemic on HIV epidemiology. We have used 194 the number of reported HIV cases; however, there is likely a substantial proportion of undiagnosed cases, 195 and it is uncertain whether the number and the proportion of undiagnosed cases changed during the 196 pandemic. It is possible that the incidence increased (or decreased) during the pandemic. Therefore, even 197 though the number of new HIV cases did not change dramatically, it does not indicate that the number of 198 tests is sufficient to identify all HIV patients. Indeed, the number of reported HIV positive cases without 199 progressed to AIDS in the second quarter of 2020 was the lowest in the last five years and the proportion of 200 HIV cases with AIDS diagnosis significantly increased. It raises a concern that the testing opportunities 201 might not be sufficient to fully capture the epidemiological situation of HIV/AIDS during the pandemic in 202

Japan. Because most of the HIV cases with AIDS diagnosis are identified in clinics or hospitals due to 203 specific symptoms, HIV cases with AIDS diagnosis are less prone to being affected by healthcare avoidance 204 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020. . https://doi.org/10.1101/2020.10.16.20213959 doi: medRxiv preprint even under the pandemic. Indeed, the number of HIV cases with AIDS diagnosis was in the same trend as 205 before the pandemic. We need to keep monitoring the situation as well as adapting testing strategies to work 206 in these unusual circumstances. 207

As the pandemic continues, we do not know how long the HIV testing opportunities provided by public 208 health centers could be disrupted and how it could affect HIV spread. Given that early detection and 209 treatment initiation for HIV is lifesaving, providing sufficient HIV testing opportunities is important. 210 UNAIDS has a proposed treatment target, "90-90-90" to control the HIV epidemic (17). A part of the target 211 is that "By 2020, 90% of all people living with HIV will know their HIV status." If the COVID-19 212 pandemic continuously disrupts testing opportunities, diagnosing 90% of people living with HIV might be 213 difficult to achieve. Self-testing and home specimen collection could be a key to fill the gap between the 214 need for HIV testing and the constraints related to the COVID-19 outbreak. 215

The strength of this study is that we used the quarterly HIV/AIDS reports in Japan, which include all the 216 diagnosed cases as physicians are required to report all diagnosed cases under the Infectious Diseases 217

Control Law(18). Further, the cases reported as HIV cases with AIDS diagnosis include only the cases of 218 newly diagnosed HIV infection co-occurring with AIDS. Therefore, we could quantify the proportion of 219 patients presenting with AIDS at the time of diagnosis, which captures late-presentation for diagnosis and is 220 more likely if testing resources are not accessible. 221 A limitation of this study is that we were not able to account for the heterogeneous epidemiology of HIV 222 between different regions. Higher HIV incidence has been observed in urban areas such as Tokyo and Osaka 223 compared with rural areas. Thus, public health centers in urban areas have allocated budgetary resources 224 towards HIV testing, whereas this has not been prioritized in rural areas. During the pandemic, the testing 225 opportunities in rural areas may have declined even further than urban areas. Our study mainly focused on 226

HIV cases with and without AIDS diagnosis and testing regardless of the patients' characteristics. One of 227 the concerns in this pandemic is that more vulnerable populations, such as sex workers, low-income 228 populations, younger population, in addition to foreigners, may have experienced disproportionate harms. 229

Further studies should focus on these populations and identify barriers to testing. We used only the number 230 of tests performed by public health centers and municipalities, thus self-tests and home specimen collection, 231 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 18, 2020. . https://doi.org/10. 1101 /2020 which are increasingly popular, and tests performed in clinics and hospitals were not counted. Further 232 investigation is necessary to focus on these types of tests to fully understand the response of the HIV CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 18, 2020. range. The observed data outside of the normal rage is considered abnormal and red colored. 307 308 309 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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The authors declare that they have no competing interests. 256 257 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted October 18, 2020 . . https://doi.org/10.1101 /2020