A02 Epidemiology

Introduction

Epidemiology is the study of the distribution and determinants of health-related states or events (including disease), and the application of this study to the control of diseases and other health problems.[1] As regards HIV/AIDS, epidemiology performs a number of key public health functions, which include: describing its occurrence in populations, examining factors at individual/population levels that affect the chance of infection and disease progression, and evaluating preventive strategies in place. Various methods can be used to carry out epidemiological investigations: surveillance and descriptive studies to assess distribution; analytical studies for exploring determinants.

It has been over thirty years since the first cases of HIV attracted the world’s attention. Epidemiological studies of HIV began in 1981 as a group of immune-compromised male homosexuals with conditions including Pneumocystis carinii pneumonia (PCP, now referred to as Pneumocystis jiroveci pneumonia) appeared. Patients with similar symptoms were later found among people who inject drugs (PWID), haemophilia patients, transfusion recipients, sex partners of people with HIV/AIDS, and infants of infected mothers. Health officials started to use the term “acquired immunodeficiency syndrome,” or AIDS in 1982, to describe the occurrence of opportunistic infections among otherwise healthy individual. In 1983, the causative agent of AIDS, human immunodeficiency virus (HIV), was identified.[2] As no effective treatment was available for AIDS in the 1980s, on average half of the people infected with HIV developed symptoms relating to complications arising from immunodeficiency and progressed to AIDS in around ten years’ time. Different classes of antiretroviral compounds (ARV) were discovered in the past few decades. In combination, they work by stopping HIV from multiplying and can suppress viral load to undetectable level. Most importantly, the life expectancy of people living with HIV/AIDS (PLWHA) on highly active antiretroviral therapy (HAART) is nearly the same as that of uninfected individual.[3] Epidemiology of HIV infection and AIDS has evolved in response to ARV-based treatment intervention.

HIV epidemiologic states

In evaluating sizes of HIV epidemics, UNAIDS/WHO and partners have defined three epidemic states – low level, concentrated or generalised, according to the HIV prevalence in the population.[Box 2.1]

Generalised epidemics are principally found in low-income African countries. It has been well-known that Sub-Saharan Africa carries the highest burden of HIV infections and HIV/AIDS related mortality in the world. The adult HIV prevalence is up to 5%. According to WHO, about 68% of all people living with HIV in mid-2010 resided in sub-Saharan Africa, a region accounting for only 12% of the global population. The 1.9 million people who became newly infected with HIV in 2010 in sub-Saharan Africa represented 70% of all the people who acquired HIV infection globally.

Concentrated epidemics have occurred in many other countries where the prevalence among different risk populations including men who have sex with men (MSM), PWID, commercial sex workers (CSW) and their clients are well above 5%.

Low-level epidemic is defined as those areas with HIV prevalence of <5% in the major at-risk subpopulation. Hong Kong was previously an example of low level epidemic, with the highest HIV prevalence among MSM of around 4%, but has surpassed the 5% threshold as reported in a survey in 2017 (section “HIV epidemiology in Hong Kong” below). The prevalence of other high risk groups is comparatively lower with around 0.53% in PWID and 0.05% in Female CSW (FSW).

Global HIV epidemiology

General situation and growth of the global epidemic

As of the end of 2017, the Joint United Nations Programme on HIV/AIDS (UNAIDS) has estimated that 36.9 million people were living with HIV globally, including 1.8 million children less than 15 years of age. There were 1.8 million new HIV infections in 2017, with 180,000 among children less than 15 years of age.[5][6]

Among all regions, Sub-Saharan Africa remains the worst-affected region in the world. The epidemic appears to have stabilized and peaked in the late 1990s with the annual number of new HIV infections steadily declining in the past two decades. Modelled estimates show that new infections (all ages) declined from a peak of 3.4 million in 1996 to 1.8 million in 2017. However, progress is far slower than what is required to reach the 2020 milestone of less than 500 000 new infections. As is the case with AIDS-related mortality, the reduction in new HIV infections between 2010 and 2017 was the strongest in sub-Saharan Africa due to sharp reductions in eastern and southern Africa (30% decline). In the Middle East and North Africa and eastern Europe and central Asia, the annual number of new HIV infections has doubled in less than 20 years. Regarding sex distribution, women continue to account for a disproportionate percentage of new HIV infections among adults (aged 15 and older) in sub-Saharan Africa: they represented 59% of the 980 000 new adult HIV infections in 2017. In other parts of the world, men accounted for 63% of the 650 000 new adult HIV infections in 2017. Globally, there were almost 90 000 more new HIV infections among men than women in 2017.

According to the UNAIDS report 47% of the new HIV infections globally in 2017 were among key populations and their sexual partners. The percentage varies by different region. Key populations and their sexual partners accounted for more than 95% of new HIV infections in eastern Europe and central Asia, Middle East and North Africa, and as high as 90% of the new infections in western and central Europe and North America. MSM accounted for an estimated 57% of new HIV infections in western and central Europe and North America in 2017, followed by an estimated 41% of new infections in Latin America. PWID accounted for more than one third of new HIV infections in eastern Europe and central Asia and in the Middle East and North Africa; while sex workers accounted for about one in 10 infections in eastern Europe and central Asia and the Middle East and North Africa. It is difficult to collect quality data and scale the size of these populations and to obtain further information such as their attitudes and practices as they are reluctant to identify themselves and hence hard to be reached.[7]

In Mainland China, based on the national case reporting data, there were 760 000 people living with HIV/AIDS who know their status at the end of 2017.[8] In 2014, medical and health institutions at all levels around the country conducted HIV antibody testing on an estimated 130 million person times and found 103,501 new cases. By the end of 2014, there were 501,000 reported cases of PLWHA (including 296,000 people living with HIV and 205,000 AIDS patients) and 159,000 deaths had been reported. The number of people living with HIV currently receiving antiretroviral therapy was 295,358 in 2014 nationwide.[9]

Genetic diversity of the HIV virus

Two types of HIV, HIV-1 and HIV-2, have been described with the latter being less virulent and geographically limited largely to West Africa. HIV-1 is further categorised into three groups, M, N, and O. Group M virus contributes to majority of the global pandemic, and further diversified into different subtypes (named A-D, F-H, J and K). HIV genetic variability is the outcome of the high mutation and recombination rates of the reverse transcriptase enzyme, jointly with high rates of virus replication. Recombinants between subtypes are designated as circulating recombinant forms (CRF). Almost 100 CRFs have already been identified, with an increasing proportion involving 3 or more different strains.(https://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html)

Tracking of the spread of different HIV-1 subtypes adds information to the epidemiology. Subtype C predominates in Africa and India, and accounted for 48% of cases of HIV-1 in 2007 worldwide, as reported in a study.[10] Subtype B predominates in western Europe, the Americas, and Australia. HIV-2 is largely confined to west Africa and causes a similar illness to HIV-1, but immunodeficiency progresses more slowly and HIV-2 is less transmissible.[11]

HIV epidemiology in Hong Kong

The first case of HIV infection in Hong Kong was reported in 1984. As of end 2018, under the voluntary and anonymous HIV/AIDS reporting system, the Department of Health has received a total of 9715 reports of HIV infection and 1996 cases of AIDS.[Box 2.2] Eighty-eight reported cases were less than 18 years of age, including 32 perinatally-transmitted and 29 transfusion-related cases. Since 2010, there were only 7 reported perinatal cases involving children born in Hong Kong and no reported case resulting from blood/blood product transfusion. As of 2016, an estimated 7000 people were living with HIV infection in Hong Kong, implying an overall prevalence of less than 0.1%. The number of AIDS reports has been maintained at a level of about 100 cases annually since the availability of HAART at around 1996, with PCP continuing to be the commonest AIDS defining illness, accounting for 42% of total number of reported AIDS cases, followed by all forms of tuberculosis (24%).[12]

Evolving pattern of HIV epidemiology in Hong Kong

Since the diagnosis of the first HIV/AIDS cases in the 1980s, the HIV epidemic in Hong Kong has gone through different phases as shaped by growth dynamics and the predominance of certain transmission routes.

Between the mid-1980s and early 1990s, a significant proportion of reported infections came from haemophilia patients who needed regular transfusions of blood products. A total of 68 cases were reported locally so far. Similar to the situation in the western countries, HIV was also introduced in the local MSM populations. Prior to the 1990s, the annual total number of new HIV infection remained stable at a low level of fewer than 50. With the introduction of blood and blood product screening in 1985, the proportion and actual number of infections transmitted via blood transfusion decreased remarkably.

Starting from the early 1990s, sexual transmission took over as the leading cause of HIV/AIDS. Heterosexual transmission gradually became more prominent during the 1990s. The overall male-to-female ratio fell from 11:1 in 1990, to 2.2:1 in 1995 and 2.1:1 in 2000. Overall, there was a steady growth that brought the total annual number from 229 cases in 2003 to a peak of 725 cases in 2015. In 2016 to 2018, the annual number appeared to reach a plateau of less than 700. Since the turn of the century, the number of new MSM infections reported increased from 30 cases in 2000 to 203 cases in 2011, while the number of heterosexual male cases remained similar at 78 and 65 correspondingly. A continuously rising trend of HIV infection among MSM was observed thereafter. In 2018, homosexual and bisexual contacts as route of transmission contributed to 58% of all HIV reported cases and 68% in all male cases. The difference in the number of heterosexually acquired infection compared to that in MSM has continue to widen. In 2018, heterosexual male accounted for only 14% of all male cases.[12][Box 2.3]

HIV transmission rate among people who inject drugs (PWID) remains low in Hong Kong. There was a peak of 58 reported cases in 2006, the number gradually settled to no more than 15 cases each year between 2013 and 2018. The HIV prevalence among PWID, as derived from the universal HIV urine testing programme at the methadone clinics, has remained low at around 1% in recent years.

As regards the location of virus transmission, some 73.8% of MSM acquired the infection in Hong Kong between 2006 and 2018. However, for heterosexual male, only 42.4% acquired the infection in Hong Kong, 24.9% in Mainland China and the remaining 32.7% were infected in other places or that the locations of infection were unknown from history.[Box 2.4][Box 2.5]

HIV transmission in MSM

MSM have continued or emerged to account for a significant proportion of newly acquired HIV infection in many areas around the world, including Hong Kong. Beginning 2006, a series of HIV Prevention and Risk behavioural Survey of MSM (PRiSM) were conducted periodically. The studies were designed as a regular public health surveillance programme to profile risk behaviours of MSM, track the epidemic and inform intervention. Following 3 rounds in 2006, 2008 and 2011, the fourth round of PRiSM was conducted in 2017, in which 4,133 MSM participated.

From the results of PRiSM 2017, the overall HIV prevalence for sexually active MSM was estimated to be 6.54%.[13] Consistent condom use between men (defined as always using a condom for anal sex in the preceding 6 months) was 52.1% for receptive sex and 52.2% for insertive sex. Recreational drug/substance use during or before sex (“chemsex” Chapter F37) was reported in 16.2% of the respondents. HIV testing rate in the past 12 months was 52.6%, higher than that in PRiSM 2011 (41%), but slightly lower than the rate (60%) recorded in another behavioural risk survey in 2016.[14] Though the results of the two surveys could not be directly compared due to different sampling frame (web-based in PRiSM 2017 vs. community-based recruitment in the latter), the overall HIV testing rate among MSM was still not satisfactory. Moreover, HIV self-testing was not common among ever-testers (10.1%) but more than 50% of ever-testers would like to try HIV self-test in the future.

Epidemiology at molecular level

In Hong Kong, over 80% of the reported cases had been successfully genotyped since 2001. Of over 6300 genotyped cases captured in the voluntary HIV reporting system, over 20 subtypes could be seen. The commonest subtypes were CRF_01AE (35.5%) and type B (27.7%), followed by CRF07_BC and CRF08_BC, C and CRF_02AG occurring in 5.6%, 4.0%, 2.8% and 2.4% of total cases respectively.[Box 2.6]

The B subtype and CRF01_AE are epidemiologically different in their characteristics. From 2001 to 2017, CRF01_AE was commoner in female than male (41.6% vs 34.0%), other Asians than Chinese (47.8% vs 35.8%), among heterosexually transmitted cases than MSM (45.9% vs 28.6%) and PWID (63.1%). On the other hand, subtype B was more prevalent in male than female (33.2% vs 3.9%) and MSM than heterosexuals (44.7% vs 11.1%). With the increased diversity of the subtypes found locally in the past few years, the overall proportion of CRF01_AE gradually fell from 41% in 2011 to 31.9% in 2017 and that of subtype B had decreased from around 30% in 2011 to 22.6% in 2017.[Box 2.6] In contrast, the contribution of other subtypes including CRF07_BC, CRF08_BC, CRF02_AG and CRF03-AB have steadily increased after 2010, e.g. CRF08_BC increased from 4.8% in 2011 to 7.6% in 2017.

HIV epidemiology in Pearl River Delta Region

The Pearl River Delta Region consists of major cities in Guangdong province, Macao and Hong Kong Special Administrative Regions (SAR). An electronic platform for HIV surveillance was launched in 2005, covering 12 participating cities, with a total population of about 74 million. The number of newly-reported HIV cases in the Region has shown a general rising trend in majority of the cities during the past decade. The greatest growth was among MSM, the prevalence of which ranged from 6% to 16% in 2016. On the other hand, HIV prevalence of PWID and female sex workers in the cities has remained stable at a relatively low level of less than 5% and less than 0.5% respectively.

Conclusion

It has been more than thirty years after the first reported case of human HIV infection. Hong Kong has been trying very hard to maintain a city of relatively low HIV prevalence. Introduction of HAART has markedly reduced the morbidity and mortality of HIV/AIDS and related complications. However, similar to some other developed regions, the expanding local HIV epidemic in MSM is currently still one of our major challenges. In addition, the high population mobility and the networking with cities/countries with a higher HIV prevalence are causes for concern.

Other potential threats to Hong Kong include the increasing HIV prevalence in the nearby regions, suboptimal coverage of HAART in neighbouring cities/countries, as well as the potential risk of HIV outbreak among PWIDs in Hong Kong.

References