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Journal of Infection and Public Health 16 (2023) 1500–1509

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Journal of Infection and Public Health


journal homepage: www.elsevier.com/locate/jiph

Review

Human immunodeficiency virus in Saudi Arabia: Current and future


challenges ]]
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Maha Al-Mozaini a, , Tahani Al-Rahabani b, Qais Dirar d, Tala Alashgar a, Ali A. Rabaan e,
Waleed Murad a, Jawaher Alotaibi c, Abdulrahman Alrajhi c
a
Immunocompromised Host Research Section, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
b
Riyadh Elm University, Riyadh, Saudi Arabia
c
Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
d
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
e
Molecular Diagnostic Laboratory, JohnsHopkins Aramco Healthcare, Dahran, Saudi Arabia

a r t i cl e i nfo a bstr ac t

Article history: Introduction: Understanding the pathophysiology of HIV infection has been crucial to the design of effective
Received 12 February 2023 anti-viral strategies. HIV infection is declining worldwide due to early diagnosis and the effective long-term
Received in revised form 23 May 2023 use of anti-retroviral therapy. New infections decreased from 3.3 million in 2002–2.3 million in 2012.
Accepted 11 June 2023
However, in the Middle East and North Africa (MENA), an estimated 83,000 individuals still acquired the
virus, with 37,000 morbidities reported. The first incidence of acquired immunodeficiency syndrome (AIDS)
Keywords:
from the Kingdom of Saudi Arabia (KSA) was reported in 1984. By the end of 2013, around 1509 patients had
Human immunodeficiency virus
Infection been diagnosed with HIV infection. HIV surveillance has improved in KSA with advances in medical care,
Saudi Arabia counseling, family planning, diagnostic evaluation, and anti-retroviral therapy, but challenges remain.
Acquired immunodeficiency syndrome Patients receiving anti-retroviral therapy still show significant morbidity and mortality. Further targeted
Epidemiology treatment regimens and preventive strategies are required to control HIV infection in KSA. Progress towards
Anti-retroviral therapy meeting the 90–90–90 goals for HIV in the MENA has also not been systematically monitored.
Health policy Method: In this review, we examine current screening programs, therapeutic modalities, the emergence of
drug resistance, and future perspectives for HIV-associated health care in KSA.
Conclusion: The aim is to offer insight for healthcare policymakers to comply with the UNAIDS 2020 vision
program and help establish the prevailing paradigms in the HIV community for an AIDS-free generation and
the 90–90–90 goals for diagnosis.
© 2023 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health
Sciences. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/
4.0/).

Contents

. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1501
. Epidemiology and the prevalence of HIV infection in the Kingdom of Saudi Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1501
. Early screening programs for HIV in the Kingdom of Saudi Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1503
. Modes of HIV transmission in the Kingdom of Saudi Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1503
. Co-infections involving HIV in the Kingdom of Saudi Arabia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1504
. HIV-1 and TB in the Kingdom of Saudi Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1505
. Unique co-infections with HIV in the Kingdom of Saudi Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1505
. HIV and coronaviruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1505
. Sexually transmitted diseases with HIV co-infection in the Kingdom of Saudi Arabia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1505
. HIV research in the Kingdom of Saudi Arabia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1506


Correspondence to: Immunocompromised Host Research Section, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, PO Box 3354
(MBC-03), Riyadh 11211, Saudi Arabia.
E-mail address: mmozaini@kfshrc.edu.sa (M. Al-Mozaini).

https://doi.org/10.1016/j.jiph.2023.06.012
1876-0341/© 2023 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY
license (http://creativecommons.org/licenses/by/4.0/).
M. Al-Mozaini, T. Al-Rahabani, Q. Dirar et al. Journal of Infection and Public Health 16 (2023) 1500–1509

. Knowledge and attitudes toward HIV/AIDS in the Kingdom of Saudi Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1506
. The national response to the AIDS epidemic . . . . . . . . . . . . . . ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1508
. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1508
. CRediT authorship contribution statement . . . . . . . . . . . . . . . . ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1508
. Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1508
. Declaration of Competing Interest . . . . . . . . . . . . . . . . . . . . . . . ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1508
. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1508

Introduction Since 2011, the Saudi Ministry of Health (MOH) initiated the release
of annual AIDS reports, which have significantly improved the
Human immunodeficiency virus (HIV) infection and AIDS remain quality of data collection and reporting.
global health problems. According to a recent report by the World Table 1 summarizes the epidemiology and prevalence of HIV
Health Organization (WHO) and the joint United Nations Program on studies performed since the first reported case in 1985. A gap in both
HIV/AIDS (UNAIDS), approximately 38.4 million individuals are reported studies and interest occurred between 1985 and 2004. The
currently infected with HIV worldwide, with 1.5 million people, in­ first two studies documenting the prevalence of HIV in specific re­
cluding 180,000 children, acquiring HIV-1 infection in 2017 alone gions of KSA occurred in 2004. A total of 410 individuals were di­
(UNAIDS; Report on the Global HIV/AIDS Epidemic). agnosed with HIV. A subsequent, more extensive study reported
While the epidemiological characteristics of HIV infection in 1285 cases of HIV infection in the KSA [1,2]. An additional epide­
Western, African, and South-East Asian countries are well char­ miological survey was performed in 2005 and showed a steady rise
acterized, the clinical scale and demography of HIV in the MENA are in cases of HIV-1 infection, reaching 7807, of which only 1743 were
poorly understood. It was estimated that approximately 240,000 Saudi nationals [3]. Most infected patients were expatriates from
people were living with HIV at the end of 2014, including 75,000 Africa and Asia who inhabited the Western province of KSA, parti­
children (Report on HIV/AIDS in Asia and Middle East regional cularly in the cities of Jeddah and Makkah. A recent longitudinal
Bureaus; USAID). To date, 12,000 people have died from AIDS in cohort study at KFSHRC of those infected with HIV-1 between 1989
MENA countries. The prevalence of HIV-infected individuals is re­ and 2010 (n = 602) reported that many patients presented with AIDS
ported to be low in MENA compared to Western countries, but at the time of initial evaluation. The study concluded an increasing
current data are limited. For the Gulf Cooperation Council (GCC) trend in HIV infections compared to developing countries [4].
countries (Kingdom of Saudi Arabia (KSA), Bahrain, Kuwait, Oman, The first Global AIDS Response Progress Report (GARP) was re­
United Arab Emirates, and Qatar), the clinical, demographical, and leased in 2010 by the National AIDS Program Manager for the KSA.
treatment-related characteristics of HIV patients are rarely reported It reported an increase of up to 10 % in new HIV-1 infections an­
due to social and cultural constraints. Despite current estimates in­ nually. However, the report highlighted a low HIV-1 prevalence,
dicating that Middle Eastern countries constitute only a proportion with approximately 1.5 new infections per 100,000 annually among
of the 36.9 million infected with HIV worldwide, the number of new Saudis and 12.5 per 10,000 among non-Saudis. From 1984 to the
infections in the MENA region has increased by 26 % since 2015 first reported HIV tests in 2013, 20,539 cases were reported, 5890
(UNAIDS). (28.7 %) in Saudi and 14,649 (71.3 %) in non-Saudi citizens. The
Since 2014, significant progress has been made toward reducing majority of non-national HIV cases were amongst those with a
the spread of HIV and achieving the UNAIDS 90–90–90 treatment higher opportunity for testing, including those tested for work
target. Despite these advances, the MENA region is the only area in permits (iqama, 34 %), foreigners with suspected HIV (23 %), and
which the number of new infections is rising, with over half of those prisoners (17 %) [3].
diagnosed at a late stage. HIV/AIDS remains a significant health Limited data describes pediatric HIV in the Middle East and Gulf
challenge in MENA, including GCC countries. Here, we provide a region. Only a single Saudi study describes the spectrum, char­
comprehensive review highlighting the unique challenges of diag­ acteristics, and outcomes of HIV infection in children [9]. This study
nosis and the prevention and management of HIV infection in KSA. was conducted before implementing preventive measures such as
We describe current issues which, if overcome, will provide clin­ ARV prophylaxis, cesarean delivery, and abstention from breast­
icians, health policymakers, and the community a unique opportu­ feeding. Between 1986 and 2003, 63 HIV-1 infected or exposed
nity to disseminate the latest advances in basic science, clinical children were treated at KFSHRC. The source of infection was either
implementation, and the stigma associated with HIV/AIDS. perinatal transmission (63.5 % of cases) or transfusion of con­
Understanding the status and current challenges facing HIV/AIDS in taminated blood or blood products (34.5 % of cases). In addition, 90 %
our country will be essential to attain the UNAIDS 90–90–90 goal of infected children were delivered by spontaneous vaginal delivery
successfully. and 10 % via cesarean section. The majority (93 %) of infected infants
were breastfed throughout infancy. All patients followed received
ART or HAART at the beginning of 1997. Of those receiving HAART, 79
Epidemiology and the prevalence of HIV infection in the % were treatment compliant and had a sustained viral load below
Kingdom of Saudi Arabia the detectable. Unfortunately, 75 % of patients diagnosed prior to
1995 died, compared to 7.7 % who died when diagnosed after 1995.
KSA has a geographic area of approximately 2240,000 km2 and In addition to the more common HIV-1 subtype, HIV type 2 (HIV-
occupies most of the Arabian Peninsula. Latest Saudi census report, 2) is common in West Africa and a significant cause of AIDS. In 2011,
2021, reported that the population was as 35 million, including 5.6 two Saudi families were identified with HIV-2 infection and AIDS. In
million non-nationals. Approximately 29.4 % of the KSA population the first family, the 30-year-old wife was HIV-positive following the
is aged less than 15 years, with 67.6 % between 15 and 64 years and 3 diagnosis of her 30-year-old husband, who later died due to AIDS-
%, above 64 years of age. KSA is geographically divided into five related disease. In the second family, HIV-2 infection was diagnosed
major regions (Fig. 1). HIV infections were first described in the early in a 50-year-old wife and an 18-year-old daughter, transmitted from
1980 s, meaning reporting the disease in the KSA has been in­ the husband, who had died of AIDS-related disease at the age of 48.
complete. Until 2004, the primary source of information regarding This case demonstrated how HIV-2 could be transmitted from mo­
the prevalence of HIV in the KSA was the UNAIDS annual report. ther to child.

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M. Al-Mozaini, T. Al-Rahabani, Q. Dirar et al. Journal of Infection and Public Health 16 (2023) 1500–1509

Fig. 1. Map of the Kingdom of Saudi Arabia. Saudi is divided into five major regions: (i) Western province, which includes the cities of Makkah, Jeddah, Taif, and Madinah; (ii)
Central province, which includes Riyadh, Hail, and Qassim; (iii) Eastern province, which includes Dammam, Ahsa, and Hafr Albaten; (iv) Southern province, which includes Abha,
Asier, Baha, Jizan, Najran, and Bisha; (v) Northern Province, which includes Joaf and Tabook.

Table 1
Epidemiological and prevalence reports of HIV infection in the Kingdom of Saudi Arabia.

Year of publication Institute Study Study Period Number of patients in the HIV Nationality Authors
Location cohort

1985 KFSHRC Riyadh 1984 1 Saudi Kingston et al. [5]


1986 MOH Riyadh 1985 2 Both Saudi Harfi and Fakhry [6]
2004 KFSHRC Riyadh 1984–2003 410 All Saudi Alrajhi et al. [7]
2004 MOH KSA* 1984–2001 6046 Saudi n = 1285 (21.3 %) Madani et. al. [2]
Non-Saudi n = 4761 (78.7 %)
2005 MOH KSA* 1984–2003 7807 Saudi n = 1743 (22.3 %) Al Mazrou et al. [3]
Non-Saudi n = 6064 (77.6 %)
2010 MOH KSA* 1984–2009 15,213 Saudi n = 4019 (%) Al Mazrou et al.
Non-Saudi n = 11,194 (%)
2012 MOH All KSA* * 2000–2009 10,217 * ** Saudi n = 2956 Mazroa et al. [8]
Non-Saudi n = 7261
2014 KFSHRC Riyadh 1984–2010 602 All Saudi Al Mozaini, M et al. [4]
2014 MOH All KSA 1984–2013 20,539 Saudi n = 5890 Report from the National AIDS
Non-Saudi n = 14,649 program-MOH

*HIV cases were reported from all regions of Saudi Arabia, with the highest prevalence observed in Jeddah and Makkah in the Western province.
** HIV cases were reported from all regions of Saudi Arabia, with the highest prevalence in Jeddah and Riyadh;
***Total number of newly reported HIV cases.

Additionally, HIV viral loads were undetectable in initial assays, (25 %), B (17.9 %), D (3.6 %), and A (1.8 %). In addition, a recombinant
but further testing confirmed the presence of HIV-2. A failure in ART subtype (CRF), CRF02_AG, was detected in 1.8 % of infected patients.
therapy was also observed, indicative of drug resistance [10]. More Despite a relatively small number of enrolled subjects, this high
recently, the number of reported cases of HIV-2 in the region has diversity of HIV-1 strains was suggestive of the introduction of HIV-1
increased (unpublished data). Thus, there is an urgent need to de­ into the KSA from several sources [11]. A later study reported sub­
velop rapid diagnostics for HIV-2 infection, which are essential for type C as the most common, occurring in 58 % of samples, followed
preventing transmission, particularly in pregnant women. by Subtype B (17 %) and subtypes A, D, and G, each found in 8 % of
Detecting HIV subtypes is essential from an epidemiological samples [12]. Recent profiling of drug resistance-associated muta­
perspective and can help trace the origin of infections. Two in­ tions in the KSA was performed in 103 HIV-1 patients undergoing
dependent studies evaluated the prevalence of each HIV subtype in HAART protocols. These analyses showed that the drug resistance
the KSA using a small sample size (n = 62). Subtype C was the most mutations in the KSA were comparable to those internationally re­
common, accounting for 39.3 % of infections, followed by subtype G ported, but some novel drug resistance strains were identified [13].

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M. Al-Mozaini, T. Al-Rahabani, Q. Dirar et al. Journal of Infection and Public Health 16 (2023) 1500–1509

The prevalence of primary or transmitted HIV drug resistance to all The development of automated large-scale molecular screening
drugs and drug classes evaluated was 66 % and 34 %. Therefore, early technologies has significantly improved the safety of blood trans­
identification of these mutants will be key to avoiding therapy fusions due to improved specificity and sensitivity relative to ser­
failure. ological screening. For example, in 2014, molecular testing was
HIV-1 entry into T cells is initiated by the binding of viral en­ implemented at the King Khalid University Hospital blood bank
velope glycoproteins (gp120-gp41) to cell surface receptor (CD4) and (Riyadh), in which approximately 25,920 donor samples were
its co-receptor (CCR5), followed by fusion at the plasma membrane. screened for HIV and viral hepatitis using serological and molecular
Genetic variants have been implicated in the susceptibility to HIV-1 techniques. Promisingly, no HIV NAT yields were detected but con­
infection. The prevalence of these mutations varies according to firmed HBV NAT infections in the KSA and MENA regions are sparse
ethnicity. In a study examining the prevalence of HIV-related var­ [19]. However, a few studies have reported how screening for the
iants in 135 Saudi nationals [14], an overwhelming majority (134/ prevalence of HIV differs amongst high-risk populations (Table 3).
135) were homozygous for wild-type CCR5. A single patient was For example, patients with tuberculosis (TB) were deemed a sig­
heterozygous for the Δ32 deletion allele, with none homozygous for nificant risk for HIV infection [26], followed by HSV-1/2, which was
the mutant allele. Therefore, the mutation in the CCR5 co-receptor significant with HSV-2 ( P < 0.0001) [27].
occurs at a low frequency in the Saudi population. However, these The rates of HIV transmission through seroconversion were
results raise concerns regarding HIV pathogenesis and the clinical evaluated in 12 Hemodialysis Units (HDU). The rates of HIV pre­
use of CCR5 antagonists in the KSA, which are currently under de­ valence were 5.7 % at one HDU, while 11 units reported rates of 0 %.
velopment as therapeutics for HIV-1 and inflammatory diseases. DNA/RNA sequencing supports patient-to-patient or common-
source transmission [28]. Infections did occur despite the low pre­
valence of HIV in Saudi Arabia and national dialysis policies em­
Early screening programs for HIV in the Kingdom of Saudi Arabia phasizing infection prevention and control practices.
In 2008, the Saudi health authority included mandatory testing
Identifying at-risk populations is key to adequate access to for HIV, HBV, and HCV in pre-marital screening programs. Although
therapy, disease prevention, and counseling. However, this cycle of the prevalence of HIV, HBV, and HCV in KSA is amongst the lowest
identification and provision is currently lacking. Reports from KSA worldwide, significant risk factors associated with the transmission
have identified blood and blood products as the primary source of of these viruses exist in the Saudi community. The initiation of this
HIV infections since adequate testing of imported blood was not program was justified considering poor knowledge regarding the
available then. In the Eastern region, a study showed that of 134,599 prevalence and epidemiology of these diseases. Accordingly, a cross-
individuals screened, 10 cases of HIV infection resulting from blood sectional descriptive study of the national pre-marital screening
and blood product transfusions occurred [15]. Table 2 summarizes program for the prevalence of these virus infections in 74,662 in­
these data [16–20]. A single study attempted to determine the pre­ dividuals was followed by a case-controlled study to identify risk
valence of HIV and other blood-borne viruses amongst Saudi blood factors responsible for infection transmission (n = 540). The average
donors by nucleic acid testing on 400 blood samples negative for HIV prevalence of HIV was 0.03 %, suggesting that automated and deep
and viral hepatitis by serology. It was found that only 381 samples gene sequencing impacted such studies. It can be argued that due to
were negative for HIV [16]. At the time of testing, the prevalence of human rights and a lack of awareness, most positive HIV patients fail
HIV in the KSA was low and poorly understood. Thus, nucleic acid to disclose their HIV status to their partners. Easy-to-use self-testing
testing of blood donors by serology was reported as adequate for programs for HIV are beginning to be introduced that should pro­
screening. mote active testing and reporting of HIV infection status in public.

Table 2 Modes of HIV transmission in the Kingdom of Saudi Arabia


Summary of blood and blood products screening for HIV-1 infection in KSA over the
last 40 years. The ability to halt the transmission of HIV is crucial to effective
Year Study Location Reported Positive for Percentage (%) Authors disease management programs. The various reported modes of
HIV/Total number transmission in the KSA are summarized in Table 4. Heterosexual
screened
transmission was Saudi patients’ most common mode of transmis­
1984 Jazan 0/85 0 Ashraf et al. sion [4,26]. HIV infection through homosexual activity was not sig­
[21] nificant, suggestive of a low prevalence of HIV-1 in men having sex
1986 Southwestern 0/3100 0 Al-Nozha
et al.
with other men (MSM), misidentification due to the social percep­
[22] tion of homosexuality, or both. MSM may not express their sexual
1989 Riyadh 0/1000 0 El-Hazmi orientation freely in the KSA. Data also indicate a steady increase in
et al. HIV infections acquired through Intravenous Drug Users (IDU), with
[23]
the maximum number of 2.8 % reported in 2003 [33,34], likely due
1991 Riyadh 1/19,775 0.005 Barri et al.
[24] to routine HIV screening of drug users in drug treatment centers in
1998 Eastern Province 10/134,599 0.007 Fathalla and KSA. Individuals that test positive are referred to a treatment facility
Al-Sheikh for HIV care. A retrospective study was performed between January
[15] 2006 and November 2012 to assess the prevalence of HIV and viral
2001 Riyadh 0/400 0 Akhter et al.
hepatitis infections amongst heroin users in KSA. Screening results
[16]
2004 Central Region 0/24,173 0 El-Hazmi revealed that 20.1 % of subjects were infection-free, while 1.1 % were
[25] infected with HIV, indicating a significant association between HIV
2006 Taif 3/3288 0.09 Bamaga et al. and HCV infections. Serious viral infections are common among
[18]
Saudi heroin users, similar to Western countries [35]. Infection
2016 Riyadh 0/25,920 0 Mohamud
et al. control, education, and harm reduction programs are therefore of
[19] paramount importance for reducing and managing blood-borne
2016 Al Baha 1/2807 0.04 Almutairi pathogenic viruses, including HIV.
et al. A paucity of studies describes the mother-to-child transmission
[20]
of HIV. Almost two decades ago, the rate of mother-to-child HIV-1

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Table 3
Screening for HIV infection in the Kingdom of Saudi Arabia. *Correlation between HSV-2 infection and other STIs was significant for HIV (P < 0.0001).

Group Year Study Location Reported positive for HIV/Total number screened Percentage (%) Authors

Mixed Population 1984 Jazan 0/85 0 Ashraf et al. [21]


1986 Riyadh 0/212 0 Al-Nozha et al. [22]
1989 Riyadh 0/203 0 El-Hazmi et al. [23]
Mixed Control Population 1988 All 4 Regions 0/370 0 El-Hazmi [29]
Sicklers 1988 All 4 Regions 0/173 0 El-Hazmi [29]
TB 2002 Riyadh 0/178 3.3 Alrajhi et al. [30]
STD 1989 Riyadh 0/170 0 El-Hazmi et al. [25]
2015 All 4 Regions 80/4985* 1.6 Memish et al.[27]
Hemodialysis Unit 2014 MOH in 12 HDUs 5.7 Mashragi et al. [28]
Hemopoietic Stem Cell Transplant 2015 Riyadh 0/263 0 Alsuhibani et al. [31]
Pre-marital Screening 2010 MOH 1/74,662 0.03 Alswaidi and O’Brien [32]

infections was reported to be high in KSA. Edathodu and colleagues 2014, none were infected with HIV, as confirmed by serology and
from KFSHRC evaluated mother-to-child transmission in a cohort of NAT testing protocols [31].
HIV-infected women enrolled in their HIV program. All infected Collectively, these data highlight heterosexual transmission as
women who became pregnant and delivered between January 1994 the predominant mode of acquiring HIV-1 amongst Saudi patients.
and June 2006 were included. Variables such as the viral load, CD4+ Women tend to acquire the virus from their spouses, while hetero­
T-lymphocyte count, and pregnancy stage were evaluated. The mode sexual men acquire HIV from extra-marital sex. Other vulnerable
of delivery was elective cesarean delivery in 70 % of patients. All groups remain less defined, and these data may not reflect actual
patients received ART during pregnancy and delivery, and none of prevalence in MSM and IDU. The potential limitation of these studies
the newborns were breastfeeding. Remarkably, all 39 newborns is that they are limited to a single institution. Therefore, there is an
tested negative for HIV infection at 18 months. urgent and pressing need for national HIV sentinel surveillance
Contrary to previous clinical experience, the diagnosis, and programs in well-defined high-risk groups.
management of HIV, in addition to ART, eliminated mother-to-child
transmission of HIV-1 (Edathodu et al., 2010). In a study comparing
horizontal versus vertical transmission [22], 25 cases were reported Co-infections involving HIV in the Kingdom of Saudi Arabia
as positive for HIV-1 infection in the southern region of KSA since
1986 that involved blood transfusion. They successfully followed up Viral co-infections in HIV/AIDS patients may result in more rapid
on 19 of these cases and their contacts. Of the patients, 17 were disease progression, representing a growing public health concern
diagnosed with AIDS or AIDS-related complex (ARC) after admission worldwide. Pathogenic viruses that are most likely to co-infect in­
to the hospital in response to deteriorating health. Moreover, all 9 dividuals with HIV include hepatitis B virus (HBV), hepatitis C virus
children born to HIV-1 infected mothers became virus positive (HCV), and Epstein-Barr virus (EBV). In particular, HBV and HCV tend
within 16 months. This highlighted the importance of advanced fa­ to occur in conjunction with HIV due to similar transmission routes.
mily planning and the discouragement of breastfeeding, a common Since HBV and HCV are endemic in KSA, numerous reports describe
practice in Saudi women for up to 2 years. their prevalence, clinical characteristics, and sero-epidemiology
A recent study among hematopoietic stem cell transplantation (Table 5). For example, in a single study, when 875 expatriates from
(HSCT) donors and recipients highlighted infectious disease pre­ the Eastern region of KSA underwent mandatory pre-employment
vention strategies in a single center adhering to international testing for HCV/HIV-specific antibodies, four samples (0.46 %) were
guidelines. Among 263 consecutive donors screened from 1996 to positive [12].

Table 4
Mode of HIV transmission in the Kingdom of Saudi Arabia.

Mode of Transmission Year Study Location Study Period Reported Positive for HIV /Positive screened Percentage (%) Authors

Heterosexual 2004 Riyadh 1984–2003 189/410 46 Alrajhi, A et al. [26]


2014 Riyadh 1984–2014 141/602 65.3 Al-Mozaini, M et al. [4]
IDU 2004 Riyadh 1984–2003 7/410 2 Alrajhi, A et al. [26]
2014 Riyadh 1984–2014 17/602 2.8 Al-Mozaini, M et al. [4]
2015 Riyadh 2006–2012 37/357 9.8 Alshomrani et al. [35]
MSM 2004 Riyadh 1984–2003 20/410 5 Alrajhi, A et al. [26]
2014 Riyadh 1984–2014 10/602 1.6 Al-Mozaini, M et al.[4]
Hemophilia 1987 Al-Baha 1984–1986 5/17 29 Al-Nozha et al. [22]
2004 Riyadh 1984–2003 57/410 14 Alrajhi, A et al. [26]
2014 Riyadh 1984–2014 60/602 9.9 Al-Mozaini, M et al. [4]
Perinatal 2004 Riyadh 1984–2003 47/410 12 Alrajhi, A et al. [26]
2010 Riyadh 1994–2010 9/40 22.5 Edathodu et al. [36]
2014 Riyadh 1984–2014 59/602 9.8 Al-Mozaini, M et al. [4]
Blood Transfusion 1985 Riyadh 1984 1 NA Kingston et al. [5]
1986 Riyadh 1984–1985 2 NA Harfi & Fakhry. [6]
1995 Al-Baha 1988–1994 25 NA Al-Nozha et al. [22]
2004 Riyadh 1984–2003 50/410 12 Alrajhi, A et al. [26]
2014 Riyadh 1984–2010 86/602 14.3 Al Mozaini, M et al. [4]
Organ Transplantation 2004 Riyadh 1984–2003 6/410 1.5 Alrajhi, A et al. [26]
2007 Jeddah 2007 23/540 4.3 Baderddine et al. [11]
2014 Riyadh 1984–2010 7/602 1.2 Al Mozaini, M et al. [4]

*Reported in Kidney transplant patients only


**NA were the first reported cases of HIV.

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Table 5
HIV mode of transmission and co-infections in KSA.

Year Study Location Reported Positive for HIV /Positive screened Percentage (%) Authors

2002 KFSHRC 2/178 1.1 Alrajhi et al.[30]


2006 KFSHRC 2/22 9 Hakawi and Alrajjhi [39]
2008 Eastern Province 4/875 0.46 AlZahrani [12]
2010 KFSHRC 16/217 7.4 Omair et al .[40]
2013 KAU/Jeddah 45/343 3.1 Fageeh. [41]
2014 KFSHRC 24/490 4.9 Al-Mozaini et al. [4]
2014 KFSHRC 11/341 3 Alhuraiji et al. [37]
2014 KFSHRC 85/450 18.8 Al-Mozaini et al. [4]
2014 KFSHRC 41/341 12 Alhuraiji et al. [37]
2014 KFSHRC 29/602 4.8 Al-Mozaini et al. [4]
2015 MOH 4985 HSV-1 0.06 Memish et al. [27]
2015 Jeddah 1/1 HSV-2 1.6 Shalhoub et al. [42]
100
2016 Western 4/142 2.8 Al-Mughales [38]
Province

HCV infection is the dominant co-infection in HIV-positive in­ Unique co-infections with HIV in the Kingdom of Saudi Arabia
dividuals, followed by HBV [4]. A 20-year longitudinal study involving
341 HIV-infected patients at KFSHRC revealed HCV co-infection in 12 % HIV and coronaviruses
of the subjects, with 88 % of patients co-infected via blood transfusion
being hemophiliacs. Heterosexual transmission was responsible for Following the first documented infections in Wuhan, China, se­
HCV and HIV co-infections in 22 % of patients. HCV Genotype 1 was the vere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) rapidly
most common (44 %), followed by genotype 4 (15 %). HBV Hepatitis B spread across the globe. Several cases of co-infection with HIV and
surface antigen was found in 3 % of patients. The most common risk SARS‐CoV‐2 have been reported, with preliminary analysis sug­
factor for HBV and HIV co-infection was heterosexual transmission in gesting that HIV‐related immunosuppression increases the risk of
nearly 73 % of patients, followed by blood/blood product transfusion severity of COVID‐19, though this remains open for debate [43]. In a
(18 %) [37]. Both studies reported HCV as the most common co-infec­ systematic review of the literature reporting cases of HIV and SARS-
tion with HIV, followed by HBV. Blood and blood product transfusion CoV-2co-infection, a favorable prognosis for HIV patients strictly
was the most common risk factor for HCV and HIV co-infection, oc­ adhering to ART was proposed [44]. This may be explained by ART
curring in 60 % of patients. The prevalence of HCV and HBV infections components showing clinical efficacy against SARS-CoV-2 [45,46] or
was 20- and 10- fold higher amongst HIV-infected patients than in the the inability of the virus to effectively disrupt the complement
general population. system and trigger inflammation due to pre-existing dysfunctional
A recent retrospective study estimated the prevalence of diag­ immune defenses of HIV patients [47]. Of note, a consensus is
nosed and undiagnosed co-infections amongst HIV, HBV, and HCV- growing in South Africa that the omicron variant that harbors 50
infected patients in the western region of KSA [38]. Co-infection of mutations from the original virus evolved during prolonged infec­
HIV with HBV and HCV occurred in 8.5 % and 2.8 %, respectively. This tion in an immunocompromised individual [48]. This raises an in­
relatively low prevalence of co-infections may be due to a significant triguing question as to whether this variant owes its origin to HIV,
proportion of cases remaining undiagnosed due to the lack of sys­ the primary cause of immunodeficiency in the region. In the KSA,
tematic screening. information on HIV and SARS-COV-2 co-infections is less well un­
derstood and will require integrating clinical, epidemiological, mi­
crobiological, and mortality data to fully understand this
HIV-1 and TB in the Kingdom of Saudi Arabia relationship.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
In KSA, international travel and migration facilitate the spread of causes severe pneumonia with significant morbidity and mortality,
tuberculosis (TB) infection. Tuberculosis (TB) is a chronic infectious particularly in patients with multiple comorbidities. A single case of
disease typically caused by Mycobacterium tuberculosis bacteria. TB MERS-CoV co-infection was documented in an HIV-infected patient.
generally affects the lungs but can involve other organs, such as the However, this patient was reported to have a successful clinical
kidneys, spine, or brain. CD4+ and CD8+ lymphocytes provide es­ outcome [42].
sential defense in the control of TB infection. In addition, CD4 lym­
phopenia is a well-defined risk factor for developing active TB co-
infection in HIV-infected patients. Sexually transmitted diseases with HIV co-infection in the Kingdom of
In a retrospective study involving 437 patients diagnosed with TB Saudi Arabia
between 1995 and 2000 in KFSHRC, 2 patients (1.1 %) were identified
as HIV positive. Males were screened more often than females (45 % Herpes simplex virus (HSV) is one of the common sexually
and 36 %, respectively) [30]. In the same cohort study screened in transmitted infections (STIs). Like HIV, data describing the pre­
2014, TB was observed in 29 patients [4]. An observational study [40] valence of HSV infections and other STIs in the KSA are limited. Only
conducted at the same institute evaluated the incidence of TB in two epidemiological studies have addressed this issue, performed at
those infected with HIV. Of 219 patients, TB was diagnosed in 16 two different institutions representing two significant cities within
AIDS patients (7.4 %). The incidence rate of TB infection was 1354/ the KSA (Table 5). The first study of STIs amongst patients with HSV
100,000 per year amongst the HIV-infected cohort. The incidence was conducted at King Abdulaziz University Hospital in Jeddah, the
rate of pulmonary TB was 762/100,000 per year and 592/100,000 per Western region of the KSA [41]. A retrospective review of medical
year for extra-pulmonary TB. Despite early diagnosis and treatment, records for 8 years (2003–2011) evaluated the prevalence of STIs
7 patients (44 %) died. This highlights a 30-fold higher prevalence of among HSV-positive patients, primarily women, who presented to
TB infections in HIV-infected individuals in KSA compared to the the emergency room and outpatient departments. They reported a
general population. variable number of patients co-infected with HIV (13.1 %), chlamydia

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(12.5 %), gonorrhea (12.8 %), and HBV (2.3 %). As such, HIV was the SAMHD1 to suppress anti-viral pro-inflammatory responses pro­
most common co-infection among HSV-positive patients. moting long-term virus latency. Vpx, therefore, holds promise as a
The second study was a sero-prevalence survey that investigated potential anti-HIV target.
the prevalence, epidemiology, and occurrence of co-infections Although these studies are significant, large-scale HIV genome
among adult Saudis with HSV [49]. Serology assays were used to sequencing projects are urgently required to understand the epide­
detect HSV-1, HSV-2, and HIV infections amongst 4985 participants miological prevalence and origins of HIV. In addition, mutations
recruited across the KSA. The overall prevalence of HSV-1 and HSV-2 within the CCR5 co-receptor in the Saudi population must be fully
in the enrolled population was 88.8 % and 1.26 %, respectively. HSV-1 understood and will dictate the clinical use of CCR5 antagonists in
infection was more prevalent amongst young working married fe­ the region. Such individuals can be seropositive but show no
males. Co-infections were significantly higher amongst those with symptoms of AIDS despite high viral loads. A recent study in a Saudi
low education levels and increased with age. HSV-1 and HIV infec­ cohort of 3025 stem cell donors concluded that the protective CCR5-
tions in the sampled population were low (0.06 %). Δ32 allele is rarely present in Saudi Arabia [52].
Similarly, the prevalence of HIV-1 among HSV-2-positive parti­ HIV/AIDS research in the KSA remains in its infancy. The current
cipants was low (1.6 %). However, the correlation between HSV-2 principal funding sources for applied research are the KACST, local
infection and HIV was significant (p < 0.0001). These reports in­ universities, and the Ministry of Health. HIV/AIDS funding from
dicate that HIV-1 and other STIs frequently co-infect patients with private donors is currently unavailable. Given the progress in HIV
HSV. Improved STI monitoring strategies will likely prevent new research in KSA, it is critical that the WHO reinstate the Kingdom as
infections in KSA, particularly HIV-1. Future studies should evaluate eligible for such programs. Each year, the KSA is becoming more
STIs in the KSA. Moreover, screening partners of those diagnosed globally connected as an organization aiming to benefit global
with STI will reduce HIV transmission. health. Funding from businesses and Philanthropic foundations alike
must match the need for our community to design, develop and
HIV research in the Kingdom of Saudi Arabia implement HIV and AIDS programs. This is not only restricted to the
government and must include private donations.
The significant challenges facing the development of an HIV
vaccine include the need to protect against globally diverse virus Knowledge and attitudes toward HIV/AIDS in the Kingdom of
strains and the unclear immune correlates of protection. In addition, Saudi Arabia
although global funds are available to fight AIDS, tuberculosis, and
malaria in the KSA, external funding sources for KSA are rare, mainly Stigma remains a significant barrier to the effective management
because the World Bank classifies the KSA as a High-Income Country of HIV in the KSA. Numerous studies have evaluated the attitude
and the WHO and its affiliates often disqualify the KSA from funding toward HIV/AIDS, which are both highly conservative and culturally
assistance programs. limited (Fig. 2). Studies targeting different cohorts of citizens, in­
Nevertheless, KFSHRC established the first HIV/AIDS research cluding secondary school students, students in medical colleges, and
laboratory in the KSA to address fundamental science and clinical health professionals, highlight the prevalence of negative attitudes
research aspects. The research explores the immunological and toward HIV. Stigmatization towards discussing AIDS, home care, and
molecular pathways involved in the immune deficiency of HIV-in­ the right to work for people with HIV/AIDS remain consistent re­
fected patients. HIV/AIDS Researchers at the KFSHRC are also in­ gardless of location or population demographics [53–55]. Apparent
volved in the production of diagnostic tools for improved patient gaps in knowledge and attitude amongst practicing physicians
treatment and have made significant contributions to understanding highlight the lack of general public information and knowledge re­
the cellular mechanisms that drive HIV infection and pathogenesis garding HIV/AIDS in the KSA [56]. It is, therefore, critical that middle
in the region. The ultimate aim is to delineate new therapeutic in­ and high school students are exposed to HIV/AIDS educational
terventions that will increase immune competence while reducing programs, which have successfully improved awareness of HIV in
patient vulnerability to infectious disease in our region and globally. previous programs.
Excluding the retrospective studies reported in this review, limited A cross-sectional survey was conducted on 204 female inmates at
basic research has been performed in KSA. Briman prison in Jeddah (Western region) to assess the knowledge of
Most studies are confined to evaluating the prevalence of HIV-1 HIV and STDs among inmates. Of the prisoners, 90 % had no or poor
subtypes [11, 12] genetic variants of CCR5 [14]. Further studies have knowledge of HIV [41]. Together, these studies suggest that more
been initiated to discover fundamental changes in the host pro­ effort should be aimed at educating high-risk populations in the
teomic profiles in response to HIV-1, HIV-2, and HIV-3 infections. KSA, such as illegal residents and prisoners. In 2015, a comprehen­
These were performed using peripheral blood plasma samples sub­ sive survey was conducted amongst 5000 illegal residents to eval­
jected to label-free quantitative liquid-chromatography tandem uate knowledge, attitudes, and practices surrounding HIV and AIDS
mass spectrometry (LC-MS/MS) [50]. Several critical contributors to in the KS. The results showed that ∼25 % of respondents were
virus pathogenesis were identified, including XRCC5 and PSME1, and unaware of HIV/AIDS, and a large number of participants (85 %)
several signaling proteins (MAP2K1, RPL23A, RPS3, CALR, PRDX1, expressed discomfort in interacting with HIV-positive people in
SOD2, LMNB1, PHB, and FGB). A high degree of similarity in protein various situations [57].
profiles of HIV-1 and HIV-2 was reported, but 6 host proteins More recently, Alghabashi & Guthrie conducted a critical meta-
showed significant changes across strains, including ETFB, PHB2, analysis of existing methods used to evaluate knowledge and atti­
S100A9, LMO2, PPP3R1, and Vif. These data provide the first example tudes towards HIV/AIDS in the KSA. A review of 16 articles demon­
of the HIV-specific protein expression changes for individual strains strated both positive and negative attitudes. All studies reported
in the region and may aid future diagnostic capabilities within high response rates. Although gender-specific tools were not de­
the KSA. veloped, transmission patterns in the KSA are gender-dependent,
In studies using an HIV-2 strain from a Saudi patient, new in­ with a higher male-to-female infection ratio. The study concluded
formation regarding the targeting of SAMHD1 during the virus life­ that current methods lack culturally appropriate tools and tend to
cycle was discovered [51]. SAMHD1 is a human host factor found in survey low-risk populations, such as students. As a result, they fail to
myeloid cells which restricts HIV replication through the depletion evaluate HIV knowledge reliably and accurately in the KSA, parti­
of the dNTP’s pools required for viral cDNA synthesis. Within the cularly in high-risk populations. Knowledge of pre-marital sex was
study, HIV-Vpx was shown to induce proteasomal degradation of reported in 31 % of the 225 study participants, comprising young

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Fig. 2. Studies performed in the Kingdom of Saudi Arabia assess the social impact of HIV/AIDS.

men in Riyadh [58], and beliefs of adolescents regarding STDs and pornographic material (OR: 6.79), and traveling alone abroad (OR:
HIV/AIDS [59]. Sexual activity was the primary response, with the 3.10) [58]. A need to detail the risks and knowledge gaps in sexual
survey indicating inadequate Knowledge regarding STIDs in 34.5 % of health awareness amongst young men is therefore present to pre­
the participants. vent the spread of STIs and HIV. This includes improving workplace
Considering the high prevalence of STDs and other associated policies, informing debate about the criminalization of HIV trans­
health problems amongst young adults globally, it is essential to mission, and promoting the realization of human rights. Stigma
identify the sexual practices that could potentially compromise index analysis represents a powerful tool to support the goal of the
health. A study on the sexual practices of young, educated men in government to reduce the stigma and discrimination linked to HIV.
KSA was conducted in 2013. In a Riyadh-based study including 225 In unpublished studies investigating the knowledge score of in­
participants, 31 % had engaged in pre-marital sexual activity at least dividuals in the KSA regarding HIV/AIDS, the general population was
once and 61 % viewed pornographic movies/materials. Only 51 % knowledgeable to a certain degree. However, it lacked a detailed
were aware of the safety of condom use in preventing STIs; 20 % understanding of the disease’s nature, transmission modes, and
were not aware that HIV could be transmitted through both homo­ existing treatment strategies. These represent critical knowledge
sexual and heterosexual contact. Pre-marital sexual activity was gaps highlighting the potential to increase the HIV epidemic in Saudi
associated with the use of illegal drugs (OR: 2.51), viewing Arabia.

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Table 6
Milestones of HIV/AIDS in the Kingdom of Saudi Arabia.

Year Reference

1984 The first case diagnosed and reported in KSA from KFSHRC [5] Kingston et al., 1985
March 1985 Approval of commercial testing for HIV infection MOH
April 1985 First published report on an AIDS case from KSA from KFSHRC [5] Kingston et al., 1985
July 1985 Screening blood donors for HIV in KSA Blood bank/KFSHRC
1986 CDC released a working definition for AIDS CDC, 1986
1987 Approval of Zidovudine, the first anti-retroviral agent FDA
1988 The inception of an HIV clinic at King Fahad Hospital, Albaha (Southwest of KSA) [22] Al-Nozha et al., 1995
1989 The inception of an HIV clinic at KFSHRC, Riyadh (Capital of KSA)
1991 Saudi Minister of Education directed all education regions and school health units to implement AIDS education in schools [54] Abolfotouh, 1995
2001 Saudi Ministry of Health released an annual epidemiologic AIDS report MOH
2004 Inception for the first HIV/AIDS annual workshop KFSHRC
2008 Pre-marital screening program included mandatory testing for HIV, HBV, and HCV viruses. MOH
2010 The inception of the National AIDS Program Manager for KSA. MOH
2013 The inception of an HIV research laboratory at KFSHRC, Riyadh (Capital of KSA)
2014 MOH’s latest report to the UNAIDS program MOH

The national response to the AIDS epidemic should be implemented throughout the community and healthcare
systems by simplifying treatment regimens and integrating services,
Significant efforts have been made in response to the AIDS epi­ particularly among critical populations. Most importantly, empow­
demic in KSA due to increased political support from key national ering civil society, including religious leaders, communities, and
stakeholders and decision-makers at the MOH and other sectors. As organizations, particularly women and young people, will be central
a result, the treatment and prevention of HIV-1 infection were offi­ to the design, implementation, and monitoring of responses. In ad­
cially announced as a national priority in the KSA. In addition, a dition, establishing new and innovative testing services, medicine
national AIDS program was established within the MOH, which co­ delivery, and using information technology to tailor services are
ordinates efforts to prevent the spread of HIV-1 and supports public required. The country is facing an array of challenges to succeed in
advocacy for the rights of people living with HIV/AIDS. Significant the journey towards 90–90–90, and we must unite and work to­
milestones have been achieved in AIDS prevention and treatment gether to achieve this challenge and beyond to reach and support the
over recent years, yet additional challenges must be addressed in the remaining 10–10–10.
future (Table 6). In 2004, the KSA MOH implemented a mandatory
pre-marital testing program to decrease the incidence of genetic CRediT authorship contribution statement
disorders in future generations (Altalhi, Saudi Annual AIDS Re­
port—2009. National AIDS Program. www.moh.gov). In 2008, this All authors read and approved the final manuscript.
program was updated to include mandatory screening for HBV, HCV,
and HIV-1 and renamed "The Program of Healthy Marriage.". Funding
Mandatory testing programs for HIV-1 and the national surveil­
lance system have revealed an increased incidence of HIV in the KSA. King Abdulaziz City for Science and Technology, Saudi Arabia, as
Governmental and non-governmental stakeholders agree that the a national initiative to combat emergent and re-emergent pathogens
number of reported cases may not reflect the true prevalence of HIV- (ETSC-RKFHRC-RCA-2017-10-12).
1 infection in the KSA due to the ever-present social stigma of HIV-
positive patients. Medical care of HIV-infected individuals faces Declaration of Competing Interest
unique challenges due to specific cultural, social, political, and eco­
nomic conditions in the KSA, which may explain the number of The authors declare no competing interests.
unreported cases of HIV infection. A paucity of research remains on
the socio-demographic and underlying factors associated with HIV
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