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Title: Clinical and laboratory features of HIV/AIDS in the Kingdom of Saudi Arabia
Author: Bajhmoum, Wail
ISNI:       0000 0004 5352 1192
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
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There are insufficient data on the epidemiology and clinical features of HIV in the Middle East. WHO statistics show the Kingdom of Saudi Arabia (KSA) to be one of the least affected countries globally. However, the Saudi National Program for HIV Control reported a 34.6% increase in cases in 2008 from the previous year. Jeddah region has the highest proportion of HIV cases in KSA (40%). Infection risk data are not always complete and coinfection rates have not been studied. The first part of these studies included a retrospective longitudinal case review of all patients attending the Jeddah clinic to obtain a clearer view of clinical and epidemiological features of that population There are few publications about resistance to antiretroviral therapy (ART) in the Arabian Peninsula, including KSA, and most are heavily biased towards assessment of patients with sequential treatment failure. Wider access to resistance testing has only become available recently and baseline local resistance patterns are largely unknown. The aim of the second part of the study was to determine patterns of ART resistance in a systematic fashion in treatment-naïve HIV positive Saudi patients and to document the presence and frequency of novel resistance HIV markers in Jeddah. Study Part 1. Clinical features and epidemiology of HIV and coinfection with TB and/or viral hepatitis in a large clinic in Jeddah, Kingdom of Saudi Arabia Aims: To describe demographic and clinical features of HIV infection in clinics and hospitals in Jeddah and to document prevalence and risks for coinfections with tuberculosis (TB) and/or hepatitis Methods: Retrospective study including all HIV positive Saudi adults attending the main treatment centre in Jeddah in the 11 years (2000-2010). Data were systematically collected from case files and summarised. Statistical comparisons included univariate analyses with a p value <5% considered significant. Results: 1383 HIV positive adults were reviewed, median (range) age 40 (18-86) years, of whom 1026 (74.2%) were male. Risk factors included heterosexual transmission in 709 (51.3%), men having sex with men (MSM) in 264 (26%), blood products in 148 (10.7%), injecting drug use (IDU) in 97 (7%) and not identified in 165 (11%). The predominant clinical presentation was with respiratory symptoms 611 (44%), followed by gastrointestinal manifestations in 312 (22%), while 29% (408) were asymptomatic. Past or present TB coinfection (clinical and/or radiology) was found in 208 (15%); 59 (5.3%) had hepatitis B serology positive (HBsAg positive) and 82 (7.4%) had hepatitis C coinfection (antibody positive). TB was associated with IDU (RR 1.67 (CI 1.13-2.41) p< 0.01) and having been in prison (RR 1.83 (1.18-2.85) p< 0.01) and these two risk factors were closely linked themselves. HBV coinfection was not linked with IDU (RR 1.89 (0.93-3.85) p=0.08) but was linked to being in prison (2.38 (1.25-4.54) p <0.01), while HCV was strongly linked with IDU (RR 4.22 (2.71-6.57) p<0.01) and MSM but not with imprisonment (RR 1.94 (1.04-3.63) p=0.07) Conclusion: HIV/AIDS and related coinfections are medical problems in Saudi Arabia with many social challenges. The Saudi National Program for HIV Control actively addresses prevention of HIV and provision of high quality care for those affected. More detailed studies are needed on clinical patterns in outpatient and inpatient settings and on locally appropriate prevention programmes in high risk groups. Study Part 2. HIV resistance in ART naïve patients in a large treatment centre in Jeddah, Kingdom of Saudi Arabia Aims: To document the prevalence and types of ART resistance in ART naïve HIV patients in Jeddah, and to compare the efficacy of Next Generation Sequencing (NGS) with standard (Sanger) genotypic methods. Methods: Plasma samples were collected from all ART-naïve patients sequentially attending the HIV clinic at King Saud Hospital, the main HIV treatment centre in Jeddah, between November 2012 and February 2013. Plasma was saved and HIV protease (Prot) and reverse transcriptase (RT) regions were sequenced according to routine in-house diagnostic protocols (Sanger) at Liverpool Specialist Virology Centre. The Stanford database was used for interpretation of resistance profiles. Neighbour-joining phylogenetic analysis was performed on samples with adequate sequence data for both Prot and RT. NGS sequencing was later performed at the Public Health England reference laboratory in Colindale. Results: Blood samples were collected from 109/116 (94%) eligible patients approached to join the study. 71 (65%) were male and 52 (48%) had been diagnosed with HIV within the last 6 months. HIV RNA was successfully amplified from 96, and sequence data obtained from 93 Prot amplicons and 87 RT amplicons by Sanger and 105 by NGS. Mutations at putative resistance sites for NNRTI NRTI and PI were detected by Sanger in 9/87 (10.3%), 1/87 (1.1%) and 6/93 (6.5%) and 24/105 (22.9%), 6/105 (5.7%) and 34/105 (32.4%) respectively by NGS. Those with significant potential to confer resistance to NNRTI were found in 9/87 (10.3%), with resistance to NRTI in 1/87 (1.1%) and PI in 6/93 (6.5%). 4.5% of the samples showed resistance to efavirenz and nevirapine. The most common HIV-1 subtype was C (38%); although a cluster of CRF2_A (7%) was also prominent. Conclusion: Clinically significant resistance is emerging (16 %) in this population. A variety of other markers included some clustering suggesting local transmission of primary resistance. The results are probably generalizable in KSA and we recommend the introduction of routine resistance testing for all HIV positive patients in the region before starting ART. Overall: These findings provide evidence for introduction of several changes to enhance the National HIV/AIDS programme in the Kingdom of Saudi Arabia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available