ART was given to 314 (96.3%) patients. Twelve patients (3.7%) either refused or deferred therapy. Among patients on ART, 35.0% (n = 110) of the patients received ART prior to 2009 while 65.0% (n = 204) received ART after the implementation of universal HIV treatment policy in 2010.

The most common ART regimen was non-nucleoside reverse transcriptase inhibitor-based therapy with nucleoside reverse transcriptase inhibitors backbone that included either combination of lamivudine/zidovudine or tenofovir disporoxil/emtricitabine. Tenofovir disoproxil based regimens were widely used after 2010. The most common protease inhibitors were lopinavir/ritonavir and atazanavir/ritonavir. Integrase inhibitors (INIs) have been used most recently as a second-line alternative for treatment failures.

Among a total of 326 HIV infected patients, 6.7% (n = 22) died and 8.9% (n = 29) were lost to follow-up. The annual mortality rate was 0.342 per 1000 per year for the last five years [Figure 1].

Discussion

To our knowledge, this is the first study describing the epidemiology, clinical, and laboratory characteristics of a cohort of 326 HIV infected patients and their outcomes in Oman. The most common mode of transmission in both genders was heterosexual contact causing 58.9% of infections. Men who have sex with men (MSM) are among the groups affected by HIV in the region.8,9 However, due to discrimination and social stigma, the true prevalence of HIV in MSM is unknown and probably underestimated with national data suggesting a prevalence of 13.9%, followed by mother-to-child (5.5%), IV drug use (4%), and blood transfusion (2.8%).9 A recent report from the MENA had indicated an increase in HIV acquisition through IV drug users (IVDUs) in countries like Oman, Bahrain, Morocco, Egypt, and KSA.5,13,14 This might be partly explained by the increase in HIV screening programs among IVDUs.

In our cohort, 45 (22.8%) male patients had an unknown mode of transmission, most likely the under-reporting is due to fear of discloser and stigma in particular among MSM population. In addition, a higher rate of mother-to-child transmission has been observed (around 16%) probably representing earlier transmissions when no antenatal screening was done, and management of HIV in pregnancy was suboptimal. Since 2009, a universal screening program for all pregnant females has been taking place in Oman with an acceptance rate of 99%.9

HIV coinfection affects the natural history and clinical outcomes of individuals infected with HBV or HCV virus, resulting in rapid progression to liver cirrhosis and hepatocellular carcinoma.15–17 The prevalence of HBV and HCV coinfection with HIV is not well documented in the region. A systematic review and meta-analysis report on the prevalence of HIV, HBV, HCV, and HIV coinfections in different subpopulations conducted in Iran estimated the prevalence rates of HIV/HBV and HIV/HCV around 1.9% and 10.9%, respectively.18 Similarly, a retrospective analysis of 142 HIV positive patients in Western Saudi Arabia estimated the prevalence of HIV/HBV and HIV/HCV coinfections at 2.8% and 8.5%, respectively.19

The prevalence of HIV/HBV and HIV/HCV coinfection seen was low at 2.8% and 5.8%, respectively. The low prevalence of HIV/HBV coinfection is probably due to the low to intermediate prevalence of HBV in the general population20 and HBV vaccination since 1990. However, a more accurate estimate is required in other high-risk groups, such as IVDUs and prisoners.21

Several studies from the MENA region have reported a correlation of HIV, HBV, and HCV with age and gender.22–25 HBsAg was more common among males in all age groups while anti-HCV was more prevalent among older females.25–28 In contrast, in our study HIV/HCV coinfection was more prevalent in young patients and predominately in men with IVDU risk. HIV/HBV coinfection did not correlate with age or gender.

In Oman, despite free access to healthcare and the significant programmatic improvement in management of HIV infection, patients still present at advanced stages due to the delay in screening and detection of HIV. This was seen in our cohort, where 51.8% of HIV infected patients already presented with symptomatic infection and 26.1% were WHO stage 4 (AIDS) at the time of first hospital visit. It is well established that patients with CD4+ cell counts < 200 cells/mm3 are at higher risk for opportunistic infections, cancers, and death.29–33 The delay in diagnosis can be attributed to several factors such as a lack of HIV awareness among individuals and health care workers, a lack of surveillance of key populations (i.e., MSM or IVDU), a limited number of voluntary counseling and testing clinics, and no access to self HIV testing. In this study, male patients presented with significantly lower CD4 T lymphocytes than female patients (46.2% vs. 25.6%, respectively). This has been observed in several studies where females infected with HIV tend to be younger, have higher CD4 T lymphocyte counts and lower HIV viral loads at the time of initial HIV diagnosis.34–37 However, correlation with transmission rates, clinical outcomes, rate of disease progression, and death has shown contradictory results. In a recent systematic review that included studies from both developed and developing countries, females starting ART had slightly better survival compared to males but showed no clear benefit in progression to either AIDS or to differences in HIV suppression and immunologic recovery.38

The difference in mortality was attributed to several explanations including a protective effect of female sex hormones and higher expression of IFN-stimulated genes in HIV-1-infected women.39 In our setting, early detection in females could be partly attributed to the antenatal screening program that was adopted in the country from 2009.

HIV RNA viral suppression defined as viral load < 20 IU/mL was seen in 169 (51.8%) patients, while 64 (19.6%) patients had viral suppression per WHO criteria (i.e., viral load of < 1000 IU/mL). Complete virological failure was seen in 81 (24.8%) patients. The high virological failure rates can be attributed to de novo drug resistance or lack of adherence and compliance with HIV medications (which is more common in our setting). Nevertheless, as a result of implementing several interventions in our clinic (i.e., counseling on compliance and adherence by trained health care workers, detailed review by clinical pharmacists each visit, using clinical pathways, and HIV resistance testing), the number of patients achieving viral suppression has increased in the last few years, making the UNAIDS target of 90% of HIV patients on treatment virally suppressed feasible by 2020.

The current wide availability of ART and recent changes in international guidelines encouraging early initiation of ART regardless of CD4+ T lymphocytes has lowered morbidity and mortality among HIV infected individuals. The total number of deaths in Oman has decreased from 200 in 2003 to 100 in 2014 (UNAIDS published data 2018). However, the annual mortality rate in our cohort was 0.342 per 1000 person-years in the last five years; significantly higher than mortality rates reported from the developed countries (0.025 deaths per 1000 person-years).40

Among the greater ongoing challenges faced in Oman, are the rises in new HIV cases and AIDS-related mortality rates despite a strong national HIV program and the free access to ART. The increase HIV cases can be attributed to increased screening, better diagnostic modalities, and early detection; however, late presentation with advanced HIV infection and high mortality rates indicate a substantial gap in the cascade of HIV care. Thus, an urgent priority is to reach the UNAIDS target where 90% of all people living with HIV will know their HIV status. The national AIDS program should establish interventions that focus on early detection and preventive strategies. By outreaching key at-risk populations, the program can offer access to health services and engage infected people in a system that enables them to access HIV testing without fear.

One of the main limitations of our study is its cross-sectional design where some data are missing as some patients were lost to follow-up either due to death or transfer to other centers. In addition, despite a large number of patients in our cohort, the study data were collected from a single center, and this might not fully be representative of the country as a whole. Our results may only apply to Oman or countries with similar HIV prevalence rates and cultural background.

Conclusion

The majority of patients acquired HIV through heterosexual transmission. One-quarter of patients in our cohort were diagnosed late with symptoms of HIV related illness and AIDS, 96.3% of the patients were initiated on ART, and 71.5% achieved virological suppression. Among the priorities in Oman are increasing HIV testing and early diagnoses in key at-risk populations, this will help in fast-tracking and linking infected individuals to appropriate services in order to reach the WHO 90-90-90 target by 2020.

Disclosure

The authors declared no conflicts of interest. No funding was received for this study.

Acknowledgements

The authors would like to thank the physicians at the Infectious Diseases Unit at the Royal Hospital and the technicians in the Virology and Hematology sections at the Royal Hospital, Muscat, Oman.

references

1. UNAIDS. Prevention gap report. 2016 [cited 2017 November 26]. Available from: www.unaids.org/sites/default/files/media_asset/2016-prevention-gap-report_en.pdf.
2. 2. Abu-Raddad LJ, Hilmi N, Mumtaz G, Benkirane M, Akala FA, Riedner G, et al. Epidemiology of HIV infection in the Middle East and North Africa. AIDS 2010 Jul;24(Suppl 2):S5-S23.
3. 3. World Bank Group. Characterizing the HIV/AIDS epidemic in the Middle East and North Africa: Time for strategic action. 2010 [cited 2017 November 26]. Available from: https://openknowledge.worldbank.org/handle/10986/2457.
4. 4. Bozicevic I, Riedner G, Calleja JM. HIV surveillance in MENA: recent developments and results. Sex Transm Infect 2013 Nov;89(Suppl 3):iii11-iii16.
5. 5. Mumtaz GR, Weiss HA, Thomas SL, Riome S, Setayesh H, Riedner G, et al. HIV among people who inject drugs in the Middle East and North Africa: systematic review and data synthesis. PLoS Med 2014 Jun;11(6):e1001663.
6. 6. Mahfoud Z, Afifi R, Ramia S, El Khoury D, Kassak K, El Barbir F, et al. HIV/AIDS among female sex workers, injecting drug users and men who have sex with men in Lebanon: results of the first biobehavioral surveys. AIDS 2010 Jul;24(Suppl 2):S45-S54.
7. 7. Mumtaz GR, Riedner G, Abu-Raddad LJ. The emerging face of the HIV epidemic in the Middle East and North Africa. Curr Opin HIV AIDS 2014 Mar;9(2):183-191.
8. 8. Gökengin D, Doroudi F, Tohme J, Collins B, Madani N. HIV/AIDS: trends in the Middle East and North Africa region. Int J Infect Dis 2016 Mar;44:66-73.
9. 9. HIV Management in Oman: A guide for health care workers. National AIDS Program, Department of Communicable Diseases, Directorate General for Disease Surveillance and Control, Ministry of Health, Oman. 3rd ed. 2015.
10. 10. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2016 [cited 2017 December 7]. Available from: www.who.int/hiv/pub/arv/arv-2016/en.
11. 11. UNAIDS. 90-90-90: An ambitious treatment target to help end the AIDS epidemic. 2017 [cited 2017 December 7]. Available from: www.unaids.org/en/resources/909090.
12. 12. World Health Organization. Interim WHO clinical staging of HIV/AIDS and HIV/AIDS case definitions for surveillance. 2005 [cited 2017 December 7]. Available from: www.who.int/hiv/pub/guidelines/casedefinitions/en.
13. 13. Mumtaz G, Hilmi N, McFarland W, Kaplan RL, Akala FA, Semini I, et al. Are HIV epidemics among men who have sex with men emerging in the Middle East and North Africa?: a systematic review and data synthesis. PLoS Med 2010 Aug;8(8):e1000444.
14. 14. Al-Mozaini MA, Mansour MK, Al-Hokail AA, Mohmed MA, Daham MA, Al-Abdely HM, et al. HIV-care outcome in Saudi Arabia: a longitudinal cohort. J AIDS Clin Res 2014 Nov;5(11):370.
15. 15. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012 May;142(6):1264-1273.e1.
16. 16. Michielsen PP, Francque SM, van Dongen JL. Viral hepatitis and hepatocellular carcinoma. World J Surg Oncol 2005 May;3:27.
17. 17. Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006;44(1)(Suppl):S6-S9.
18. 18. Bagheri Amiri F, Mostafavi E, Mirzazadeh A. HIV, HBV and HCV coinfection prevalence in Iran - a systematic review and meta-analysis. PLoS One 2016 Mar;11(3):e0151946.
19. 19. Al-Mughales JA. Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia. J Med Virol 2016 Sep;88(9):1545-1551.
20. 20. Kaminski G, Alnaqdy A, Al-Belushi I, Nograles J, Al-Dhahry SH. Evidence of occult hepatitis B virus infection among Omani blood donors: a preliminary study. Med Princ Pract 2006;15(5):368-372.
21. 21. Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis 2016 Jul;16(7):797-808.
22. 22. El-Sherif A, Abou-Shady M, Abou-Zeid H, Elwassief A, Elbahrawy A, Ueda Y, et al. Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients. J Gastroenterol 2009;44(4):359-364.
23. 23. Rebbani K, Ouladlahsen A, Bensghir A, Akil A, Lamdini H, Issouf H, et al. Co-infections with hepatitis B and C viruses in human immunodeficiency virus-infected patients in Morocco. Clin Microbiol Infect 2013 Oct;19(10):E454-E457.
24. 24. Heijnen M, Mumtaz GR, Abu-Raddad LJ. Status of HIV and hepatitis C virus infections among prisoners in the Middle East and North Africa: review and synthesis. J Int AIDS Soc 2016 May;19(1):20873.
25. 25. Chaabna K, Mohamoud YA, Chemaitelly H, Mumtaz GR, Abu-Raddad LJ. Protocol for a systematic review and meta-analysis of hepatitis C virus (HCV) prevalence and incidence in the Horn of Africa sub-region of the Middle East and North Africa. Syst Rev 2014 Dec;3:146.
26. 26. Daw MA, Shabash A, El-Bouzedi A, Dau AA; Association with the Libyan Study Group of Hepatitis & HIV. Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya. PLoS One 2014 Jun;9(6):e98793.
27. 27. Akhtar A, Khan AH, Sulaiman SA, Soo CT, Khan K. HBV and HIV co-infection: Prevalence and clinical outcomes in tertiary care hospital Malaysia. J Med Virol 2016 Mar;88(3):455-460.
28. 28. Chen X, He JM, Ding LS, Zhang GQ, Zou XB, Zheng J. Prevalence of hepatitis B virus and hepatitis C virus in patients with human immunodeficiency virus infection in Central China. Arch Virol 2013 Sep;158(9):1889-1894.
29. 29. Miller V, Mocroft A, Reiss P, Katlama C, Papadopoulos AI, Katzenstein T, et al. Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study. Ann Intern Med 1999 Apr;130(7):570-577.
30. 30. Farizo KM, Buehler JW, Chamberland ME, Whyte BM, Froelicher ES, Hopkins SG, et al. Spectrum of disease in persons with human immunodeficiency virus infection in the United States. JAMA 1992 Apr;267(13):1798-1805.
31. 31. Hanna DB, Gupta LS, Jones LE, Thompson DM, Kellerman SE, Sackoff JE. AIDS-defining opportunistic illnesses in the HAART era in New York City. AIDS Care 2007 Feb;19(2):264-272.
32. 32. Frisch M, Biggar RJ, Engels EA, Goedert JJ; AIDS-Cancer Match Registry Study Group. Association of cancer with AIDS-related immunosuppression in adults. JAMA 2001 Apr;285(13):1736-1745.
33. 33. Cheung MC, Pantanowitz L, Dezube BJ. AIDS-related malignancies: emerging challenges in the era of highly active antiretroviral therapy. Oncologist 2005 Jun-Jul;10(6):412-426.
34. 34. Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB, Quinn TC. Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. N Engl J Med 2001 Mar;344(10):720-725.
35. 35. Nicastri E, Angeletti C, Palmisano L, Sarmati L, Chiesi A, Geraci A, et al; Italian Antiretroviral Treatment Group. Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy. AIDS 2005 Mar;19(6):577-583.
36. 36. Cornell M, Schomaker M, Garone DB, Giddy J, Hoffmann CJ, Lessells R, et al; International Epidemiologic Databases to Evaluate AIDS Southern Africa Collaboration. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study. PLoS Med 2012;9(9):e1001304.
37. 37. Mosha F, Muchunguzi V, Matee M, Sangeda RZ, Vercauteren J, Nsubuga P, et al. Gender differences in HIV disease progression and treatment outcomes among HIV patients one year after starting antiretroviral treatment (ART) in Dar es Salaam, Tanzania. BMC Public Health 2013 Jan;13:38.
38. 38. Castilho JL, Melekhin VV, Sterling TR. Sex differences in HIV outcomes in the highly active antiretroviral therapy era: a systematic review. AIDS Res Hum Retroviruses 2014 May;30(5):446-456.
39. 39. Addo MM, Altfeld M. Sex-based differences in HIV type 1 pathogenesis. J Infect Dis 2014 Jul;209(Suppl 3):S86-S92.
40. 40. Centers for Disease Control and Prevention. National Center for Health Statistics USA. 2016 [cited 2017 December 7]. Available from: https://www.cdc.gov/nchs/index.htm.