HIV/AIDS in Sierra Leone: Characterizing the Hidden Epidemic George A

AIDS Reviews. 2018;20

Contents available at PubMed www.aidsreviews.com PERMANYER AIDS Rev. 2018;20:104-113 www.permanyer.com

HIV/AIDS in Sierra Leone: Characterizing the Hidden Epidemic George A. Yendewa1,2*, Eva Poveda3, Sahr A. Yendewa4, Foday Sahr4,5, Miguel E. Quiñones-Mateu1,6,7 and © Permanyer 2018 Robert A. Salata1,2

1Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; 2Division of Infectious Diseases and HIV Medicine, University. Hospitals Cleveland Medical Center, Cleveland, Ohio, USA; 3Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur)-Complexo Hospitalario Universitario de Vigo, SERGAS-UVigo, Spain; 4College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 534 Military Hospital, Republic of Sierra Leone Armed Forces, Freetown, Sierra Leone; 6Department of Pathogenesis, Case Western Reserve University, Cleveland, Ohio, USA; 7Center for AIDS Research at Case Western University/University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA of the publisher

Abstract

Sierra Leone is a low-income West African country that has dealt with waves of economic, political, and public health challenges in its recent past, including a decade-long brutal civil war and the Ebola epidemic of 2014-2016. The HIV/AIDS epidemic, which has raged on in the country since 1987, has long been characterized as stable. The latest UNAIDS report estimates a countrywide HIV prevalence rate of 1.7% in 2016 among adults aged 15-49 years. However, there are indications that the epidemic may be in fact es- calating and unless arrested urgently, has the potential to deteriorate into a major public health emergency. Although there are high levels of HIV awareness among adults (over 94%), uptake in voluntary HIV testing has remained low (< 30%), and under one-third (29%) of the country’s 60,000 people living with HIV/AIDS were on antiretroviral therapy in 2015. This review attempts to address the paucity of scientific information on the subject by presenting the historical and epidemiological background to the HIV/AIDS epidemic in Sierra Leone. Other aspects of the HIV/AIDS epidemic in Sierra Leone are examined, including routine HIV screening and diagnosis, linkage to and retention in HIV care, clinical characteristics and molecular epidemiology, treatment coverage, and prevention strategies. Finally, we identify four key areas of challenge that are hampering current efforts attempting to bring the epidemic under control, and perspec- tive is offered on the way forward. (AIDS Rev. 2018;20:104-113) Corresponding author: George A. Yendewa, [email protected]

Key words

HIV. Sierra Leone. Antiretroviral therapy. Diagnostics. Resource-limited settings.

Correspondence to: George A. Yendewa Division of Infectious Diseases and HIV Medicine University Hospitals Cleveland Medical Center No part of this publication may be reproduced or photocopying without the prior written permission 11100 Euclid Ave Received in original form: 27/04/2018 Cleveland 44106, Ohio, USA Accepted in final form: 14/05/2018 E-mail: [email protected] doi: 10.24875/AIDSRev.M18000022

104 Yendewa, et al.: HIV/AIDS in Sierra Leone

and molecular characteristics of the HIV/AIDS epidemic verview of the HIV/AIDS landscape in O in Sierra Leone, current treatment and prevention strat- Sierra Leone egies, and the challenges faced by public health offi- cials in the uphill fight to surmount the epidemic. Sierra Leone is a small, low-income country in West Africa. It has a total population of 7.4 million people History of the prevalence of HIV/AIDS in and a gross domestic product per capita income of Sierra Leone 587 United States dollar, with over 60% of its inhabit- ants living below the poverty line1. Since gaining inde- The earliest known cases of HIV/AIDS in Sierra Leone© Permanyer 2018 pendence from Great Britain in 1961, the country has

were documented in 1987, consisting of 10 HIV-positive grappled with myriad political, economic, and public . individuals among commercial sex workers5. Since health challenges. During the 1990s, Sierra Leone re- then, the countrywide prevalence rate has steadily in- ceived much-unwanted attention on account of a brutal creased and appears to have peaked at 14.9% during civil war that decimated the country’s already fragile the civil war years (1990-2001)6-8. Following the civil health infrastructure, leaving it with some of the worst war, the Government of Sierra Leone and the United indicators of health. The World Health Organization of the publisher States Centers for Disease Control and Prevention (WHO) reported that, in 2010, there were only 0.024 jointly conducted the first ever countrywide HIV serop- physicians per 1000 of the population, one of the low- est anywhere in the world2. The Sierra Leone Demo- revalence study in 2002, which recorded a weighted 9 graphic Health Survey of 2013 (SLDHS 2013) recorded population HIV prevalence rate of 0.9% . More recent an average life expectancy of 47 years at birth, infant countrywide population surveys have consistently re- mortality rate of 96/1000 live births, under-five mortal- ported an apparent plateauing of the HIV prevalence ity rate of 156/1000 live births, and maternal mortality rate at 1.5-1.7%, representing an estimated total of rate of 1165/100,000 births3 (Fig. 1). 67,000 adults and children living with HIV/AIDS in Si- 3,4 The recent Ebola epidemic of 2014-2016 has gener- erra Leone (Table 1). The majority of HIV-infected ated unprecedented interest in various public health individuals appear to be concentrated in the capital city challenges in the country, including the epidemic as- of Freetown (2.5% prevalence), in other urban popula- sociated with HIV/AIDS. The latest Joint United Nations tions around the country, and in regions of high eco- 10 Programme on HIV and AIDS (UNAIDS) report of 2016 nomic activity such as in the diamond mining areas . recorded a countrywide HIV prevalence rate of 1.7%, In 2013, the National HIV/AIDS Secretariat (NAS) of characterizing Sierra Leone as a low prevalence coun- Sierra Leone and UNAIDS conducted a countrywide try4. However, the true nature and scope of the HIV/ population size estimation (PSE) survey, which identi- AIDS epidemic in Sierra Leone have not been fully fied “key populations” (KP groups) exhibiting high-risk examined before, and these figures appear to be un- behaviors or activities that disproportionately increased der-reporting a major and hidden public health prob- their likelihood of being affected by the HIV/AIDS epi- lem. There is a dearth of reliable scientific data on the demic11. The KP groups identified were female sex epidemiological, clinical, and molecular characteristics workers (FSW) and their partners and clients, long- of the HIV/AIDS epidemic in the scientific literature. As distance truck drivers, members of the fishing com- of February 1, 2018, a search in PubMed using the munity, members of the uniformed armed services, and words “HIV+Sierra Leone” (https://www.ncbi.nlm.nih. migrants. Men who have sex with men (MSM) and injec- gov/pubmed/?term=HIV+Sierra+Leone) yielded only tion drug users (IDU) emerged as relatively new and 88 scientific articles, many of them addressing the major demographic representations for new HIV infec- country’s HIV prevalence. All other aspects of HIV tions. The KP groups made up only 4% of the total care, including routine screening and diagnosis, initia- population but accounted for 44% of known HIV cases tion of antiretroviral therapy (ART), HIV drug resistance, in the country. In 2015 alone, 1000 new infections were linkage to and retention in HIV care, socio-cultural im- directly attributable to the KP groups, establishing their plications of HIV-positive status, access to vital allied position as the major and perhaps most important driv- support services (e.g., mental health and social sup- er of the HIV/AIDS epidemic in the country11 (Table 1). port), and quality of life issues for persons living with The PSE survey was followed by the HIV SeroprevaNo part of this publication may be reproduced or photocopying without the prior written permission - HIV have not been sufficiently studied. lence study of the KP in 2015, which reported that HIV This review summarizes some of the currently avail- prevalence rates were highest in the self-identified able scientific data on the epidemiological, clinical, transgender male-to-female category (22.4%), followed 105 AIDS Reviews. 2018;20 © Permanyer 2018

. of the publisher

Figure 1. Map and demographic information of Sierra Leone. Data were summarized from the World Bank Report on Sierra Leone1, the World Health Organization Statistics Summary on Sierra Leone2, and the Sierra Leone Health and Demographic Survey3. Gross domestic product; United States dollar.

by MSM (14%), IDU (8.5%), and FSW (6.7%)12. Other suppression, which has been shown to improve HIV/ KP groups with high prevalence rates were the trans- AIDS-related morbidity and mortality and interrupt the gender female-to-male category (6.7%), clients of com- HIV transmission cycle across all demographic mercial sex workers (2.9%), and prisoners (2.2%)11. In groups17,18. Towards achieving these goals, UNAIDS a separate study, Djibo et al.13 observed that the HIV announced its ambitious global 90-90-90 strategy in prevalence rate was 3.3% among members of the Si- 2014, which aims for 90% of all HIV-infected people erra Leone Armed Forces. Although not considered a to know their HIV-positive status, 90% of those in- KP group per se, pregnant women are a high-risk fected to be on effective antiretroviral treatment, and group, with an estimated prevalence rate of 3.2% re- 90% of people on treatment to achieve virological sup- corded in 201010. In addition, considerable overlap pression by the year 202019. In response, the Govern- was found among members of the KP groups, implying ment of Sierra Leone unveiled its own “National Stra- a mixed HIV transmission dynamic in the country12. tegic Plan (NSP) on HIV and AIDS 2016-2020 - Toward As anticipated, the HIV prevalence rates of the KP Making HIV and AIDS no longer a Public Health Threat groups are significantly higher than the prevalence rate in Sierra Leone by 2020”, in which routine HIV testing of the general population, i.e., 2.2–22.4% versus 1.5- for all listed as one of three key components of the 1.7%, respectively (Table 1). While the data are broad- national strategy to combating the HIV/AIDS epidem- ly reflective of comparable at-risk demographics in the ic11. However, voluntary HIV testing levels have been Sub-Saharan African region14, there may be serious reported as low in the country. Brima et al.20 examined limitations to these estimates. For example, the serop- the impact of voluntary HIV testing from the results of revalence study of the KP groups was conducted at the SLDHS of 20083, in which 6,475 participants were the height of the Ebola epidemic in 2015, when the surveyed countrywide. Of the 96 people that tested level of respondent participation and their contact time HIV-positive (prevalence rate 1.5%), the majority with health-care facilities may have been highly con- (78%) had been unaware of their HIV status and had strained due the prevailing public health emergency in previously never taken a HIV test. It was further ob- the country, thus potentially leading to an underestima- served that (i) young adulthood, i.e., age group 25- tion of the scale of the problem among KP groups12,15,16. 44 years, (ii) residing in urban areas, (iii) female gender, (iv) higher level of education, (v) first sexual

HIV screening and diagnosis intercourse at age 17 years or older, and (vi) usingNo part of this publication may be reproduced or photocopying without the prior written permission a condom during the most recent sexual encounter were Timely diagnosis of HIV infection is the crucial first all independently associated with higher rates of vol- step to early initiation of ART and achieving virologic untary HIV testing20. 106 Yendewa, et al.: HIV/AIDS in Sierra Leone

Table 1. HIV‑1 prevalence in Sierra Leone through the years Period HIV‑1 prevalence (%) Population Route of HIV‑1 Reference transmission

1990‑2001 3‑14.9 Countrywide n.d. Boillot et al.6, (civil war) Spiegel et al.7, Willough by et al.8

2002 0.9 Countrywide n.d. Kaiser et al.9 © Permanyer 2018 2004 ‑2006 9.7 Seeking VCT in n.d. Kouyoumdjian et al.22

Kenema district .

2008 1.5 Countrywide n.d. Brima et al.20

2012 ‑2013 8.9 Febrile patients, n.d. Ansumana et al.32 Bo district 2013 22.4 Countrywide Transgender male NAS12 of the publisher to female

14 Countrywide MSM

8.5 Countrywide IDU

6.7 Countrywide Transgender female to male

2.9 Countrywide Clients of commercial sex workers

2.2 Countrywide Prison population

2013 3.3 Sierra Leone Armed n.d. Djibo et al.13 Forces

2014 2.5 Freetown n.d. NAS10

1 Rural areas n.d.

2016 1.7 Countrywide n.d. UNAIDS4

aAmong people aged 15‑49 years. VCT: voluntary counseling and testing; MSM; men who have sex with men; IDU: injected drug users; n.d.: not determined; NAS: national HIV/AIDS Secretariat

The alarmingly low uptake in HIV testing in Sierra routine HIV testing) was 12.6% in women and 6.7% Leone has been confirmed in other studies. A survey in men. of 285 young adults (classified as age 18-35 years) Stigmatization at both the individual and community conducted in Bo District reported that only 33% of levels has been advanced as a major impediment to study participants had ever undergone HIV testing21. voluntary testing, for HIV in particular and sexually The rate of HIV testing was found to be higher among transmitted diseases in general, in Sierra Leone and women compared with men (i.e., 44% vs. 25%), re- other Sub-Saharan African countries23-26. As a conse- spectively. While over 85% of the study respondents quence, UNAIDS estimated that < 36% of people living expressed willingness to undergo HIV testing, the with HIV in Sierra Leone know their status4 (Fig. 2a). majority (> 90%) preferred to be tested privately. In A more precise understanding of how behaviors, per- 22

another study, Kouyoumdjian et al. found that the ceptions, and local social and cultural pressuresNo part of this publication may be reproduced or photocopying without the prior written permission are HIV prevalence rate among 2230 individuals who shaping attitudes toward HIV testing would be instru- underwent voluntary counseling and testing (1213 mental in helping craft and implement effective evi- through antenatal testing and 1017 specifically for dence-based strategies aimed at reducing stigmatiza- 107 AIDS Reviews. 2018;20

tion and increasing the utilization of HIV testing services in the country. A 80,000 Access to and retention in HIV care 100% 60,000 67,000 Once diagnosed with HIV infection and initiated on ART, adherence to treatment and retention in HIV care 40,000 are critical to maintaining sustained virologic suppres- 35.8% sion and preventing the emergence of drug resistance 20,000 26.9% © Permanyer 2018 27 Number of individuals 24,000

mutations . However, there is limited data describing 18,000 . access to treatment and the various components of the 0 cascade of HIV care in Sierra Leone. In 2015, under People People People one-third (29%) of the estimated 67000 people living living living living with HIV with HIV with HIV with HIV/AIDs in Sierra Leone were on ART, with treat- who know who are ment coverage projected to increase to 35% in 2017, B their status on ART of the publisher and up to 80% by 202010,28. 400 29 100%

Recent prospective data by Kelly et al. assessed d 300 338 the cascade of care of 338 newly HIV diagnosed indi- 81.6% viduals attending the largest HIV clinic in the country 255 during a 12-month period. ART eligibility was defined 200 as CD4 cell counts ≤350 cells/mm3 and/or WHO clinical individuals 33.7% Stage 3 or 4. Of the 225 participants staged for initia- 100 22.8% 114 tion of ART, more people in the pre-ART compared with Number of HIV-infecte 77 the ART-eligible group (59.6% vs. 41.8%, p = 0.03) 0 were retained in care, defined as attending clinic at Newly Staged Retained Effective least once during the past 3 months of the 12-month diagnosed for cART in care HIV care study period. 77 of 388 (22.8%) newly diagnosed HIV- positive individuals from both the pre-ART and ART- Figure 2. A: Number of adults and children living with HIV in Sierra eligible groups remained in “effective HIV care”, de- Leone, including those who know their HIV status and patients who fined as having completed the cascade of care for the are on antiretroviral treatment, antiretroviral therapy. Data extracted 4 entire 12-month study period. Of patients retained in from the UNAIDS Global AIDS Update 2016 report . B: Cascade of HIV care for newly diagnosed patients in Freetown, Sierra Leone care, ART adherence was estimated at 57.5% (50 of over a 12-month period. Adapted from Kelly et al.29. 87 persons). Loss to follow-up (LTFU) was a major impediment to completing the cascade of HIV care, observations are worth noting that may be impacting with the majority of LTFU cases (66.3%) occurring dur- the scale and direction of the HIV/AIDS epidemic. ing the pre-ART period (Fig. 2b). In the era of widespread ART availability, treatment HIV and coinfections coverage should be scaled up in Sierra Leone to meet the UNAIDS 90-90-90 targets and the Government of Endemic to Sierra Leone is a multitude of viruses Sierra Leone’s own strategic policy objectives. Imple- (e.g., Lassa virus, LASV; and Ebola virus, EBOV) that mentation of evidence-based approaches to optimize may be cocirculating with HIV in the general population. linkage to and retention in care will assist the realization Interestingly, HIV has shared routes of transmission of the full benefits of treatment in individual patients, and with many of these pathogens (through sexual contact additionally have ripple public health effects in interrupt- and/or bloodborne exposure). Significant bidirectional ing the HIV transmission cycle in the wider population. effects have previously been described in HIV coinfection with hepatitis B virus, hepatitis C virus, herpes Clinical characteristics of the HIV/AIDS simplex virus, and human papillomavirus - these in-

epidemic clude increased HIV transmissibility, acceleratedNo part of this publication may be reproduced or photocopying without the prior written permission progression to AIDS, and overall worse clinical out- While few studies have examined the clinical charac- comes30,31. It is likely that coinfection with these teristics of the HIV/AIDs epidemic in Sierra Leone, three endemic viruses and other non-viral pathogens may be 108 Yendewa, et al.: HIV/AIDS in Sierra Leone influencing the pathogenesis of HIV infection and alter- rently comprised at least 14 subtypes (A1 to K) and 90 ing disease outcome in coinfected individuals in Sierra circulating recombinant forms41,42. Over 90% of current Leone in thus far undetermined ways. and new HIV infections are associated with HIV-1 Group M strains and are responsible for the global HIV/ Late HIV diagnosis AIDS epidemic38. There are limited data describing the circulating Late diagnosis remains a major hurdle to early initia- HIV strains, transmitted drug resistance, or the prev- tion of HIV treatment and achieving virologic suppres- alence and characteristics of drug resistance in pa- sion. Considering that there are significant gaps at tients failing ART in Sierra Leone. The 2005 country© Permanyer 2018 - every level of the cascade of HIV care in an under- wide HIV seroprevalence study reported that 91% of

. resourced health-care system in Sierra Leone29, it is HIV infections in the general population of Sierra possible that a significant proportion of new HIV diag- Leone were associated with HIV-1, with 4.5% related noses is late presenters (defined as CD4 count to HIV-2 mono-infections, and 4.5% to HIV-1/HIV-2 < 350 cells/mm3 and/or AIDS-defining criteria present dual-infections43. A few case reports have docu- with CD4 count > 350 cells/mm3). Late HIV diagnosis mented the HIV-1 subtype A and CFR02_AG strains, represents a missed opportunity at timely ART initiation identified mainly in individuals migrating toof the publisher Eu- and interrupting the HIV transmission cycle – treatment rope44-48. as prevention (TAP). HIV-2 is endemic in West Africa and is postulated to have ancestry from simian immunodeficiency virus- Fever, an emerging confounder in HIV specific to the sooty mangabey primates (SIVsm)33,34. diagnosis Interestingly, several studies have previously documented the endemicity of SIVsm in primates in Sierra An extremely common but often overlooked observa- Leone49,51. The virological and clinical characteristics tion is the emerging role of fever as an important clin- of HIV-2 differ significantly from HIV-152-54, an important ical presentation and feature of new HIV infection. In a fact to remember in the diagnosis, treatment and clin- recent study, Ansumana et al.32 showed that up to 24% ical follow-up of HIV-2 infected individuals in Sierra of newly diagnosed HIV-positive patients had a febrile Leone and other places with populations having recent illness at presentation. In an earlier study, Willough by origin or ties to West Africa. HIV-2 infection is gener- et al.8 had reported a 92.5% occurrence of fever in ally characterized by a more indolent asymptomatic 106 patients presenting with strong clinical suspicion course, slower CD4 cell count decline and lower plas- for HIV infection during a 2-year period. This observa- ma RNA levels compared with HIV-1 infection52-54. At tion is of paramount importance in Sierra Leone and present, there are no FDA-approved assays for quan- Sub-Saharan Africa, where fever is a cardinal and ex- tification of HIV-2 RNA; infected patients are usually tremely common presenting feature of a host of com- monitored by measurement of CD4 cell count55. Similar mon infections, suspicion usually being highest for to viruses from the HIV-1 Group O56-58, HIV-2 strains malaria and typhoid fever. As a result, it is possible are intrinsically resistant to first-generation non-nucle- that unless a high index of suspicion is assumed, a otide reverse transcriptase inhibitors (NNRTIs), significant proportion of new HIV cases initially pre- (i.e., efavirenz [EFV] and nevirapine [NVP])59,60, which senting with febrile illness may be missed, thus con- constitute the first-line treatment and currently the most tinuing the onward transmission of HIV infection in the widely used ART regimens in the country61 (see treat- general population. ment and prevention strategies section). The preferred regimen for treatment of HIV-2 infection combines a HIV molecular epidemiology and drug two-drug nucleoside or NRTI backbone with a select resistance protease inhibitor62 (e.g., darunavir, lopinavir, or saqui- navir - currently in short supply) or integrase strand Two types of HIV resulting from distinct zoonotic in- transfer inhibitor63 (e.g., dolutegravir and DTG - cur- troductions have been recognized: HIV Type 1 (HIV-1), rently unavailable in the country). ART options are,

predominant throughout the world, and HIV Type 2 therefore, limited for HIV-2 infected patients in No part of this publication may be reproduced or photocopying without the prior written permission Sierra (HIV-2), found primarily in West Africa33-36. HIV-1 has Leone, and their clinical management requires the op- been subdivided into four highly divergent groups, timal harnessing of the currently available ART drugs i.e., M, O, N, and P37-40. The HIV-1 group M is cur- in the country. 109 AIDS Reviews. 2018;20

Treatment and prevention strategies count monitoring capability is available at the largest HIV clinic in Freetown since 2006; this technology is, Treatment, monitoring, and routine clinical however, still not widely accessible in rural areas where follow-up the WHO staging is used to guide clinical decision- making. Routine plasma HIV viral load measurement The main goals of HIV treatment are to achieve and by polymerase chain reaction was recently introduced maintain durable virological suppression, preserve or in 201668; however, this technology is not widely avail- improve immune function, and prevent the selection of able for use in most clinics and health-care centers in drug-resistance mutations64. Due to its success in main- Sierra Leone. HIV drug resistance testing is currently© Permanyer 2018

taining sustained undetectability when adherence levels not available in clinical practice. . are high, ART is now considered one of the most effective prevention strategies in HIV care (TAP or “undetect- HIV prevention able equals untransmit table”)65. Current international treatment guidelines recommend ART for all HIV-infect- With ART coverage effectively below 35%, condom ed individuals, regardless of CD4 cell count64,66,67. use rather than ART TAP remains the most widely used of the publisher Of the 60,000 HIV-positive individuals in Sierra Le- preventive strategy in the country. The SLDHS 2013 one, in 2015, under one-third (about 29%) were esti- report estimated that overall, 4.7% of sexual women mated to be on ART10. In its NSP on HIV/AIDS 2016- and 12.6 % of men aged 15-49 reported using a con- 2020, the Ministry of Health and Sanitation highlighted dom regularly3. Condom use was found to be posi- the enrolment and retention of all known HIV-positive tively associated with (i) adolescence or young adult- individuals in the country on ART as a key policy pre- hood (age 15-24 years) (70.7%); (ii) higher level of scription in the effort to bring the HIV/AIDS epidemic education (80.3%); (iii) higher socioeconomic status under control. During the first 2 years of the implemen- (80.3%); and (iv) residence in urban areas (87.8%)3. tation of this strategic plan (2016-2017), the objective The NAS reported that, in 2015, the majority of FSW was to provide ART treatment to all patients with CD4 (88.2%) surveyed reported the use of a condom with cell count < 500 cells/mm3; with the goal of further their most recent client28. Notwithstanding, the low rate expanding ART coverage to all HIV-positive individuals of condom usage in the general population, there ap- in the country by 2018, regardless of CD4 cell count10,28. pears to be a high level of awareness that condoms The latest antiretroviral treatment guidelines for Si- can prevent HIV transmission (79% men vs. 68% wom- erra Leone (adapted from the WHO) were published in en)3. Programmatic efforts to increase access to con- 200661. No further updates or revisions have been un- doms and other preventive methods should be scaled dertaken since; clinical practitioners rely on interna- up to realize their full benefits in reducing transmission tional guidelines and other reference sources in the rates. More studies should be undertaken aiming to clinical management of HIV patients. In keeping with examine the local religious, social, and cultural barriers standard practice, a regimen based on a two-drug to HIV prevention. NRTI backbone plus either a NNRTI or boosted-PI is used in treatment. The current recommended first-line Facing the goals and challenges of the ART regimens for adults are zidovudine/lamivudine future plus EFV or NVP61. However, the most widely used regimen in the country for all demographic groups in- In Sierra Leone, the HIV/AIDS epidemic poses more cluding pregnant women and children currently ap- than just a pressing public health problem that now pears to be the single pill once-daily coformulation of needs tackling urgently. As in many low-middle income tenofovir/lamivudine/EFV. Integrase inhibitors, which countries (LMICs) in Sub-Saharan Africa where the are the first-line therapy recommended by current in- HIV/AIDS epidemic has not been brought under control, ternational treatment guidelines, are presently not there are huge economic and developmental dimen- available for use in the country. sions to the problem. The 2016-2020 NSP recognizes Routine clinical monitoring is recommended for all this complex interplay of factors in its policy adaptation

patients on ART every 3-6 months by measurement of of the United Nations’ Sustainable Development Goals,No part of this publication may be reproduced or photocopying without the prior written permission CD4 cell count, viral load, complete blood count, se- which seeks to eliminate HIV/AIDS as a public health rum chemistry, and liver function tests61. CD4 cell threat in Sierra Leone by 2030. This strategic policy

110 Yendewa, et al.: HIV/AIDS in Sierra Leone

Mental Health Healthcare Resources Personnel Governmental Private

Laboratory Testing Routine HIV Capabilities for Testing Diagnosis & Clinical Follow-up Philantrophy Public

HIV Care International . Partners Social Support Global Services

Healthcare Delivery & Funding Public Health Systems Social, Behavioral & Research Gender Aspects Capacity Medical of the publisher Stigmatization Universities Poverty Institutions

International Gender Collaborations Issues Education HIV/AIDs Networks

Discrimination Governmental

Figure 3. Challenges and key areas of improvement to control the HIV/AIDS epidemic in Sierra Leone. plan aims to achieve the triple objectives of “Zero new ent, Sierra Leone suffers massively from a shortage of infections, Zero AIDS-related deaths, and Zero AIDS- human resources in the HIV field, including doctors, related discrimination”10. As ambitious as this agenda nurses, and other allied health-care personnel – exac- is, the road ahead is fraught with uncertainty, and the erbated further by the chronic “brain drain” phenom- resources and political commitment invested in ad- enon that has become the fate of many Sub-Saharan dressing these challenges here and now will ultimately African countries69,70. All other aspects of HIV care determine the long-term successes of efforts. This will require urgent updating and scaling up, including rou- require visionary thinking, innovativeness, bold leader- tine HIV testing, linkage to and retention in HIV care, ship, and multi-sectoral collaborative approaches. We access to ART, laboratory facilities, mental health, and identify four keys areas that need new impetus and social welfare services for people living with HIV. strengthening (Fig. 3). Funding challenges Sustainable health-care delivery and public health systems Historically, the national HIV/AIDS response has been funded mainly by international health and agen- A decade-long civil war, a stunted economy, cies. Since May 2005, the Global Fund has served as and competing governmental priorities have left an the primary source of funding for the HIV/AIDS control impoverished country with a feeble public health sys- program in Sierra Leone and has to date committed tem that was swiftly overpowered by the recent Ebola $129 million US dollars71, accounting for 95% of pro- 10

epidemic. To address current challenges and prepare gram costs . International support will remain vitalNo part of this publication may be reproduced or photocopying without the prior written permission for for inevitable future threats, a restructuring of the pub- the foreseeable future. However, increasing govern- lic health system is imperative, within which the expan- ment budget allocation will be crucial in bringing the sion of HIV/AIDS services will need prioritizing. At pres- epidemic under control. 111 AIDS Reviews. 2018;20

Social, cultural, and gender aspects References

. 1 The World Bank 2016. Data Sierra Leone. Available from: http://www. Being a largely traditional society, stigmatization and worldbank.org/en/country/sierraleone. [Last accessed on 2017 gender inequality are deeply entrenched in the society Dec 14]. 2. The World Health Organization 2016. Sierra Leone Statistics Summary and remain major challenges that are off-setting efforts (2002 - present). Available from: http://www.apps.who.int/gho/data/ node.country.country-SLE. [Last accessed on 2017 Dec 14]. aiming to eradicate the threat of the HIV/AIDS epi- 3. Statistics Sierra Leone. Sierra Leone Health and Demographic Survey; demic23-26. Effective community-based educational and 2013.Available from: https://www.dhsprogram.com/pubs/pdf/fr297/ fr297.pdf. [Last accessed on 2017 Dec 14]. sensitization programs can help reduce stigma and 4. UNAIDS 2016. Country Sierra Leone 2016. Available from: http://www.

unaids.org/en/regionscountries/countries/sierraleone. [Last accessed© Permanyer 2018 attitudes toward people living with HIV/AIDS. on 2017 Dec 14].

5. National HIV/AIDS Secretariat. Sierra Leone National AIDS Response Progress Report 2015. Freetown: National HIV/AIDS Secretariat;. 2015. Research capacity building 6. Boillot F, Peeters M, Kosia A, Delaporte E. Prevalence of the human immunodeficiency virus among patients with tuberculosis in Sierra Leone, established from dried blood spots on filter paper. Int J Tuberc There is a paucity of reliable scientific data on the Lung Dis. 1997;1:493-7. 7. Spiegel PB, Bennedsen AR, Claass J, et al. Prevalence of HIV infection characteristics of the HIV/AIDS epidemic in Sierra Le- in conflict-affected and displaced people in seven Sub-Saharan African countries: a systematic review. Lancet. 2007;369:2187-95. one. Research capacity building of local institutions will of the publisher 8. Willoughby VR, Sahr F, Russell JB, Gbakima AA. The usefulness of be vital in helping generate reliable, high-quality scien- defined clinical features in the diagnosis of HIV/AIDS infection in Si- erra Leone. Cell Mol Biol (Noisy-le-grand). 2001;47:1163-7. tific data that will underpin clinical decision-making for 9. Kaiser R, Spiegel P. HIV Sero Prevalence and Behavioral Risk Factor individual patients, as well as inform public health strat- Survey in Sierra Leone. Atlanta: Centers for Disease Control and Pre- vention; 2002. egies and policies at the wider population level. The 10. National HIV/AIDS Secretariat. National Strategic Plan 2016-2020; 2015. Available from: http://www.nas.gov.sl/images/stories/publica- long-term utility and impact of international partnerships tions/Sierra Leone National Strategic Plan 2016-2020.pdf. [Last ac- between institutions in wealthy countries and LMICs to cessed on 2017 Dec 13]. 11. National HIV/AIDS Secretariat 2015. Population Size Estimation of Key solve global challenges have faced scrutiny in recent Populations. Available from: http://www.nas.gov.sl/images/stories/pub- 72-73 lications/Population%20Size%20Estimation%20Study%20Report%20 years but will undoubtedly continue to play in the August%202013.pdf. [Last accessed on 2017 Dec 14]. Sierra Leone context in one form or another. Sierra 12. National HIV/AIDS Secretariat 2015. HIV Sero-prevalence Study for Key Populations; 2015. Available from: http://www.nas.gov.sl/images/sto- Leone can draw from the extensive experiences of East ries/publications/Seroprevalence%20Study%20of%20Key%20Popula- tions.pdf. [Last accessed on 2017 Dec 15]. and Southern African countries, which have enjoyed 13. Djibo DA, Sahr F, McCutchan JA, et al. Prevalence and risk factors for long, uninterrupted, and fruitful partnerships with inter- human immunodeficiency virus (HIV) and syphilis infections among military personnel in Sierra Leone. Curr HIV Res. 2017;15:128-36. national research institutions that have led to tremen- 14. The World Health Organization 2016. Global AIDS Update 2016. Avail- dous gains in the fight to bring the HIV/AIDS epidemic able from: http://www.who.int/hiv/pub/arv/global-AIDS-update-2016_ en.pdf. [Last accessed on 2017 Dec 15]. under control in that part of the world. These partner- 15. Gamanga AH, Owiti P, Bhat P, Harries AD, Kargbo-Labour I, Koroma M. The ebola outbreak: effects on HIV reporting, testing and care in ships have incubated and fostered of a culture of public Bonthe district, rural Sierra Leone. Public Health Act. 2017;7 Suppl health research in issues relevant to the local context, 1:S10-15. 16. Brolin Ribacke KJ, Saulnier DD, Eriksson A, von Schreeb J. Effects of facilitated the transfer of scientific expertise and tech- the West Africa Ebola virus disease on health-care utilization-a systematic review. Front Public Health. 2016;4:222. nology in the region, and most crucially sought to pro- 17. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection mote local ownership the latter being key to achieving with early antiretroviral therapy. N Engl J Med. 2011;365:493-505. 18. Insight Start Study Group, Lundgren JD, Babiker AG, et al. Initiation of long-term sustainability of efforts and gains74,75. antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795-807. 19. UNAIDS 2014. 90-90-90 An ambitious treatment target to help end the Conflict of interest AIDS epidemic. Available from: http://www.unaids.org/sites/default/ files/media_asset/90-90-90_en.pdf. [Last accessed on 2017 Dec 15]. 20. Brima N, Burns F, Fakoya I, Kargbo B, Conteh S, Copas A. Factors associated with HIV prevalence and HIV testing in Sierra Leone: find- The authors declare no conflicts of interest. This work ings from the 2008 Demographic Health Survey. PLoS One. was supported in part by grants from NIH-T32 AI07024 2015;10:E0137055. 21. Bhoobun S, Jetty A, Koroma MA, et al. Facilitators and barriers related Training in Geographic Medicine and Infectious Dis- to voluntary counseling and testing for HIV among young adults in Bo, eases, School of Medicine, Case Western Reserve Sierra Leone. J Community Health. 2014;39:514-20. 22. Kouyoumdjian FG, Seisay AL, Kargbo B, Khan SH. The voluntary HIV University (G.A.Y), the Roe Green Travel Medicine counselling and testing service in Kenema District, Sierra Leone, 2004- 2006: a descriptive study. BMC Int Health Hum Rights. 2010;10:4. Award 2017, University Hospitals Cleveland Medical 23. Kelly JD, Weiser SD, Tsai AC. Proximate context of HIV stigma and its Center (M.E.Q-M, G.A.Y), and the P30 AI036219 association with HIV testing in Sierra Leone: a population-based study. AIDS Behav. 2016;20:65-70. 24. Kelly JD, Reid MJ, Lahiff M, Tsai AC, Weiser SD. Community-level HIV

CWRU/UHCMC, and Center for AIDS Research No part of this publication may be reproduced or photocopying without the prior written permission stigma as a driver for HIV transmission risk behaviors and sexually (M.E.Q-M). The views expressed in this review are transmitted diseases in Sierra Leone: a population-based study. J those of the authors and do not necessarily reflect Acquir Immune Defic Syndr. 2017;75:399-407. 25. Yuh JN, Ellwanger K, Potts L, Ssenyonga J. Stigma among HIV/AIDS those of the institutions for which they work. patients in Africa: a critical review. Proc Soc Behav Sci. 2014;140:581-5. 112 Yendewa, et al.: HIV/AIDS in Sierra Leone

26. The People Living with HIV Stigma Index, January 2013. Available from: man transmissions of SIVs ancestral to HIVs: studies in these popula- http://www.stigmaindex.org/sites/default/files/reports/SierraLeoneStig- tions may provide crucial insights for treatment and prevention of HIV maIndex-Feb252015-Finalcr.pdf. [Last accessed on 2018 Jan 18]. infection. Med Hypotheses. 2005;64:433-7. 27. Nachega JB, Marconi VC, van Zyl GU, et al. HIV treatment adherence, 52. Simon F, Matheron S, Tamalet C, et al. Cellular and plasma viral load drug resistance, virologic failure: evolving concepts. Infect Disord Drug in patients infected with HIV-2. AIDS. 1993;7:1411-7. Targets. 2011;11:167-74. 53. Marlink R, Kanki P, Thior I, et al. Reduced rate of disease development 28. National HIV/AIDS Secretariat, 2015. National HIV/AIDS Monitoring and after HIV-2 infection as compared to HIV-1. Science. 1994;265:1587-90. Evaluation Plan 2016-2020. Available from: http://www.nas.gov.sl/im- 54. Popper SJ, Sarr AD, Travers KU, et al. Lower human immunodefi- ages/stories/publications/2016%20-%202020%20HIV%20M&E-Plan. ciency virus (HIV) type 2 viral load reflects the difference in pathoge- pdf. [Last accessed on 2018 Jan 18]. nicity of HIV-1 and HIV-2. J Infect Dis. 1999;180:1116-21. 29. Kelly JD, Schlough GW, Conteh S, Barrie MB, Kargbo B, Giordano TP. 55. Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency The majority of the pre-antiretroviral population who were lost to follow- virus (HIV)-2 infection. Clin Infect Dis. 2011;52:780-7. up stopped their care in Free town, Sierra Leone: A 12-month prospec- 56. Quiñones-Mateu ME, Albright JL, Mas A, Soriano V, Arts EJ. Analysis

tive cohort study starting with HIV Diagnosis. PLoS One. of pol gene heterogeneity, viral Quasispecies, and drug resistance© Permanyer 2018 in 2016;11:e0149584. individuals infected with group O strains of human immunodeficiency 30. Chun HM, Carpenter RJ, Macalino GE, Crum-Cianflone NF. The role of virus type 1. J Virol. 1998;72:9002-15.

sexually transmitted infections in HIV-1 Progression: a comprehensive 57. Quiñones-Mateu ME, Soriano V, Domingo E, Menéndez-Arias . L. Char- review of the literature. J Sex Transm Dis. 2013;2013:176459. acterization of the reverse transcriptase of a human immunodeficiency 31. Mbopi-Keou FX, Robinson NJ, Mayaud P, Belec L, Brown DW. Herpes virus Type 1 group O isolate. Virology. 1997;236:364-73. simplex virus type 2 and heterosexual spread of human immunodefi- 58. Quinones-Mateu ME, Ball SC, Arts EJ. Role of human immunodeficiency virus infection in developing countries: Hypotheses and re- ciency virus type 1 group O in the AIDS pandemic. AIDS Rev. search priorities. Clin Microbiol Infect. 2003;9:161-71. 2001;2:190-202. 32. Ansumana R, Dariano DF, Jacobsen KH, et al. Prevalence of markers 59. Gallant JE, Gerondelis PZ, Wainberg MA, et al. Nucleoside and nucle- of HIV infection among febrile adults and children in Bo, Sierra Leone, otide analogue reverse transcriptase inhibitors: a clinical review of 2012-2013. BMC Res Notes. 2017;10:565. antiretroviral resistance. Antivir Ther. 2003;8:489-506. of the publisher 33. Gao F, Yue L, Robertson DL, et al. Genetic diversity of human immu- 60. Parkin NT, Schapiro JM. Antiretroviral drug resistance in non-subtype nodeficiency virus type 2: evidence for distinct sequence subtypes with B HIV-1, HIV-2 and SIV. Antivir Ther. 2004;9:3-12. differences in virus biology. J Virol. 1994;68:7433-47. 61. National HIV/AIDS Secretariat, 2006. Sierra Leone ARV Guidelines; 34. Gao F, Bailes E, Robertson DL, et al. Origin of HIV-1 in the chimpanzee 2006. Available from: http://www.nas.gov.sl/images/stories/publica- pan troglodytes troglodytes. Nature. 1999;397:436-41. tions/Sierra%20Leone%20ARV%20Guidelines%20August%202006. 35. Clavel F, Guétard D, Brun-Vézinet F, et al. Isolation of a new human pdf. [Last accessed on 2018 Jan 9]. retrovirus from west african patients with AIDS. Science. 1986;233:343-6. 62. Brower ET, Bacha UM, Kawasaki Y, Freire E. Inhibition of HIV-2 prote- 36. Korber B, Hahn B, Foley B, et al. Human retroviruses and AIDS. A ase by HIV-1 protease inhibitors in clinical use. Chem Biol Drug Des. compilation and analysis of nucleic acid and amino acid sequences. 2008;71:298-305. Theoretical Biology and Byophysics Group. Los Alamos, NM: Los Ala- 63. Gottlieb GS, Smith RA, Dia Badiane NM, et al. HIV-2 integrase variation mos National Laboratory; 1997. in integrase inhibitor-naïve adults in Senegal, West Africa. PLoS One. 37. Janssens W, Buvé A, Nkengasong JN. The puzzle of HIV-1 subtypes 2011;6:e22204. in Africa. AIDS. 1997;11:705-12. 64. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guide- 38. Tebit DM, Arts EJ. Tracking a century of global expansion and evolution lines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and of HIV to drive understanding and to combat disease. Lancet Infect Adolescents. Available from: https://www.aidsinfo.nih.gov/contentfiles/ Dis. 2011;11:45-56. lvguidelines/adultandadolescentgl.pdf. [Last on accessed on 2018 Feb 39. Simon F, Mauclère P, Roques P, et al. Identification of a new human 19]. immunodeficiency virus type 1 distinct from group M and group O. Nat 65. World Health Organization 2012. Antiretroviral Treatment as Prevention Med. 1998;4:1032-7. (TasP) of HIV and TB: 2012 update. Available from: http://www.apps. 40. Plantier JC, Leoz M, Dickerson JE, et al. A new human immunodefi- who.int/iris/bitstream/10665/70904/1/WHO_HIV_2012.12_eng.pdf. [Last ciency virus derived from gorillas. Nat Med. 2009;15:871-2. on accessed on 2018 Jan 18]. 41. Quinones-Mateu ME, Arts EJ. Recombination in HIV-1: update and 66. European AIDS Clinical Society 2017. EACS Guidelines Version 9.0 implications. AIDS Rev. 1999;1:89-100. October 2017. Available from: http://www.eacsociety.org/files/ 42. Foley B, Leitner T, Apetrei C, et al. HIV and SIV Nomenclature. HIV guidelines_9.0-english.pdf. [Last on accessed on 2018 Feb 18]. Sequence Compendium - Published by Theoretical Biology and Bio- 67. Documento de consenso de Gesida/Plan Nacional sobre el SIDA re- physics Group. Los Alamos, NM: Los Alamos National Laboratory, NM, specto al tratamiento antiretroviral en adultos infectados por el virus LA-UR 17-25240; 2017. de la inmunodeficiencia humana. Available from: http://www.gesida- 43. National HIV/AIDS Secretariat 2005. National Population-Based HIV seimc.org/wcontent/uploads/2018/01/gesida_TAR_Gesida_y_ Sero Prevalence Survey Sierra Leone; 2005. Available from: http://www. PNS_2018.pdf. [Last on accessed on 2018 Jan 18; Last updated 2018 nas.gov.sl/images/stories/publications/National%20Population- Jan]. Based%20HIV%20Seroprevalence%20Survey.pdf. [Last accessed on 68. National HIV/AIDS Secretariat, 2016. Re-advitised TOR and Request 2018 Jan 12]. for Expression of Interest for Viral Load Monitoring and EID; 2016. 44. Williamson C, Martin DP. HIV-1 genetic diversity. In: Abdool Karim SS, Available from: http://www.nas.gov.sl/component/content/article/4- Abdool Karim Q, editors. HIV/AIDS in South Africa. Cambridge: Cam- newsflash/151-re-advitised-tor-and-request-for-expression-of-interest- bridge University Press; 2010. for-viral-load-monitoring-and-eid-august-2016. [Last on accessed on 45. Lospitao E, Alvarez A, Soriano V, Holguín A. HIV-1 subtypes in Spain: 2018 Jan 12]. a retrospective analysis from 1995 to 2003. HIV Med. 2005;6:313-20. 69. Kasper J, Bajunirwe F. Brain drain in sub-Saharan Africa: contributing 46. Davanos N, Panos G, Gogos CA, Mouzaki A. HIV-1 subtype charac- factors, potential remedies and the role of academic medical centres. teristics of infected persons living in southwestern greece. HIV AIDS Arch Dis Child. 2012;97:973-9. (Auckl). 2015;7:277-83. 70. Duvivier RJ, Burch VC, Boulet JR. A comparison of physician emigra- 47. Paraskevis D, Magiorkinis E, Magiorkinis G, et al. Molecular character- tion from Africa to the United States of America between 2005 and ization of a complex, recombinant human immunodeficiency virus type 2015. Hum Resour Health. 2017;15:41. 1 (HIV-1) isolate (A/G/J/K/?): evidence to support the existence of a 71. The Global Fund, 2016. Country profile Sierra Leone. Available from: novel HIV-1 subtype. J Gen Virol. 2001;82:2509-14. https://www.theglobalfund.org/en/portfolio/ 48. Hamers RL, Wensing AM, Back NK, Arcilla MS, Frissen JP. Multi-nu- country/?loc=SLE&k=d9728bba-df64-4ff5-9968-f195de080917. [Last cleoside reverse transcriptase inhibitor resistant HIV type-1 in a patient on accessed on 2018 Jan 14]. from Sierra Leone failing stavudine, lamivudine and nevirapine. Antivir 72. Jones N, Bailey M, Lyytikäineni M. Research Capacity Strengthening Ther. 2011;16:115-8. in Africa: trends, Gaps and Opportunities. London: Overseas Develop- 49. Apetrei C, Metzger MJ, Richardson D, et al. Detection and partial ment Institute; 2007. characterization of simian immunodeficiency virus SIVsm strains from 73. Ijsselmuiden C, Marais DL, Becerra-Posada, Ghannem H. Africa’s ne- bush meat samples from rural Sierra Leone. J Virol. 2005;79:2631-6. glected area of human resources for health research-the way forward. 50. Ling B, Telfer P, Reed P, Robertson DL, Marx PA. A link between SIVsm S Afr Med J. 2012;102:228-9. in sooty mangabeys (SM) in wild-living monkeys in Sierra Leone and 74. Marjanovic, S, Hanlin R, Diepeveen S, Chataway J. Research capacity No part of this publication may be reproduced or photocopying without the prior written permission SIVsm in an American-based SM colony. AIDS Res Hum Retroviruses. building in Africa: networks, institutions and local ownership. J Int 2004;20:1348-51. Devel. 2013;25:936-46. 51. Parsyan AE. Protective correlates against HIVs may have evolved in 75. Grabowski MK, Serwadda DM, Gray RH, et al. HIV prevention efforts human populations in the areas of historic occurrence of primate-to- and incidence of HIV-1 in Uganda. N Engl J Med. 2017;377:2154-66.

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