HIV Non-Occupational Post Exposure Prophylaxis in Nigeria: A Systematic Review of Research Evidence and Practice

2.1. Data Source and Literature Search

We conducted electronic searches on PubMed, PubMed Central (PMC), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Medline, Embase and Google Scholar for published studies from January 2002 to December 2018 using various combinations of the following keywords: “HIV”, “non-occupational”, “nonoccupational”, “post exposure”, “post-exposure”, “prophylaxis,” and “Nigeria”.

2.2. Study Selection

2.2.2. Selection process

A comprehensive search of the above-named databases yielded a total of 369 initial potentially relevant abstracts and articles. During the preliminary review of the abstracts and articles, 341 items were excluded based on the exclusion criteria. Following this, 27 articles were eligible for further evaluation. Of this number, 22 of the articles were excluded because the studies did not specifically report on nPEP. Only 5 articles met the inclusion criteria and were used for the current study. Figure 1 displays the flowchart of the selection process. The 5 articles were independently reviewed by two of the researchers (SI, OM). The researchers identified the following key themes based on literature review: socio-demographic characteristics of study sample, awareness, knowledge and use of PEP, reasons for seeking HIV nPEP, timeliness in presenting for PEP, adherence to guidelines and recommendations for nPEP by healthcare institutions, ARVs used for nPEP, side effects and adherence, monitoring and follow-up visits and strength of research evidence of the reviewed studies. These themes formed the basis for the independent review of the articles by the researchers. All information and findings obtained independently were collated and reconciled, where necessary, and the final synthesized version of the work was used for this study.

Close

Figure 1

Flowchart of nPEP Research Studies Selection Process

Export to PPT

2.3. Types of Studies

One of the five studies reviewed was a cross sectional survey that examined the level of awareness and knowledge of PEP and PrEP among students of two Nigerian universities.41 Two of the five studies involved retrospective reviews of medical records.42,43 Onyedum et al. assessed the clinico-demographic characteristics of patients who received PEP and nPEP services from the University of Nigeria Teaching Hospital, Ituku Ozalla, between January 2007 and June 2009.42 Olowookere et al. examined the pattern of presentation and outcome of patients who were given PEP at the antiretroviral clinic, Yaba, Lagos, from January 2005 to December 2006.43 One study was a retrospective review design.44 Nwokeukwu et al. evaluated the socio-demographic characteristics and prevalent mode of exposure of patients who received PEP services and adequacy of PEP services received from September 2008 to July 2011 at the Federal Medical Center (FMC) Umuahia, in the Southeast region of Nigeria.44 One of the five studies was reported as a retrospective cohort study.45 However, on a closer examination, it lacked any control or unexposed groups to compare with the cohort nor was an absolute risk estimate performed in the study, hence it was really a retrospective review of medical records.46 Ekama et al. evaluated the nature of exposure, time of presentation and treatment outcomes of patients who utilized PEP services at the HIV treatment center of the National Institute of Medical Research, Lagos.45

3.1. Socio-demographic Characteristics of Study Sample

In the four studies carried out in a healthcare setting, a total of 331 patients presented for nPEP services.42-45 Ajayi et al.41 surveyed a total of 748 university students to determine their level of knowledge and awareness of PEP. Table 1 shows the summary of the 5 HIV nPEP related studies conducted in Nigeria that were eligible for inclusion in this review. Across the four studies that examined exposed victims, the age of exposed victims ranged from 0 to 64 years. Two studies reported mean ages of 27.9±12.3 years43 and 29.01±7.96 years.42 Females represented 64%-78% of the exposed victims across all four studies that examined patients who presented for nPEP.42-45 This is similar to a study in nPEP that reported that 81% of individuals seeking nPEP were females.47 Ekama et al. reported that 67.2% of patients in the study had a tertiary education, 70.7% were employed and 62.1% were single.45 Olowookore et al. reported that 31.3% were students and 18.8% were civil servants.43 In the study by Ajayi et al. among university students, most of the study participants were below the age of 24, lived in off campus residencies and were Christians.41 The other four studies did not report on the residency and religion of the study participants.

3.3. Awareness, Knowledge and Prior use of PEP

Out of the five studies reviewed, only one study assessed the level of awareness, knowledge and prior use of nPEP.41 Among university students who participated in the study conducted by Ajayi et al., only 25.4% were aware of postexposure prophylaxis.41 While ever tested for HIV, nude picture exchanges, sex without condom, knowledge of partner’s HIV status were the significant determinants of awareness of PEP, awareness of PEP was not associated with sex and age.41 Students who had ever tested for HIV were one and a half times more likely to be aware of PEP compared to those who had never tested for HIV.41 Only 10.6% and 1.5% of the patients indicated that they knew where to get HIV prophylaxis (either PrEP or PEP) and had ever used them, respectively.41

3.3. Reasons for Seeking HIV nPEP

Table 2 presents the reasons for HIV non-occupational post exposure prophylaxis. Four out of five studies reported on the mode of exposure that led individuals to seek nPEP.42,44,45,48 Rape was the most frequently occurring reason for seeking nPEP (25.9% to 64.1%) in all the four studies conducted in hospital settings.42-45 This is similar to two other studies conducted in Kenya and Canada where rape accounted for 82% and 68% of non-occupational exposure respectively.49,50 A contrasting result was reported by a study carried out in Seattle, Washington were rape accounted for only 22% of nPEP exposure.51 Other reasons, as indicated in Table 2, include human bite, and blade cut.

3.4. Timeliness in Presenting for PEP

Four out of five studies reported on patient’s timeliness in seeking for nPEP after HIV exposure.42,44,45,48 Most patients across four of the studies reviewed presented for PEP within 72 hours of exposure.42,44,45,48 In the study by Ekama et al., only about 2% of exposed patients reported for PEP after 72 hours.45 In two of the studies, the majority of the exposed patients reported within 24 hours of exposure (77.5%44 and 50%42) which contrasts with one study where the majority (82%)45 presented for PEP after 48 hours, with only 6% presenting for PEP within 24 hours. Of the 10 patients who reported after 72 hours in the study by Onyedum et al., majority were sexual assault victims.42 Being male was associated with early presentation for PEP.42 We found no other study that explored this relationship between gender and early presentation for PEP.

3.5. ARVs used for nPEP, Side Effects and Adherence

Only two out of the five studies reported the type of ARVs used for nPEP for patients. Olowookore et al. reported that 56% of patients had nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral (HAART).43 while Ekama et al. reported that 76% of patients were placed on the three-drug protease inhibitor (PI)-based HAART.45 Low risk patients were placed on a two-drug regimen,43,45 while patients at no risk were not given any drugs because their source of exposure was HIV negative.43 The most reported adverse effects of the drugs were nausea/vomiting, dizziness/body weakness, bad dreams/poor sleep, diarrhea, skin rash, dysuria and headache.43,45 About 23.8% of the clients could not complete the drug therapy because of these adverse effects.43 However, Onyedum et al. reported no side effects in patients who received the nPEP drug regimens.42

3.6. Monitoring and Follow-up Visits

One out of the five studies reported an 83.3% follow-up rate at the sixth month.43 In contrast, two out of the five studies42,44 reported that there was no follow-up visit by any of the patients. Ekama et al. reported that 57% of patients returned to the clinic only once and only 2% of patients completed the sixth month follow-up visits.45

3.7. Adherence to Guidelines and Recommendations for nPEP by Healthcare Institutions

Treatment guidelines

According to the National guideline for HIV Prevention Treatment and Care by the Federal Ministry of Health, Nigeria, the likelihood of the source of exposure being HIV positive, the time that has transpired since the event, and the risk associated with exposure characteristics should guide the recommendation of nPEP for individuals exposed to HIV infection and victims of sexual assault.18,52 For sexual assault victims, when the assailant’s HIV status is unknown, occurrence of vaginal or anal penetration, ejaculation on mucous membrane, involvement of multiple assailants, presence of mucous lesion on the victim or the assailant, and other predisposing characteristics of the victims must be considered in risk assessment for HIV exposure following sexual assault. For other forms of exposure, patients must be assessed to determine, if exposure was low risk or high risk (see Table 3). A three drug regimen with TDF+ 3TC (or FTC) as the preferred backbone is recommended for nPEP for adults and adolescents and must be initiated as soon as possible up to 72 hours of the assault occurring.18,52 For children less than 10 years of age, the preferred backbone for the three drug regimen for nPEP is AZT+3TC.18 It is recommended that follow up visits be slated at baseline, 2 weeks, 6 weeks, 3 months and 6 months after the event. It is also advised that patients be counseled on benefits and known toxicities of ARV, benefits of early initiation of nPEP, adherence to ARV regimen and necessary follow-up visits.18,52 Table 3 shows a summary of nPEP guidelines and recommendations by the Federal Ministry of Health in Nigeria. We assessed the practice of health care institutions where the data for the studies were collected using the following key measures culled from the National guideline for HIV Prevention Treatment and Care by the Federal Ministry of Health, Nigeria; (a) basis for treatment initiation (b) HIV exposure risk assessment (c) patient counseling, (d) ARVs used for nPEP and (e) follow up visit scheduling.

Summary of adherence to guidelines and recommendations for nPEP by healthcare institutions

Table 4 summarizes the adherence of the selected healthcare institutions to nPEP guidelines and recommendations based on the studies reviewed. The selected institutions in the reviewed studies include: University of Nigeria Teaching Hospital (UNTH), Ituku Ozalla, Enugu; Antiretroviral Clinic of the University College Hospital (UCH), Ibadan, Nigeria; Federal Medical Centre (FMC), Umuahia; and HIV Treatment Centre at the Clinical Sciences Department of the Nigerian Institute of Medical Research (NIMR), Lagos. The HIV Treatment Center at the NIMR, Yaba, Lagos, followed the guideline recommendation for ARV drug regimen and follow up visit scheduling.45 The ARV Clinic at UCH, Ibadan in Oyo state, followed the guidelines and recommendations for ARV drug regimen and HIV risk assessment.43 In the study conducted at UNTH, Ituku Ozalla, Enugu, only baseline and 6 months follow-up visits were reported.42 In the study by Nwokeukwu et al.44 at FMC, Umuahia, Abia state, rape, unknown HIV status of assailant and the negative HIV status of all but one of the victims was in line with the guidelines and recommendations for treatment initiation of nPEP. None of the studies reviewed reported about patient counselling.

3.8. Strength of Evidence of Reviewed Studies

• a) Data Used: One of the five studies used primary data41 while the remaining four studies used secondary data.42,44,45,48 Four studies reported missing and incomplete data.41,42,45,48

• b) Sample Size: Sample sizes ranged from n=784 in the study by Ajayi et al.41 to n=48 in the study by Olowookore et al.48 All the four studies conducted in the healthcare setting reported low sample sizes due to loss to follow up, incomplete and missing data.42,44,45,48

• c) Study Design: One of the five studies reviewed was a cross sectional survey.41 Two of the five studies were retrospective reviews of medical records.42,43 One of the five studies was reported as a retrospective cohort study.45 One study was a retrospective review design.44

• d) Statistical Analysis: Two out of the five studies assessed carried out inferential statistics to determine the associations between key dependent and independent variables.41,42 Onyedum et al. carried out bivariate analysis to determine the association between clinical and sociodemographic characteristics with time of presentation for PEP.42 Ajayi et al. used logistic regression to determine the correlates of awareness of PrEP and PEP.41 Of the two studies that carried out inferential statistical analysis, only one of the studies41 carried out power analysis to determine the sample size required to estimate a meaningful effect. Three of the five studies assessed reported only descriptive statistics such as means, frequencies and percentages.43-45

• e) Study Ethics: Three out of five studies reported obtaining ethical approval from their respective institutional board before carrying out the study.41,42,45

4.1. Limitations and Strengths of Study

This review is limited by the fact that there are very few studies that address non-occupational post exposure prophylaxis in Nigeria. Furthermore, none of the articles reviewed were solely focused on non-occupational post exposure prophylaxis and this may have shadowed the full impact of occupational post exposure prophylaxis outcomes. Consequently, our findings on nPEP based on the current review should be interpreted with utmost caution. While this is a limitation, it serves to further highlight the importance of this review as it revealed a huge knowledge gap in the state of science of nPEP in Nigeria. Our review work is also further limited by the fact that only studies published in English language were reviewed. However, there may be some relevant studies omitted if they were published outside the time frame of this review. Accordingly, we cannot guarantee that all the literatures published on nPEP in Nigeria are included in the current review. Despite these limitations, the strength and relevance of the current study lies in being a foundational work that attempts to assess the state of science of nPEP in Nigeria. The work has helped to highlight the obvious knowledge gaps in research evidence on nPEP use and practice in Nigeria, and lay a road map of important areas to focus future research efforts on.

4.2. Public Health and Practice Implications

As observed in the study by Ajayi et al, there is low knowledge of HIV post exposure prophylaxis especially among young people.41 This implies that if the need arises for nPEP following non-occupational exposure, majority of the young people may not access needed services because they do not have the knowledge, thus potentially leading to new HIV infections that could have otherwise been prevented. The demographics of individuals affected by non-occupational exposure to potential HIV infection through sexual assault is disproportionally tilted towards women. Young women in Nigeria are twice as vulnerable to HIV infection as their male counterparts.26 This is similar to other parts of Sub-Saharan Africa where incidence rate of HIV infections among young women aged 15-24 were significantly higher than among young men of the same age.56,57 This exposes the effect of gender gap, the unequal balance of power among men and women in Nigeria, which is ranked 122 out of 144 countries in gender gap globally.93 Consequently, there is need for policy changes to strengthen the protection for women against sexual assault in Nigeria and interventions to educate more women on where and how to access needed care especially nPEP. Gender inequalities, including gender-based violence has been reported to exacerbate women and girls’ vulnerability to HIV and tend to hinder their access to HIV prevention, treatment and care services.63

Low follow up visits prevent health providers from effectively monitoring patients especially with respect to medication adherence and monitoring for possible seroconversion. This is important because antiretroviral drugs require strict adherence without which the drug will not work effectively and may lead to resistance. Better counselling by healthcare providers, especially pharmacists who serve as important point of contact in dispensing nPEP drugs, might help to improve the problem of poor follow up visits. Lack of adherence to all key areas of the guidelines and recommendations by health institutions could mar the goal of eradication of new HIV infections by 2030. The government must invest in translational research in Nigeria, to bridge the gap between research, guidelines and recommendations and the actual practice by healthcare providers.

No study was found that explored nPEP in the South-South geopolitical zone of Nigeria which has the highest HIV prevalence in Nigeria.80 Studies need to be carried out on the awareness, knowledge and pattern of HIV nPEP utilization in the different geopolitical zones of Nigeria to determine the disparities that might exist and to inform health intervention programs that will address existing gaps. Furthermore, since Nigeria is a culturally diverse country where culture and health behavior often overlap,94,95 it is important for researchers to assess how cultural differences might affect nPEP utilization across geographical regions in Nigeria. Findings from such studies will enable more culturally sensitive interventions to be planned and implemented, where necessary.

Other factors that affect nPEP services in Nigeria include, poor accounting in disbursement of HIV/AIDS funding, noncompliance96,97 and violence and insurgency.80 Use of obsolete accounting software and technology makes it difficult to adequately audit disbursed HIV funding thus leaving room for inappropriate handling of funds. To prevent this, regular audit of funding must be carried out by internal and external auditors and obsolete accounting tools should be replaced with modern accounting software and tools that can track and monitor financial disbursements in real time. This is important because, without putting in place the proper structure, the national strategic framework will simply not work as intended.

In order to achieve the goal of eradicating new infections in Nigeria by 2030,80 the federal government of Nigeria must effectively implement and enforce policies where necessary, and ensure that HIV prevention interventions are carefully planned and tailored to target high-risk groups in other to increase knowledge, awareness and eradicate barriers to access HIV prophylaxis. Also, healthcare providers must continuously undergo training to adapt to the changing treatment, care and prevention needs of patients thereby improving their practice. In addition, HIV specialists and researchers from academic medical centers or urban clinics can use video conferencing technology to provide real-time clinical expertise and support to providers in the rural areas. This approach could enhance the reach and allow many Nigerians gain access to available and necessary nPEP services could help reduce the transmission of HIV.

4.3. Global Health Implications

With a population of over 195 million persons, Nigeria is the most populous country in Africa98 and among the most populous countries in the world. About 1.9 million Nigerians out of 36.9 million persons globally, are currently living with HIV.5 This makes Nigeria one of the worst hit countries by HIV. Due to its regional status and high HIV epidemic, it serves as an important epicenter in the fight against HIV in Africa and continues to receive funding and technical support for research in the area of HIV prevention. In view of this, the paucity of research on nPEP in HIV prevention in Nigeria is worrisome as nPEP has been included by UNAIDS as part of the global strategy to prevent HIV especially among adolescent girls and young women.99 The Fast-Track targets for HIV prevention and treatment which includes a 75% reduction in new HIV infections globally by 2020 as compared to 2010,100 can only be achieved with tailored interventions informed by adequate research. Prevention of new HIV infections is very important especially in low income countries like Nigeria because increased incidence rates can lead to significant drain on resources available for the elimination of AIDS as a public health threat. For Nigeria which depends largely on international funding for its HIV response,101,102 the situation is dire as global HIV funding for middle and low-income countries continue to reduce.103 To meet up to global prevention goals for HIV, Nigeria’s HIV AIDS Strategic Plan must be updated to include sex-disaggregated data and tailored responses to key groups in a manner similar to South Africa’s NSP56; Nigerian Health care providers must be continually trained to give quality care to individuals seeking nPEP services; and more studies on nPEP must be carried out in a rigorous manner to strengthen the body of research evidence available to inform HIV prevention policies and intervention programs in Nigeria.

4.5. Conclusions

The state of the science regarding nPEP in Nigeria is still at the developmental stage with most of the research evidence on nPEP considered weak following the sample size, study design and analytical approach involved. We noted the existence of low awareness of PEP and inadequate knowledge of where and how to access it among college students.41 Although our findings cannot be generalized, the study points to an obvious knowledge gap in HIV prevention efforts that needs to be addressed among this subpopulation. Sexual assault was identified as the major reason for non-occupational exposure to risk of HIV infection in Nigeria. There was late presentation for PEP and poor follow-up visit rates among exposed victims in most of the studies reviewed. Since all studies included both occupational and non-occupational post exposure prophylaxis, our findings on nPEP based on the current review must be interpreted cautiously. For nPEP to have a population-level impact on HIV prevention, nPEP education and promotion must be intensified and targeted especially towards young adolescent females who are the most vulnerable group to sexual assault. It is recommended that a rigorous and comprehensive research study or a national study using a large sample size be conducted on nPEP in Nigeria, and efforts made in such studies to focus on the themes identified in this review including the determinants of nPEP services utilization, and adherence to the national guidelines and recommendations on PEP by the healthcare providers.