Virologic response to antiretroviral therapy among human immunodeficiency virus-infected adults in a tertiary healthcare facility in Enugu State Nigeria

Izuchukwu F Obi; Ijeoma L Okoronkwo; Cajetan C Onyedum; Adebayo M Fashola; Martins Onuoha; Emmanuel A Nwobi; Obinna D Onodugo; Chinwe Chukwuka

doi:10.4103/ijmh.IJMH_68_20

ORIGINAL ARTICLE

Year : 2022 | Volume : 27 | Issue : 1 | Page : 92-98

Virologic response to antiretroviral therapy among human immunodeficiency virus-infected adults in a tertiary healthcare facility in Enugu State Nigeria

Izuchukwu F Obi¹, Ijeoma L Okoronkwo², Cajetan C Onyedum³, Adebayo M Fashola⁴, Martins Onuoha⁴, Emmanuel A Nwobi⁵, Obinna D Onodugo⁶, Chinwe Chukwuka³
¹ Department of Community Medicine, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu State, Nigeria; Nigeria Field Epidemiology and Laboratory Training Programme, Asokoro, Abuja, Nigeria; Antiretroviral Clinic University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu State, Nigeria
² Department of Health Administration and Management, Faculty of Health Sciences and Technology, University of Nigeria, Enugu Campus, Enugu State
³ Department of Medicine, Faculty of Medical Sciences, University of Nigeria, Enugu Campus, Enugu State, Nigeria; Antiretroviral Clinic University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu State, Nigeria
⁴ Nigeria Field Epidemiology and Laboratory Training Programme, Asokoro, Abuja, Nigeria
⁵ Department of Community Medicine, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu State, Nigeria; Antiretroviral Clinic University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu State, Nigeria
⁶ Department of Medicine, Faculty of Medical Sciences, University of Nigeria, Enugu Campus, Enugu State, Nigeria

Date of Submission	11-Oct-2020
Date of Decision	11-Apr-2021
Date of Acceptance	11-May-2021
Date of Web Publication	3-Dec-2021

Correspondence Address:
Izuchukwu F Obi
Department of Community Medicine, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu State.
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmh.IJMH_68_20

Abstract

Background: Early and sustained viral suppression with antiretroviral therapy (ART) has been linked to good clinical outcome in HIV-infected patients. The global target is that at least 90% of the patients on ART should be virally suppressed. Objectives: We assessed the virologic response to first-line ART in the first year of treatment in our center and determined the factors influencing early viral load suppression among patients. Materials and Methods: We conducted a retrospective study involving review of the records of all eligible HIV-infected adults initiated on ART in our facility between 2009 and 2014, who did not miss any follow-up appointment during the first year on ART. Data were extracted with a proforma and analyzed with Epi Info 7. Frequencies and proportions were used to summarize patients who achieved undetectable viremia (viral load < 400 copies/mL]) at 12 and 24 weeks, whereas χ² and logistic regression were done at 5% alpha to determine the factors influencing early viral load suppression. Results: The mean age of 478 participants was 38.6 (19.0) years and 310 (64.8%) were females. While 332 (69.5%) patients achieved undetectable viremia at 12 weeks of ART, 356 (74.5%) achieved it at 24weeks. After 24 weeks on ART, 121 (80.7%) of the150 patients on tenofovir/emtricitabine/efavirenz, 195 (71.2%) of the 274 patients on zidovudine/lamivudine/nevirapine, and 35 (71.4%) of the 49 patients on tenofovir/lamivudine+nevirapine achieved undetectable viremia (P = 0.13). Patients’ age, sex, marital status, baseline CD4 count, TB co-infection status, WHO clinical stage of disease, and plasma viral load at ART initiation were not significantly associated with early viral load suppression (p > 0.05). Conclusion: Three out of every four participants initiated on first-line ART achieved undetectable viremia after 24 weeks of treatment in our setting. The three ART regimens assessed have comparable effectiveness. The sociodemographic and clinical variables assessed did not influence viral suppression.

Keywords: Antiretroviral therapy, human immunodeficiency virus, Nigeria, viral suppression, virologic response

How to cite this article:
Obi IF, Okoronkwo IL, Onyedum CC, Fashola AM, Onuoha M, Nwobi EA, Onodugo OD, Chukwuka C. Virologic response to antiretroviral therapy among human immunodeficiency virus-infected adults in a tertiary healthcare facility in Enugu State Nigeria. Int J Med Health Dev 2022;27:92-8

How to cite this URL:
Obi IF, Okoronkwo IL, Onyedum CC, Fashola AM, Onuoha M, Nwobi EA, Onodugo OD, Chukwuka C. Virologic response to antiretroviral therapy among human immunodeficiency virus-infected adults in a tertiary healthcare facility in Enugu State Nigeria. Int J Med Health Dev [serial online] 2022 [cited 2023 Mar 29];27:92-8. Available from: https://www.ijmhdev.com/text.asp?2022/27/1/92/331734

Introduction

Human immunodeficiency virus (HIV) infection remains an important public health problem with over 38 million people living with HIV (PLWH) globally at the end of 2019 and additional 1.7 million new infections occurring the same year.^[1] Globally, in 2019 alone, about 690,000 people died from acquired immune deficiency syndrome (AIDS)-related illnesses. Moreover, about 32.7 million people are estimated to have died from AIDS-related illnesses since the beginning of the epidemic, with Sub-Saharan Africa being disproportionately more affected.^[1] Highly active antiretroviral therapy (HAART) improves the quality of life and overall survival of PLWH. Furthermore, early viral suppression and good immunologic recovery have been shown to improve clinical outcomes in HIV-infected patients on HAART.^[2],[3],[4] The plasma viral load of patients started on first-line HAART is expected to fall to undetectable levels by 24 weeks.^[5],[6] The current global target is to achieve viral suppression to undetectable levels in at least 90% of the patients on ART.^[7]

However, the Joint United Nations Program on HIV/AIDS (UNAIDS) reported that out of the 24.5 million PLWH accessing HAART in 2019, only 59% have full viral suppression.^[1] In Nigeria, the 2018 National AIDS Indicator and Impact Survey (NAIIS) revealed that only 44.5% of the patients aged 15–64 years on ART achieved full viral load suppression, with lower values (38.2%) reported for Southeast Nigeria.^[8] Failure to fully suppress the plasma viral load after 48 weeks on HAART, with optimal drug adherence, means that the virus will continue to ravage the immune system. This could also be a pointer to early virologic failure.^[9] It is imperative to regularly monitor the virologic response in patients commenced on HAART to ensure that viral replication is suppressed, thereby enhancing immune recovery. This becomes more important in a developing country like ours where resistance testing prior to ART commencement is not practiced due to resource constraint. Regular monitoring of virologic response to ART enables early detection of cases of virologic failure needing possible switch to second-line ART. Different factors have been shown to influence virologic response to ART. Whereas studies agree on the effect of adherence to ART on the achievement of viral suppression, there are conflicting evidence on the effect of patient’s age, TB co-infection, hepatitis B and/or C co-infection, and baseline CD4 count.^{[10],[11],[12],[13],[14]} There is limited evidence on the virologic response to commonly used first-line ART regimen in our setting as well as factors influencing such response. Contextual evidence on the effectiveness of commonly used first-line ART in our setting is necessary to guide practice. We therefore assessed the virologic response to first-line ART in the first year of treatment in our center and also identified factors influencing early viral load suppression among patients.

Materials and Methods

Study area and setting

The study was conducted at the antiretroviral (ARV) clinic of the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu State, Nigeria. Enugu State is located in Southeast Nigeria and has 17 local government areas (LGAs): five urban and 12 rural with Enugu Metropolitan city as the capital.^[15] Enugu State has a population of 4.2 million, HIV prevalence of 1.2 (1.7–2.2) with 38.2% of the HIV patients on HAART being virally suppressed.^[15],[16] UNTH Ituku-Ozalla is located in both Awgu and Nkanu West rural LGAs. The ARV clinic of UNTH offers comprehensive HIV treatment services and attracts clients from different states in the Southeast geopolitical zone and beyond. At the end of 2019, the adult clinic has over 4000 adult patients on ART. The first-line antiretroviral drugs used at the study facility at the time of this study include: Atripla (tenofovir/emtricitabine/efavirenz), tenofovir/lamivudine+nevirapine, zidovudine/lamivudine+nevirapine or efavirenz, abacavir/amivudine+efavirenz, or nevirapine. Choice of regimen was guided by the national HIV treatment guideline, toxicity profile of each medication, pill burden, and other clinical considerations.

Study design and population

A retrospective cross-sectional study was conducted from October 2016 to April 2017 involving review of treatment records of ART-naive adult HIV-infected patients commenced on first-line ART between January 1, 2009 and December 31, 2014 at the HIV clinic of UNTH Ituku-Ozalla, Enugu State, Nigeria. Only the records of patients who have signed informed consent forms in their case-folders, attended all scheduled drug pick-up visits (proxy index used to assess adherence to ART), and have all scheduled viral load results available in their records were included in the study.

Sample size determination and sampling procedure

The minimum sample size required for the study was determined using the Cochran formula^[17] for single proportion. A sample size of 363 participants was calculated for the study based on a type 1 error (alpha) of 0.05, a tolerable error margin (precision) of 0.05, and the proportion of HIV-infected adults commenced on HAART in Enugu State who achieved early viral load suppression as 0.38.^[16] We however reviewed the records of all the consenting eligible 478 adults commenced on first-line HAART in the study facility during the study period to increase the robustness of estimates.

Data collection

The principal researcher and two research assistants (university graduates) trained for 2 days on the study protocol, data abstraction with the study instrument (proforma), and principles of ethical conduct of research used a pre-tested structured proforma to extract relevant data from the case-folders of eligible participants. The proforma has the following sections: sociodemographic information (age, sex, education, marital status, occupation, alcohol use, and HIV status of spouse); clinical information (WHO clinical stage, TB status, ART regimen, date started on ART); and laboratory information (viral load results at baseline, 12 weeks, 24 weeks, and 1 year on ART).

Data processing and analysis

Data were entered into Epi Info version 7.1.4 software, cleaned, and analyzed. Descriptive statistics were summarized as frequency and percentages. χ² test was used to determine association between viral load suppression at 24 weeks and independent variables at 5% level of significance. Binary logistic regression was also conducted to determine the independent predictors of viral load suppression at 24 weeks. The results were expressed as odds ratios with 95% confidence intervals (CIs).

Ethical considerations

Ethical clearance (reference number: UNTH/CSA/329/OL.5) for this study was obtained from the Human Research Ethics Committee (HREC) of the University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu State, Nigeria. Written informed consent was obtained from patients who permitted use of their data for research purposes. Only the records of such patients were analyzed in this study. The abstracted data were de-identified and only the patients’ unique identification numbers retained. Data collected were kept confidential and hidden in zipped passworded folders only accessible to the researchers. Research assistants were trained on maintaining strict confidentiality of participants’ data.

Results

Sociodemographics and baseline clinical characteristics of respondents

The records of 478 participants were reviewed in this study. The mean (SD) age of participants was 38.6 (19.0) years, the majority 310 (68.8%) were females, 299 (62.5%) attended at least secondary school, 221 (46.2%) were currently married, and 464 (97.1%) were exposed through heterosexual route [Table 1].

Table 1: Sociodemographic and exposure characteristics of HIV-infected adults started on ART in a tertiary healthcare facility in Enugu State, Nigeria, 2017

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The median baseline viral load (IQR) for the participants was 134,690 (334,008), whereas the median (IQR) baseline CD4 count was 156 (135). Thirty (6.3%) of the participants had TB-HIV co-infection, whereas 314 (65.7%) were in early stage of the disease (WHO clinical stages 1 and 2) [Table 2].

Table 2: Baseline clinical and laboratory profile of HIV-infected adults started on ART in a tertiary healthcare facility in Enugu State, Nigeria, 2017

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Virologic response of patients in the first 6 months on first-line ART

Of the 478 patients commenced on first-line ART medication, 332 (69.5%) were virally suppressed (HIV viral load <400 copies/mL) at 12 weeks, whereas 356 (74.5%) were virally suppressed at 24 weeks on HAART.

Of the 150 participants on Atripla (TDF/FTC/EFV), 121 (80.7%) achieved undetectable viremia at 24 weeks, whereas for the 49 participants on TDF/3TC+NVP, 35 (71.4%) achieved undetectable viremia at 24 weeks. For the 274 patients on AZT/3TC/NVP, 195 (71.2%) achieved undetectable viremia at 24 weeks [Table 3].

Table 3: Virologic response to different first-line ART regimens in the first 6 months of treatment in a tertiary healthcare facility in Enugu State Nigeria, 2017

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Factors associated with early viral load suppression

Participants below 40 years of age were less likely to achieve undetectable viremia at 24 weeks, compared with those older than 40 years. This association was, however, not statistically significant [adjusted odds ratio (AOR)=0.97, 95% CI = 0.62–1.51]. Also participants initiated on ART at an early stage of the disease (WHO Stage I and II) were 19% more likely to achieve undetectable viremia compared with those at WHO stages III and IV. This finding was also not statistically significant (AOR=1.20, 95% CI = 0.82–1.86). Participants with baseline CD4 count lower than 200 cells/mL were 19% more likely to achieve viral load suppression when compared with those with baseline CD4 count greater than 200 cells/mL. This finding was, however, not statistically significant (AOR= 1.19, 95% CI = 0.77–1.85). Other variables found not to be significantly associated with achievement of early viral load suppression include sex, marital status, TB co-infection, and plasma HIV viral load at initiation of ART [Table 4].

Table 4: Factors associated with plasma viral load suppression in HIV-infected patients in a tertiary healthcare facility in Enugu State Nigeria, 2017

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Discussion

In this study involving the review of the treatment records of 478 adults started on first-line ART between 2009 and 2014 in a treatment facility to determine the virologic response to ART and factors influencing it, majority of the study participants were females, below 40 years of age. A possible reason for the predominance of women among the study participants could be the previously reported feminization of HIV burden in Nigeria.^[8] Also one of the inclusion criteria in this study, which is 100% compliance with drug pick-up appointments within the first year of HAART commencement, tends to favor women as they are usually more likely to keep to clinic appointments compared with men. The majority of the participants were enrolled for treatment at CD4 counts below 200 cells/mm³ due to restrictions to early commencement of ART by the national HIV treatment policy in use at the time of study.^[18]

Three quarters of the study participants were able to achieve full suppression of their plasma HIV load to technically undetectable levels (viral load <400 copies/mL) after taking HAART for 24 weeks. Viral load suppression was similar for the two nevirapine-based first-line HAART regimens (tenofovir/lamivudine/nevirapine and zidovudine/lamivudine/nevirapine) and a bit higher for the efavirenz-based regimen (tenofovir/emtricitabine/efavirenz). The observed similarity in viral load suppression among the different combination drugs studied could be because these first-line regimens contain drugs from similar classes of ARV drugs (nucleoside and non-nucleoside reverse transcriptase inhibitors). Our finding suggests that these regimens effectively achieved one of the key therapeutic goals of HIV treatment, which is timely viral load suppression, in the majority of the patients. However, achieving viral suppression in about 75% of the patients still falls short of the global and national target of ensuring optimal viral suppression in at least 90% of the patients on treatment.^[7] Furthermore, our finding of undetectable viremia in 75% of the patients may in reality not be as good as it appears when interpreted in the light of the current cut-off for undetectable viremia (viral load <20 copies/mL) as against a more relaxed cut-off of <400 copies/mL used at the time of this study. Contrary to our finding, a more recent national survey conducted in Nigeria reported a much lower viral suppression rate of 38% among patients on ART in Enugu State. The higher suppression rate in our study could be attributed to the more relaxed cut-off point as earlier explained, the hospital-based nature of our study, and the fact that our study included only patients who did not miss any drug pick-up appointment during the study period. Similar to our finding, some facility-based studies assessing virologic response to first-line ART in Nigeria^[19],[20] and other African countries^[12],[21] have reported undetectable viral load suppression in 71.4–80% of patients on HAART.

Unlike our study which found similar virologic response in participants on the two nevirapine-based first-line regimens studied, a multi-center retrospective cohort study in Nigeria^[22] reported that patients on tenofovir/lamivudine/nevirapine were 1.8 times more likely to experience virologic failure compared with those on zidovudine/lamivudine/nevirapine after 48 weeks on therapy. This difference could be due to the longer duration of follow-up in the later study and the fact that the said study assessed virologic failure while ours focussed on early virologic response. The failure to suppress the plasma viral load in about 26% of the patients could in part be attributable to drug adherence issues as adherence was only measured by compliance with appointments which is rather inadequate. There is also the remote possibility that some of these patients may have HIV strains that are resistant to the first-line ART regimen they were initiated on. Further research will be needed to shed more light on the occurrence of baseline transmission of resistant viral strains in our environment. This becomes very important in a setting like ours in which resistance testing prior to HAART commencement is not practiced due to resource constraints.

Patients’ sociodemographic characteristics (age, sex, marital status) and baseline clinical characteristics (CD4 count, plasma viral load, WHO clinical stage of disease, and TB co-infection status) were found not to be significantly associated with early viral load suppression in our study. Although some studies done in Nigeria and beyond have similarly reported that sex/gender, baseline CD4 count, baseline viral load, TB co-infection, and hepatitis B/C co-infection do not predict achievement of undetectable viremia in patients started on ART,^{[11],[13],[14],[22]} others have found women patients in the younger age group and patients with supportive partners to be more likely to achieve viral load suppression^{[11],[12],[23]} as they usually have better ART adherence profile.^[24],[25] A plausible reason for the lack of significant association between patients’ sociodemographic characteristics (age, sex, and marital status) and early viral load suppression in our study could be the fact that we selected only patients with potentially good ART adherence, measured by 100% compliance with drug pick-up appointments, for our study. This may have annulled a possible association between these variables and early viral load suppression as these variables are known to exert their influence through the ART adherence pathway. Moreover, a cross-sectional study done in Nigeria reported that baseline CD4 count ≤100 cells/mm³ and viral load ≥100,000 copies/mL predicted virologic failure,^[22] whereas another cross-sectional study in Cameroon found TB co-infection to predict virologic failure.^[12] The outcome of interest in these studies was however virologic failure and not early virologic response to ART, which is the outcome of interest in our study.

Conclusion

Three out of the four patients initiated on first-line ART achieved undetectable viremia after 24 weeks of treatment in our setting. The three ART regimens assessed have comparable effectiveness. The persistent viremia in a quarter of these patients may be a pointer to adherence issues or resistant virus. Patient age, sex, marital status, baseline CD4 count, TB co-infection status, WHO clinical stage of disease, and plasma viral load at ART initiation were not significantly associated with early viral load suppression. We recommend strengthened drug adherence and targeted use of first-line ART in our setting with baseline resistance testing prior to ART initiation.

Study limitations

In this study, we analyzed the data of patients assumed to have optimal adherence to ART as assessed by their compliance with drug pick-up appointments. However, diligence in collecting antiretroviral medications may not necessarily translate to optimal adherence in taking the medications. Furthermore, a lot of patients initiated on HAART during the study period were excluded for not meeting the eligibility criteria. However, the number of patients studied far exceeded the required minimum sample size for the study.

Acknowledgements

The authors are grateful to the patients at the ARV clinic of the University of Nigeria Teaching Hospital who consented to the use of their data and the clinic management who granted access to patients’ records for this study. The findings of this study were presented and feedback received at the Nigerian Center for Disease Control/Nigeria Field Epidemiology and Laboratory Training Program 2^nd Annual Scientific Conference which held at Abuja, Nigeria in July 2017 and also at European Scientific Conference on Applied Infectious Disease Epidemiology, Stockholm, Sweden in October 2017.

Financial support and sponsorship

This study had no external funding source.

Conflicts of interest

There are no conflicts of interest.

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