Integrating community pharmacy into community based anti-retroviral therapy program: A pilot implementation in Abuja, Nigeria

Background The landscape of Human Immunodeficiency Virus (HIV) epidemic control is shifting with the United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 benchmarks for epidemic control. Community-based Antiretroviral Therapy (CART) models have improved treatment uptake and demonstrated good clinical outcomes. We assessed the feasibility of integrating community pharmacy as a task shift structure for differentiated community ART in Abuja-Nigeria. Methods Stable patients on first line ART regimens from public health facilities were referred to community pharmacies in different locations within the Federal Capital Territory, Abuja for prescription refills and treatment maintenance. Bio-demographic and clinical data were collected from February 25, 2016 to May 31st, 2017 and descriptive statistics analysis applied. The outcomes of measure were prescription refill and patient retention in care at the community pharmacy. Results Almost 10% of stable patients on treatment were successfully devolved from eight health facilities to ten community pharmacies. Median age of the participants was 35 years [interquartile range (IQR); 30, 41] with married women in the majority. Prescription refill was 100% and almost all the participants (99.3%) were retained in care after they were devolved to the community pharmacies. Only one participant was lost-to-follow-up as a result of death. Conclusion Excellent prescription refill and high retention in care with very low loss-to-follow-up were associated with the community pharmacy model. The use of community pharmacy for community ART is feasible in Nigeria. We recommend the scale up of the model in all the 36 states of Nigeria

Cervical cancer risk factors among HIV-infected Nigerian women

Background: Cervical cancer is the third most common cancer among women worldwide, and in Nigeria it is the second most common female cancer. Cervical cancer is an AIDS-defining cancer; however, HIV only marginally increases the risk of cervical pre-cancer and cancer. In this study, we examine the risk factors for cervical pre-cancer and cancer among HIV-positive women screened for cervical cancer at two medical institutions in Abuja, Nigeria. Methods: A total of 2,501 HIV-positive women participating in the cervical cancer screen-and-treat program in Abuja, Nigeria consented to this study and provided socio-demographic and clinical information. Log-binomial models were used to calculate relative risk (RR) and 95% confidence intervals (95%CI) for the risk factors of cervical pre-cancer and cancer. Results: There was a 6% prevalence of cervical pre-cancer and cancer in the study population of HIV-positive women. The risk of screening positivity or invasive cancer diagnosis reduced with increasing age, with women aged 40 years and older having the lowest risk (RR=0.4; 95%CI=0.2–0.7). Women with a CD4 count of 650 per mm3 or more also had lower risk of screening positivity or invasive cancer diagnosis (RR=0.3, 95%CI=0.2–0.6). Other factors such as having had 5 or more abortions (RR=1.8, 95%CI=1.0–3.6) and the presence of other vaginal wall abnormalities (RR=1.9, 95%CI=1.3–2.8) were associated with screening positivity or invasive cancer diagnosis. Conclusion: The prevalence of screening positive lesions or cervical cancer was lower than most previous reports from Africa. HIV-positive Nigerian women were at a marginally increased risk of cervical pre-cancer and cancer. These findings highlight the need for more epidemiological studies of cervical cancer and pre-cancerous lesions among HIV-positive women in Africa and an improved understanding of incidence and risk factors

Ease and equity of access to free DR-TB services in Nigeria- a qualitative analysis of policies, structures and processes

Introduction: Persistent low rates of case notification and treatment coverage reflect that accessing diagnosis and treatment for drug-resistant tuberculosis (DR-TB) in Nigeria remains a challenge, even though it is provided free of charge to patients. Equity in health access requires availability of comparable, appropriate services to all, based on needs, and irrespective of socio-demographic characteristics. Our study aimed to identify the reasons for Nigeria’s low rates of case-finding and treatment for DR-TB. To achieve this, we analyzed elements that facilitate or hinder equitable access for different groups of patients within the current health system to support DR-TB management in Nigeria. Methods: We conducted documentary review of guidelines and workers manuals, as well as 57 qualitative interviews, including 10 focus group discussions, with a total of 127 participants, in Nigeria. Between August and November 2017, we interviewed patients who were on treatment, their treatment supporter, and providers in Ogun and Plateau States, as well as program managers in Benue and Abuja. We adapted and used Levesque’s patient-centered access to care framework to analyze DR-TB policy documents and interview data. Results: Thematic analysis revealed inequitable access to DR-TB care for some patient socio-demographic groups. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Health system factors including positive provider attitudes and financial support provided to the patients facilitated equity and ease of access. However, limited coverage and the absence of patients’ access rights protection and considerations in the treatment guidelines and workers manuals likely hampered access. Conclusion: In the context of Nigeria’s low case-finding and treatment coverage, applying an equity of access framework was necessary to highlight gaps in care. Differing social contexts of patients adversely affected their access to DR-TB care. We identified several strengths in DR-TB care delivery, including the current financial support that should be sustained. Our findings highlight the need for government’s commitment and continued interventions

Influence of Spirituality and Modesty on Acceptance of Self-Sampling for Cervical Cancer Screening.

INTRODUCTION: Whereas systematic screening programs have reduced the incidence of cervical cancer in developed countries, the incidence remains high in developing countries. Among several barriers to uptake of cervical cancer screening, the roles of religious and cultural factors such as modesty have been poorly studied. Knowledge about these factors is important because of the potential to overcome them using strategies such as self-collection of cervico-vaginal samples. In this study we evaluate the influence of spirituality and modesty on the acceptance of self-sampling for cervical cancer screening. METHODOLOGY: We enrolled 600 participants in Nigeria between August and October 2014 and collected information on spirituality and modesty using two scales. We used principal component analysis to extract scores for spirituality and modesty and logistic regression models to evaluate the association between spirituality, modesty and preference for self-sampling. All analyses were performed using STATA 12 (Stata Corporation, College Station, Texas, USA). RESULTS: Some 581 (97%) women had complete data for analysis. Most (69%) were married, 50% were Christian and 44% were from the south western part of Nigeria. Overall, 19% (110/581) of the women preferred self-sampling to being sampled by a health care provider. Adjusting for age and socioeconomic status, spirituality, religious affiliation and geographic location were significantly associated with preference for self-sampling, while modesty was not significantly associated. The multivariable OR (95% CI, p-value) for association with self-sampling were 0.88 (0.78-0.99, 0.03) for spirituality, 1.69 (1.09-2.64, 0.02) for religious affiliation and 0.96 (0.86-1.08, 0.51) for modesty. CONCLUSION: Our results show the importance of taking cultural and religious beliefs and practices into consideration in planning health interventions like cervical cancer screening. To succeed, public health interventions and the education to promote it must be related to the target population and its preferences

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women

Background: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol’s Iodine (VILI) for diagnosis. Methods: A retrospective cohort study was conducted, recruiting participants from the cervical cancer “see and treat” program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. Results: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm3 was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). Conclusion: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression

In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix.

Protease inhibitors (PIs) are the second- and last-line therapy for the majority of HIV-infected patients worldwide. Only around 20% of individuals who fail PI regimens develop major resistance mutations in protease. We sought to explore the role of mutations in gag-pro genotypic and phenotypic changes in viruses from six Nigerian patients who failed PI-based regimens without known drug resistance-associated protease mutations in order to identify novel determinants of PI resistance. Target enrichment and next-generation sequencing (NGS) with the Illumina MiSeq system were followed by haplotype reconstruction. Full-length Gag-protease gene regions were amplified from baseline (pre-PI) and virologic failure (VF) samples, sequenced, and used to construct gag-pro-pseudotyped viruses. Phylogenetic analysis was performed using maximum-likelihood methods. Susceptibility to lopinavir (LPV) and darunavir (DRV) was measured using a single-cycle replication assay. Western blotting was used to analyze Gag cleavage. In one of six participants (subtype CRF02_AG), we found 4-fold-lower LPV susceptibility in viral clones during failure of second-line treatment. A combination of four mutations (S126del, H127del, T122A, and G123E) in the p17 matrix of baseline virus generated a similar 4-fold decrease in susceptibility to LPV but not darunavir. These four amino acid changes were also able to confer LPV resistance to a subtype B Gag-protease backbone. Western blotting demonstrated significant Gag cleavage differences between sensitive and resistant isolates in the presence of drug. Resistant viruses had around 2-fold-lower infectivity than sensitive clones in the absence of drug. NGS combined with haplotype reconstruction revealed that resistant, less fit clones emerged from a minority population at baseline and thereafter persisted alongside sensitive fitter viruses. We used a multipronged genotypic and phenotypic approach to document emergence and temporal dynamics of a novel protease inhibitor resistance signature in HIV-1 matrix, revealing the interplay between Gag-associated resistance and fitness

Prevalence of hypertension among patients aged 50 and older living with Human Immunodeficiency Virus

Background: Hypertension is one of the common medical conditions observed among patients aged 50 years and elder living with HIV (EPLWH) and to date no systematic review has estimated its global prevalence. Purpose: To conduct a systematic review to estimate the global prevalence of hypertension among EPLWH. Data Sources: PubMed/MEDLINE, Embase, the Cochrane Library, and Global Health databases for relevant publications up till May 25, 2018. Study Selection: Observational studies (cohort or cross-sectional studies) that estimated the prevalence of hypertension among EPLWH. Data Extraction: Required data were extracted independently by three reviewers and the main outcome was hypertension prevalence among EPLWH. Data Synthesis: The 24 (n = 29,987) eligible studies included were conducted in North America, Europe, Africa, and Asia. A low level bias threat to the estimated hypertension prevalence rates was observed. The global prevalence of hypertension among EPLWH was estimated at 42.0% (95% CI 29.6%–55.4%), I 2 = 100%. The subgroup analysis showed that North America has the highest prevalence of hypertension 50.2% (95% CI 29.2% –71.2%) followed by Europe 37.8% (95% CI 30.7%–45.7%) sub-Saharan Africa 31.9% (95% CI 18.5% –49.2%) and Asia 31.0% (95% CI 26.1%–36.3%). We found the mean age of the participants explaining a considerable part of variation in hypertension prevalence. Conclusion: This study demonstrated that two out of five EPLWH are hypertensive. North America appears to have the highest prevalence of hypertension followed by Europe, sub-Saharan Africa (SSA) and Asia respectively. Findings from this study can be utilized to integrate hypertension management to HIV management package. (Registration number: CRD42018103069

Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.

BACKGROUND: A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. METHODS: A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4  1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program's own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)-based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07-1.40)] and less common among those who entered care at the program's VCT center as compared to other entry points [0.79 (0.64-0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16-0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16-0.22)]. Virologic failure was more common among PLWH who entered care at the program's VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11-1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36-2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. CONCLUSIONS: In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations

High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.K.E.B. is supported by Wellcome Trust award number 170461. N.N. is supported by NIH R01 AI147331-01. R.K.G. is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). This study was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of U2G GH002099-01 and PA GH17-1753 (ACHIEVE)

Addressing the under-reporting of adverse drug reactions in public health programs controlling HIV/AIDS, tuberculosis and malaria: A prospective cohort study

Background Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. Methods A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. Results Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. Conclusion Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings