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Kanki, Phyllis

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Kanki

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Phyllis

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Kanki, Phyllis
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    Time-Dependent Predictors of Loss to Follow-Up in a Large HIV Treatment Cohort in Nigeria
    (Oxford University Press, 2014) Meloni, Seema Thakore; Chang, Charlotte; Chaplin, Beth; Rawizza, Holly; Jolayemi, Oluwatoyin; Banigbe, Bolanle; Okonkwo, Prosper; Kanki, Phyllis
    Background: Most evaluations of loss to follow-up (LTFU) in human immunodeficiency virus (HIV) treatment programs focus on baseline predictors, prior to antiretroviral therapy (ART) initiation. As risk of LTFU is a continuous issue, the aim of this evaluation was to augment existing information with further examination of time-dependent predictors of loss. Methods: This was a retrospective evaluation of data collected between 2004 and 2012 by the Harvard School of Public Health and the AIDS Prevention Initiative in Nigeria as part of PEPFAR-funded program in Nigeria. We used multivariate modeling methods to examine associations between CD4+ cell counts, viral load, and early adherence patterns with LTFU, defined as no refills collected for at least 2 months since the last scheduled appointment. Results: Of 51 953 patients initiated on ART between 2004 and 2011, 14 626 (28%) were LTFU by 2012. Factors associated with increased risk for LTFU were young age, having nonincome-generating occupations or no education, being unmarried, World Health Organization (WHO) stage, having a detectable viral load, and lower CD4+ cell counts. In a subset analysis, adherence patterns during the first 3 months of ART were associated with risk of LTFU by month 12. Conclusions: In settings with limited resources, early adherence patterns, as well as CD4+ cell counts and unsuppressed viral load, at any time point in treatment are predictive of loss and serve as effective markers for developing targeted interventions to reduce rates of attrition.
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    Retention in Differentiated Care: Multiple Measures Analysis for a Decentralized HIV Care and Treatment Program in North Central Nigeria
    (2018) Agaba, Patricia A; Genberg, Becky L; Sagay, Atiene S; Agbaji, Oche O; Meloni, Seema; Dadem, Nancin Y; Kolawole, Grace O; Okonkwo, Prosper; Kanki, Phyllis; Ware, Norma
    Objective: Differentiated care refers collectively to flexible service models designed to meet the differing needs of HIV-infected persons in resource-scarce settings. Decentralization is one such service model. Retention is a key indicator for monitoring the success of HIV treatment and care programs. We used multiple measures to compare retention in a cohort of patients receiving HIV care at “hub” (central) and “spoke” (decentralized) sites in a large public HIV treatment program in north central Nigeria. Methods: This retrospective cohort study utilized longitudinal program data representing central and decentralized levels of care in the Plateau State Decentralization Initiative, north central Nigeria. We examined retention with patient- level (retention at fixed times, loss-to-follow-up [LTFU]) and visit-level (gaps-in-care, visit constancy) measures. Regression models with generalized estimating equations (GEE) were used to estimate the effect of decentralization on visit-level measures. Patient-level measures were examined using survival methods with Cox regression models, controlling for baseline variables. Results: Of 15,650 patients, 43% were enrolled at the hub. Median time in care was 3.1 years. Hub patients were less likely to be LTFU (adjusted hazard ratio (AHR)=0.91, 95% CI: 0.85-0.97), compared to spoke patients. Visit constancy was lower at the hub (−4.5%, 95% CI: −3.5, −5.5), where gaps in care were also more likely to occur (adjusted odds ratio=1.95, 95% CI: 1.83-2.08). Conclusion: Decentralized sites demonstrated better retention outcomes using visit-level measures, while the hub achieved better retention outcomes using patient-level measures. Retention estimates produced by incorporating multiple measures showed substantial variation, confirming the influence of measurement strategies on the results of retention research. Future studies of retention in HIV care in sub-Saharan Africa will be well-served by including multiple measures.
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    A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals
    (Public Library of Science (PLoS), 2018) Herrera, Bobby Brooke; Hamel, Donald; Oshun, Philip; Akinsola, Rolake; Akanmu, Alani S.; Chang, Charlotte; Eromon, Philomena; Folarin, Onikepe; Adeyemi, Kayode T.; Happi, Christian T.; Lu, Yichen; Ogunsola, Folasade; Kanki, Phyllis
    Background Ebola virus (EBOV) caused more than 11,000 deaths during the 2013–2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. Methodology/Principle findings Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. Conclusion/Significance Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.
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    Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria
    (Public Library of Science, 2013) Rawizza, Holly; Chaplin, Beth; Meloni, Seema T.; Darin, Kristin M.; Olaitan, Oluremi; Scarsi, Kimberly K.; Onwuamah, Chika K.; Audu, Rosemary A.; Chebu, Philippe R.; Imade, Godwin E.; Okonkwo, Prosper; Kanki, Phyllis
    Background: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. Methods and Findings: From 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0–5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0–6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. Conclusions: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.
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    Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria
    (Hindawi Publishing Corporation, 2014) Okonkwo, Prosper; Sagay, Atiene S.; Agaba, Patricia A.; Yohanna, Stephen; Agbaji, Oche O.; Imade, Godwin E.; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A.; Idoko, John A.; Kanki, Phyllis
    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.
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    Cross-reactivity to human T-lymphotropic virus type III/lymphadenopathy-associated virus and molecular cloning of simian T-cell lymphotropic virus type III from African green monkeys.
    (Proceedings of the National Academy of Sciences, 1986) Hirsch, V.; Riedel, N.; Kornfeld, H.; Kanki, Phyllis; Essex, Myron; Mullins, J. I.
    Simian T-lymphotropic retroviruses with structural, antigenic, and cytopathic features similar to the etiologic agent of human acquired immunodeficiency syndrome, human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), have been isolated from a variety of primate species including African green monkeys (STLV-IIIAGM). This report describes nucleic acid cross-reactivity between STLV-IIIAGM and HTLV-III/LAV, molecular cloning of the STLV-IIIAGM genome, and evaluation of its structure and genetic relationship to other retroviruses. Overlapping clones from a cell line infected with virus from a single animal were found to encompass the entire STLV-IIIAGM genome and exhibit a limited degree of restriction-site variability. Specific hybridizing fragments were detected in DNA from this and other STLV-IIIAGM-infected cell lines. A fraction of viral DNA present in at least two STLV-IIIAGM lines persists as unintegrated viral DNA, a characteristic of infection with cytopathic retroviruses. Strongest cross-reactivity was detected between HTLV-III/LAV pol- and gag- genes and STLV-IIIAGM, whereas no cross-reactivity was detected between STLV-IIIAGM and molecular clones of human T-lymphotropic virus types I and II (HTLV-I and -II), visna virus, bovine leukemia virus, or feline leukemia virus.
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    High-risk human papilloma virus and cervical abnormalities in HIV-infected women with normal cervical cytology
    (BioMed Central, 2014) Musa, Jonah; Achenbach, Chad; Taiwo, Babafemi; Berzins, Baiba; Silas, Olugbenga; Daru, Patrick H; Agbaji, Oche; Imade, Godwin; Sagay, Atiene S; Idoko, John A; Kanki, Phyllis; Murphy, Robert L
    Background: The prevalence of High-Risk Human papilloma virus (HR-HPV), a necessary cause of invasive cervical cancer (ICC) is relatively high in HIV infected women. Gaps exist in our knowledge of the optimal approaches for managing women who have HR-HPV with normal cervical cytology (NCC) particularly in settings of HIV infection. Methods: Between May 2012 and June 2013 we conducted a colposcopic assessment of HIV-infected women with prior (NCC) and known HR-HPV status to compare cervical abnormalities in women with and without HR-HPV. Colposcopic examinations were done at the Operation Stop Cervical Cancer (OSCC) unit of the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Abnormal colposcopic finding (ACF) was defined as areas of aceto-white epithelium involving the squamo-coulumnar junction, areas of punctation, mosaic pattern or atypical vessels. We compared proportions of ACF as well as histologic grades of cervical intra-epithelial neoplasia (CIN) in women with or without HR-HPV. Statistical analysis was done on STATA. Results: We conducted colposcopic examinations in 78 out of 89 (86.5%) eligible women. The mean age of the cohort was 32.4 years (SD ±4.6) with a median 32 years (IQR 29–36). After a mean follow up time of 20.1 months from the initial cervical pap cytology and HR-HPV testing, we found 12 of 78 (15.4%) women with ACF. The odds for an ACF was statistically higher [OR = 4.0 (95% CI: 1.1-14.7)] in women with HR-HPV compared to those without. Of the twelve women with ACF, subsequent histologic examination of colposcopically directed cervical biopsies confirmed CIN 1 in 4 cases (33.3%), CIN 2 in 1 case (8.3%), CIN 3 in 2 cases (16.7%), carcinoma-in-situ (CIS) in 2 cases (16.7%), and normal cervix in 3 (25.0%). Overall, the proportion of women detected with any grade of CIN was 11.5% (9/78) and 6.4% (5/78) were CIN 2 or greater lesion (CIN2+). Conclusion: HIV-infected women with NCC and HR-HPV had a four-fold higher likelihood for an ACF. The practice of early colposcopic examination of HIV-infected women with prior NCC and HR-HPV may increase early detection of higher grade CIN and CIS cancer stages in our setting.
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    Building laboratory capacity to support HIV care in Nigeria: Harvard/APIN PEPFAR, 2004–2012
    (2015) Hamel, Donald; Sankalé, Jean-Louis; Samuels, Jay Osi; Sarr, Abdoulaye D.; Chaplin, Beth; Ofuche, Eke; Meloni, Seema T.; Okonkwo, Prosper; Kanki, Phyllis
    Introduction: From 2004–2012, the Harvard/AIDS Prevention Initiative in Nigeria, funded through the US President’s Emergency Plan for AIDS Relief programme, scaled up HIV care and treatment services in Nigeria. We describe the methodologies and collaborative processes developed to improve laboratory capacity significantly in a resource-limited setting. These methods were implemented at 35 clinic and laboratory locations. Methods: Systems were established and modified to optimise numerous laboratory processes. These included strategies for clinic selection and management, equipment and reagent procurement, supply chains, laboratory renovations, equipment maintenance, electronic data management, quality development programmes and trainings. Results: Over the eight-year programme, laboratories supported 160 000 patients receiving HIV care in Nigeria, delivering over 2.5 million test results, including regular viral load quantitation. External quality assurance systems were established for CD4+ cell count enumeration, blood chemistries and viral load monitoring. Laboratory equipment platforms were improved and standardised and use of point-of-care analysers was expanded. Laboratory training workshops supported laboratories toward increasing staff skills and improving overall quality. Participation in a World Health Organisation-led African laboratory quality improvement system resulted in significant gains in quality measures at five laboratories. Conclusions: Targeted implementation of laboratory development processes, during simultaneous scale-up of HIV treatment programmes in a resource-limited setting, can elicit meaningful gains in laboratory quality and capacity. Systems to improve the physical laboratory environment, develop laboratory staff, create improvements to reduce costs and increase quality are available for future health and laboratory strengthening programmes. We hope that the strategies employed may inform and encourage the development of other laboratories in resource-limited settings.
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    Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort
    (Oxford University Press, 2015) Scarsi, Kimberly K.; Eisen, Geoffrey; Darin, Kristin M.; Meloni, Seema T.; Rawizza, Holly; Tchetgen Tchetgen, Eric; Agbaji, Oche O.; Onwujekwe, Daniel I.; Gashau, Wadzani; Nkado, Reuben; Okonkwo, Prosper; Murphy, Robert L.; Kanki, Phyllis
    Background. Despite sparse efficacy data, tenofovir–emtricitabine or tenofovir–lamivudine plus nevirapine is used in many resource-constrained settings. Methods. This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir–emtricitabine or lamivudine (tenofovir group) or zidovudine–lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. Results. A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21–1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03–1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40–.63) and increasing age (HR, 0.98; 95% CI, .97–.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. Conclusions. Compared with zidovudine–lamivudine, the use of tenofovir–lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection.
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    Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children
    (European HIV/AIDS and Infectious Diseases Academy, 2016) Ebonyi, Augustine Odo; Oguche, Stephen; Ejeliogu, Emeka U; Agbaji, Oche O; Shehu, Nathan Y; Abah, Isaac O; Sagay, Atiene S; Ugoagwu, Placid O; Okonkwo, Prosper; Idoko, John A; Kanki, Phyllis
    Introduction: Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria. Methods: We performed a retrospective analysis of 876 children, aged 2 months – 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection. Results: The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007). Conclusion: In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes.