Pretreatment and Acquired Drug Resistance in Children With Human Immunodeficiency Virus Type 1 in Jos, Nigeria.

We determined pretreatment and acquired human immunodeficiency virus (HIV) drug resistance among children with HIV type 1 (HIV-1) in Jos, Nigeria. The majority (71%) of those who failed first-line antiretroviral therapy were on a nevirapine-containing regimen. The prevalence of pretreatment (48%) and acquired (76%) HIV drug resistance mutations was high in our study. Wider access to HIV drug resistance testing after treatment failure is necessary to optimize second-line treatment options among children with HIV in Nigeria.

Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions.

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

The HIV-2 proviral landscape is dominated by defective proviruses.

BACKGROUND: Compared with HIV-1 infection, HIV-2 infection is associated with a slower progression to AIDS. Understanding the persistence of HIV-2 infection might inform the mechanisms responsible for differences in the pathogenicity of HIV-2 versus HIV-1. METHODS: In this study, we analyzed the genetic composition of the proviral reservoir in archived blood samples collected from 13 untreated HIV-2-infected adults from Senegal. We used single-genome, near-full-length individual proviral sequencing (FLIP-Seq) to assess the relative frequency of intact and defective proviruses. RESULTS: Ten out of 13 (77%) study participants demonstrated virologic suppression (<90 HIV RNA copies/ml) while the remaining 3 (23%) had detectable HIV RNA. We obtained 363 proviral sequences from peripheral blood mononuclear cells (PBMCs) from the 13 study participants. Within these sequences, 342 (94%) defective proviruses were detected. Twenty-one (6%) intact proviruses were detected from three study participants, with one study participant displaying a large clone consisting of 16 genome-intact sequences. CONCLUSION: This data suggests that similar to HIV-1 infection, the proviral landscape of HIV-2 is dominated by defective proviruses.

Chikungunya virus antepartum transmission and abnormal infant outcomes in a cohort of pregnant women in Nigeria.

OBJECTIVES: Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. METHODS: Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV. RESULTS: Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions. CONCLUSION: In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.

Arbovirus surveillance in pregnant women in north-central Nigeria, 2019-2022.

BACKGROUND: The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. Although originally discovered in sub-Saharan Africa the non-specific clinical presentation of arbovirus infection may have hampered our detection of adverse clinical outcomes and outbreak. OBJECTIVE: This prospective study of arbovirus infection in pregnant women in north-central Nigeria sought to characterize the prevalence of acute arbovirus infection and determine the impact on pregnancy and infant outcomes. METHODS: In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019-2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays. RESULTS: The prevalence of acute infection (IgM+) was 3.8 %, 9.9 % and 11.8 % for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5 % of all infections. The prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p = 0.014). CONCLUSIONS: Over three rainy seasons, regular acute infection with ZIKV, DENV, and CHIKV was observed with significantly higher rates in pregnant women without symptoms. The potential association arbovirus infection with abnormal birth outcome warrants further prospective study to ascertain the clinical significance of these endemic arboviruses in Africa.

Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions.

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

Arbovirus surveillance in pregnant women in north-central Nigeria, 2019-2022.

The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019-2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays. Prevalence of acute infection (IgM+) was 3.8%, 9.9% and 11.8% for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5% of all infections. Prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p=0.014). Further prospective studies will contribute to our understanding of the clinical significance of these endemic arboviruses in Africa.

Chikungunya virus antepartum transmission and abnormal infant outcomes in Nigeria.

Chikungunya virus (CHIKV) has become a global public health concern since the reemergence of the Indian Ocean lineage and expansion of the Asian genotype. CHIKV infection causes acute febrile illness, rash, and arthralgia and during pregnancy may affect both mothers and infants. The mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. We screened 1006 pregnant women at two clinics in Nigeria between 2019 and 2022 and investigated the prevalence and MTCT of CHIKV. Of the 1006, 119 tested positive for CHIKV IgM, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with 8 normal and 4 abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis and jaundice. CHIKV IgM testing identified 3 antepartum transmissions, further studies will determine its impact in antepartum infection.

High SARS-CoV-2 seroprevalence in Lagos, Nigeria with robust antibody and cellular immune responses.

Background: Early evidence suggested that the impact of the COVID-19 pandemic was less severe in Africa compared to other parts of the world. However, more recent studies indicate higher SARS-CoV-2 infection and COVID-19 mortality rates on the continent than previously documented. Research is needed to better understand SARS-CoV-2 infection and immunity in Africa. Methods: In early 2021, we studied the immune responses in healthcare workers (HCWs) at Lagos University Teaching Hospital (n = 134) and Oxford-AstraZeneca COVID-19 vaccine recipients from the general population (n = 116) across five local government areas (LGAs) in Lagos State, Nigeria. Western blots were used to simultaneously detect SARS-CoV-2 spike and nucleocapsid (N) antibodies (n = 250), and stimulation of peripheral blood mononuclear cells with N followed by an IFN-γ ELISA was used to examine T cell responses (n = 114). Results: Antibody data demonstrated high SARS-CoV-2 seroprevalence of 72·4% (97/134) in HCWs and 60·3% (70/116) in the general population. Antibodies directed to only SARS-CoV-2 N, suggesting pre-existing coronavirus immunity, were seen in 9·7% (13/134) of HCWs and 15·5% (18/116) of the general population. T cell responses against SARS-CoV-2 N (n = 114) were robust in detecting exposure to the virus, demonstrating 87·5% sensitivity and 92·9% specificity in a subset of control samples tested. T cell responses against SARS-CoV-2 N were also observed in 83.3% of individuals with N-only antibodies, further suggesting that prior non-SARS-CoV-2 coronavirus infection may provide cellular immunity to SARS-CoV-2. Conclusions: These results have important implications for understanding the paradoxically high SARS-CoV-2 infection with low mortality rate in Africa and supports the need to better understand the implications of SARS-CoV-2 cellular immunity.

Sars-Cov-2 antigen tests predict infectivity based on viral culture: comparison of antigen, PCR viral load, and viral culture testing on a large sample cohort.

OBJECTIVE: To define the relationship of SARS-CoV-2 antigen, viral load determined by RT-qPCR, and viral culture detection. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals and thereby inform how and where to most appropriately deploy antigen and nucleic acid amplification-based diagnostic testing modalities. METHODS: We compared the antigen testing results from three lateral flow and one microfluidics assay to viral culture detection and viral load determination performed in parallel in up to 189 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. RESULTS: Antigen tests were predictive of viral culture positivity, with the LumiraDx microfluidics method showing enhanced sensitivity (90%; 95% CI 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver operator characteristic curves of 0.94 to 0.97 and 0.92, respectively. A viral load threshold of 100 000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Adjusting for sample dilution inherent in our study design, sensitivities of antigen tests were ≥95% for detection of viral culture positive samples with viral loads >106 genome copies/mL, although specificity of antigen testing was imperfect. DISCUSSION: Antigen testing results and viral culture were correlated. For culture positive samples, the sensitivity of antigen tests was high at high viral loads that are likely associated with significant infectivity. Therefore, our data provides support for use of antigen testing in ruling out infectivity at the time of sampling.

Acceptability of and Preferences for Long-Acting Injectable HIV PrEP and Other PrEP Modalities among Sexual Minority Men in Nigeria, Africa.

Sexual minority men (SMM) in Nigeria have been disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) reduces risk for HIV acquisition among SMM by over 90%. The current study investigated the association between demographics, socioeconomic marginalization, sexual health and willingness to use long-acting injectable (LAI-) PrEP and preferences for other PrEP modalities in a sample of HIV-negative SMM in Nigeria. Between March and June 2019, SMM residing in Abuja, Delta, Lagos, and Plateau completed a quantitative survey. To examine willingness to use LAI-PrEP and PrEP modality preferences, multivariable binomial and multinomial logistic regression models were fit. We found that 88% were willing to use LAI-PrEP and 44% preferred LAI-PrEP to other PrEP modalities. Participants who reported interest in LAI-PrEP were more likely to be single, engage in inconsistent condom use, and report having a primary care provider. Compared to participants who preferred daily oral PrEP, participants who preferred other PrEP modalities had higher odds of having some university education/university degree or higher and reporting low financial hardship. It is imperative that SMM in Nigeria are prioritized for access to new HIV prevention interventions, as they bear a disproportionate burden of HIV and are especially vulnerable to HIV infection.

Standardization of Aspergillus IgG diagnostic cutoff in Nigerians.

BACKGROUND AND OBJECTIVES: Commercial Aspergillus IgG antibody assays have become pivotal in the current diagnosis of chronic pulmonary aspergillosis (CPA). However, diagnostic cutoffs have been found to vary from manufactures' recommendations in different settings. This study aimed to establish the Aspergillus IgG reference range among Nigerians and determine a diagnostic cutoff for CPA. METHODS: Sera from 519 prospectively recruited healthy blood donors and 39 previously confirmed cases of CPA were analysed for Aspergillus IgG levels using the Bordier test kit (Bordier Affinity Products SA, Crissier, Switzerland). Accuracy versus cutoff profile and receiver operating characteristics (ROC) curve were analysed for both CPA cases and controls using the R-Studio (2020), (Window desktop, version 4.0.2 software with R packages "nnet" and "ROCR"). RESULTS: Among healthy blood donors, 141 (27.2%) were aged 16-25 years with median (interquartile range, IQR) of 22 (20-24) years; 304 (58.6%) were aged 26-40 years with median (IQR) of 32 (29-36) years; while 74 (14.2%) were aged 41-60 years with median (IQR) of 46 (44-49.75). Median IgG level in respective age groups were 0.069 (0.009-0.181), 0.044 (0.014-0.202) and 0.056 (0.01-0.265) with no significant difference found in the three age categories (p = 0.69). The overall diagnostic cutoff for the diagnosis of CPA was 0.821 with an accuracy of 97.1% and area under the curve (AUC) = 0.986. CONCLUSION: The optimal diagnostic cutoff for diagnosing CPA in Nigerians using the Bordier kit was 0.821 which is lower than the manufacturer's recommended cutoff of 1.0. The determination of this cutoff among Nigerians will significantly enhance accurate identification of CPA and assessment of its true burden in Nigeria.

Derangement of protein S and C4b-binding protein levels as acquired thrombophilia in HIV-infected adult Nigerians.

BACKGROUND: HIV is a chronic inflammatory state with the production of many acute-phase-reactant proteins. Some of these proteins have procoagulant activities that predispose HIV-infected patients to thrombosis. OBJECTIVES: The aim of the study was to evaluate the effects of HIV infection on the serum levels of C4b-binding protein (C4BP) and protein S as markers of predisposition to thrombosis in HIV-infected adults. METHODS: The study population comprised of 61 HIV-infected adults on antiretroviral treatment (ART) who had achieved virological suppression, 58 HIV-infected adults not yet on ART and 59 HIV-negative healthy controls. The serum levels of free protein S, C4BP and the euglobulin clot lysis time (ECLT) were determined. RESULTS: The mean plasma-free protein S level of HIV-infected patients on ART (86.9% ± 25.8%) was significantly higher than that of treatment-naïve HIV-infected patients (75.7% ± 27.3%) (p = 0.005). Conversely, there was no statistically significant difference between the protein S levels of the HIV-infected subjects on ART (86.9% ± 25.8%) and those of the controls (94.9% ± 7.9%) (p = 0.119). The mean C4BP was significantly higher in the treatment-naïve HIV-infected subjects (36.7 ± 1.7 ng/dL) than that in those on ART (30.7 ± 2.6 ng/dL) and that in the controls (22.4 ± 2.4 ng/dL) (p < 0.0001). Protein S deficiency was more prevalent among the subjects with elevated C4BP (p = 0.023). The mean ECLT was significantly more prolonged in the treatment-naïve HIV-infected subjects (241.9 ± 34.7 s) than controls (189.5 ± 40.7 s) (p < 0.0001). CONCLUSION: HIV infection causes elevated levels of C4BP and diminishes the serum levels of free protein S. We infer that the risk of thrombosis (as measured by these biomarkers) decreases with the use of antiretroviral drugs.

Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART.

BACKGROUND: Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia. METHODS: We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study. RESULTS: Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) µg·h/mL. Four participants had AUC0-24 below 3.8 µg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 µg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications. CONCLUSIONS: In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.

Effects of selenium supplementation on pregnancy outcomes and disease progression in HIV-infected pregnant women in Lagos: A randomized controlled trial.

OBJECTIVE: To examine the effects of selenium supplementation on pregnancy outcomes and disease progression among HIV-infected pregnant women in Lagos. METHODS: A randomized, placebo-controlled trial conducted among HIV-positive pregnant women between September 2018 and August 2019. At enrollment, 90 women were randomly assigned into each treatment arm to receive either a daily tablet of 200 µg elemental selenium or a placebo. Relevant participants' sociodemographic and clinical data were collected at enrollment and delivery. RESULTS: Women in the selenium arm had a significantly lower risk of preterm delivery (relative risk [RR] 0.32, 95% confidence interval [CI] 0.11-0.96) and a non-significant reduction in the risk of delivering term neonates with a low delivery weight (RR 0.24, 95% CI 0.05-1.19). Supplemental selenium does not increase the risk of perinatal death and adverse drug events. CONCLUSION: The study reported a beneficial effect of prenatal selenium supplements on the risk of preterm delivery with no further reduction in risk among HIV-infected women who used the supplements for more than 14 weeks. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR201809756724274).

Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria-A pilot study.

In Nigeria, about 150000 babies are born annually with sickle cell disease (SCD), and this figure has been estimated to increase by 100% by the year 2050 without effective and sustainable control strategies. Despite the high prevalence, newborn screening for SCD which allows for early prophylactic treatment, education of parents/guardians and comprehensive management is not yet available. This study explored a strategy for screening in early infancy during the first and second immunization visits, determined the prevalence, feasibility and acceptability of early infant screening for SCD and the evaluation of the HemoTypeSC diagnostic test as compared to the high-performance liquid chromatography (HPLC) gold standard. A cross-sectional study was conducted in two selected primary health care centres in Somolu local government area (LGA) in Lagos, Nigeria. Two hundred and ninety-one mother-infant pairs who presented for the first or second immunization visit were consecutively enrolled in the study following written informed consent. The haemoglobin genotype of mother-infant pairs was determined using the HemoTypeSC rapid test kit. Confirmation of the infants' Hb genotype was done with HPLC. Data were analysed with SPSS version 22. Validity and Predictive value of HemotypeSC rapid screening test were also calculated. Infant screening for SCD was acceptable to 86% of mothers presenting to the immunization clinics. The prevalence of SCD among the infant cohort was 0.8%. The infants diagnosed with SCD were immediately enrolled in the paediatric SCD clinic for disease-specific care. The HemoTypeSC test had 100% sensitivity and specificity for sickle cell disease in early infancy compared to HPLC. This study affirms that it is feasible and acceptable for mothers to implement a SCD screening intervention program in early infancy in Lagos State. The study also demonstrates the utility of the HemotypeSC rapid testing for ease and reduced cost of screening infants for SCD.

The impact of HIV-1 subtypes on virologic and immunologic treatment outcomes at the Lagos University Teaching Hospital: A longitudinal evaluation.

INTRODUCTION: HIV is a highly diverse virus with significant genetic variability which may confer biologic differences that could impact on treatment outcomes. MATERIALS AND METHODS: We studied the association between HIV subtypes and immunologic and virologic outcomes in a longitudinal cohort of 169 patients on combination antiretroviral therapy. Participants were followed up for 5 years. Demographic data, CD4 cell count and viral loads (VL) were extracted from medical records. Whole protease gene and codon 1-300 of the reverse transcriptase gene were sequenced and analysed. RESULTS: Sixty-four percent of participants were females with a median age of 35 years. Twelve different subtypes were observed, the commonest being CRF 02_AG (55.0%) and subtypes G (23.1%). All subtypes showed steady rise in CD4 count and there was no difference in proportion who achieved CD4+ cell count rise of ≥100 cells/µL from baseline within 12 months' post-initiation of ART, or ≥350 cells/µL at 60 months' post-initiation. Median time to attaining a rise of ≥350 cells/µL was 24 months (6-48 months). The proportion that achieved undetectable VL at month 6 and 12 post-initiation of ART were comparable across subtypes. At end of 5th year, there was no statistical difference in proportion with virologic failure. CONCLUSION: No association between HIV subtypes and immunologic or virologic response to therapy was observed, suggesting that current first-line ART may have similar efficacy across subtype predominating in South-West Nigeria.

Longitudinal evaluation of adherence, retention, and transition patterns of adolescents living with HIV in Nigeria.

INTRODUCTION: Adherence to antiretroviral therapy (ART) and retention in treatment programs are required for successful virologic suppression and treatment outcomes. As the number of adolescents living with HIV continues to increase globally, more information about adherence and retention patterns during and through transition from child- to adult-centered care is needed to ensure provision of a high level of care and inform development of targeted interventions to improve patient outcomes in this vulnerable population. In this analysis, we sought to describe long-term trends in adherence, retention, and virologic suppression in adolescents receiving ART at a pediatric HIV clinic in Nigeria through transition to the adult clinic. SETTING: The Jos University Teaching Hospital, United States President's Emergency Plan for AIDS Relief (PEPFAR)-funded HIV clinic in Jos, Plateau State, Nigeria. METHODS: We conducted a retrospective observational longitudinal evaluation of data that had been collected during the course of care in a large pediatric ART program in Nigeria. We used descriptive statistics to define our patient population and quantify retention from ART initiation through adolescence and transition to adult-centered care. Logistic regression was used to evaluate predictors of loss to follow-up. We used medication possession ratio (MPR) to quantify adherence for each year a patient was on ART. To evaluate adherence and virologic suppression, we measured the proportion of patients with ≥95% MPR and the proportion with virologic suppression (viral load ≤400 copies/mL) within each age cohort, and used bivariate analyses to examine any association between MPR and VL suppression for all person-years observed. RESULTS: A total of 476 patients received at least one dose of ART as an adolescent (ages 10-19 years). The proportions of patients lost to follow-up were: 11.9% (71/597) prior to adolescence, 19.1% (31/162) during adolescence, and 13.7% (10/73) during transition to adult-centered care. While over 80% of patients had ≥95% medication adherence in all age groups, their viral load suppression rates through adolescence and post-transition were only 55.6%-64.0%. For patients that successfully transitioned to adult-centered care, we observed 87.7% (50/57) retention at month 12 post-transition, but only 34.6% (9/26) viral load suppression. CONCLUSIONS: Our evaluation found considerable proportions of adolescents lost to follow-up throughout the ART program cascade. We also found discrepancies between the proportions of patients with ≥95% MPR and the proportions with VL suppression, suggesting that true medication adherence in this population may be poor. Significant attention and targeted interventions to improve retention and adherence focused on adolescents are needed in order for global programs to achieve 90-90-90 goals.