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.

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study.

BACKGROUND: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. RESULT: Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. CONCLUSION: This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance.

Status of HIV-infected patients classified as lost to follow up from a large antiretroviral program in southwest Nigeria.

BACKGROUND: Loss to follow-up (LTFU) is a term used to classify patients no longer being seen in a clinical care program, including HIV treatment programs. It is unclear if these patients have transferred their care services elsewhere, died, or if there are other reasons for their LTFU. To better understand the status of patients meeting the criteria of LTFU, we traced a sample of HIV-infected patients that were LTFU from the Lagos University Teaching Hospital (LUTH) antiretroviral program. METHODS: We conducted a cross-sectional study of HIV-infected adult patients who enrolled for care between 2010 and 2014 at LUTH and were considered LTFU. Patients with locator information were traced using phone calls. Face-to-face interviews were used to collect data from successfully traced and consenting participants. Predictors of LTFU from LUTH, disengagement from care and willingness to re-engage in care in LUTH were assessed. RESULTS: Of 6108 registered patients, 3397 (56%) were LTFU and being unmarried was a predictor of being LTFU from LUTH. Of 425 patients that were traced, 355 (84%) were alive and 70 (16%) were dead. Two hundred and sixty-eight patients consented to interviews; 96 (35.8%) of these had transferred to another clinic for care while 172 (64.2%) were disengaged from care. More than half (149/268; 55.6%) were not on antiretroviral therapy (ART). Some of the primary reasons for LTFU were; long distance to clinic (56%) and feeling healthy (6.7%). Predictor of disengagement from care within the interviewed cohort was not having started ART. The predictors of willingness to re-engage in care included, not having started ART, male sex and longer duration in HIV care prior to LTFU. CONCLUSION: Most of the interviewed cohort that was LTFU were truly disengaged from care and not on ART. Interventions are required to address processes of re-engagement of patients that are LTFU.

Predictors of tuberculosis knowledge, attitudes and practices in urban slums in Nigeria: a cross-sectional study.

INTRODUCTION: Nigeria is among six countries responsible for the majority of tuberculosis (TB) cases in the world. The Nigerian government has emphasized community-based case finding to increase detection of TB. This process requires efforts to improve knowledge, attitudes and practices (KAP) of TB, particularly in the poorest of communities. This study presents data from a KAP survey administered in two underserved Nigerian communities. METHODS: a structured survey was administered by trained interviewers among adult residents in two slum communities in Lagos, Nigeria. Participants were selected through multistage random sampling. KAP scores were computed and the predictors of higher scores were assessed. RESULTS: a total of 504 respondents were surveyed. The mean KAP scores were relatively low: 9.8 ± 7.1 for knowledge (out of a maximum 34), 5.3 ± 3.4 for attitude (maximum = 10), and 5.2 ± 1.5 for practice (maximum = 7). The predictors of good knowledge were increasing age, post secondary education and professional occupation. The predictors of positive attitude were post secondary education and good TB knowledge. Good knowledge was a predictor of good practice. CONCLUSION: our findings underscore the need to improve the education about TB in underserved communities. Improving KAP scores will ultimately lead to higher rates of TB detection and treatment.

The role of point-of-care viral load monitoring in achieving the target of 90% suppression in HIV-infected patients in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS 90-90-90 goal envisions 90% of all people receiving antiretroviral therapy to be virally suppressed by 2020. Implied in that goal is that viral load be quantified for all patients receiving treatment, which is a challenging undertaking given the complexity and high cost of standard-of-care viral load testing methods. Recently developed point-of-care viral load testing devices offer new promise to improve access to viral load testing by bringing the test closer to the patient and also returning results faster, often same-day. While manufactures have evaluated point-of-care assays using reference panels, empiric data examining the impact of the new technology against standard-of-care monitoring in low- and middle-income settings are lacking. Our goal in this trial is to compare a point-of-care to standard-of-care viral load test on impact on various clinical outcomes as well to assess the acceptability and feasibility of using the assay in a resource-limited setting. METHODS: Using a two-arm randomized control trial design, we will enroll 794 patients from two different HIV treatment sites in Nigeria. Patients will be randomized 1:1 for point-of-care or standard-of-care viral load monitoring (397 patients per arm). Following initiation of treatment, viral load will be monitored at patients' 6- and 12-month follow-up visits using either point-of-care or standard-of-care testing methods, based on trial assignment. The monitoring schedule will follow national treatment guidelines. The primary outcome measure in this trial is proportion of patients with viral suppression at month 12 post-initiation of treatment. The secondary outcome measures encompass acceptability, feasibility, and virologic impact variables. DISCUSSION: This clinical trial will provide information on the impact of using point-of-care versus standard-of-care viral load testing on patient clinical outcomes; the study will also supply data on the acceptability and feasibility of point-of-care viral load monitoring in a resource-limited setting. If this method of testing is acceptable and feasible, and also superior to standard of care, the results of the trial and the information gathered will inform future scaled implementation and further optimization of the clinic-laboratory network that is critical for monitoring achievement of the 90-90-90 goals. TRIAL REGISTRATION: US National Institutes of Health Clinical Trials.gov: NCT03533868 . Date of Registration: 23 May 2018. Protocol Version: 10. Protocol Date: 30 March 2018.

Retention in Differentiated Care: Multiple Measures Analysis for a Decentralized HIV Care and Treatment Program in North Central Nigeria.

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.

Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.

Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. We retrospectively reviewed genotype data from paired samples in a cohort of HIV-1-infected Nigerian patients failing first-line antiretroviral therapies containing zidovudine (AZT) or tenofovir (TDF). Samples for each patient were taken at initial confirmed virological failure ≥1000 copies/ml (S1) and then at the latest available sample with viral load ≥1000 copies/ml before switch to second line (S2). Among 103 patients failing AZT, 19 (18.4%) had TAM-1s, 29 (28.2%) TAM-2s, and 21 (20.4%) mixed TAMs by S2. In contrast, in the 87 patients failing TDF, drug resistance mutations at S2 included K65R in 56 (64.4%), TAM-1s in 1 (1.1%), and TAM-2s in 25 patients (28.7%). Interestingly, 30.4% of patients with K65R in our study developed TAMs. These were exclusively K219E ± D67N and were not predicted to confer a resistance cost to future AZT-containing regimens.

Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options.

BACKGROUND: Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring. METHODS: Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University's HIVdb program. RESULTS: Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0-6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with >6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. CONCLUSIONS: In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.

Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program.

BACKGROUND: For patients on antiretroviral therapy (ART), treatment interruptions can impact patient outcomes and result in the accumulation of drug resistance mutations leading to virologic failure. There are minimal published data on the impact of an ART stock shortage on development of drug resistance mutations (DRMs). In this report, we evaluate data from patients enrolled in the Government of Nigeria National ART Program that were receiving treatment at the time of a national drug shortage in late 2003. METHODS: We conducted a cross-sectional evaluation of samples collected between December 2004 and August 2005 from ART patients in virologic failure that either had a treatment interruption or did not during the late 2003 drug shortage period at the Jos University Teaching Hospital (JUTH). Plasma virus was genotyped, sequence data were edited and analyzed, and mutation profiles were categorized to evaluate predicted drug susceptibility. Data were analyzed to examine factors associated with development of resistance mutations. A genotypic sensitivity score to the alternate recommended regimen was computed to assess drug susceptibility if regimens were changed. RESULTS: A total of 56 patients were included in this evaluation (28 interrupted, 28 uninterrupted). Patients in the interrupted group had more DRMs than those in the uninterrupted group (p < 0.001); interrupted patients were more likely than uninterrupted patients to have one or more TAM-2 mutations (57.1% interrupted vs. 21.3% uninterrupted; p = 0.04). There was a statistically significant difference in resistance to both d4T (53.7% interrupted vs. 17.9 uninterrupted; p = 0.011) and AZT (64.3% interrupted vs. 25.0% uninterrupted; p = 0.003) by drug interruption status. Examining genotypic sensitivity scores, we found that 67.9% of the interrupted patients, as compared to 25.0% of the uninterrupted patients, did not have full susceptibility to one drug in the regimen to which guidelines recommended they be switched (p = 0.001). DISCUSSION: In this small observational study, we found evidence of a difference in resistance profiles and ART susceptibility between those that were stocked-out of drug versus those that were not. We believe that these data are relevant for many other low- and middle-income countries (LMIC) that also experienced similar ART shortages as they rapidly scaled up their national programs.

Factors associated with early menopause among women in Nigeria.

OBJECTIVES: Effective antiretroviral therapy has prolonged the survival of patients with HIV. Accordingly, studies of the consequences of ageing are increasingly important. We determined the prevalence of early menopause (EM) and its associated factors in a cohort of HIV-infected and HIV-negative controls in Jos, Nigeria. METHODS: HIV-infected women accessing care in an ambulatory setting and their negative counterparts from the general population were included. Menopause was defined as having gone one year since the last menstrual period. EM was defined as the onset of menopause at ≤45 years of age. Baseline characteristics were compared and logistic regression analyses were used to determine factors independently associated with EM. RESULTS: Out of a total of 253 women included, 58 attained menopause early, giving an EM prevalence of 22.9% (95% confidence interval [CI] 17.9-28.6%). Women with EM were younger (P<0.001) and had been infected with HIV for a shorter period (P=0.007). Baseline CD4+ cell count (P=0.66) and viral load (P=0.15) were similar among those with and without EM. For all subjects, HIV infection (adjusted odds ratio [AOR}=10.95, 95% CI 1.39-86.33) and sexual activity (AOR=2.37, 95% CI 1.24-4.52) were associated with EM while early menarche (AOR=14.88, 95% CI 1.37-161.10) and sexual activity (AOR=2.02, 95% CI 1.03-3.96) were independently associated with EM. CONCLUSION: Over a quarter of our postmenopausal women attained menopause early. No HIV-related factor predicted EM in this study. A better understanding of ageing in these women is important to determine a more appropriate disease-management approach during this period of life.

Prevalence and predictors of severe menopause symptoms among HIV-positive and -negative Nigerian women.

We compared the prevalence of menopause symptoms between women living with HIV to their HIV-negative peers and determined predictors of severe menopause symptoms in Jos, Nigeria. This descriptive cross-sectional study included 714 women aged 40-80 years. We compared prevalence and severity of menopause symptoms using the menopause rating scale (MRS). Logistic regression analysis was used to determine the predictors of severe symptoms. Six-hundred and seven (85.0%) were HIV-positive, with a mean duration of infection of 5.6 ± 2.7 years. The mean age of the cohort was 46 ± 5 years. The most prevalent menopause symptoms were hot flushes (67.2%), joint and muscle discomfort (66.2%), physical/mental exhaustion (65.3%), heart discomfort (60.4%), and anxiety (56.4%). The median MRS score was higher for HIV-positive compared to HIV-negative women (p = 0.01). Factors associated with severe menopause symptoms included HIV-positive status (aOR: 3.01, 95% CI: 1.20-7.54) and history of cigarette smoking (aOR: 4.18, 95% CI: 1.31-13.26). Being married (aOR: 0.49, 95% CI: 0.32-0.77), premenopausal (aOR: 0.60, 95% CI: 0.39-0.94), and self-reporting good quality of life (aOR: 0.62. 95% CI: 0.39-0.98) were protective against severe menopause symptoms. We found HIV infection, cigarette smoking, quality of life, and stage of the menopause transition to be associated with severe menopause symptoms. As HIV-positive populations are aging, additional attention should be given to the reproductive health of these women.

Sexual dysfunction and its determinants among women infected with HIV.

OBJECTIVE: To describe the prevalence of female sexual dysfunction (FSD) and its determinants among women with HIV infection enrolled for care and treatment in an ambulatory care setting. METHODS: A questionnaire-based cross-sectional survey was conducted among women attending the HIV clinic of Jos University Teaching Hospital, Nigeria, between March 2013 and February 2014. The self-administered Female Sexual Function Index (FSFI) was used to assess FSD; a score of less than 26.55 indicated FSD. Pearson coefficient was used to assess interdomain correlation, and multiple linear regression was used to identify factors associated with FSD. RESULTS: Among 370 participants, 330 (89.2%, 95% confidence interval [CI] 85.6%-92.2%) had FSD. The overall median FSFI score was 19.2 (interquartile range [IQR] 6.4-23.9). The arousal domain had the lowest subscore (median 2.7, IQR 0.0-3.6). The highest interdomain correlations were between lubrication and orgasm (r=0.87), arousal and lubrication (r=0.84), and arousal and orgasm (r=0.81) domains. Satisfactory health (ß=3.34, 95% CI 1.16-5.52) and history of alcohol use (ß=2.38, 95% CI 0.28-4.47) were independently associated with FSD. CONCLUSION: FSD was prevalent among women with HIV infection. Care providers need to routinely address FSD as part of a comprehensive care package in the study setting.

Treatment Outcomes Among Older Human Immunodeficiency Virus-Infected Adults in Nigeria.

BACKGROUND: Older age at initiation of combination antiretroviral therapy (cART) has been associated with poorer clinical outcomes. Our objectives were to compare outcomes between older and younger patients in our clinical cohort in Jos, Nigeria. METHODS: This retrospective cohort study evaluated patients enrolled on cART at the Jos University Teaching Hospital, Nigeria between 2004 and 2012. We compared baseline and treatment differences between older (≥50 years) and younger (15-49 years) patients. Kaplan-Meier analysis and Cox proportional hazard models estimated survival and loss to follow-up (LTFU) and determined factors associated with these outcomes at 24 months. RESULTS: Of 8352 patients, 643 (7.7%) were aged ≥50 years. The median change in CD4 count from baseline was 151 vs 132 (P = .0005) at 12 months and 185 vs 151 cells/mm3 (P = .03) at 24 months for younger and older patients, respectively. A total of 68.9% vs 71.6% (P = .13) and 69.6% vs 74.8% (P = .005) of younger and older patients achieved viral suppression at 12 and 24 months, with similar incidence of mortality and LTFU. In adjusted hazard models, factors associated with increased risk of mortality were male sex, World Health Organization (WHO) stage III/IV, and having a gap in care, whereas being fully suppressed was protective. The risk of being LTFU was lower for older patients, those fully suppressed virologically and with adherence rates >95%. Male sex, lack of education, WHO stage III/IV, body mass index <18.5 kg/m2, and having a gap in care independently predicted LTFU. CONCLUSIONS: Older patients achieved better viral suppression, and older age was not associated with increased mortality or LTFU in this study.

Quantifying an Adherence Path-Specific Effect of Antiretroviral Therapy in the Nigeria PEPFAR Program.

Since the early 2000s, evidence has accumulated for a significant differential effect of first-line antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV) viral load suppression. This finding was replicated in our data from the Harvard President's Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Investigators were interested in finding the source of these differences, i.e., understanding the mechanisms through which one regimen outperforms another, particularly via adherence. This question can be naturally formulated via mediation analysis with adherence playing the role of a mediator. Existing mediation analysis results, however, have relied on an assumption of no exposure-induced confounding of the intermediate variable, and generally require an assumption of no unmeasured confounding for nonparametric identification. Both assumptions are violated by the presence of drug toxicity. In this paper, we relax these assumptions and show that certain path-specific effects remain identified under weaker conditions. We focus on the path-specific effect solely mediated by adherence and not by toxicity and propose an estimator for this effect. We illustrate with simulations and present results from a study applying the methodology to the Harvard PEPFAR data. Supplementary materials are available online.

On Partial Identification of the Natural Indirect Effect.

In causal mediation analysis, nonparametric identification of the natural indirect effect typically relies on, in addition to no unobserved pre-exposure confounding, fundamental assumptions of (i) so-called "cross-world-countterfactuals" independence and (ii) no exposure-induced confounding. When the mediator is binary, bounds for partial identification have been given when neither assumption is made, or alternatively when assuming only (ii). We extend existing bounds to the case of a polytomous mediator, and provide bounds for the case assuming only (i). We apply these bounds to data from the Harvard PEPFAR program in Nigeria, where we evaluate the extent to which the effects of antiretroviral therapy on virological failure are mediated by a patient's adherence, and show that inference on this effect is somewhat sensitive to model assumptions.

Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria.

BACKGROUND: While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. METHODS: We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. RESULTS: Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29-41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78-220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients retained through 84 months maintained ≥95% adherence. CONCLUSION: While improved access to HIV care and treatment remains a challenge in Nigeria, our study shows that a high quality of care was achieved as evidenced by strong long-term clinical, immunologic and virologic outcomes.

Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort.

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.

Tuberculosis Incidence and Risk Factors Among Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy in a Large HIV Program in Nigeria.

Background. Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods. This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results. Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7-27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4(+) cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions. The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections.

Mother-to-Child Transmission Outcomes of HIV-Exposed Infants Followed Up in Jos North-Central Nigeria.

OBJECTIVE: Since 2010, Nigeria has adopted World Health Organization (WHO) 'Option B' which requires administration of triple antiretroviral prophylaxis or treatment (ART) to all HIVinfected pregnant women. We studied the transmission outcomes of HIV-exposed children up to 18 months of age. DESIGN: This was a retrospective, observational study of HIV-infected pregnant women and their exposed infants who accessed prevention of mother to child transmission (PMTCT) services at Jos University Teaching Hospital, Jos, North-central Nigeria. METHODS: HIV-infected women were enrolled during antenatal care or at labor/delivery between January 1, 2010 and December 31, 2012. Antiretroviral (ARV) prophylaxis/therapy was provided according to the 2010 Nigerian PMTCT guidelines (adapted WHO 2010 guidelines); Infant HIV diagnosis was performed at 6 weeks and at 6 months. HIV antibody diagnosis was used for exposed children at 18 months. RESULTS: A total of 996 HIV-exposed children were followed up. Of those children, 140 (14.1%) were lost to follow up by 18 months of age. Twelve children (1.4%) died (all HIV negative) before 18 months of age and six infants (0.7%) were confirmed to be HIV-infected (4 by the age of 6 months and 2 thereafter) and were referred for treatment. A total of 838 (84.1%) children tested HIV negative at 18 months and were discharged. Mother-to-child transmission (MTCT) of HIV by 18 months was lower among women on ART before pregnancy compared to those women who started ART/Triple ARV prophylaxis during pregnancy/delivery. (0.4%; 3/700 vs 2.0%; 3/150 P=0.05). Home delivery was associated with higher transmission than facility delivery (p=0.03). Mode of delivery or method of infant feeding had no significant impact on vertical transmission by 18 months. CONCLUSION: In North-central Nigeria where HIV is prevalent, ART started before pregnancy is enormously effective in preventing mother-to-child transmission. Adoption of WHO 'Option B+' deserves serious consideration in such settings.