Person:

Meloni, Seema

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.

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.

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.