Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration.

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors

Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria.We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p < 0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml(3)) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100-200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p < or = 0.001) were more likely to be adherent.These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence

Immunological profile in persons under antiretroviral therapy in a rural Nigerian hospital

Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART) in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males) with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF). Fourty-four percent, 23% and 33% of patients were on TDF, D4T & AZT based regimen, respectively (P=0.66). Increment of >100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF & D4T compared with those in AZT based regimens (ANOVA; P<0.0003). Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P<0.0001). Equally, multivariate logistic regression found age, platelet count and CD4 lymphocyte count at 12 months showed to be significant predictors of CD4 lymphocyte increment above 100 cells/µL (P<0.0001). Despite advanced disease presentation and a very large-scale program, high quality HIV/AIDS care was achieved as indicated by good short-term, immunologic outcomes, while TDF & D4T induce higher immunological recovery compared with AZT. This report suggests that quality HIV care and treatment can be effective despite the challenges of a resource-limited setting

Maintaining Continuity of Care for Expectant Mothers in Kenya During the COVID-19 Pandemic: A Study of MomCare

In Kenya, early coronavirus disease (COVID-19) modeling studies predicted that disruptions in antenatal care and hospital services could increase indirect maternal and neonatal deaths and stillbirths. As the Kenyan government enforced lockdowns and a curfew, many mothers-to-be were unable to safely reach hospital facilities, especially at night. Fear of contracting COVID-19, increasing costs of accessing care, stigma, and falling incomes forced many expectant mothers to give birth at home. MomCare, which primarily serves communities in remote areas and urban slums, links mothers-to-be with payers and health care providers, following a standardized pregnancy program based on World Health Organization guidelines at a predetermined cost and quality. Expectant mothers gain access to care through a mobile wallet on their feature phone (voice, text, and basic internet), and providers are paid after appropriate care is given. Within the first 3 weeks of the pandemic in Kenya, the following services were added to the MomCare bundle: emergency ambulance services during curfew hours, extended bed allowances to encourage early care, phone calls to check on mothers approaching their delivery dates and to promote the generation of a birth plan, SMS messages to inform mothers of open facilities and COVID-19 protocols, and training for clinic staff in managing COVID-19 patients and infection prevention. We compare data collected through the MomCare platform during the 6 months before the first confirmed COVID-19 case in Kenya (September 2019-February 2020) with data collected during the 6 months that followed. This study shows that care-seeking behaviors (enrollment, antenatal/postnatal care, skilled deliveries) increased for mothers-to-be enrolled in MomCare during the COVID-19 lockdowns, while quality of care and outcomes were maintained. Public health practitioners can promote interactive, patient-driven technology like MomCare to augment traditional responses, quickly linking payments with patients and providers in times of crisis

Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen

Associations with Pharmacy Refill (Rx) <95% Among Treatment-Naïve Adult Nigerian Patients based on GEE.

a<p>Totals do not always sum to 4,529 due to missing data;</p>b<p>A total of 3,136 subjects included in the adjusted model; OR, odds ratio; CI, confidence interval.</p

Cox Regression Analyses of Characteristics Associated with Loss to Follow-Up (LTFU) Among Treatment-Naïve Adult Nigerian Patients.

a<p>Totals always do not sum to 5,760 due to missing data;</p>b<p>A total of 4,177 subjects included in the adjusted model; HR, hazard ratio; CI, confidence interval.</p

Modeled Probability of Non-adherence within the First 12 Months of ART Initiation.

<p>Modeled Probability of Non-adherence within the First 12 Months of ART Initiation.</p

Characteristics of the Study Population (N = 5760).

<p>Characteristics of the Study Population (N = 5760).</p

Study Population of Patients Initiating ART between March 2005 and July 2006.

<p>Study Population of Patients Initiating ART between March 2005 and July 2006.</p