Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa.

BACKGROUND: KwaZulu-Natal (KZN) Province in South Africa has the highest HIV disease burden in the country, with an estimated population prevalence of 24.7%. A pilot sentinel surveillance project was undertaken in KZN to classify the proportion of adult patients failing first-line ART and to describe the patterns of drug resistance mutations (DRMs) in patients with virological failure (VF). METHODS: Cross-sectional surveillance of acquired HIV drug resistance was conducted in 15 sentinel ART clinics between August and November 2013. Two population groups were surveyed: on ART for 12-15 months (Cohort A) or 24-36 months (Cohort B). Plasma specimens with viral load ≥1000 copies/mL were defined as VF and genotyped for DRMs. RESULTS: A total of 1299 adults were included in the analysis. The prevalence of VF was 4.0% (95% CI 1.8-8.8) among 540 adults in Cohort A and 7.7% (95% CI 4.4-13.0) of 759 adults in Cohort B. Treatment with efavirenz was more likely to suppress viral load in Cohort A (P = 0.005). Independent predictors of VF for Cohort B included male gender, advanced WHO stage at ART initiation and treatment with stavudine or zidovudine compared with tenofovir. DRMs were detected in 89% of 123 specimens with VF, including M184I/V, K103N/S, K65N/R, V106A/M and Y181C. CONCLUSIONS: VF in adults in KZN was <8% up to 3 years post-ART initiation but was associated with a high frequency of DRMs. These data identify key groups for intensified adherence counselling and highlight the need to optimize first-line regimens to maintain viral suppression.

The use of entertainment and communication technologies before sleep could affect sleep and weight status: a population-based study among children.

BACKGROUND: Short sleep duration and poor sleep quality have been demonstrated to be associated with childhood obesity. It has been suggested that electronic entertainment and communication devices (EECDs) including TVs, computers, tablets, video games and cell phones interfere with sleep in children and youth. The aim of this study was to assess the impact that the use of EECDs in the hour before bedtime has on sleep and weight status to inform sleep promotion interventions and programs to prevent childhood obesity. METHODS: A provincially representative sample of 2334 grade 5 children and their parents in Alberta, Canada was surveyed. Parents reported their child's bedtime and wake-up time along with how often their child snored, felt sleepy during the day, woke-up at night and woke-up in the morning feeling unrefreshed. Sleep duration, sleep quality and sleep efficiency were derived from these indicators. Parents also reported on the presence of EECDs in their child's bedroom, while children reported use of EECDs during the day and frequency of using each of these devices during the hour before sleep. The height and weight of children were measured. Multivariable mixed effect linear and logistic regression models were used to determine how sleep duration, sleep quality, sleep efficiency and weight status are influenced by (i) access to EECDs in children's bedrooms, (ii) use of EECDs during the hour before sleep, and (iii) calming activities specifically reading during the hour before sleep. RESULTS: Sleep duration was shorter by -10.8 min (cell phone), -10.2 min (computer) and -7.8 min (TV) for those with bedroom access to and used these EECDs during the hour before sleep compared to no access and no use. Good sleep quality was hindered by bedroom access to and use of all EECDs investigated during the hour before sleep, particularly among users of cell phones (OR = 0.64, 95% CI: 0.58-0.71) and computers (OR = 0.72, 95% CI: 0.65-0.80). Very good sleep efficiency was decreased by access to and frequent use of a TV (54%), cell phone (52%), tablet (51%) and video games (51%). Odds of obesity were doubled by bedroom access to and use of a TV and computer during the hour before sleep. Children who rarely read a printed book in the bedroom during the hour before sleep had a shorter sleep duration and poorer sleep quality and sleep efficiency compared to their peers. Having access to an EECD in the bedroom was associated with increased obesity despite frequently reading during the hour before sleep. CONCLUSIONS: Our findings suggest that sleep duration, sleep quality, sleep efficiency and weight status are better among children who do not have EECDs in the bedroom and frequently read a book during the hour before sleep as opposed to those who use EECDs during this hour. Education of limits against EECD use by parents may improve sleep outcomes. These findings will inform health promotion messages and may give rise to national recommendations regarding EECD use. TRIAL REGISTRATION: ClinicalTrials.gov NCT01914185 . Registered 31 July 2013 Retrospectively registered.

Determinants of loss to follow-up in patients on antiretroviral treatment, South Africa, 2004-2012: a cohort study.

BACKGROUND: The number of Human Immunodeficiency Virus (HIV) infected people eligible for initiation on antiretroviral Therapy (ART) is increasing. ART programmatic success requires that patients who are taking ART remain on treatment and are followed up regularly. This study investigated factors associated with being lost to follow-up, in a cohort of patients enrolled in a pharmacovigilance study in South Africa. METHODS: This was a retrospective observational cohort study performed at one of the Medunsa National Pharmacovigilance Centre's (MNPC) ART sentinel surveillance sites. Loss to Follow-up (LTFU) was defined as "a patient who had been followed up at the sentinel site, who had not had contact with the health facility for 180 days or more since their last recorded expected date of return or if there were 180 days or more between the expected date of return and the next clinic visit". RESULTS: Out of 595 patients, 65.5% (n = 390) were female and 23.4% (n = 139) were LTFU. The median time on ART before LTFU was 21.5 months (interquartile range: 12.9 - 34.7 months). The incidence rate of LTFU was 103 per 1000 person-years in the first year on ART and increased to 405 per 1000 person-years in the eighth year of taking ART. Factors associated with becoming LTFU included not having a committed partner (Adjusted Hazard Ratio (aHR): 2.9, 95% Confidence Interval (CI):1.19-6.97, p = 0.019), being self-employed (aHR: 13.9, 95% CI:2.81 - 69.06, p = 0.001), baseline CD4 count > 200 cells/ml (aHR: 3.8, 95% CI: 1.85-7.85, p < 0.001), detectable last known Viral Load (VL) (aHR: 3.6, 95% CI:1.98-6.52, p < 0.001) and a last known World Health Organisation clinical stage three or four (aHR: 2.0, 95% CI:1.22-3.27, p = 0.006). Patients that previously had an ART adverse event had a lower risk (aHR: 0.6, 95% CI: 0.38 - 0.99, p = 0.044) of becoming LTFU than those that had not. CONCLUSION: The incidence rate of LTFU increases with additional years on ART. Intensified measures to improve patient retention on ART must be prioritised with increasing patient time on ART and in patients that are at increased risk of becoming lost to follow-up.

Early warning indicators for HIV drug resistance in adults in South Africa at 2 pilot sites, 2008-2010.

BACKGROUND: Approximately 5.2 million people in South Africa were infected with human immunodeficiency virus (HIV) by the year 2010, with just over 30% initiated on highly active antiretroviral therapy by 2011. With such numbers involved, the potential for the emergence of HIV drug resistance (HIVDR) is high. This study piloted early warning indicators (EWIs) for HIVDR at 2 clinics in South Africa. METHODS: HIV-infected individuals aged ≥15 years and receiving antiretroviral drugs were enrolled into this cohort study between March 2008 and February 2010. All analyses were performed using the 2012 World Health Organization EWI score card. RESULTS: A total of 1144 subjects were enrolled. Clinic A reached the target for 2 of the 5 EWIs but missed the desired target for on-time pill pickup, pharmacy stockouts, and virological suppression. Clinic B reached the target for 1 of 4 EWIs, namely, dispensing practices. Targets were missed for on-time pill pickup, retention in care, and virological suppression. Pharmacy stockouts could not be calculated at this site. CONCLUSIONS: Actual performance against the levels that the pilot sites should reach to minimize HIVDR was low. Improvements in follow-up procedures, internal adherence support, monitoring for drug stockouts, and adherence are all aspects that need support to ensure that all records are complete. This pilot study may help to inform the South African government as EWI monitoring is implemented.

A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 - 2011.

BACKGROUND: Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. METHODS: A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. RESULTS: After HAART initiation, with an average lapse of 17.8 months (range: 0 - 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). CONCLUSION: The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should introduce less toxic first-line ARV regimens. Future efforts will aim to initiate patients on HAART and enrol them into the study simultaneously to determine early risk profiles of ARV medicines.