Statistical Nature of Atomic Disorder in Irradiated Crystals.

Atomic disorder in irradiated materials is investigated by means of x-ray diffraction, using cubic SiC single crystals as a model material. It is shown that, besides the determination of depth-resolved strain and damage profiles, x-ray diffraction can be efficiently used to determine the probability density function (PDF) of the atomic displacements within the crystal. This task is achieved by analyzing the diffraction-order dependence of the damage profiles. We thereby demonstrate that atomic displacements undergo Lévy flights, with a displacement PDF exhibiting heavy tails [with a tail index in the γ=0.73-0.37 range, i.e., far from the commonly assumed Gaussian case (γ=2)]. It is further demonstrated that these heavy tails are crucial to account for the amorphization kinetics in SiC. From the retrieved displacement PDFs we introduce a dimensionless parameter f_{D}^{XRD} to quantify the disordering. f_{D}^{XRD} is found to be consistent with both independent measurements using ion channeling and with molecular dynamics calculations.

Non-ignorable loss to follow-up: correcting mortality estimates based on additional outcome ascertainment.

Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programs for patients with human immunodeficiency virus (HIV), mortality estimates can be biased if the LTFU mechanism is non-ignorable, that is, mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example, through linkage to national registries or through survey-based methods. In this paper, we demonstrate how this additional information can be used to construct estimators based on inverse probability weights (IPW) or multiple imputation. We use simulations to contrast the performance of the proposed estimators with methods widely used in HIV cohort research for dealing with missing data. The practical implications of our approach are illustrated using South African ART data, which are partially linkable to South African national vital registration data. Our results demonstrate that while IPWs and proper imputation procedures can be easily constructed from additional outcome ascertainment to obtain valid overall estimates, neglecting non-ignorable LTFU can result in substantial bias. We believe the proposed estimators are readily applicable to a growing number of studies where LTFU is appreciable, but additional outcome data are available through linkage or surveys of patients LTFU.

Prevention of vertical transmission of HIV in Khayelitsha, South Africa: A contemporary review of services after 20 years.

BACKGROUND: The first vertical transmission of HIV prevention (VTP) programme in South Africa was launched in 1999 in Khayelitsha, Western Cape Province (WC). Since then, VTP guidelines have expanded in complexity and scope. OBJECTIVES: To describe contemporary VTP uptake in Khayelitsha and quantify vertical transmission (VT) risk factors based on linked routine electronic health data. METHODS: In the WC, all patients at public health facilities have a unique identifier allowing linkage across electronic health platforms through a health information exchange hosted within the WC Department of Health. We conducted a cohort analysis of mother-infant pairs where the mother was living with HIV and attended any obstetric care in Khayelitsha in 2017. Descriptive statistics assessed VTP coverage along the care cascade, including maternal viral load (VL) testing and early infant diagnosis (EID). Logistic regression analysis quantified a priori-defined risk factors associated with VT. RESULTS: Antenatal HIV prevalence in the cohort was 31.3%, and VT was 1.8% by 12 months. Of women living with HIV, 88.3% knew of their positive status at the first antenatal visit and 77.9% were already receiving antiretroviral therapy (ART). Most women diagnosed prior to delivery (94.5%) were initiated on ART; 85.0% received an antenatal VL test, of whom 88.0% were virologically suppressed. Women who were not virally suppressed had a five-fold (adjusted odds ratio (aOR) 5.3; 95% confidence interval (CI) 2.5 - 12.3) increased VT risk compared with those who were suppressed. Women who attended no antenatal care were at higher risk of VT (aOR 1.6; 95% CI 0.7 - 3.6) than those who did attend. EID coverage was suboptimal: a birth HIV polymerase chain reaction (PCR) test was available for 79.2% of infants, and a low proportion with a negative birth test had a repeat test around 10 weeks (57.9%). Data linkage identified an additional 15 infants living with HIV who were not detected by HIV-PCR testing alone. CONCLUSION: Although most women presented to care already knowing their HIV status, ART initiation was suboptimal prior to the first antenatal visit but improved over the course of pregnancy. The VT rate based on laboratory HIV-PCR testing alone underestimated HIV transmission: linked data from multiple sources suggested higher VT than programme-reported rates based on HIV-PCR testing alone.

Interferon release does not add discriminatory value to smear-negative HIV-tuberculosis algorithms.

Clinical algorithms for evaluating HIV-infected individuals for tuberculosis (TB) prior to isoniazid preventive therapy (IPT) perform poorly, and interferon-γ release assays (IGRAs) have moderate accuracy for active TB. It is unclear whether, when used as adjunct tests, IGRAs add any clinical discriminatory value for active TB diagnosis in the pre-IPT assessment. 779 sputum smear-negative HIV-infected persons, established on or about to commence combined antiretroviral therapy (ART), were screened for TB prior to IPT. Stepwise multivariable logistic regression was used to develop clinical prediction models. The discriminatory ability was assessed by receiver operator characteristic area under the curve (AUC). QuantiFERON-TB Gold in-tube (QFT-GIT) was evaluated. The prevalence of smear-negative TB by culture was 6.4% (95% CI 4.9-8.4%). Used alone, QFT-GIT and the tuberculin skin test (TST) had comparable performance; the post-test probability of disease based on single negative tests was 3-4%. In a multivariable model, the QFT-GIT test did not improve the ability of a clinical algorithm, which included not taking ART, weight <60 kg, no prior history of TB, any one positive TB symptom/sign (cough ≥ 2 weeks) and CD4+ count <250 cells per mm(3), to discriminate smear-negative culture-positive and -negative TB (72% to 74%; AUC comparison p=0.33). The TST marginally improved the discriminatory ability of the clinical model (to 77%, AUC comparison p=0.04). QFT-GIT does not improve the discriminatory ability of current TB screening clinical algorithms used to evaluate HIV-infected individuals for TB ahead of preventive therapy. Evaluation of new TB diagnostics for clinical relevance should follow a multivariable process that goes beyond test accuracy.

The next generation: Pregnancy in adolescents and women living with perinatally acquired HIV in South Africa.

BACKGROUND: An increasing number of girls living with perinatally acquired HIV (PHIV) are reaching adolescence and adulthood and becoming pregnant. Youth living with PHIV (YLPHIV) may have HIV-associated infections/complications, long-term exposure to antiretroviral treatment (ART), drug resistance and increased psychosocial challenges, which may adversely affect pregnancy outcomes. There is a lack of published studies on pregnancy in YLPHIV in sub-Saharan Africa. Objectives. To describe characteristics of pregnant South African (SA) YLPHIV and their pregnancy outcomes. METHODS: We retrospectively identified pregnancies in YLPHIV, who were diagnosed with HIV when they were <12 years old and before their first pregnancy (as a proxy for perinatal route of infection), from routinely collected data in Western Cape Province, SA (2007 - 2018). We combined these with pregnancies from a Johannesburg cohort of YLPHIV. Results. We identified 258 pregnancies among 232 females living with likely PHIV; 38.8% of pregnancies occurred in YLPHIV ≤16 years old, 39.1% at age 17 - 19 years and 22.1% at age ≥20 years. In recent years, a steady increase in the number of pregnancies in YLPHIV was noted; more than two-thirds occurred during 2016 - 2018. ART was commenced prior to pregnancy in 84.9% of YLPHIV, during pregnancy in 6.6% and was not commenced by pregnancy end date in 8.5%. Of the pregnancies in young women with documented outcomes (88.8%; n=229), 80.3% were live births, 14.4% terminations, 3.1% miscarriages and 2.2% stillbirths. Mother-to-child transmission of HIV occurred in 2.2% of infants, 75.3% were uninfected when last tested and 22.6% had unknown HIV status. Among YLPHIV with CD4 counts available within 12 months of pregnancy end date (n=202), 20.3% had a CD4 count <200 cells/µL, 43.1% CD4 count 200 - 499 cells/µL and 36.6% CD4 count ≥500 cells/µL. Among those with a viral load (VL) available within 12 months of pregnancy end date (n=219), 66.7% had a VL <400 copies/mL, 5.0% VL 400 - 999 copies/mL and 28.3% VL ≥1 000 copies/mL. Of 186 neonates, 20.4% were preterm deliveries (<37 weeks' gestation). Among neonates with known birthweight (n=176), the mean birthweight was 2 900 g (95% confidence interval (CI) 2 747 - 2 935 g) and 20.5% had a low birthweight (<2 500 g). One congenital malformation (musculoskeletal) and 2 neonatal deaths were recorded. CONCLUSIONS: In recent years, the number of pregnancies in YLPHIV has increased. A considerable proportion of pregnancies occurred in YLPHIV ≤16 years old. A high proportion of pregnancies was electively terminated. The prevalence of elevated VL and poor immunological status among pregnant YLPHIV is concerning.

Risk factors for and clinical characteristics of severe hyperlactataemia in patients receiving antiretroviral therapy: a case-control study.

BACKGROUND: Symptomatic hyperlactataemia and lactic acidosis (SHLA) are potentially life-threatening complications associated with stavudine (d4T), an antiretroviral therapy (ART) drug widely used in developing countries. METHODS: Cases comprised all symptomatic patients with measured lactates >or= 5 mmol/L referred to a South African hospital between August 2003 and November 2005. Matched controls were selected according to facility and duration on ART. RESULTS: Seventy-one cases and 142 controls were included in the study. The majority of cases presented between 6 and 18 months on ART. Female sex [adjusted odds ratio (AOR) 23.4; 95% confidence interval (CI) 4.0-136.6], a baseline weight between 60 and 75 kg (AOR 4.5; 95% CI 1.4-14.1) or, in particular, >or= 75 kg (AOR 19.4; 95% CI 4.1-82.5) at ART initiation and gaining >or= 6 kg in the first 3 months on therapy (AOR 3.5; 95% CI 1.3-9.5) were independent risk factors identifying patients who may subsequently develop SHLA. Weight loss of >or= 2 kg (AOR 6.1; 95% CI 2.0-18.3), a rise in alanine aminotransferase (ALT) >or= 10 U/L (AOR 3.1; 95% CI 1.1-8.9), the presence of at least one of three major symptoms (vomiting, nausea and abdominal pains) of SHLA (AOR 12.6; 95% CI 3.3-47.2) and peripheral neuropathy (AOR 3.4; 95% CI 1.1-9.8) were the clinical parameters that were most able to identify patients with early manifestations of SHLA. CONCLUSIONS: This is the first case-control study for SHLA in Southern Africa. Given these findings, we advise that stavudine is avoided in overweight women. Weight loss, a rise in ALT, peripheral neuropathy and/or gastrointestinal symptoms should prompt healthcare workers to assess for SHLA, especially at between 6 and 18 months on ART.

Symmetry degeneration and room temperature ferroelectricity in ion-irradiated SrTiO3.

Polar phonon modes associated with room temperature ferroelectricity are observed in SrTiO3 single crystals irradiated with Ti ions. Quantitative strain analysis reveals that irradiation-induced out-of-plane strain drives the centrosymmetric cubic SrTiO3 to a tetragonal-like structure in the maximum damaged region. Energy transfer from ions to electrons during ion irradiation yields defects in SrTiO3 that also plays an important role for the room temperature ferroelectricity. Different from thin film techniques, the ferroelectricity in the ion irradiated SrTiO3 can occur for much larger thicknesses, depending on the energy and type of ion.

How accurately do routinely reported HIV viral load suppression proportions reflect progress towards the 90-90-90 target in the population on antiretroviral treatment in Khayelitsha, South Africa?

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) third 90-90-90 target requires 90% of patients on antiretroviral treatment (ART) to be virally suppressed (<1 000 copies/mL). In Khayelitsha, Cape Town, South Africa viral load (VL) suppression of <400 copies/mL was reported as 89% in 2016, but only 56% of patients had a result recorded in routine data. We conceived a VL 'cascade' to represent the steps required for an expected VL to be reported as complete in routine data and thus contribute to reported VL suppression: among those for whom a VL is 'expected', a sample must be collected and tested ('done'), a result must be 'filed' in the patient folder, 'noted' by a clinician and electronically 'captured'. The low reported completion suggested gaps along the VL cascade and cast doubt on the validity of reported suppression. OBJECTIVES: To assess the validity of routinely reported VL suppression and identify barriers to VL completion. METHODS: A retrospective cohort study between 1 July 2015 and 30 June 2016, which included all Khayelitsha patients receiving ART, with a routine VL expected, was conducted. We obtained data routinely captured on site and VL data from the laboratory system. A sample of 1 035 patient folders was reviewed. VL suppression was calculated using laboratory data, including all tests done, and compared with reported suppression based on on-site captured electronic data. Successful progression through each step on the VL cascade was estimated. We used logistic regression to identify factors associated with laboratory data and reported VL testing. RESULTS: Of 22 991 patients for whom a routine VL test was due, 84% were done, 79% filed, 76% noted and 55% captured. Using all laboratory data, VL suppression was  estimated as 82%, 87%, 89% and 91% at the 50, 200, 400 and 1 000 copies/mL thresholds, respectively, but reported suppression using captured results was 80%, 86%, 88% and 89% at those thresholds. Routine VL testing is more likely to be done in children <15 years old (adjusted odds ratio (aOR) 1.89, 95% confidence interval (CI) 1.45 - 2.48) and pregnant women (aOR 1.90, 95% CI 1.28 - 2.81) than in men, adjusted for facility. CONCLUSIONS: Despite a low reported completion, VL testing completion was high. Reported suppression using captured data was similar to suppression calculated using all laboratory data, which provided an accurate measure of progress towards the 90-90-90 target. More work is needed to reach the 16% of patients missed by routine testing.

Data Centre Profile: The Provincial Health Data Centre of the Western Cape Province, South Africa.

INTRODUCTION: The Western Cape Provincial Health Data Centre (PHDC) consolidates person-level clinical data across government services, leveraging sustained investments in patient registration systems, a unique identifier, and maturation of administrative and clinical digital health systems. OBJECTIVES: The PHDC supports clinical care directly through tools for clinicians which integrate patient data or identify patients in need of interventions, and indirectly through supporting operational and epidemiological analyses. METHODS: The PHDC is housed entirely within government. Data are processed from a range of source systems, usually daily, through distinct harmonisation and curation, beneficiation, and reporting processes. Linkage is predominantly through the unique identifier which doubles as a pervasive folder number, augmented by other identifiers. Further data processing includes triangulation of multiple data sources for enumerating health conditions, with assignment of certainty levels for each enumeration. Outputs include patient-specific email alerts, a web-based consolidated patient clinical viewing platform, filterable line-listings of patients with specific conditions and associated characteristics and outcomes, management reports and dashboards, and data releases in response to operational and research data requests. Strict architectural, administrative and governance processes ensure privacy protection. RESULTS: In the past decade 8 million unique people are recorded as having sought healthcare in the provincial public sector health services, with current utilisation at 15 million attendances or admissions a year. Cross-sectional enumeration of health conditions includes over 430 000 people with HIV, 500 000 with hypertension, 235 000 with diabetes. Annually 110 000 pregnancies and 54 000 patients with tuberculosis are enumerated. Over 50 data requests are processed each year for internal and external requesters in accordance with data request and release governance processes. CONCLUSIONS: The single consolidated environment for person-level health data in the Western Cape has created new opportunities for supporting patient care, while improving the governance around access to and release of sensitive patient data.

Exploring HIV risk perception and behaviour in the context of antiretroviral treatment: results from a township household survey.

The objective of this cross-sectional household survey was to assess factors influencing HIV risk perception, behaviour and intervention uptake in a community characterised by high HIV prevalence and availability of antiretroviral therapy (ART). The survey was conducted in Khayelitsha, South Africa and involved two-stage sampling with self-weighting clusters and random selection of households within clusters. One man and woman between 14 and 49 years old was interviewed in each household; 696 men and 879 women were interviewed for a response rate of 84% and 92% respectively. Ninety-three percent and 94% were sexually active with median age of sexual debut 15.3 and 16.5 years. Eighty-three percent and 82% reported a partner at the time of interview and 29% and 8% had additional partner(s). Forty-one percent and 33% reported condom use during the last sexual encounter. Thirty-seven percent of men not using condoms did not as they believed their partner to be faithful, whilst 27% of women did not as their partner refused. Twenty-eight percent and 53% had been tested for HIV. Having undergone HIV testing was not associated with condom usage, whilst current relationship status was the strongest association with condom usage for both men and women. In spite of a relatively high uptake of condoms and testing as well as ART availability, the HIV epidemic has continued unabated in Khayelitsha. Even greater coverage of preventive interventions is required, together with a national social and political environment that builds on the availability of both preventive and treatment services.

Assessing the value of Western Cape Provincial Government health administrative data and electronic pharmacy records in ascertaining medicine use during pregnancy.

BACKGROUND: In African settings, where there is a high disease burden, there is a need to improve the science of documenting and analysing accurate information regarding medicine exposures in women immediately before and during pregnancy to assess the extent of use and safety in pregnant women and their unborn children. OBJECTIVES: To compare evidence of medicine use during pregnancy, as documented in paper-based clinical records (maternity case records (MCRs)) against electronic health information resources (Provincial Health Data Centre (PHDC)) and assess the level of concordance between the two as part of baseline investigations before piloting a provincial pregnancy exposure registry and birth defect surveillance system. The PHDC consolidates electronic clinical and pharmacy data. METHODS: A folder review of completed pregnancies between November 2013 and January 2016 was conducted on randomly selected MCRs from midwife-run obstetric units and a secondary maternity hospital in Cape Town, South Africa. Medication exposures in the MCR were captured and compared with a customised PHDC data extract. The type and timing of drug exposures were compared. Total exposures were compiled from all data sources. RESULTS: Two hundred and six MCRs from three facilities were sampled: 83 women had documented antiretroviral therapy (ART) exposure; all but 1 (1%) had been recorded in the PHDC extract. There was no evidence of ART use in the MCRs of 4 (5%) cases, despite evidence in the PHDC. There were imprecise drug names in the MCRs of 14 (17%) ART patients, discordant dates of onset between the MCRs and PHDC extracts in 10/83 (12%) and inaccurate medicine names and incorrect dates in 1 (1%) case each. Nine of 10 (90%) women who were administered antituberculosis medication were recorded in the PHDC extract. Ten of 21 (48%) isoniazid preventive therapy treatments appeared in the MCRs and PHDC; 9 (42%) in the PHDC only and 2 (10%) in the MCRs only. Half (n=18/36) of all antibiotic use was reflected only in the MCRs, while 13/36 (36%) appeared only in the PHDC extract. In the former cases, antibiotics used for treatment of sexually transmitted infections and urinary tract infections were dispensed from ward stock and not captured electronically. Antibiotics reflected only in the PHDC were either dispensed at a referral facility or before the first recorded antenatal clinic visit. Folic acid and iron were mostly documented in the MCR only (n=79/99 (80%) and n=107/128 (84%), respectively). However, analgesics and antihistamines more often appeared in the PHDC extract only (n=11/16 (73%) and n=5/5 (100%), respectively). CONCLUSIONS: The PHDC extract provided a better and more complete reflection of chronic drug exposures compared with the MCRs, especially when women sought care at facilities other than the antenatal care unit where they first attended, or when exposures occurred before the initial antenatal visit. The exception was antibiotics dispensed from ward stock to treat sexually transmitted and urinary tract infections.

Reciprocal-space mapping of epitaxic thin films with crystallite size and shape polydispersity.

A development is presented that allows the simulation of reciprocal-space maps (RSMs) of epitaxic thin films exhibiting fluctuations in the size and shape of the crystalline domains over which diffraction is coherent (crystallites). Three different crystallite shapes are studied, namely parallelepipeds, trigonal prisms and hexagonal prisms. For each shape, two cases are considered. Firstly, the overall size is allowed to vary but with a fixed thickness/width ratio. Secondly, the thickness and width are allowed to vary independently. The calculations are performed assuming three different size probability density functions: the normal distribution, the lognormal distribution and a general histogram distribution. In all cases considered, the computation of the RSM only requires a two-dimensional Fourier integral and the integrand has a simple analytical expression, i.e. there is no significant increase in computing times by taking size and shape fluctuations into account. The approach presented is compatible with most lattice disorder models (dislocations, inclusions, mosaicity, ...) and allows a straightforward account of the instrumental resolution. The applicability of the model is illustrated with the case of an yttria-stabilized zirconia film grown on sapphire.

A case study of using artificial neural networks for classifying cause of death from verbal autopsy.

BACKGROUND: Artificial neural networks (ANN) are gaining prominence as a method of classification in a wide range of disciplines. In this study ANN is applied to data from a verbal autopsy study as a means of classifying cause of death. METHODS: A simulated ANN was trained on a subset of verbal autopsy data, and the performance was tested on the remaining data. The performance of the ANN models were compared to two other classification methods (physician review and logistic regression) which have been tested on the same verbal autopsy data. RESULTS: Artificial neural network models were as accurate as or better than the other techniques in estimating the cause-specific mortality fraction (CSMF). They estimated the CSMF within 10% of true value in 8 out of 16 causes of death. Their sensitivity and specificity compared favourably with that of data-derived algorithms based on logistic regression models. CONCLUSIONS: Cross-validation is crucial in preventing the over-fitting of the ANN models to the training data. Artificial neural network models are a potentially useful technique for classifying causes of death from verbal autopsies. Large training data sets are needed to improve the performance of data-derived algorithms, in particular ANN models.

Community-based treatment of drug-resistant tuberculosis in Khayelitsha, South Africa.

SETTING: Khayelitsha, South Africa, a peri-urban township with high burdens of tuberculosis (TB), drug-resistant tuberculosis (DR-TB), and human immunodeficiency virus (HIV) infection. OBJECTIVE: To describe case detection and patient outcomes in a community-based DR-TB programme. DESIGN: DR-TB management was integrated into primary health care in Khayelitsha from 2007 onwards. Implementation was incremental, and included training and clinician support, counselling and home visits, tuberculous infection control, a local in-patient service, and routine monitoring. Patients received treatment rapidly through their local clinic, and were only hospitalised if clinically unwell. RESULTS: DR-TB case notification (any rifampicin resistance) increased from 28 per 100 000 population per year (2005-2007) to 55/100 000/year in 2009-2011 (72% HIV-infected). From 2008 to 2011, 754 patients received treatment (86% of those diagnosed). The median time between diagnostic sputum and treatment decreased over the years of implementation to 27 days in 2011 (P < 0.001). Treatment success was 52% in 2010, with 31% default, 13% death and 4% treatment failure. Two-year survival was 65%, with poorer survival in those with HIV (HR 2.0, 95%CI 1.4-2.8), second-line drug resistance (HR 3.3, 95%CI 2.2-4.8), and diagnosis in earlier programme years (HR 1.4, 95%CI 1.1-2.0). CONCLUSION: Community-based DR-TB management is feasible, and contributes to improved case detection, reduced treatment delay and improved survival. Treatment outcomes remain poor, highlighting the poor efficacy, tolerability and lengthy duration of current treatment.

Measles vaccination coverage in high-incidence areas of the Western Cape, following the mass vaccination campaign.

BACKGROUND: Despite significant advances in measles control, large epidemics occurred in many African countries in 2009 - 2011, including South Africa. South Africa's control strategy includes mass vaccination campaigns about every 4 years, the last of which was conducted nationally in April 2010 and coincided with the epidemic. AIM: A community survey was conducted in the Western Cape to assess measles vaccination coverage attained by routine and campaign services, in children aged 6 months to 59 months at the time of the mass campaign, from high-incidence areas. METHODS: Households were consecutively sampled in high-incidence areas identified using measles epidemic surveillance data. A caregiver history of campaign vaccination and routine vaccination status from the child's Road to Health card were collected. Pre- and post-campaign immunity was estimated by analytical methods. RESULTS: Of 8 332 households visited, there was no response at 3 435 (41.2%); 95.1% (1 711/1 800) of eligible households participated; and 91.2% (1 448/1 587; 95% confidence interval 86 - 94%) of children received a campaign vaccination. Before the campaign, 33.0% (103/312) of 9 - 17-month-olds had not received a measles vaccination, and this was reduced to 4.5% (14/312) after the campaign. Of the 1 587 children, 61.5% were estimated to have measles immunity before the campaign, and this increased to 94.0% after the campaign. DISCUSSION: Routine services had failed to achieve adequate herd immunity in areas with suspected highly mobile populations. Mass campaigns in such areas in the Western Cape significantly increased coverage. Extra vigilance is required to monitor and sustain adequate coverage in these areas.

Clinician Compliance with Laboratory Monitoring and Prescribing Guidelines in HIV-1-Infected Patients Receiving Tenofovir

BACKGROUND:Tenofovir is part of the preferred first-line regimen for HIV-infected patients in South Africa (SA); but is associated with kidney toxicity. SA antiretroviral therapy (ART) guidelines recommend creatinine monitoring at baseline (ART start) and at 3; 6 and 12 months; and substituting tenofovir with zidovudine; stavudine or abacavir should creatinine clearance (CrCl) decrease to etlt;50 mL/min. OBJECTIVE:To assess clinician compliance with tenofovir monitoring and prescribing guidelines.METHODS:We described the proportion of adult patients on tenofovir-based first-line ART who were screened for baseline renal impairment; were monitored according to the SA antiretroviral treatment guidelines; and were switched from tenofovir if renal function declined.RESULTS:We included 13 168 patients who started ART from 2010 to 2012. Creatinine concentrations were recorded in 11 712 (88.9%) patients on tenofovir at baseline; 9 135/11 657 (78.4%) at 3 months; 5 426/10 554 (51.4%) at 6 months; and 5 949/ 8 421 (70.6%) at 12 months. At baseline; 227 (1.9%) started tenofovir despite a CrCl etlt;50 mL/min. While on tenofovir; 525 patients had at least one CrCl of etlt;50 mL/min. Of 382 patients with =3 months' follow-up after a CrCl etlt;50 mL/min; 114 (29.8%) stopped tenofovir within 3 months. Clinicians were more likely to stop tenofovir in patients with lower CrCl and CD4 count. Of 226 patients who continued to receive tenofovir and had further CrCls available; 156 (69.0%) had a CrCl =50 mL/min at their next visit.CONCLUSIONS:Creatinine monitoring is feasible where access to laboratory services is good. Kidney function recovered in most patients who continued to receive tenofovir despite a CrCl etlt;50 mL/min. Further research is needed to determine how best to monitor renal function with tenofovir in resource-limited settings