Renal dysfunction by baseline CD4 cell count in a cohort of adults starting antiretroviral treatment regardless of CD4 count in the HIV Prevention Trials Network 071 [HPTN 071; Population Effect of Antiretroviral Therapy to Reduce HIV Transmission (PopART)] study in South Africa.

OBJECTIVES: Renal dysfunction is a significant cause of morbidity and mortality among HIV-positive individuals. This study evaluated renal dysfunction in a cohort of adults who started antiretroviral treatment (ART) regardless of CD4 count at three Department of Health (DOH) clinics included in the HIV Prevention Trials Network 071 (HPTN 071) Population Effect of Antiretroviral Therapy to Reduce HIV Transmission (PopART) trial. METHODS: A retrospective cohort analysis of routine data for HIV-positive individuals starting ART between January 2014 and November 2015 was completed. Incident renal dysfunction was defined as an estimated glomerular filtration rate (eEGFR) < 60 mL/min after ART initiation among individuals with a baseline (pre-ART) eGFR ≥ 60 mL/min. RESULTS: Overall, 2423 individuals, with a median baseline CD4 count of 328 cells/µL [interquartile range (IQR) 195-468 cells/µL], were included in the analysis. Forty-seven individuals had a baseline eGFR < 60 mL/min. Among 1634 nonpregnant individuals started on a tenofovir-containing ART regimen and with a baseline eGFR ≥ 60 mL/min, 27 developed an eGFR < 60 mL/min on ART. Regression analysis showed lower odds of baseline eGFR < 60 mL/min at baseline CD4 counts of > 500 cells/µL [adjusted odds ratio (aOR) 0.29; 95% confidence interval (CI) 0.11-0.80], 351-500 cells/µL (aOR 0.22; 95% CI 0.08-0.59) and 201-350 (aOR 0.48; 95% CI: 0.24-0.97) compared with baseline CD4 counts < 200 cells/µL. CONCLUSIONS: This study showed low rates of renal dysfunction at baseline and on ART, with lower rates of baseline renal dysfunction among individuals with baseline CD4 counts > 200 cells/µL. Strategies that use baseline characteristics, such as age, to identify individuals at high risk of renal dysfunction on ART for enhanced eGFR monitoring may be effective and should be the subject of future research.

Outcomes of community-based differentiated models of multi-month dispensing of antiretroviral medication among stable HIV-infected patients in Lesotho: a cluster randomised non-inferiority trial protocol.

BACKGROUND: Current World Health Organization (WHO) guidelines recommend early initiation of HIV positive patients on antiretroviral therapy (ART) irrespective of their clinical or immunological status known as the test and start approach. Lesotho, like many other countries introduced this approach in 2016 as a strategy to reach epidemic control. There will be rapidly growing number of HIV-infected individuals initiating treatment leading to practical challenges on health systems such as congestion, long waiting time for patients and limited time to provide quality services to patients. Differentiated models of ART delivery is an innovative solution that helps to increase access to care, while reducing the burden on existing health systems. Ultimately this model will help to achieve retention and viral suppression. We describe a demonstration study designed to evaluate a community-based differentiated model of multi-month dispensing (MMD) approaches of ART among stable HIV patients in Lesotho. METHODS: This study will be a three-arm cluster randomised trial, which will enrol approximately 5760 HIV-infected individuals who are stable on ART in 30 selected clusters. The clusters, which are health facilities, will be randomly assigned into the following differentiated model of care arms: (i) 3 monthly ART supply at facilities (Control), (ii) 3 monthly ART supply through community ART groups (CAGs) and (iii) 6 monthly ART supply through community ART distribution points (CAD). Primary outcomes are retention in care and virologic suppression, and secondary outcomes include feasibility and cost effectiveness. DISCUSSION: Important lessons will be learnt to allow for improved implementation of such demonstration projects, including various needs for reliable supply of medication, access to quality clinical data including access to viral loads (VLs) results, frameworks to support lay worker cadre, involvement of community stakeholders, and reliable data systems including records of key indicators. MMD will have positive implications including improved retention, virologic suppression, convenience and access to medication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03438370 . Accepted on 16 February 2018.

Impact of 'Ideal Clinic' implementation on patient waiting time in primary healthcare clinics in KwaZulu-Natal Province, South Africa: A before-and-after evaluation.

BACKGROUND: Long waiting times are a major source of dissatisfaction for patients attending public healthcare facilities in South Africa (SA). The National Department of Health has identified this as one of six priority areas for improvement. Health system-strengthening (HSS) interventions to improve patient waiting time are being implemented in public health facilities across SA as part of the 'Ideal Clinic' model. The effect of these interventions on patient waiting time needs to be assessed and evidence generated for system improvement. OBJECTIVES: To determine the effect of Ideal Clinic HSS intervention on patient waiting time in public health facilities in Amajuba District, KwaZulu-Natal Province, SA. METHODS: We implemented 12 months of HSS activity, including facility reorganisation and patient appointment scheduling. The major outcome of interest was the total time spent by patients in a facility during a visit. This was calculated as the median time spent, obtained through a 'before-and-after' intervention survey. Univariate and multivariate factors associated with waiting time were determined. RESULTS: A total of 1 763 patients from nine clinics were surveyed before and after the intervention (n=860 at baseline and n=903 at follow-up). The median overall waiting time after the intervention was 122 minutes (interquartile range (IQR) 81 - 204), compared with 116 minutes (IQR 66 - 168) before (p<0.05). Individual facility results after the intervention were mixed. Two facilities recorded statistically significant reductions in patient waiting time, while three recorded significant increases (p<0.05). Patient load per nurse, type of service received and time of arrival in facilities were all independently associated with waiting time. Patients' arrival patterns, which were determined by appointment scheduling, played a significant role in the results obtained. CONCLUSIONS: Implementation of the Ideal Clinic model in the selected facilities led to changes in patient waiting time. Observed changes were positive when a clinic appointment system was successfully implemented and negative when this was unsuccessful. We recommend strengthening of the appointment system component of the Ideal Clinic model to improve patient waiting time. Assessing facility waiting time performance in terms of average time spent by patients during a clinic visit was shown to be inadequate, and we suggest the inclusion of 'proportion of clients who spent above the national waiting time threshold during their visit' as a sensitive measure of performance.

A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over time. METHODS: Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered. RESULTS: In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml(-1) (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml(-1) or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml(-1) (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%. CONCLUSIONS: CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis.

Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa.

BACKGROUND: South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy. OBJECTIVE: To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories. METHODS: A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as 24 years old and adolescents as 19 years. The effect of younger maternal age categories on MTCT and maternal and child health outcomes was assessed using log-binomial and Cox regression controlling for confounding, using women aged > 24 years as the comparison group. RESULTS: Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25). CONCLUSION: An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals.

The first 5 years of the family clinic for HIV at Tygerberg Hospital: family demographics, survival of children and early impact of antiretroviral therapy.

BACKGROUND: Family clinics address the problems of HIV-infected children and their families. The aims were to document demographics of the children and caregivers attending the Family Clinic for HIV at Tygerberg Academic Hospital (TAH) and to investigate factors affecting disease progression in children. METHODS: A retrospective folder review of children and parents attending the Family Clinic at TAH between January 1997 and December 2001, a period noted for its lack of antiretroviral treatment. RESULTS: Of 432 children seen for testing, 274 children, median age 16.9 months, were HIV-infected. During follow-up, 46 children died (median age 23 months) and 113 were lost to follow-up. The majority of children were malnourished. Those <2 years of age had lower weight for age Z-scores (WAZ) than older children (p<0.001). At presentation, 47 per cent were in clinical stage B and two-thirds had moderate or severe CD4+ T cell depletion. Seventeen children had received highly active antiretroviral therapy (HAART), 12 dual and 31 monotherapy. HAART was associated with improved survival compared to dual or monotherapy. Risk of death was reduced from eleven-fold for a WAZ <-4 to four-fold between -2 and -3. There was no association with immunological and clinical classification at entry and risk of mortality. Only 18 per cent of parents were evaluated in the clinic. Non-parental care was documented for 25 per cent of families. CONCLUSIONS: A low WAZ is associated with poor survival in children. Nutritional status should receive more attention in HIV disease classification in children. Parent utilization of the clinic was inadequate. Even in the absence of HAART, extended survival in children is possible.