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The design of questions in news interviews and news conferences has proven to be an illuminating window into the tenor of press-state relations. Quantitative studies have charted aggregate variations in adversarial questioning, but less is known about variations in the intensity of adversarialness within any particular question. Such variation is captured by the vernacular distinction between "hardball" versus "softball" questions. Hardballs advance an oppositional viewpoint vigorously, while softballs do so at most mildly. In this paper we investigate recurrent language practices through which journalists modulate the oppositionality of a question, thereby either hindering or facilitating response. The objective is to better understand how adversarialness is enacted in direct encounters between politicians and journalists.

BackgroundAdherence to care and treatment are essential for HIV‐infected individuals to benefit from antiretroviral therapy (ART). We sought to quantify the effects on treatment outcomes of missing visits soon after initiating ART.MethodsWe analyzed data from HIV‐infected patients initiating ART at Themba Lethu Clinic, Johannesburg, South Africa, from April 2004 to August 2008. We used log‐binomial regression to evaluate the relative risk of missing visits during the first six months of ART on immunological response and virologic suppression. Cox models were used to evaluate the relationship between missed visits and mortality and loss to follow up over 12 months.ResultsOf 4476 patients, 65% missed no visits, while 26% missed one visit, 7% missed two and 1.6% missed three or more visits during the first six months on treatment. Patients who missed three or more medical or antiretroviral (ARV) visits had a two‐fold increased risk of poor CD4 response by six months, while the risk of failing to achieve virologic suppression by six months increased two‐ to five‐fold among patients who missed two and three or more medical or ARV visits. Adjusted Cox models showed that patients who missed two (HR 2.1; 95% CI: 1.0‐4.3) and three or more (HR 4.7; 95% CI: 1.4‐16.2) medical visits had an increased risk of death, while those who missed two ARV (HR 3.8; 95% CI: 2.5‐5.8) or three or more medical (HR 3.0; 95% CI: 1.1‐8.1) visits had an increased risk of loss to follow up.ConclusionsThirty‐five percent of patients missed one or more visits in the first six months on treatment, increasing their risk of poorer outcomes. These patients could be targeted for additional adherence counselling to help improve ART outcomes.

BackgroundAs stavudine remains an important and widely prescribed drug in resource‐limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.MethodsWe analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six‐ and/or 12‐month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.ResultsBetween 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13‐2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86‐5.25), lipoatrophy (OR 11.8; 95% CI 3.2‐43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83‐18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.ConclusionsLower stavudine dosage is associated with fewer reports of several stavudine‐associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.

BackgroundCurrent guidelines for providing antiretroviral therapy (ART) in South Africa's public sector programme call for switching patients from first‐line to second‐line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first‐line therapy, rather than switching all failures to second‐line therapy.MethodsCosts were estimated for three scenarios: routine maintenance (standard care without resistance testing, switch all failures to second line); resistance testing (resistance test for patients with failure, switch those with resistance); and limited testing (resistance test for patients with failure in the first three years, switch those with resistance). A Markov model was used to estimate the cost of each arm over five years after first line initiation. Rates of treatment failure, viral resistance and treatment costs were estimated with primary data from a large HIV treatment cohort at a public facility in Johannesburg. Future costs were discounted at 3%.ResultsVirological failure rates over five years were 19.8% in routine maintenance and 20.2% in resistance testing and limited testing; 16.8% and 11.4% of failures in routine and limited testing, respectively, did not have any resistance mutations, resulting in 3.1% and 2.0% fewer patients switching to second‐line ART by the end of five years. Treatment costs were estimated at US$526 and $1268 per patient per year on first‐line and second‐line therapy, respectively; a resistance test cost $242. The total average cost per patient over five years was $2780 in routine maintenance; $2775 in resistance testing; and $2763 in limited testing.ConclusionsIncorporating resistance testing into treatment guidelines in South Africa is potentially cost‐neutral and can identify other reasons for failure, conserve treatment options, and generate information about emerging resistance patterns.

IntroductionAs global policy evolves toward initiating lifelong antiretroviral therapy (ART) regardless of CD4 count, initiating individuals newly diagnosed with HIV on ART as efficiently as possible will become increasingly important. To inform progress, we conducted a systematic review of pre‐ART interventions aiming to increase ART initiation in sub‐Saharan Africa.MethodsWe searched PubMed, Embase and the ISI Web of Knowledge from 1 January 2008 to 1 March 2015, extended in PubMed to 25 May 2016, for English language publications pertaining to any country in sub‐Saharan Africa and reporting on general adult populations. We included studies describing interventions aimed at increasing linkage to HIV care, retention in pre‐ART or uptake of ART, which reported ART initiation as an outcome. We synthesized the evidence on causal intervention effects in meta‐analysis of studies belonging to distinct intervention categories.Results and discussionWe identified 22 studies, which evaluated 25 interventions and included data on 45,393 individual patients. Twelve of twenty‐two studies were observational. Rapid/point‐of‐care (POC) CD4 count technology (seven interventions) (relative risk, RR: 1.26; 95% confidence interval, CI: 1.02–1.55), interventions within home‐based testing (two interventions) (RR: 2.00; 95% CI: 1.36–2.92), improved clinic operations (three interventions) (RR: 1.36; 95% CI: 1.25–1.48) and a package of patient‐directed services (three interventions) (RR: 1.54; 95% CI: 1.20–1.97) were all associated with increased ART initiation as was HIV/TB service integration (three interventions) (RR: 2.05; 95% CI: 0.59–7.09) but with high imprecision. Provider‐initiated testing (three interventions) was associated with reduced ART initiation (RR: 0.91; 95% CI: 0.86–0.97). Counselling and support interventions (two interventions) (RR 1.08; 95% CI: 0.94–1.26) had no impact on ART initiation. Overall, the evidence was graded as low or moderate quality using the GRADE criteria.ConclusionsThe literature on interventions to increase uptake of ART is limited and of mixed quality. POC CD4 count and improving clinic operations show promise. More implementation research and evaluation is needed to identify how best to offer treatment initiation in a manner that is both efficient for service providers and effective for patients without jeopardizing treatment outcomes.

BackgroundWhile the number of HIV‐positive patients on antiretroviral therapy (ART) in resource‐limited settings has increased dramatically, some patients eligible for treatment do not initiate ART even when it is available to them. Understanding why patients opt out of care, or are unable to opt in, is important to achieving the goal of universal access.MethodsWe conducted a cross‐sectional survey among 400 patients on ART (those who were able to access care) and 400 patients accessing home‐based care (HBC), but who had not initiated ART (either they were not able to, or chose not to, access care) in two rural and two urban sites in Zambia to identify barriers to and facilitators of ART uptake.ResultsHBC patients were 50% more likely to report that it would be very difficult to get to the ART clinic than those on ART (RR: 1.48; 95% CI: 1.21‐1.82). Stigma was common in all areas, with 54% of HBC patients, but only 15% of ART patients, being afraid to go to the clinic (RR: 3.61; 95% CI: 3.12‐4.18). Cost barriers differed by location: urban HBC patients were three times more likely to report needing to pay to travel to the clinic than those on ART (RR: 2.84; 95% CI: 2.02‐3.98) and 10 times more likely to believe they would need to pay a fee at the clinic (RR: 9.50; 95% CI: 2.24‐40.3). In rural areas, HBC subjects were more likely to report needing to pay non‐transport costs to attend the clinic than those on ART (RR: 4.52; 95% CI: 1.91‐10.7). HBC patients were twice as likely as ART patients to report not having enough food to take ART being a concern (27% vs. 13%, RR: 2.03; 95% CI: 1.71‐2.41), regardless of location and gender.ConclusionsPatients in home‐based care for HIV/AIDS who never initiated ART perceived greater financial and logistical barriers to seeking HIV care and had more negative perceptions about the benefits of the treatment. Future efforts to expand access to antiretroviral care should consider ways to reduce these barriers in order to encourage more of those medically eligible for antiretrovirals to initiate care.

IntroductionThe prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear.MethodsThis was a cohort study of HIV‐positive adults initiating antiretroviral therapy (ART) between April 2004 and August 2007 who achieved viral suppression (<400 copies/ml) by six months on treatment in South Africa. Immunological response at six months was defined as: (1) absolute CD4 reached (<200 vs. ≥200 cells/ml); (2) absolute CD4 reached (0–49, 50–200 and ≥200 cells/ml); and (3) CD4 increase from ART initiation (<0, 0–49, 50–199 and ≥200 cells/ml). We used Cox regression models to determine the relationship between each definition and both new AIDS‐defining condition and death.ResultsA total of 4129 patients were eligible for analysis; 212 (5.1%) of those patients experienced a new AIDS‐defining condition and 154 (3.7%) died. Smaller CD4 gains by six months were associated with higher hazards of progression to AIDS (CD4<50 vs. ≥200 cells/ml; adjusted hazard ratio (aHR): 2.6; 95% CI: 1.2–2.1) and death (aHR: 2.8; 95% CI: 1.4–5.7). A decrease in CD4 count since ART initiation through six months (aHR: 2.4; 95% CI: 1.2–4.9) and smaller CD4 count gains (0–49 cells/ml; aHR: 2.0; 95% CI: 1.2–3.4 and 50–199 cells/ml; aHR: 1.5; 95% CI: 0.9–2.2) were also associated with greater risk of progression to AIDS compared to an increase of ≥200 cells/ml. When we examined mortality differences by gender among this virally suppressed cohort, a higher proportion of males died compared to females, 4.7% versus 3.2%, p=0.01. However, in multivariable analysis, we did not observe any significant differences: aHR: 1.39; 95% CI: 0.98–1.95.ConclusionsPatients on ART with poor CD4 recovery early in treatment are at greater risk of progression to new AIDS diagnosis or death despite viral suppression. Approaches to managing this sub‐group of patients need further investigation.

Abstract
IntroductionPolicies for Universal Test & Treat (UTT) and same‐day initiation (SDI) of antiretroviral therapy (ART) were instituted in South Africa in September 2016 and 2017 respectively. However, there is limited evidence on whether these changes have improved patient retention after HIV diagnosis.MethodsWe enrolled three cohorts of newly diagnosed HIV‐infected adults from two primary health clinics in Johannesburg from April to November 2015 (Pre‐UTT, N = 144), May‐September 2017 (UTT, N = 178) and October‐December 2017 (SDI, N = 88). A baseline survey was administered immediately after HIV diagnosis after which follow‐up using clinical records (paper charts, electronic health records and laboratory data) ensued for 12 months. The primary outcome was patient loss to follow‐up (being >90 days late for the last scheduled appointment) at 12 months post‐HIV diagnosis. We modelled attrition across HIV policy periods with Cox proportional hazard regression.ResultsOverall, 410 of 580 screened HIV‐positive patients were enrolled. Overall, attrition at 12 months was 30% lower in the UTT guideline period (38.2%) compared to pre‐UTT (47.2%, aHR 0.7, 95% CI: 0.5 to 1.0). However, the total attrition was similar between the SDI (47.7%) and pre‐UTT cohorts (aHR 1.0, 95% CI: 0.7 to 1.5). Older age at HIV diagnosis (aHR 0.5 for ≥40 vs. 25 to 29 years, 95% CI: 0.3 to 0.8) and being in a non‐marital relationship (aHR 0.5 vs. being single, 95% CI: 0.3 to 0.8) protected against LTFU at 12 months, whereas LTFU rates increased with longer travel time to the diagnosing clinic (aHR 1.8 for ≥30 minutes vs. ≤15 minutes, 95% CI: 1.1 to 3.1). In analyses adjusted for the time‐varying ART initiation status, compared to the pre‐ART period of care, the hazard of on‐ART LTFU was 90% higher among participants diagnosed under the SDI policy compared to pre‐UTT (aHR 1.9, 95% CI: 1.1 to 2.9).ConclusionsOverall, nearly two‐fifths of HIV positive patients are likely to disengage from care by 12 months after HIV diagnosis under the new SDI policy. Furthermore, the increase in on‐ART patient attrition after the introduction of the SDI policy is cause for concern. Further research is needed to determine the best way for rapidly initiating patients on ART and also reducing long‐term attrition from care.

AbstractIntroductionSame‐day initiation (SDI) of antiretroviral therapy (ART) for HIV consistently increases ART uptake, but concerns remain about higher attrition from care after initiation. We analysed 12‐month retention in the SLATE SDI trials.MethodsSLATE I (Simplified Algorithms for Treatment Eligibility I, enrolment 06 March–28 July 2017) and SLATE II (enrolment 14 March–18 September 2018) were individually randomized trials at public outpatient clinics in Johannesburg that enrolled patients not yet on ART and administered the SLATE I or II algorithm. This included a symptom self‐report, medical history, brief physical examination and readiness questionnaire to assess the eligibility for SDI. The studies compared the offer of SDI using the SLATE algorithms to standard of care initiation procedures. ART uptake and early retention were previously reported. Using routine clinic records, we conducted a pooled analysis of retention in care and HIV viral suppression 14 months after study enrolment, a time point equivalent to 12 months potential on ART, with an additional month allowed on either end to initiate ART and to return for the 12‐month visit.Results and discussionWe enrolled 1193 study participants (standard arms, n = 599, 50%; intervention arms, n = 594, 50%) and analysed by originally assigned groups. By 14 months after enrolment, 50% of intervention arm patients and 46% of standard arm patients remained in care at the initiating site (crude risk difference 4% (95% confidence interval −1%‐10%); crude relative risk 1.10 (0.97–1.23), with similar viral suppression between arms. Observed attrition from care at site by 14 months was high in both study arms, but we found no evidence that the offer of SDI led to greater overall attrition or lower rates of viral suppression 1 year after starting ART and may have generated small improvements. SDI may have shifted some attrition from before to after dispensing of the first dose of medication.ConclusionsAn offer of SDI of ART, following a carefully designed protocol to identify patients who are eligible and ready to start treatment, is not inherently associated with an overall increase in patient attrition from care and leads to similar rates of viral suppression.Trial registrationClinicaltrials.gov NCT02891135, registered 01 September 2016. First participant enrolled 06 March 2017 in South Africa. Clinicaltrials.gov NCT03315013, registered 19 October 2017. First participant enrolled 14 March 2018.

Introduction: Little is known about the impact of antiretroviral therapy (ART) guideline changes on the durability of second‐line ART and continuity of care. This study examines predictors of early drug substitutions and treatment interruptions using a cohort analysis of HIV positive adults switched to second‐line ART between January 2004 and September 2013 in Johannesburg, South Africa.Methods: The main outcomes were having a drug substitution or treatment interruption in the first 24 months on second‐line ART. Kaplan Meiers analyses and Cox proportional hazards regression were used to identify predictors of drug substitutions and treatment interruptions.Results: Of 3028 patients on second‐line ART, 353 (11.7%) had a drug substitution (8.6 per 100PY, 95% CI: 7.8–9.6) and 260 (8.6%) had a treatment interruption (6.3 per 100PY, 95% CI: 5.6–7.1). While treatment interruptions decreased from 32.5 per 100PY for the 2004 cohort to 2.3 per 100PY for the 2013 cohort, the rates of drug substitutions steadily increased, peaking at an incidence of 26.7 per 100PY for the 2009 cohort and then decreased to 4.2 per 100PY in the 2011 cohort. Compared to the 2004 to 2008 cohorts, the hazard of early drug substitutions was highest among patients switched to AZT + ddI + LPVr in 2009 to 2010 (aHR 5.1, 95% CI: 3.4–7.1) but remained low over time among patients switched to TDF + 3TC/FTC + LPVr or AZT/ABC + 3TC + LPVr. The main common predictor of both treatment interruption and drug substitution was drug toxicity.Conclusions: Our results show a rapid transition between 2004 and 2010 ART guidelines and concurrent improvements in continuity of care among second‐line ART patients. Drug toxicity reporting and monitoring systems need improvements to inform timely regimen changes and ensure that patients remain in care. However, reasons for drug substitutions should be closely monitored to ensure that patients do not run out of treatment options in the future.

IntroductionPrevious research has raised concerns that patients given nevirapine (NVP)‐based regimens experience more virologic failure than patients given efavirenz (EFV)‐based regimens. We investigated this hypothesis in a cohort of HIV‐positive patients at a large HIV treatment clinic in South Africa.MethodsAll antiretroviral therapy (ART)‐naïve non‐pregnant patients, ≥18 years old, without tuberculosis, who initiated treatment with either NVP or EFV from April 2004 to August 2011 at the Themba Lethu Clinic in Johannesburg, South Africa, were included. Log‐binomial regression and modified Poisson regression were used to estimate risk ratios (RR) with 95% confidence intervals (CI) for predictors of virologic failure, virologic suppression, and loss to follow‐up (LTF), whereas a Cox proportional hazards model was used to estimate the risk of death, all within one year.ResultsOf 12,840 included patients, 62.0% were female and the median baseline CD4 count was 98 cells/mm3 (36–169). Of these patients, 93.2% initiated an EFV‐based regimen. After adjusting for baseline characteristics, no difference in death (adjusted Hazards Ratio (aHR): 0.92; 95% CI: 0.68–1.25), LTF (adjusted Risk Ratio (aRR): 1.00; 95% CI: 0.79–1.25), nor suppression (aRR: 0.98; 95% CI: 0.95–1.00) at one year was found between regimens. Among patients with ≥1 viral load ≥4 months after ART initiation, 4% (n=350) experienced virologic failure within 12 months of initiation. Patients initiating NVP‐based regimens were 60% more likely to fail than patients initiating EFV‐based regimens (aRR: 1.58; 95% CI: 1.13–2.22).ConclusionsIn this cohort, patients initiating NVP‐based regimens experienced more virologic failure than patients initiating EFV‐based regimens. Future guidelines should consider the implications of different efficacy profiles when making recommendations for which drugs to prioritize.