When to start antiretroviral therapy in adults: the results of HPTN 052 move us closer to a ‘test-and-treat’ policy

When is the best time to initiate antiretroviral therapy (ART) in adults? This is a vital question in HIV treatment and prevention services. More specifically, is the 350 cells/μl CD4 count threshold recommended by current World Health Organization (WHO) guidelines sufficient, or should we move to a ‘test-and-treat’ approach in which anyone who tests HIV-positive is offered ART, irrespective of their CD4 count? The recently announced results of the HPTN 052 trial take us closer, but not all the way, to a test-and-treat approach

World Health Organization guidelines should not change the CD4 count threshold for antiretroviral therapy initiation

The World Health Organization (WHO) currently recommends that HIV-positive adults start antiretroviral therapy (ART) at CD4 counts <350 cells/μl. Several countries have changed their guidelines to recommend ART irrespective of CD4 count or at a threshold of 500 CD4 cells/μl. Consequently, WHO is currently revising its treatment guidelines and considering recommending ART initiation at CD4 counts <500 cells/μl. Such decisions are critically important, as WHO guidelines inform healthcare policies in developing countries and are used by activists in their advocacy work. Changing the CD4 initiation point from 350 to 500 cells/μl would, however, be premature and have profound cost implications on Global Fund, President’s Emergency Plan for AIDS Relief (PEPFAR) and developing country health budgets. We should be willing to campaign for such a change in guidelines despite cost implications, if supported by evidence. However, the evidence remains outstanding.S Afr J HIV Med 2013;14(1):6-7. DOI:10.7196/SAJHIVMED.90

The development of passive health surveillance by a sentinel network of family practitioners in South Africa

Objective. For the South African Sentinel Practitioner Research Network (SASPREN), a volunteer network of family practitioners in South Africa, to develop a health surveillance system through the surveillance of important health events.Motivation. The incidence of important preventable diseases and the burden of disease are not reliably known in South Africa, both in the public and private sector. Incidence rates determined at primary care level could help with planning and delivery of appropriate health services and monitoring of the impact of intervention programmes.Methods. Altogether 183 sentinel practitioners were recruited in nine provinces, from 2 478 doctors invited to participate. Of these 120 were active in reporting all their new cases of 13 selected health events to the study centre on mailed postcards. After data-capturing, incidence rates were calculated for defined periods. Feedback was given to the sentinels through a newsletter and personalised reports.Results. A network of sentinel family practitioners has been established in South Africa, and can provide incidence rates for both diseases and interventions through a simple and cheap surveillance system. The calculated rates demonstrated periodic trends for certain events, as well as inter-provincial, -gender and -population group differences.Conclusions. As the validity of the dataset and its generalisation to the whole population is uncertain, its usefulness as point estimates of incidence rates isunknown. This information serves as an important pointer for further research. The trends of these rates may provide a valuable tool for monitoring the impact of public health policies

One size doesn't fit all: Tailoring adult antiretroviral treatment

Advances in antiretroviral treatment mean that patients in the public health system can be given more options in the management of their treatment. Although public health programmes tend to offer one-size-fits-all approaches, patients might benefit from a more flexible approach. In particular, we propose that people with HIV should be given more choice with regard to when to start treatment, and patients who experience efavirenz side-effects should be encouraged to switch to other medications, which will be facilitated by faster registration and lower prices of newer antiretrovirals

Auditory Perception of Self-Similarity in Water Sounds

Many natural signals, including environmental sounds, exhibit scale-invariant statistics: their structure is repeated at multiple scales. Such scale-invariance has been identified separately across spectral and temporal correlations of natural sounds (Clarke and Voss, 1975; Attias and Schreiner, 1997; Escabi et al., 2003; Singh and Theunissen, 2003). Yet the role of scale-invariance across overall spectro-temporal structure of the sound has not been explored directly in auditory perception. Here, we identify that the acoustic waveform from the recording of running water is a self-similar fractal, exhibiting scale-invariance not only within spectral channels, but also across the full spectral bandwidth. The auditory perception of the water sound did not change with its scale. We tested the role of scale-invariance in perception by using an artificial sound, which could be rendered scale-invariant. We generated a random chirp stimulus: an auditory signal controlled by two parameters, Q, controlling the relative, and r, controlling the absolute, temporal structure of the sound. Imposing scale-invariant statistics on the artificial sound was required for its perception as natural and water-like. Further, Q had to be restricted to a specific range for the sound to be perceived as natural. To detect self-similarity in the water sound, and identify Q, the auditory system needs to process the temporal dynamics of the waveform across spectral bands in terms of the number of cycles, rather than absolute timing. We propose a two-stage neural model implementing this computation. This computation may be carried out by circuits of neurons in the auditory cortex. The set of auditory stimuli developed in this study are particularly suitable for measurements of response properties of neurons in the auditory pathway, allowing for quantification of the effects of varying the statistics of the spectro-temporal statistical structure of the stimulus

Quality of counselling and support provided by the South African National AIDS Helpline: Content analysis of mystery client interviews

Background. Telephone helplines can facilitate referral, education and support for patients living with HIV or those concerned about the infection. The anonymity of helplines facilitates discussion of sensitive issues that are difficult to raise face to face. These services could support the expansion of HIV self-testing. However, maintaining quality and standardising messages in rapidly evolving fields such as HIV is challenging. Objectives. To evaluate the quality of the South African (SA) National AIDS Helpline. Methods. Mystery clients posing as members of the public made 200 calls to the service in 2014. They presented several scenarios, including having received HIV-positive results from a doctor’s secretary or through self-testing. Following the call, ‘clients’ completed a semistructured questionnaire on the information received and the caller-counsellor interaction. Results. Calls were answered within a median of 5 seconds (interquartile range 2 - 14). Conversations took place in 8 of the 11 SA official languages, though mainly in English. Overall, 75% of callers felt that with the information they received they could locate a nearby clinic for further services. Counsellors expressed appropriate levels of concern about inadequate counselling that callers had received and confidentiality breaches in some scenarios. Eight counsellors incorrectly mentioned the need for a waiting period to confirm a positive result. Consistent with policy, almost all said that being foreign would not affect HIV treatment access. About 90% explained the need for CD4+ testing and antiretroviral therapy, but only 78% discussed HIV prevention. Counsellors were mostly empathetic (83%), though some adopted a neutral tone (10%) or were brusque (6%) or unhelpful (2%). Conclusions. Overall, helpline counsellors were proficient at providing information about local clinics, HIV testing and steps needed for initiating ART. Dissatisfaction with the caller-counsellor interactions, instances of incorrect information and the relatively low attention accorded to HIV prevention are worrying, however. Training for both refreshing and updating knowledge, and supervision and monitoring of calls, could target these areas.S Afr Med J 2018;108(7):596-60

Treatment goals and changes over time in older patients with non-curable cancer

PURPOSE: To investigate the treatment goals of older patients with non-curable cancer, whether those goals changed over time, and if so, what triggered those changes. METHODS: We performed a descriptive and qualitative analysis using the Outcome Prioritization Tool (OPT) to assess patient goals across four conversations with general practitioners (GPs) over 6 months. Text entries from electronic patient records (hospital and general practice) were then analyzed qualitatively for this period. RESULTS: Of the 29 included patients, 10 (34%) rated extending life and 9 (31%) rated maintaining independence as their most important goals. Patients in the last year before death (late phase) prioritized extending life less often (3 patients; 21%) than those in the early phase (7 patients; 47%). Goals changed for 16 patients during follow-up (12 in the late phase). Qualitative analysis revealed three themes that explained the baseline OPT scores (prioritizing a specific goal, rating a goal as unimportant, and treatment choices related to goals). Another three themes related to changes in OPT scores (symptoms, disease course, and life events) and stability of OPT scores (stable situation, disease-unrelated motivation, and stability despite symptoms). CONCLUSION: Patients most often prioritized extending life as the most important goal. However, priorities differed in the late phase of the disease, leading to changed goals. Triggers for change related to both the disease (e.g., symptoms and course) and to other life events. We therefore recommend that goals should be discussed repeatedly, especially near the end of life. TRIAL REGISTRATION: OPTion study: NTR5419

Complementary Control of Sensory Adaptation by Two Types of Cortical Interneurons

Reliably detecting unexpected sounds is important for environmental awareness and survival. By selectively reducing responses to frequently, but not rarely, occurring sounds, auditory cortical neurons are thought to enhance the brain\u27s ability to detect unexpected events through stimulus-specific adaptation (SSA). The majority of neurons in the primary auditory cortex exhibit SSA, yet little is known about the underlying cortical circuits. We found that two types of cortical interneurons differentially amplify SSA in putative excitatory neurons. Parvalbumin-positive interneurons (PVs) amplify SSA by providing non-specific inhibition: optogenetic suppression of PVs led to an equal increase in responses to frequent and rare tones. In contrast, somatostatin-positive interneurons (SOMs) selectively reduce excitatory responses to frequent tones: suppression of SOMs led to an increase in responses to frequent, but not to rare tones. A mutually coupled excitatory-inhibitory network model accounts for distinct mechanisms by which cortical inhibitory neurons enhance the brain\u27s sensitivity to unexpected sounds