Search

Progression in the development of antiretroviral therapy has been remarkable, with new agents continuing to appear as options for modern regimens, including in low-and-middle income countries where the HIV epidemic is concentrated. Here, we reflect on progress made in guiding regimen changes to public health programmes, and the challenges facing selection of newer agents.

Objective: Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. Design: We analysed serum folate concentrations from stored plasma among women enrolled in the South African ADVANCE trial. Methods: We compared changes in mean serum folate and occurrence of low serum folate (

Background Dolutegravir is associated with more weight gain than efavirenz. Loss-of-function polymorphisms in CYP2B6 result in higher efavirenz concentrations, which we hypothesized would impair weight gain among people living with human immunodeficiency virus (HIV; PLWH) starting efavirenz-based antiretroviral therapy (ART). Methods We studied ART-naive participants from the ADVANCE study randomized to the efavirenz /emtricitabine/tenofovir disoproxil fumarate (TDF) and dolutegravir/emtricitabine/TDF arms. We compared changes in weight and regional fat on DXA from baseline to week 48 between CYP2B6 metabolizer genotypes in the efavirenz arm, and with the dolutegravir arm. Results There were 342 participants in the dolutegravir arm and 168 in the efavirenz arm who consented to genotyping. Baseline characteristics were similar. Weight gain was greater in women than men. In the efavirenz arm CYP2B6 metaboliser genotype was associated with weight gain (P = .009), with extensive metabolizers gaining the most weight, and with changes in regional fat in women, but not in men. Weight gain was similar in CYP2B6 extensive metabolizers in the efavirenz arm and in the dolutegravir arm (P = .836). The following variables were independently associated with weight gain in all participants: baseline CD4 count, baseline human immunodeficiency virus type 1 (HIV-1) RNA, and CYP2B6 metaboliser genotype. Conclusions CYP2B6 metaboliser genotype was associated with weight gain in PLWH starting efavirenz-based ART. Weight gain was similar between CYP2B6 extensive metabolizers in the efavirenz arm and in the dolutegravir arm, suggesting that impaired weight gain among CYP2B6 slow or intermediate metabolizers could explain the increased weight gain on dolutegravir compared with efavirenz observed in ADVANCE and other studies., CYP2B6 metabolizer genotype was associated with weight gain and changes in regional fat in women, but not in men starting efavirenz-based antiretroviral therapy (ART). Weight gain was similar in CYP2B6 extensive metabolizers in the efavirenz arm and in the dolutegravir arm.

International audience; Obesity develops in a substantial number of people initiating and maintaining modern antiretroviral therapy. The comorbidities associated with obesity make significant weight gain and metabolic changes a major consideration in clinical trials studying different regimens' potency and safety. It is as yet unclear what role individual antiretrovirals or classes play in weight gain but the issue is a complex one for clinical trial design, especially when deciding when "too much" weight has been gained, in a context where we do not yet know if switching to alternative regimens will slow, halt or reverse weight gain or metabolic changes. In addition, clinician and trial participant opinion on acceptable weight gain may differ. We offer preliminary guidance for discussion for future antiretroviral clinical trial design.

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met.

This contribution is a review of the research handbook in comparative constitutional law, titled Comparative Constitutional Theory edited by Gary Jacobsohn and Miguel Schor. It was published in 2018 by Edward Elgar Publishing. Every law library worthy of the name should acquire it for the benefit of constitutional scholars and advanced students of constitutional comparison.

Objective Integrase inhibitors, including dolutegravir (DTG), are associated with weight gain and obesity, especially when combined with tenofovir alafenamide (TAF). Obesity increases the risk of adverse pregnancy outcomes (APOs). This study aimed to predict the risk of APOs caused by treatment-associated obesity, using a hypothetical sample based on the ADVANCE trial. Design Risk prediction. Methods Firstly, a meta-analysis was performed to determine the relative risk (RR) for APOs in women with obese (≥30) versus normal prepregnancy BMIs (18.5-24.9). For the hypothetical sample, 3000 nonpregnant women with normal BMIs at Week 0 of treatment were evenly allocated across the following treatment arms: TAF/FTC+DTG, TDF/FTC+DTG, TDF/FTC/EFV. The treatment-associated obesity rates from ADVANCE were used to calculate the number of women with obese and normal BMIs expected at Week 96 in our sample. This was combined with the APO RRs to predict the number of women at risk of APOs, in each treatment arm, assuming they conceived at Week 96. Results At Week 96, the percentage of women predicted to be obese was 14.1% with TAF/FTC+DTG, 7.9% with TDF/FTC+DTG and 1.5% with TDF/FTC/EFV. The RR in women with obese versus normal BMIs was significantly higher for most APOs. Therefore, the number of women at risk of APOs was higher with TAF/FTC+DTG than TDF/FTC+DTG and TDF/FTC/EFV. For example, 11/1000 additional gestational hypertension cases were predicted with TAF/FTC+DTG, 6/1000 with TDF/FTC+DTG and 1/1000 with TDF/FTC/EFV. Conclusion Treatment-associated obesity increased the APO risk in women. This risk is likely to increase, as preliminary data from ADVANCE demonstrates ongoing weight gain beyond Week 96.

IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors.ResultsIn total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p ConclusionHIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

Africa’s readiness to the respond to the SARS-COV-2 pandemic was tested due to reliance on rapid turn-around-time of polymerase chain reaction results for clinical management, isolation and quarantine decisions. The HIV Molecular Laboratory in Johannesburg, South Africa is one of the largest automated HIV molecular laboratories worldwide, performing 1.2 million tests annually. Despite its extensive molecular capacity and experience in managing high volumes acquired from a large HIV program, significant challenges were encountered during its rapid transition to largescale SARS-CoV-2 testing. Here, we describe the strategies employed to manage challenges related to policy, staff, introduction of new assays and workflow efficiencies, and to mitigate the risks of reprioritization of resources on routine HIV tests, that resulted in a 50% improvement in SARS-COV-2 turn-around-time during the first wave peak during which approximately 25 000 samples were tested per month, and further improvement during the second wave, with 91% within targeted turn-around-time.

BACKGROUND: The use of a combination of the integrase inhibitor, cabotegravir, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form is being considered as an antiretroviral treatment option for people with HIV in sub-Saharan Africa. We aimed to model the effects of injectable cabotegravir-rilpivirine to help to inform its potential effectiveness and cost-effectiveness under different possible policies for its introduction. METHODS: We used an existing individual-based model of HIV to predict the effects of introducing monthly injections of cabotegravir-rilpivirine for people with HIV in low-income settings in sub-Saharan Africa. We evaluated policies in the context of 1000 setting scenarios that reflected characteristics of HIV epidemics and programmes in sub-Saharan Africa. We compared three policies for introduction of injectable cabotegravir-rilpivirine with continued use of dolutegravir-based oral regimens for: all individuals on antiretroviral therapy (ART); individuals with a recently measured viral load of more than 1000 copies per mL (signifying poor adherence to oral drugs, and often associated with drug resistance); and individuals with a recently measured viral load of less than 1000 copies per mL (a group with a lower prevalence of pre-existing drug resistance). We also did cost-effectiveness analysis, taking a health system perspective over a 10 year period, with 3% discounting of disability-adjusted life-years (DALYs) and costs. A cost-effectiveness threshold of US$500 per DALY averted was used to establish if a policy was cost-effective. FINDINGS: In our model, all policies involving the introduction of injectable cabotegravir-rilpivirine were predicted to lead to an increased proportion of people with HIV on ART, increased viral load suppression, and decreased AIDS-related mortality, with lesser benefits in people with a recently measured viral load of less than 1000 copies per mL. Its introduction is also predicted to lead to increases in resistance to integrase inhibitors and non-nucleoside reverse transcriptase inhibitors if introduced in all people with HIV on ART or in those with a recently measured viral load of less than 1000 copies per mL, but to a lesser extent if introduced in people with more than 1000 copies per mL due to concentration of its use in people less adherent to oral therapy. Consistent with the effect on AIDS-related mortality, all approaches to the introduction of injectable cabotegravir-rilpivirine are predicted to avert DALYs. Assuming a cost of $120 per person per year, use of this regimen in people with a recently measured viral load of more than 1000 copies per mL was borderline cost-effective (median cost per DALY averted across setting scenarios $404). The other approaches considered for its use are unlikely to be cost-effective unless the cost per year of injectable cabotegravir-rilpivirine is considerably reduced. INTERPRETATION: Our modelling suggests that injectable cabotegravir-rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives. FUNDING: Bill & Melinda Gates Foundation, including through the HIV Modelling Consortium (OPP1191655).

Introduction With over 500 000 infections and nearly 12 000 deaths, South Africa (SA) is the African epicenter of the current Coronavirus (COVID-19) pandemic. SA has implemented a 5-stage Risk-Adjusted Strategy which includes a phased national lockdown, requiring social distancing, frequent hand washing and wearing face masks. Strict adherence to this strategy is crucial to reducing COVID-19 transmission, flattening the curve, and preventing resurgence. As part of the 22-country International Citizens Project COVID-19 (ICPcovid), this study aimed to describe the SA adherence to the Risk-Adjusted Strategy and identify determinants of adherence. Method During 24 April-15 May 2020, people were electronically invited, through social media platforms and a text blast, to complete an online survey, accessible via www.icpcovid.com. The survey investigated COVID-19 testing and preventative adherence measures, then used logistic regression analysis to identify predictors of adherence. Results There were 951 participants, with 731(76.9%) 25 to 54 years. Most (672;70.7%) were female, and 705(74.1%) had a university degree. Since the epidemic started, 529(55.6%) and 436(45.9%) participants stated they were eating healthier and taking more vitamins, respectively. Only 82(8.6%) had been COVID-19 tested, and 1(1.2%) tested positive. In public, 905(95.2%) socially distanced, however 99(10.4%) participants had recently attended meetings with over ten people. Regular hand washing was practiced by 907(95.4%) participants, 774(81.4%) wore face masks and 854(89.8%) stayed home when they experienced flu-like symptoms. The odds of adhering to the guidelines were lower among men versus women (AOR 0.72, 95% confidence interval [CI] = 0.528, 0.971) and those who had flu-like symptoms (AOR 0.42, 95% CI = 0.277, 0.628). In contrast, increased odds were reported for those who reported increased vitamin intake (AOR 1.37, 95% CI = 1.044,1.798), and were either cohabiting or married (AOR 1.39, 95% CI = 1.042,1.847). Conclusion Despite high reported adherence, face mask use and symptomatic individuals not self-isolating, were areas for improvement. However, these factors cannot solely account for SA’s increasing COVID-19 cases. Larger general population studies are needed to identify other adherence predictors for a strengthened SA COVID-19 response. While the government must continue to educate the entire population on preventative measures, provide personal protective equipment and stress the importance of adherence, there also needs to be implementation of prioritised prevention strategies for men and single individuals to address their demonstrated lower adherence.

Persistence of symptoms or development of new symptoms relating to SARS-CoV-2 infection late in the course of COVID-19 is an increasingly recognised problem facing the globally infected population and its health systems. ‘Long-COVID’ or ‘COVID long-haulers’ generally describes those persons with COVID-19 who experience symptoms for >28 days after diagnosis, whether laboratory confirmed or clinical. Symptoms are as markedly heterogeneous as seen in acute COVID-19 and may be constant, fluctuate, or appear and be replaced by symptoms relating to other systems with varying frequency. Such multisystem involvement requires a holistic approach to management of long-COVID, and descriptions of cohorts from low- and middle-income countries are eagerly awaited. Although many persons with long-COVID will be managed in primary care, others will require greater input from rehabilitation medicine experts. For both eventualities, planning is urgently required to ensure that the South African public health service is ready and able to respond.

Summary: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles

HIV-1 cell entry is mediated by binding to the CD4-receptor and chemokine co-receptors CCR5 (R5) or CXCR4 (X4). R5-tropic viruses are predominantly detected during early infection. A switch to X4-tropism often occurs during the course of infection. X4-tropism switching is strongly associated with accelerated disease progression and jeopardizes CCR5-based HIV-1 cure strategies. It is unclear whether host immunological factors play a causative role in tropism switching. We investigated the relationship between immunological factors and X4-tropism in a cross-sectional study in HIV-1 subtype C (HIV-1C)-infected patients and in a longitudinal HIV-1 subtype B (HIV-1B) seroconverter cohort. Principal component analysis identified a cluster of immunological markers (%HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD8+ T-cells, %CD70+ CD4+ T-cells, %CD169+ monocytes, and absolute CD4+ T-cell count) in HIV-1C patients that was independently associated with X4-tropism (aOR 1.044, 95% CI 1.003–1.087, p = 0.0392). Analysis of individual cluster contributors revealed strong correlations of two markers of T-cell activation (%HLA-DR+ CD4+ T-cells, %HLA-DR+CD38+ CD4+ T-cells) with X4-tropism, both in HIV-1C patients (p = 0.01;p = 0.03) and HIV-1B patients (p = 0.0003;p = 0.0001). Follow-up data from HIV-1B patients subsequently revealed that T-cell activation precedes and independently predicts X4-tropism switching (aHR 1.186, 95% CI 1.065–1.321, p = 0.002), providing novel insights into HIV-1 pathogenesis and CCR5-based curative strategies.

ObjectivesLong-haul truck drivers (TDs) may have lifestyles that promote cardiovascular disease (CVD), including diet, sleep and activity issues. Most studies conducted among truckers investigated the relationship between poor sleep and cardiometabolic health, but none assessed whether suspected obstructive sleep apnoea (OSA) and shortened sleep were associated with markers of cardiometabolic risk. We determined whether sleep disorders and circadian misalignment were associated with chronic inflammation and CVD risk in TDs from Southern Africa.MethodsParticipants were recruited at roadside wellness centres in Gauteng and Free State Provinces, South Africa. OSA risk was assessed using the Berlin Questionnaire, while sleep duration and sleep quality were assessed using items from the Pittsburgh Sleep Quality Index. Clinical information, neck circumference (NC), metabolic profile, elevated BP, HIV status and C-reactive protein (CRP) were collected. CVD risk was assessed using the Framingham Risk Score (FRS).ResultsOut of 575 participants aged on average 37.7 years, 17.2% were at OSA risk, 72.0% had elevated BP, 9.4% had HIV and 28.0% were obese. Mean sleep duration was 7.4±1.8 hours, and 49.6% reported working night shift at least once a week. Shortened sleep, OSA risk, age, body mass index, NC and years as full-time TD were associated with greater FRS independently of HIV status and night shift. Working night shift was associated with higher CRP levels in HIV+ compared with HIV− participants.ConclusionsCircadian misalignment in HIV, and OSA and short sleep duration in all truckers were associated with increased CVD risk. Truckers should be given careful attention in terms of health management and sleep education.

BACKGROUND: Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir- containing regimens. Mechanisms underlying such weight gain are unknown. SETTING: Data and DNA from antiretroviral therapy-naïve participants who were randomized to initiate dolutegravir with emtricitabine plus either tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) in the ADVANCE study (NCT03122262) were used to characterize associations between human genetic polymorphisms and magnitude of weight gain. METHODS: Associations with percent weight gain from baseline to week 48 were assessed using multivariable linear regression models. Primary analyses a priori considered 59 polymorphisms and 10 genes of potential relevance to dolutegravir, TAF or TDF pharmacokinetics. We also explored genome-wide associations. RESULTS: Among the 314 (92%) of 340 dolutegravir recipients who were successfully genotyped, 160 (47%) and 154 (45%) were randomized to TAF/emtricitabine and TDF/emtricitabine, respectively. In target gene analyses, the lowest P-values for the dolutegravir and tenofovir groups were ABCG2 rs4148149 (P = 7.0×10(−4)) and ABCC10 rs67861980 (P = 1.0×10(−2)), respectively, which were not significant after correction for multiple testing. In genome-wide analyses the lowest P-values for dolutegravir, was rs7590091 in TMEM163 (P = 3.7×10(−8)), rs17137701 in LOC105379130 (P = 6.4×10(− 8)) for TAF, and rs76771105 in LOC105371716 (P = 9.7×10(−8)) for TDF. CONCLUSION: Among South African participants in a randomized clinical trial of dolutegravir plus either TAF/emtricitabine or TDF/emtricitabine, we identified several potential genetic associations with weight gain. Only TMEM163 rs7590091 withstood correction for multiple testing. These associations warrant replication in other cohorts.

Background: SARS-CoV-2 is a novel coronavirus discovered in December 2019 and is currently the cause of the global COVID-19 pandemic. A critical aspect of fighting this pandemic is to obtain accurate and timely test results so that patients who have tested positive for COVID-19 can be identified and isolated to reduce the spread of the virus. Research has shown that saliva is a promising candidate for SARS-CoV-2 diagnostics because its collection is minimally invasive and can be reliably self-administered. However, little research has been conducted on saliva testing and SARS-CoV-2 self-sampling (SARS-CoV-2SS) in Sub-Saharan Africa. Objective: The primary objective of this study is to comparatively evaluate the clinical sensitivity and specificity of nasal and oral samples self-collected by individuals for SARS-CoV-2 testing against a reference method involving sample collection and testing by a health care professional. The secondary objectives of this study are to evaluate the usability of nasal self-sampling and saliva self-sampling as a sample collection method for SARS-CoV-2 diagnostic testing by using failure mode and error assessment. Methods: Participants will be recruited from the general population by using various methods, Participants will be screened progressively as they present at the clinical trial sites as well as in primary health care catchment areas in the inner city of Johannesburg, South Africa. In the event that recruitment numbers are low, we will use a mobile van to recruit participants from outlying areas of Johannesburg. We aim to enroll 250 participants into this study in approximately 6 weeks. Two sample types—a self-administered nasal swab and a self-administered saliva sample—will be collected from each participant, and a health care professional will collect a third sample by using a nasopharyngeal swab (ie, the standard reference method). Results: This protocol has been approved by the University of the Witwatersrand Human Research Ethics Committee on July 31, 2020 (Protocol number EzCov003). As of May 13, 2021, 120 participants have been enrolled into the study. Conclusions: SARS-CoV-2SS may offer many benefits to individuals, by allowing for initial self-identification of symptoms and collection of samples without involving third parties and potential risk of infection provided the sample can be safely processed via a collection system. The results of this study will provide preliminary data on the acceptability, feasibility, and usability of SARS-CoV-2SS among the general population for its future implementation.

BackgroundGlobally the trucking industry employs millions of people. Recently the prevalence of chronic pain in Southern African truck drivers was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so.MethodsSouthern African truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n=614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated.ResultsSix hundred and fourteen male truck drivers were recruited. Multivariate analysis showed that working ≥ 2 nights/week (OR=2.68, 95% CI=1.55-4.68) was associated with chronic pain and physical activity was protective (OR=0.97, 95% CI 0.95-0.98). In an exploratory analysis, greater depressive symptoms (p=0.004), daytime sleepiness (p=0.01) and worse sleep quality (p=0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p=0.006), but not daytime sleepiness or depressive symptoms (p>0.05).ConclusionsThere is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.

No abstract available.

Systemic biomarkers of inflammation, including cytokines and chemokines, are potentially useful in the management of both HIV infection and non-AIDS-defining disorders. However, relatively little is known about the utility of measurement of circulating biomarkers of platelet activation as a strategy to monitor the efficacy of combination antiretroviral therapy (cART), as well as the persistence of systemic inflammation following virally-suppressive therapy in HIV-infected persons. These issues have been addressed in the current study to which a cohort consisting of 199 HIV-infected participants was recruited, 100 of whom were cART-naïve and the remainder cART-treated and virally-suppressed. Fifteen healthy control participants were included for comparison. The study focused on the effects of cART on the responsiveness of three biomarkers of platelet activation, specifically soluble CD40 ligand (sCD40L), sCD62P (P-selectin), and platelet-derived growth factor-BB (PDGF-BB), measured using multiplex suspension bead array technology. Most prominently sCD40L in particular, as well as sCD62P, were significantly elevated in the cART-naïve group relative to both the cART-treated and healthy control groups. However, levels of PDGF-BB were of comparable magnitude in both the cART-naïve and –treated groups, and significantly higher than those of the control group. Although remaining somewhat higher in the virally-suppressed group relative to healthy control participants, these findings identify sCD40L, in particular, as a potential biomarker of successful cART, while PDGF-BB may be indicative of persistent low-level antigenemia.

Like HIV infection, smoking, which is common among HIV-infected persons, is associated with chronic, systemic inflammation. However, the possible augmentative effects of HIV infection and smoking and other types of tobacco usage on indices of systemic inflammation and the impact of combination antiretroviral therapy (cART) thereon remain largely unexplored and represent the focus of the current study. Of the total number of HIV-infected persons recruited to the study (n=199), 100 were categorised as pre-cART and 99 as virally suppressed (HIV viral load<40 copies/mL). According to serum cotinine levels, 144 and 55 participants were categorised as nonusers and users of tobacco, respectively. In addition to cytokines (IL-6, IL-8, and TNF-α) and chemokines (IP-10, MIG, IL-8, MCP-1, and RANTES), other biomarkers of systemic inflammation included C-reactive protein (CRP), β2-microglobulin, and those of neutrophil activation [ICAM-1, L-selectin, matrix metalloproteinase-9 (MMP-9)], microbial translocation (soluble CD14, LPS-binding protein), and oxidative stress (cyclophilin A, surfactant D). These were measured using multiplex bead array, ELISA, and immunonephelometric procedures. Viral suppression was associated with significant decreases in the levels of most of the biomarkers tested (P<0.0037-0.0008), with the exceptions of CRP, cyclophilin A, and MMP-9. With respect to tobacco usage, irrespective of cART status, circulating levels of β2-microglobulin, cyclophilin A, and RANTES were significantly elevated (P<0.042-0.012) in users vs nonusers. Additional analysis of the groups of tobacco users and nonusers according to cART status revealed high levels of RANTES in pre-cART/tobacco users relative to the three other subgroups (P<0.004-0.0001), while more modest increases in cyclophilin A and MMP-9 (P<0.019-0.027) were observed in comparison with the cART/tobacco user subgroup. Notwithstanding the efficacy of cART in attenuating HIV-associated, chronic systemic inflammation, the current study has identified RANTES as being significantly and seemingly selectively increased in those with active HIV infection who use tobacco, a mechanism which may underpin augmentative proinflammatory activity.

Background Long-distance truck drivers are occupationally susceptible to poor health outcomes. Their patterns of healthcare utilisation and the suitability of healthcare services available to them are not well documented. We report on truck driver healthcare utilisation across South Africa and characterise the client population of the clinics serving them for future service development. Methods We analysed anonymised data routinely collected over a two-year period at nine Roadside Wellness Centres. Associations between services accessed and socio-demographic characteristics were assessed using univariable and multivariable logistic regression models. Results We recorded 16,688 visits by 13,252 individual truck drivers (average of 1.26 visits/person) who accessed 17,885 services for an average of 1.07 services/visit and 1.35 services/person. The mean age of truck drivers was 39 years. Sixty-seven percent reported being in stable relationships. The most accessed services were primary healthcare (PHC)(62%) followed by HIV (32%). Low proportions (≤6%) accessed STI,TB and malaria services. Most visits were characterised by only one service being accessed (93%, n = 15,523/16,688). Of the remaining 7% of visits, up to five services were accessed per visit and the combination of TB /HIV services in one visit remained extremely low (

South Africa is a country with a high incidence of tuberculosis (TB), complicated by coinfection with human immunodeficiency virus (HIV). The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is used in South Africa as the test for the initial diagnosis of TB, and other molecular platforms such as the m 2000 (Abbott Molecular, Des Plaines, IL, USA) are widely used for molecular monitoring of HIV load. The latter platform is now also equipped with the RealTi m e (RT) MTB and RealTi m e MTB RIF/INH assays for TB and first-line drug resistance screening but has not been evaluated in settings of HIV and TB coinfection. A prospective clinical validation study was conducted at a community health center in Johannesburg, South Africa, and consenting individuals with presumptive pulmonary TB were enrolled. The performance of the Abbott assays was compared with those of the Xpert MTB/RIF, liquid culture, drug susceptibility testing, and clinical case definitions. A statistical analysis was performed on 206 individuals (73% were HIV positive). The sensitivity and specificity of the RT MTB were 82.5% (confidence interval [CI], 67.2 to 92.7) and 93.1% (CI, 86.2 to 97.2) on raw sputum and 77.5% (CI, 61.5 to 89.2) and 95.1% (CI, 88.9 to 98.4) on concentrated sputum, respectively, compared with those from liquid culture. The RT MTB correctly identified 17/35 more smear-negative culture-positive specimens than the Xpert MTB/RIF. Both the RT MTB and the Xpert MTB/RIF displayed sensitivities >70% and specificities >90% in HIV-positive individuals. The available drug resistance results concurred with MTBDR plus and drug susceptibility profiles. The RT MTB assay has similar diagnostic performance to the Xpert MTB/RIF and is suited to testing presumptive TB patients coinfected with HIV. The existing laboratory information system connectivity, training, and technical support make this a viable polyvalent option to scale up TB alongside HIV laboratory testing services in South Africa.

BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens.METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted.FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain.INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators.FUNDING: Bill & Melinda Gates Foundation.

Introduction Most clinical trials for new antiretroviral (ARV) agents are conducted among narrowly defined adult populations. Only after safety and efficacy have been clearly demonstrated among adults living with HIV are trials including adolescents, children and infants conducted. This approach contributes to significant delays in the availability of optimal new ARV regimens for infants, children and adolescents. This commentary discusses issues related to the inclusion of adolescents aged 12 to 18 years in initial HIV clinical phase 3 trials of novel antiretrovirals (ARVs) or conducting parallel phase 3 clinical trials among adolescents. Discussion The absorption, metabolic and excretion or elimination pathways for drugs do not significantly differ between adolescents and adults. In fact, dosing recommendations for ARVs are the same for adults and adolescents who meet the age and weight criteria. Although conducting clinical trials among adolescents present special challenges (e.g. consenting minors and concerns about trial completion and contraception), these challenges can be addressed to obtain high‐quality trial results. Importantly, new agents and optimized combinations have more favourable dosing schedules and side‐effect profiles and are more effective ARV agents with higher HIV drug resistance thresholds, which would be extremely beneficial to improve outcomes among HIV‐positive adolescents. Conclusions Adolescents may not present with significantly different pharmacokinetic characteristics from those in adults. Including HIV‐positive adolescents in phase 3 ARV clinical trials, either with adults or in specific adolescent studies conducted in parallel, would allow adolescents to access promising, more effective treatment for HIV years earlier than with the current stepwise approach.

Background In South Africa, the trucking industry employs over 70,000 people and the prevalence of chronic pain in this occupational group was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so. Methods Southern African male, long-distance truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n = 614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated. Results Multivariate analysis showed that working ≥ 2 nights/week (OR = 2.68, 95% CI = 1.55–4.68) was associated with chronic pain and physical activity was protective (OR = 0.97, 95% CI 0.95–0.98). In an exploratory analysis, greater depressive symptoms (p = 0.004), daytime sleepiness (p = 0.01) and worse sleep quality (p = 0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p = 0.006), but not daytime sleepiness or depressive symptoms (p>0.05). Conclusions There is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.

Author(s): Lippman, Sheri A; El Ayadi, Alison M; Grignon, Jessica S; Puren, Adrian; Liegler, Teri; Venter, WD Francois; Ratlhagana, Mary J; Morris, Jessica L; Naidoo, Evasen; Agnew, Emily; Barnhart, Scott; Shade, Starley B | Abstract: IntroductionTo achieve epidemic control of HIV by 2030, countries aim to meet 90-90-90 targets to increase knowledge of HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression by 2020. We assessed the progress towards these targets from 2014 to 2016 in South Africa as expanded treatment policies were introduced using population-representative surveys.MethodsData were collected in January to March 2014 and August to November 2016 in Dr. Ruth Segomotsi Mompati District, North West Province. Each multi-stage cluster sample included 46 enumeration areas (EA), a target of 36 dwelling units (DU) per EA, and a single resident aged 18 to 49 per DU. Data collection included behavioural surveys, rapid HIV antibody testing and dried blood spot collection. We used weighted general linear regression to evaluate differences in the HIV care continuum over time.ResultsOverall, 1044 and 971 participants enrolled in 2014 and 2016 respectively with approximately 77% undergoing HIV testing. Despite increases in reported testing, known status among people living with HIV (PLHIV) remained similar at 68.7% (95% Confidence Interval (CI)n=n60.9-75.6) in 2014 and 72.8% (95% CIn=n63.6-80.4) in 2016. Men were consistently less likely than women to know their status. Among those with known status, PLHIV on ART increased significantly from 80.9% (95% CIn=n71.9-87.4) to 91.5% (95% CIn=n84.4-95.5). Viral suppression (l5000 copies/mL using DBS) among those on ART increased significantly from 55.0% (95% CIn=n39.6-70.4) in 2014 to 81.4% (95% CIn=n72.0-90.8) in 2016. Among all PLHIV an estimated 72.0% (95% CIn=n63.8-80.1) of women and 45.8% (95% CIn=n27.0-64.7) of men achieved viral suppression by 2016.ConclusionsOver a period during which fixed-dose combination was introduced, ART eligibility expanded, and efforts to streamline treatment were implemented, major improvements in the second and third 90-90-90 targets were achieved. Achieving the first 90 target will require targeted and improved testing models for men.

IntroductionHIV self-testing (HIVST) presents a convenient, private approach that removes barriers to providing HIV testing services. The Self-Testing Africa (STAR) Initiative aims to scale up HIVST among priority and undertested populations. HIVST has the potential to help maintain testing services during the social distancing restrictions implemented to prevent the spread of COVID-19. This project evaluates linkage to confirmatory testing and treatment for HIV-positive clients for the STAR South Africa site.Methods and analysisThis secondary data analysis protocol aims to evaluate different HIVST distribution models from a prospective study implemented during November 2017 and December 2020 by Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute. Routinely collected distribution and self-reported HIVST outcomes data will be deidentified and analysed. The main outcomes of interest are linkage to care and treatment among HIVST users who report a reactive HIVST result. Additionally, we plan to determine sociodemographic factors associated with linkage to care and treatment among HIVST users. Descriptive statistics will be used to describe the variables of interest, and modified Poisson regression with robust variance estimation will be performed to identify factors associated with linkage to care and treatment among HIVST users who report a reactive HIVST result. Risk ratios and 95% CIs for the risk ratios will be reported.Ethics and disseminationThe study protocol has been approved by the University of Witwatersrand Human Research Ethics Committee. The dissemination plan for the study findings will include presentations to local and international health authorities, international conferences and publications in open access journals.

The underpinning theme of the 2016 INTEREST Conference held in Yaoundé, Cameroon, 3–6 May 2016 was ending AIDS as a public health threat by 2030. Focused primarily on HIV treatment, pathogenesis and prevention research in resource-limited settings, the conference attracted 369 active delegates from 34 countries, of which 22 were in Africa. Presentations on treatment optimization, acquired drug resistance, care of children and adolescents, laboratory monitoring and diagnostics, implementation challenges, HIV prevention, key populations, vaccine and cure, hepatitis C, mHealth, financing the HIV response and emerging pathogens, were accompanied by oral, mini-oral and poster presentations. Spirited plenary debates on the UNAIDS 90-90-90 treatment cascade goal and on antiretroviral pre-exposure prophylaxis took place. Joep Lange career guidance sessions and grantspersonship sessions attracted early career researchers. At the closing ceremony, the Yaoundé Declaration called on African governments; UNAIDS; development, bilateral, and multilateral partners; and civil society to adopt urgent and sustained approaches to end HIV by 2030.

In Uganda and other sub-Saharan African countries women’s gender roles center on marriage and motherhood. According to these roles women’s duties include caring for other members of the household tending to household chores and caring for the sick. Women are expected to consult with their husbands and obey their husbands’ decisions in all matters. A man’s primary role is to be the head of the family. Men are expected to bring in income to pay for shelter food and school and they are expected to represent the family. Unlike women who are expected to be faithful or monogamous men are expected to have multiple partners (wives or girlfriends) thus signaling their masculinity. As other investigators have observed these gender roles interfere with HIV prevention efforts. Gender roles may also constrain women’s access to health services including those for the prevention of mother-to-child transmission of HIV (PMTCT). Globally all countries are working toward achieving the goal of having 90 percent of people diagnosed with HIV on sustained antiretroviral therapy (ART) by 2020. PMTCT programs in sub-Saharan Africa have had difficulty pursuing this goal owing to countries’ weak health systems and a variety of individual interpersonal and cultural factors. A number of studies have examined barriers to PMTCT participation. Common constraints are fear of HIV stigma fear of divorce or abandonment upon HIV disclosure side effects of ART lack of funds for transport to the clinic negative interactions with health workers and lack of male involvement. Most studies of barriers to PMTCT were conducted prior to the implementation of Option B+ which places HIV-positive pregnant or breastfeeding women on lifelong ART at diagnosis. By examining how gender interacts with individual interpersonal health system and community factors that cause people to discontinue PMTCT this study fills an important gap in knowledge about Option B+ programs. In partnership with the Child Health and Development Centre at Makerere University MEASURE Evaluation—funded by the United States Agency for International Development (USAID) and the United States President’s Emergency Fund for AIDS Relief (PEPFAR)—conducted qualitative research at eight health facilities (four urban and four rural) and their surrounding communities from 2015 to 2016. The purpose of this study was to describe gender-related factors at the individual interpersonal and programmatic or systemic levels that influence women’s participation in the elimination of mother-to-child transmission of HIV (EMTCT) program in Uganda. We used in-depth interviews and focus group discussions (FGDs) to obtain data from women participating in EMTCT (n=32) women who were lost to follow-up (LTFU) (n=16) health workers involved in providing EMTCT services (n=8) stakeholders in organizations supporting EMTCT services (n=8) and men in the community (8 focus group discussions (FGDs) n=73 participants).

Summary Background Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. Methods We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787. Findings Between April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification. Interpretation Protease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings. Funding European and Developing Countries Clinical Trials Partnership (EDCTP), UK Medical Research Council, Instituto de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, Merck, ViiV Healthcare, WHO.

Background: HIV-associated peripheral neuropathy (PN) is common in people living with HIV. Its management is mostly symptomatic utilising pharmacological approaches. Objectives: This study determined the effects of an exercise intervention on PN among Rwandan people living with HIV receiving antiretroviral therapy (ART). Methods: A 12-week single-blinded randomised controlled trial using the Brief Peripheral Neuropathy Screen (BPNS) as the assessment tool tested the effects of an exercise intervention on PN, followed by a 12-week non-intervention period. A total of 120 people with HIV- associated PN on ART were randomised to an exercise or no exercise group. Both groups continued receiving routine care. A bivariate analysis using Pearson’s chi-square test for significant differences in PN symptoms and signs, between groups, at baseline, after the 12 weeks intervention and 12 weeks post-intervention using generalised linear regression models to determine predictors of treatment outcomes was undertaken, utilising an intention-to-treat analysis (alpha p ≤ 0.05). Results: At 12 weeks, the intervention group compared to the control: neuropathic pain 70% versus 94% ( p < 0.005), PN symptoms severity – mild and/or none in 85% versus 60% ( p < 0.001) and radiation of PN symptoms reduced, 80% versus 37% ( p < 0.001). There were no differences in PN signs at 12 weeks intervention and at 12 weeks post-intervention. Having changed the antiretroviral (ARV) and having developed PN symptoms after the start on ARVs predicted treatment improvement, while demographic factors did not predict any treatment outcome. Conclusion: A physiotherapist-led exercise intervention improved PN symptoms, but with non-significant improvement in PN signs. Factors related to early diagnosis and treatment of PN were facilitators for the improvement of PN symptoms. Clinical implications: Physiotherapist-led exercises should be integrated into the routine management of people living with HIV on ART with PN symptoms.

ObjectivesLifestyle and working conditions of truck drivers predisposes them to risk-factors associated with communicable and non-communicable diseases, but little is known about the health status of African truck driver. This study aims to assess a cross-section of truckers in South Africa to describe their health information.SettingThe study took place across three truck-stop rest areas in the South African provinces of Free State and Gauteng.ParticipantsEligibility criteria included being males aged 18 years and older, full-time employment as a long-distance truck driver. A total of 614 male truck drivers participated; 384 (63%) were Zimbabwean and 325 (55%) completed high-school.Primary and secondary outcome measuresThe trucker survey explored demographics; working conditions; sexual, eating and sleeping behaviours; mental health status, medical history and cardiac risk-factors. Medical assessments included physical measurements, glucose and lipid measurements, ECG, carotid intima-media thickness (CIMT) and cardiac ultrasound.ResultsIn the previous month, 554 (91%) participants were sexually active; 522 (86%) had sex with a regular partner; 174 (27%) with a casual partner; 87 (14%) with a sex worker. Average time driving was 10 hours/day, 20 days/month, 302 (50%) never worked night shifts and 74 (12%) worked nights approximately four times per week. 112 (18%) experienced daytime sleepiness and 59 (10%) were ever hospitalised from an accident. Forty-seven (8%, 95% CI 5.3 to 9.5) were HIV-positive, with half taking antiretrovirals. Forty-eight (8%) truckers had some moderate depression, while 21 (4%) suffered from post-traumatic stress disorder. Reported tuberculosis, myocardial infarction, and diabetes were 15 drinks/week) (n=54, 9%), overweight/obesity (n=417, 69%), and hypertension (n=220, 36%,95% CI 32.1 to 39.7). ECG results showed 23 (4.9%) and 29 (5.3%) drivers had left ventricular hypertrophy using the Cornell criterion and product, respectively. CIMT measurements indicated nine (4.2%) drivers had a carotid atherosclerotic plaque.ConclusionThis first holistic assessment of health among southern African male truck drivers demonstrates substantial addressable cardiovascular risk factors, mental health issues and sexual risk behaviours.

No abstract available.

No abstract available.

There are currently approximately 16 million people taking NNRTI-based first-line treatment in low-income and middle-income countries. Most of these patients are using the combination of tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV). The integrase inhibitor dolutegravir (DTG) has shown an improved safety profile compared with EFV in randomized studies. DTG also has a high barrier to development of drug resistance. New co-formulated tablets with TDF/3TC/DTG are being introduced into LMICs, for a median price of $75 per person-year. The prodrug of TDF, tenofovir alafenamide (TAF) is cheaper to manufacture than TDF. A combined pill with TAF/3TC/DTG is also being launched in LMICs, at a similar low price. However, the clinical development programmes for DTG and TAF did not include extensive analysis of several key populations: pregnant women, people with HIV-tuberculosis (TB) coinfection taking rifampicin-based treatment, and treatment-naive or pretreated patients with NRTI drug resistance. An observational study in Botswana has shown an increased risk of neural tube defects when dolutegravir is used in early pregnancy. In LMICs, only 50% of patients have access to regular viral load testing, and genotypic resistance testing is rarely performed. There is currently no clinical data to support switching patients from TDF/3TC/EFV directly to TDF/3TC/DTG if their viral load is either detectable or unknown. New clinical trials and observational studies will be needed to better understand the consequences of this switch of treatment in LMICs. Clinical trials of new antiretrovirals in key populations should be conducted earlier in their development. This will ensure that new treatments can be introduced into LMICs soon after their launch in high-income countries.

Pre-exposure prophylaxis (PrEP) for HIV prevention has evolved significantly over the years where clinical trials have now demonstrated the efficacy of oral PrEP, and the field is scaling-up implementation. The WHO and UNAIDS have made PrEP implementation a priority for populations at highest risk, and several countries have developed guidelines and national plans accordingly, largely based on evidence generated by demonstration projects. PrEP presents the opportunity to change the face of HIV prevention by offering a new option for protection against HIV and disrupting current HIV prevention systems. Nevertheless, as with all new technologies, both practical and social requirements for implementation must be taken into account if there is to be sustained and widespread adoption, which will also apply to forthcoming prevention technologies. Defining and building success for PrEP within the scope of scale-up requires careful consideration. This review summarises where the PrEP field is today, lessons learned from the past, the philosophy and practicalities of how successful programming may be defined, and provides perspectives of costs and affordability. We argue that a successful PrEP programme is about effective intervention integration and ultimately keeping people HIV negative.

Background. The provision of starter packs for human immunodeficiency virus postexposure prophylaxis (PEP) is practiced in many settings to facilitate rapid initiation by nonexperts and encourage adherence. However, the impact of starter packs on PEP completion rates has not been systematically assessed. We systematically reviewed the evidence on outcomes associated with starter packs for PEP compared to full prescriptions. Methods. Four databases and 2 conference abstract sites were searched up to December 2013; this search was updated in 1 database in June 2014. PEP completion rates, stratified by prescribing practice, were pooled using random-effects meta-analysis. Results. Fifty-four studies provided data on 11 714 PEP initiations. Thirty-seven studies, including 3 randomized controlled trials (RCTs) and 34 observational cohorts, provided information on starter packs (although none of the RCTs specifically assessed starter packs), and 17 studies, including 2 RCTs and 15 observational cohorts, provided information on full prescriptions. Overall, outcomes were better when participants were offered a full 28-day course of PEP at initial presentation to healthcare, with fewer refusals (11.4% [95% confidence interval {CI}, 5.3%– 17.5%] vs 22% [95% CI, 16.7%–28.1%]) and highercompletion rates (70% [95% CI, 56.7%–77.3%] vs 53.2% [95% CI, 44.4%–62.2%]). More than a quarter (28% [95% CI, 21.4%–34.5%]) of individuals provided with a PEP starter pack failed to return for their subsequent appointment and therefore defaulted prior to receiving a full course of PEP. The quality of the evidence overall was rated as very low. Conclusions. The findings of this review suggest that starter packs do not improve adherence to PEP and may result in lower adherence and completion rates.

In many low-to-middle income countries (LMICs) access to essential medications is limited and the number of clinical trials conducted is small because of regulatory issues and a lack of infrastructure. In this article,Nature Reviews Nephrologyasks three experts their opinions on how to improve drug access and increase the numbers of clinical trials conducted in LMICs. Access to essential medications is limited in many low-to-middle income countries (LMICs) and those that are available may be prohibitively expensive to the general population. Clinical trials have been suggested as an approach to improve drug access in LMICs but the number of trials conducted in these countries is small because of regulatory issues and a lack of infrastructure. In this article, Nature Reviews Nephrology asks three experts their opinions on how to improve drug access and increase the numbers of clinical trials conducted in LMICs.

The gap in HIV testing remains significant and new modalities such as HIV self-testing (HIVST) have been recommended to reach key and under-tested populations. In December 2016, the World Health Organization (WHO) released the Guidelines on HIV Self-Testing and Partner Notification: A Supplement to the Consolidated Guidelines on HIV Testing Services (HTS) and urged member countries to develop HIVST policy and regulatory frameworks. In South Africa, HIVST was included as a supplementary strategy in the National HIV Testing Services Policy in 2016, and recently, guidelines for HIVST were included in the South African National Strategic Plan for HIV, sexually transmitted infections and tuberculosis 2017–2022. This document serves as an additional guidance for the National HIV Testing Services Policy 2016, with specific focus on HIVST. It is intended for policy advocates, clinical and non-clinical HTS providers, health facility managers and healthcare providers in private and public health facilities, non-governmental, community-based and faith-based organisations involved in HTS and outreach, device manufacturers, workplace programmes and institutes of higher education.

Background For the prevention and control of chronic diseases, two strategies are frequently highlighted: that public health should be evidence based, and that it should develop a multisectoral approach. At the end of a natural experimental study of the health impacts of new transport infrastructure, we took the opportunity of a knowledge exchange forum to explore how stakeholders assessed, negotiated and intended to apply multisectoral evidence in policy and practice at the intersection of transport and health. We aimed to better understand the challenges they faced in knowledge exchange, as well as their everyday experiences with working in multisectoral remits. Methods In 2015, we conducted participant observation during an interactive event with 41 stakeholders from national and local government, the third sector and academia in Cambridge, UK. Formal and informal interactions between stakeholders were recorded in observational field notes. We also conducted 18 semistructured interviews reflecting on the event and on knowledge exchange in general. Results We found that stakeholders negotiated a variety of challenges. First, stakeholders had to negotiate relatively new formal and informal multisectoral remits; and how to reconcile the differing expectations of transport specialists, who tended to emphasise the importance of precedence in guiding action, and health specialists’ concern for the rigour and synthesis of research evidence. Second, research in this field involved complex study designs, and often produced evidence with uncertain transferability to other settings. Third, health outcomes of transport schemes had political traction and were used strategically but not easily translated into cost-benefit ratios. Finally, knowledge exchange meant multiple directions of influence. Stakeholders were concerned that researchers did not always have skills to translate their findings into understandable evidence, and some stakeholders would welcome opportunities to influence research agendas. Conclusions This case study of stakeholders’ experiences indicates that multisectoral research, practice and policymaking requires the ability and capacity to locate, understand and communicate complex evidence from a variety of disciplines, and integrate different types of evidence into clear business cases beyond sectoral boundaries. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-3940-x) contains supplementary material, which is available to authorized users.

Background Observed adverse effects of antiretroviral therapy (ART) on the lipid profile could be of significance in pregnancy. This systematic review aims to summarize studies that investigated the association between HIV, ART and serum lipids during pregnancy and adverse pregnancy outcomes. Methods A systematic search was conducted in five electronic databases to obtain articles that measured serum lipid concentrations or the incidence of dyslipidaemia in HIV-infected pregnant women. Included articles were assessed for quality according to the Cochrane Risk of Bias Tool. The extracted data was analysed through descriptive analysis. Results Of the 1264 articles screened, 17 articles were included in this review; eleven reported the incidence of dyslipidaemia, and twelve on maternal serum lipid concentrations under the influence of HIV-infection and ART. No articles reported pregnancy outcomes in relation to serum lipids. Articles were of acceptable quality, but heterogenic in methods and study design. Lipid levels in HIV-infected women increased 1.5–3 fold over the trimesters of pregnancy, and remained within the physiological reference range. The percentage of women with dyslipidaemia was variable between the studies [0–88.9%] and highest in the groups on first generation protease inhibitors and for women on ART at conception. Conclusion This systematic review observed physiologic concentrations of serum lipids for HIV-infected women receiving ART during pregnancy. Serum lipids were increased in users of first generation protease inhibitors and for those on treatment at conception. There was no information available about pregnancy outcomes. Future studies are needed which include HIV-uninfected control groups, control for potential confounders, and overcome limitations associated with included studies. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2581-8) contains supplementary material, which is available to authorized users.

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2014 and the update on when to initiate antiretroviral therapy in 2015. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART) in southern Africa has continued. New antiretroviral drugs have become available with improved efficacy, safety and robustness. The guidelines are intended for countries in the southern African region, which vary between lower and middle income.

BackgroundThe largest proportion of people living with HIV resides in sub-Saharan Africa (SSA). Evidence from developed countries suggests that HIV infection increases the relative risk of cardiovascular disease (CVD) by up to 50%. Differences in lifestyle, gender distribution, routes of HIV transmission and HIV subtype preclude generalisation of data from Western countries to the SSA situation. The Ndlovu Cohort Study aims to provide insight into the burden of cardiovascular risk factors and disease, the mechanisms driving CVD risk and the contribution of HIV infection and its treatment to the development of CVD in a rural area of SSA.DesignThe Ndlovu Cohort Study is a prospective study in the Moutse area, Limpopo Province, South Africa.MethodsA total of 1000 HIV-positive and 1000 HIV-negative participants aged 18 years and older with a male to female ratio of 1:1 will be recruited. Measurements of CVD risk factors and HIV-related characteristics will be performed at baseline, and participants will be followed-up over time at 6–month intervals. The burden of CVD will be assessed with repeated carotid intima–media thickness and pulse wave velocity measurements, as well as by recording clinical cardiovascular events that occur during the follow-up period.ConclusionThis project will contribute to the understanding of the epidemiology and pathogenesis of CVD in the context of HIV infection in a rural area of SSA. The ultimate goal is to improve cardiovascular risk prediction and to indicate preventive approaches in the HIV-infected population and, potentially, for non-infected high-risk populations in a low-resource setting.

We argue that there are no compelling ethical grounds for not allowing the sale of HIV self-tests to the public, so long as reasonably robust protections are in place to protect against coerced testing, and so long as the ease of use of the test is validated carefully in each country in which it is used, with attention to information about linkage to treatment, social and psychological support. The tests are not likely to be harmful in a way that justifies restricting people's access to them, and have plausible benefits. Whether and how self-testing should be used in public health programs will depend on complex policy questions concerning priorities, efficacy and cost.