Preferred antiretroviral drugs for the next decade of scale up

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings

Discontinuation of cART postpartum in a high prevalence district of South Africa in 2014

BACKGROUND: Combination antiretroviral therapy (cART) is the current strategy to prevent mother-to-child transmission (PMTCT) of HIV. Women initiated on cART should continue taking treatment life-long or stop after cessation of breastfeeding depending on their CD4 cell count or on their World Health Organization (WHO) staging. Keeping people living with HIV on treatment is essential for the success of any antiretroviral therapy (ART) programme. There has been a rapid scale-up of cART in the PMTCT programme in South Africa. cART is supposed to be taken life-long or until cessation of breastfeeding, but premature or unmanaged discontinuation of cART postpartum is not unusual in South Africa and is confirmed by studies from around the world. Discontinuation of cART can lead to mother-to-child transmission (MTCT), drug resistance and poor maternal outcomes. The extent of this problem in the South African context however is unclear. This study aims to determine the prevalence of and identify risk factors associated with discontinuation of cART postpartum amongst women who were initiated on antiretroviral treatment during their index pregnancy. METHODS: An observational analytic cross-sectional study design will be conducted in six health facilities in a high prevalence district in KwaZulu-Natal, South Africa over a period of 3 months in 2014. An interviewer-administered questionnaire will be used to collect data from mothers who initiated cART during their index pregnancy. The prevalence of discontinuation of cART postpartum will be measured, and the association between those who discontinue cART postpartum and independent variables will be estimated using multivariable-adjusted prevalence odds ratios for discontinuation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13012-014-0139-3) contains supplementary material, which is available to authorized users

Can the UNAIDS 90-90-90 target be achieved? A systematic analysis of national HIV treatment cascades

Background In 2014, the Joint United Nations Programme on HIV and AIDS (UNAIDS) and partners set the ‘90-90-90 targets’; aiming to diagnose 90% of all HIV positive people, provide antiretroviral therapy (ART) for 90% of those diagnosed and achieve viral suppression for 90% of those treated, by 2020. This results in 81% of all HIV positive people on treatment and 73% of all HIV positive people achieving viral suppression. We aimed to analyse how effective national HIV treatment programmes are at meeting these targets, using HIV care continuums or cascades. Methods We searched for HIV treatment cascades for 196 countries in published papers, conference presentations, UNAIDS databases and national reports. Cascades were constructed using reliable, generalisable, recent data from national, cross-sectional and longitudinal study cohorts. Data were collected for four stages; total HIV positive people, diagnosed, on treatment and virally suppressed. The cascades were categorised as complete (four stages) or partial (3 stages), and analysed for ‘break points’ defined as a drop >10% in coverage between consecutive 90-90-90 targets. Results 69 country cascades were analysed (32 complete, 37 partial). Diagnosis (target one—90%) ranged from 87% (the Netherlands) to 11% (Yemen). Treatment coverage (target two—81% on ART) ranged from 71% (Switzerland) to 3% (Afghanistan). Viral suppression (target three—73% virally suppressed) was between 68% (Switzerland) and 7% (China). Conclusions No country analysed met the 90-90-90 targets. Diagnosis was the greatest break point globally, but the most frequent key break point for individual countries was providing ART to those diagnosed. Large disparities were identified between countries. Without commitment to standardised reporting methodologies, international comparisons are complex

Interruptions of antiretroviral therapy in children and adolescents with HIV infection in clinical practice: a retrospective cohort study in the USA.

INTRODUCTION: Changes in combination antiretroviral therapy (cART) throughout childhood challenge the continuity of paediatric HIV treatment. This study aimed to evaluate the prevalence of treatment interruption (TI), including lamivudine (3TC) monotherapy, and the relationship of TI to virologic and immunologic parameters in HIV-infected paediatric patients. METHODS: Nested within a prospective observational study of a city-wide cohort of HIV-infected persons in the District of Columbia, this sub-study collected retrospective data on antiretroviral therapy, enrolment (endpoint) and historic (lifelong) CD4 counts and HIV RNA viral load (VL) of the paediatric cohort. TI was defined as interruption of cART ≥4 consecutive weeks. Data on TI, including 3TC monotherapy TI (MTI), were collected. Descriptive statistics and univariate testing were used to compare children with TI and MTI to children on continuous treatment (CT). RESULTS: Thirty-eight (28%) out of 136 enrolled children (median age=12.9 years) experienced TI, with 14 (37%) of those placed on 3TC MTI. Significantly lower endpoint median CD4 counts (598 cells/mm(3) vs. 815 cells/mm(3); p=0.003) and CD4% (27.5% vs. 33%; p=0.006) were observed in the TI cohort as compared to the CT cohort. The median endpoint VL in the overall TI cohort was ~4 times higher than among the CT cohort (1427 copies/mL vs. 5581 copies/mL; p CONCLUSIONS: In our study, we observed high frequency of the TI in HIV in paediatric HIV clinical practice. All TIs, including 3TC MTI, were associated with significantly lower endpoint median CD4 counts and higher median VLs, as compared to CT in paediatric patients. The high frequency of TI and associated poor outcomes suggest a need for a better strategy in managing the course of the paediatric and adolescent cART

Unstructured treatment interruption: an important risk factor for arterial stiffness in adult Malawian patients with antiretroviral treatment

OBJECTIVE: The aim of the study was to evaluate the impact of unstructured antiretroviral treatment (ART) interruption on arterial stiffness in adult Malawians who are on ART for at least 35 years. DESIGN: The number of treatment interruption events for at least 60 days during ART treatment was quantified in patients for at least 35 years using retrospective routinely collected clinic data. Treatment interruption data were linked to patient carotid-femoral pulse wave velocity (PWV); PWV more than 10 m/s was set as the threshold for clinically significant cardiovascular disease risk. METHODS: PWV was measured in patients (on ART >= 18 months), during routine ART clinic visits in Blantyre, Malawi, between November 2014 and July 2015. Multivariable linear regression was used to estimate the change in PWV m/s associated with treatment interruption. Multivariable logistic regression was used to estimate risk of PWV more than 10 m/s. All models were controlled for demographic and cardiometabolic risk factors. RESULTS: In 220 patients (median age 45 years, range 37–80 years), 86 (37.4%) patients had at least one treatment interruption event. Median length of treatment interruption events was 75 days (range 31 days to 8 years). Overall, 31 (14%) patients had a PWV more than 10 m/s. In multivariable analysis, we found a 0.2 increase in PWV m/s per treatment interruption event (0.2, 95% confidence interval 0.1–0.4) and a two-fold increased risk of PWV more than 10 m/s per treatment interruption event (adjusted odds ratio 2.2, 95% confidence interval 1.2–4.0). CONCLUSIONS: Treatment interruption in patients with ART for at least 35 years is a common and important risk factor for arterial stiffness. Therefore, the link between treatment interruption and cardiovascular disease in this setting in which traditional risks factors are less prevalent needs to be explored further

Flexible linear mixed models with improper priors for longitudinal and survival data

We propose a Bayesian approach using improper priors for hierarchical linear mixed models with flexible random effects and residual error distributions. The error distribution is modelled using scale mixtures of normals, which can capture tails heavier than those of the normal distribution. This generalisation is useful to produce models that are robust to the presence of outliers. The case of asymmetric residual errors is also studied. We present general results for the propriety of the posterior that also cover cases with censored observations, allowing for the use of these models in the contexts of popular longitudinal and survival analyses. We consider the use of copulas with flexible marginals for modelling the dependence between the random effects, but our results cover the use of any random effects distribution. Thus, our paper provides a formal justification for Bayesian inference in a very wide class of models (covering virtually all of the literature) under attractive prior structures that limit the amount of required user elicitation

The case for Option B and Optional B+: Ensuring that South Africa’s commitment to eliminating mother-to-child transmission of HIV becomes a reality

In a previous issue of the Southern African Journal of HIV Medicine, Pillay and Black summarised the trade-offs of the safety of efavirenz use in pregnancy (Pillay P, Black V. Safety, strength and simplicity of efavirenz in pregnancy. Southern African Journal of HIV Medicine 2012;13(1):28-33.). Highlighting the benefits of the World Health Organization’s proposed options for the prevention of mother-to-child transmission (PMTCT) of HIV, the authors argued that the South African government should adopt Option B as national PMTCT policy and pilot projects implementing Option B+ as a means of assessing the individual- and population-level effect of the intervention. We echo this call and further propose that the option to remain on lifelong antiretroviral therapy, effectively adopting PMTCT Option B+, be offered to pregnant women following the cessation of breastfeeding, for their own health, following the provision of counselling on associated benefits and risks. Here we highlight the benefits of Options B and B+