HIV and TB in Eastern and Southern Africa: Evidence for behaviour change and the impact of ART

The United Nations Joint Programme on HIV/AIDS (UNAIDS) has set a target to ensure that 15 million HIV-positive people in the world would be receiving combination anti-retroviral treatment (ART) by 2015. This target is likely to be reached and new targets for 2020 and 2030 are needed. Eastern and Southern Africa (ESA) account for approximately half of all people living with HIV in the world and it will be especially important to set reachable and affordable targets for this region. In order to make future projections of HIV and TB prevalence, incidence and mortality assuming different levels of ART scale-up and coverage, it is first necessary to assess the current state of the epidemic. Here we review national data on the prevalence of HIV, the coverage of ART and the notification rates of TB to provide a firm basis for making future projections. We use the data to assess the extent to which behaviour change and ART have reduced the number of people living with HIV who remain infectious

Determinants of sexual transmission of HV: implications for control

The extent to which ART (anti-retroviral therapy) reduces HIV transmission has received attention in recent years. Using data on the relationship between transmission and viral load we show that transmission saturates at high viral loads. We fit a power-law model and an exponential converging to an asymptote. Using data on the viral load in HIV-positive people we show that ART is likely to reduce transmission by 91.6% (81.7%-96.2%) under the first and 99.5% (98.5%-99.8%) under the second model. The role of the acute phase in HIV transmission is still debated. High levels of transmission during the acute phase have been used to argue that failure to identify people in the acute phase of HIV may compromise the impact of treatment on preventing new infections and that having concurrent sexual partners during the acute phase is an important driver of the epidemic. We show that the acute phase probably accounts for less than 1% of overall transmission. We also show that even if a significant proportion of infections are transmitted during the acute phase, this will not compromise the impact of treatment on population levels of transmission given the constraint implied by the doubling time of the epidemic. This analysis leads to other relevant conclusions. First, it is likely that discordant-couple studies significantly underestimate the risk of infection. Second, attention should be paid to the variability in set point viral load which determines both the infectiousness of HIV-positive people and the variability in the susceptibility of HIV-negative people. Third, if ART drugs are in short supply those with the highest viral load should be given priority, others things including age, gender and opportunistic infections being equal, but to reduce transmission ART should be offered to all those with a viral load above about 10k/mm.3Comment: 14 page

Optimal pooling strategies for laboratory testing

We consider the optimal strategy for laboratory testing of biological samples when we wish to know the results for each sample rather than the average prevalence of positive samples. If the proportion of positive samples is low considerable resources may be devoted to testing samples most of which are negative. An attractive strategy is to pool samples. If the pooled samples test positive one must then test the individual samples, otherwise they can all be assumed to be negative. The pool should be big enough to reduce the number of tests but not so big that the pooled samples are almost all positive. We show that if the prevalence of positive samples is greater than 30% it is never worth pooling. From 30% down to 1% pools of size 4 are close to optimal. Below 1% substantial gains can be made by pooling, especially if the samples are pooled twice. However, with large pools the sensitivity of the test will fall correspondingly and this must be taken into consideration. We derive simple expressions for the optimal pool size and for the corresponding proportion of samples tested.Comment: Three page

HIV, TB and ART: the CD4 enigma

The concentration of CD4 T-lymphocytes (CD4 count), in a person's plasma is widely used to decide when to start HIV-positive people on anti-retroviral therapy (ART) and to predict the impact of ART on the future course of HIV and tuberculosis (TB). However, CD4 cell-counts vary widely within and among populations and depend on many factors besides HIV-infection. The way in which CD4 counts decline over the course of HIV infection is neither well understood nor widely agreed. We review what is known about CD4 counts in relation to HIV and TB and discuss areas in which more research is needed to build a consensus on how to interpret and use CD4 counts in clinical practice and to develop a better understanding of the dynamics and control of HIV and HIV-related TB.Comment: 6 pages. Updated details of the meeting at which this material was first presented in the footnote on page

The first nine years of \u27accounting history\u27 : 1996 to 2004

This paper adds to the prior literature examining publishing patterns in the accounting history discipline by undertaking a content analysis of publications in the first nine years of the new series of the journal Accounting History. The paper commences by providing an historical background to the introduction of the new series of the journal and the journal\u27s editorial team. This is followed by an authorship analysis of the journal\u27s research publications. This analysis examines patterns of authorship (single and multi-authored papers), the journal\u27s most published authors, institutional and geographical affiliations of authors (including international collaboration and changes over the nine year period) and author gender.<br /

Affordability, cost and cost-effectiveness of universal anti-retroviral therapy for HIV

If people at risk of HIV infection are tested annually and started on treatment as soon as they are found to be HIV-positive it should be possible to reduce the case reproduction number for HIV to less than one, eliminate transmission and end the epidemic. If this is to be done it is essential to know if it would be affordable, and cost effective. Here we show that in all but eleven countries of the world it is affordable by those countries, that in these eleven countries it is affordable for the international community, and in all countries it is highly cost-effective.Comment: Several typographical errors have been corrected. Main change is the addition of data on the cost of military spending in each country and a comparison with the cost of universal AR

Homotopy RG Flow and the Non-Linear σ\sigma-model

The purpose of this note is two give a mathematical treatment to the low energy effective theory of the two-dimensional sigma model. Perhaps surprisingly, our low energy effective theory encodes much of the topology and geometry of the target manifold. In particular, we relate the $\beta$-function of our theory to the Ricci curvature of the target, recovering the physical result of Friedan.Comment: Fixed referenc

Elimination of HIV in South Africa through expanded access to antiretroviral therapy: Cautions, caveats and the importance of parsimony

In a recent article Hontelez and colleagues investigate the prospects for elimination of HIV in South Africa through expanded access to antiretroviral therapy (ART) using STDSIM, a micro-simulation model. One of the first published models to suggest that expanded access to ART could lead to the elimination of HIV, referred to by the authors as the Granich Model, was developed and implemented by the present author. The notion that expanded access to ART could lead to the end of the AIDS epidemic gave rise to considerable interest and debate and remains contentious. In considering this notion Hontelez et al. start by stripping down STDSIM to a simple model that is equivalent to the model developed by the present author3 but is a stochastic event driven model. Hontelez and colleagues then reintroduce levels of complexity to explore ways in which the model structure affects the results. In contrast to our earlier conclusions Hontelez and colleagues conclude that universal voluntary counselling and testing with immediate ART at 90% coverage should result in the elimination of HIV but would take three times longer than predicted by the model developed by the present author. Hontelez et al. suggest that the current scale-up of ART at CD4 cell counts less than 350 cells/microL will lead to elimination of HIV in 30 years. I disagree with both claims and believe that their more complex models rely on unwarranted and unsubstantiated assumptions.Comment: Two pages. One figure embedded in tex

Ending AIDS in South Africa: How long will it take? How much will it cost?

South Africa has more people infected with HIV but, by providing access to anti-retroviral therapy (ART), has kept more people alive than any other country. The effectiveness, availability and affordability of potent anti-retroviral therapy (ART) make it possible to contemplate ending the epidemic of HIV/AIDS. We consider what would have happened without ART, the impact of the current roll-out of ART, what might be possible if early treatment becomes available to all, and what could have happened if ART had been provided much earlier in the epidemic. In 2013 the provision of ART has reduced the prevalence of HIV from an estimated 15% to 9% among adults not on ART, the annual incidence from 2% to 0.9%, and the AIDS related deaths from 0.9% to 0.3% p.a. saving 1.5 million lives and USD727M. Regular testing and universal access to ART could reduce the prevalence among adults not on ART in 2023 to 0.06%, annual incidence to 0.05%, and eliminate AIDS deaths. Cumulative costs between 2013 ands 2023 would increase by USD692M only 4% of the total cost of USD17Bn. If a universal testing and early treatment had started in 1998 the prevalence of HIV among adults not on ART in 2013 would have fallen to 0.03%, annual incidence to 0.03%, and saved 2.5 million lives. The cost up to 2013 would have increased by USD18Bn but this would have been cost effective at US$7,200 per life saved. Future surveys of HIV among women attending ante-natal clinics should include testing women for the presence of anti-retroviral drugs, measuring their viral loads, and using appropriate assays for estimating HIV incidence. These data would make it possible to develop better and more reliable estimates of the current state of the epidemic, the success of the current ART programme, levels of viral load suppression for those on ART and the incidence of infection

Could ART increase the population level incidence of TB?

HIV increases the likelihood that a person will develop TB. Starting them on anti-retroviral therapy (ART) reduces their risk of TB but not to the level in HIV negative people. Since HIV-positive people who are on ART can expect to live a normal life for several decades this raises the possibility that their elevated risk of infection, lasting for a long time, could lead to an increase in the population level incidence of TB. Here we investigate the conditions under which this could happen and show that provided HIV-positive people start ART when their CD4+ cell count is greater than 350/microL and that there is high coverage, ART will not lead to a long-term increase in HIV. Only if people start ART very late and there is low coverage of ART might starting people on ART increase the population level incidence of TB.Comment: 3 page