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

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

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

R0 and the elimination of HIV in Africa: Will 90-90-90 be sufficient?

The Joint United Nations Programme on HIV and AIDS (UNAIDS) has set a new 90-90-90 global target for the coverage of anti-retroviral therapy (ART) to be reached by 2020. This would mean that 90% of all people infected with HIV know their status, 90% of them are on ART and 90% of them will have full viral load suppression. Here we first estimate the case reproduction number, R0, for countries in sub-Saharan Africa and for India using data on the rate at which the prevalence of HIV increased at the start of the epidemic and the life expectancy of people living with HIV who are not on ART. R0 determines the magnitude of the control problem, that is to say, the extent to which transmission must be reduced to eliminate HIV. We show that in sub-Saharan Africa the median value of R0 is 4.6 and in all but five countries R0 is less than 6.3. If the 90-90-90 target is reached, 73% of all those living with HIV will have full viral load suppression. If this is maintained it should guarantee elimination in 70% of all countries in sub-Saharan Africa and will reduce R0 to less than 2 in the remaining 12 countries, making elimination easy to achieve by increasing the availability of other high impact methods of prevention.Comment: We have updated the previous version for two reasons. First, we have given a better approximation for the estimation of R0 from epidemic doubling times. Second, we have added comments on the new UNAIDS '90-90-90' strategy which puts the results into a broader contex

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

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

Biological and Statistical Heterogeneity in Malaria Transmission

In a study of the heterogeneity in malaria infection rates among children Smith et al.1 fitted several mathematical models to data from community studies in Africa. They concluded that 20% of children receive 80% of infections, that infections last about six months on average, that children who clear infections are not immune to new infections, and that the sensitivity and specificity of microscopy for the detection of malaria parasites are 95.8% and 88.4%, respectively. These findings would have important implications for disease control, but we show here that the statistical analysis is unsound and that the data do not support their conclusions.Comment: Updated the text to make the connection between the AIC and the likelihood ratio explici

HIV/AIDS in South Africa: the beginning of the end?

In several countries in southern Africa, including South Africa, the prevalence of HIV remains stubbornly high in spite of considerable efforts to reduce transmission and to provide anti-retroviral therapy (ART). It is important to know the extent to which the high prevalence of HIV reflects the increasing number of people on ART in which case the prevalence of those not on ART may be falling. Unfortunately, direct measures of the proportion of HIV-positive people who are on ART are lacking in most countries and we need to use dynamical models to estimate the impact of ART on the prevalence of HIV. In this paper we show that the current level of ART provision in South Africa has probably reduced the prevalence of HIV among those not on ART by 1.9 million, averted 259 thousand new infections and 428 thousand deaths.Comment: Two typographical errors have been corrected. Two lines from the bottom of page 1 '2010' has been replaced by '2012'. In the fourth line of the discussion 'over the next twenty years' has been replaced by 'up to 2020

Anti-retroviral therapy for HIV: who should we test and who should we treat?

In most countries CD4+ cell counts are still used for deciding when to start HIV-positive people on anti-retroviral therapy. However, various CD4+ thresholds, 200, 350 or 500/\muL, are chosen arbitrarily and for historical reasons. Here we consider the optimal CD4+ threshold at which asymptomatic HIV-positive people living in Botswana, South Africa and Zimbabwe should start treatment depending on their prognosis given their CD4+ cell counts or viral load. We also examine the optimal interval at which people should be retested if they are HIV-negative. This analysis shows that while the use of CD4+ cell counts or viral load tests could have been useful in deciding how to triage patients for treatment at the start of the epidemic this is no longer the case except possibly for those aged about 15 to 25 years. In order not to do harm to individual patients everyone should be started on ART as soon as they are found to be HIV-positive.Comment: The lines in Figure 2 were labelled from left to right but should have been labelled right to left. This has been corrected in the caption. Equation 4 is an approximation and a footnote to this effect has been added. Ia(t) has now been defined immediately after Equation

Extragalactic Transients in the Era of Wide-Field Radio Surveys. I. Detection Rates and Light Curve Characteristics

The impending era of wide-field radio surveys has the potential to revolutionize our understanding of astrophysical transients. Here we evaluate the prospects of a wide range of planned and hypothetical radio surveys using the properties and volumetric rates of known and hypothetical classes of extragalactic synchrotron radio transients (e.g., on- and off-axis gamma-ray bursts [GRB], supernovae, tidal disruption events [TDE], compact object mergers). Utilizing these sources and physically motivated considerations we assess the allowed phase-space of radio luminosity and peak timescale for extragalactic transients. We also include for the first time effects such as redshift evolution of the rates, K-corrections, and non-Euclidean luminosity distance, which affect the detection rates of the most sensitive surveys. The number of detected events is calculated by means of a Monte Carlo method, using the various survey properties (depth, cadence, area) and realistic detection criteria that include a cut on the minimum variability of the transients during the survey and an assessment of host galaxy contamination. Near-term GHz frequency surveys (ASKAP/VAST, Very Large Array Sky Survey) will detect few events: <~30-50 on- and off-axis long GRBs and off-axis tidal disruption events, and ~10-20 neutron star binary mergers if ~1% of the mergers result in a stable millisecond magnetar. Low-frequency surveys (e.g., LOFAR) are unlikely to detect any transients, while a hypothetical large-scale mm survey may detect ~40 on-axis long GRBs. On the other hand, SKA surveys at ~0.1-1 GHz have the potential to uncover thousands of transients, mainly on- and off-axis long GRBs, on-axis short GRBs, off-axis TDEs, and neutron star binary mergers with magnetar remnants.Comment: 25 pages, 5 figures, 1 appendix, submitted to Ap