Hence, >50% of MSM 29 years or older at HIV diagnosis would be recommended to commence ART based on a 500 CD4+ T cells per cubic millimeters guideline. On these figures, programs that aim to commence ART at least at this 500 CD4+ T cell per cubic millimeters level will struggle to enroll even 50% of MSM at diagnosis with CD4 counts more than this value, especially in the older age groups.
CD4+ T-cell counts at HIV diagnosis for women also significantly decrease with age (P < 0.0001; Fig. 1B). Women newly diagnosed were more likely to present with a lower CD4+ T-cell count, and median CD4+ T-cell counts at HIV diagnosis for 11 of the 13 age groups were lower for women than for MSM (P = 0.01, signed rank test).
Although the likelihood of early diagnosis has increased over the course of the epidemic for MSM, it has stabilized at only 15% of MSM diagnosed at PHI (Fig. 1C), with older MSM significantly less likely to be diagnosed in this stage (P = 0.002). This improvement in early diagnoses is also reflected by the average age of MSM diagnosed during PHI roughly overlapping the average age of diagnoses in chronic stages of HIV infection (CHI), whereas there was a 4-year age difference between PHI and CHI diagnoses in 1995 (Fig. 2A). In contrast, the percentage of women diagnosed in PHI has remained at 5% over the last 20 years and has not changed with time (P = 0.9).
CD4+ T-cell counts at PHI differed significantly with age (P = 0.003 MSM and P = 0.02 women) being lower for MSM, 55 years and older, and for women, 60 years and older than their younger counterparts (Table 1). Significant differences between CD4 counts at PHI compared with all diagnoses occurred for age groups from 25 to 59 years for MSM and for ages 20–39 years plus 60–64 years for women (Table 1).
MSM aged 50 years and older at diagnosis were significantly less likely to have been tested at all, even over the last decade: a median of 32% of MSM aged 50 and older had previously been tested for HIV, compared with 44% and 45% of the 2 youngest groups (P < 0.0001; Fig. 1D). Having previously been tested did increase the likelihood of presenting with a higher CD4 count at diagnosis in 2010 for MSM diagnosed in CHI (mean 519 CD4+ T cells per cubic millimeters compared to 362 CD4+ T cells per cubic millimeters for those not previously tested). Women were much less likely to have been previously tested. Over the last decade, the youngest female group exhibited the highest testing percentages of 16% (compared with 44% in this same age group for MSM), but this was not significantly different to levels in the other age groups (P = 0.1).
Spare Capacity for ART
Uptake of ART among MSM decreased in Australia between 1997 and 2007,19 with younger diagnosed men being significantly more likely to delay commencement of therapy. Although 80% of MSM who were 50 years and older with diagnosed HIV infection in 2007 surveyed in the Gay Community Periodic Surveys were enrolled for ART, this figure was only 25% for MSM younger than 30 years (Fig. 2B). This delay in the commencement of ART for younger MSM is consistent with their diagnoses at higher CD4+ T-cell counts (Table 1) (Fig. 1) and postponement of ART until CD4-guided commencement times are reached. Approximately 50% of the 30- to 39-year age groups were diagnosed with <500 CD4+ T cells per cubic millimeters (Fig. 1), and approximately this same percentage of 30- to 39-year olds were receiving ART (Fig. 2B).
The Size and Age-Profile of the HIV Epidemic in Australia
Using the diagnoses and death notifications within the National HIV/AIDS Registry, we used a mathematical procedure involving aging of diagnoses over time with AIDS and non-AIDS estimated deaths to determine numbers of MSM and women living with HIV infection over time (see Methods16). According to these calculations, numbers of MSM living with HIV infection plateaued briefly in 1994, when deaths mostly from AIDS closely matched numbers of new diagnoses (Fig. 3), but from that time, numbers have increased because of lower AIDS mortality with the introduction of combination ART in the mid 1990s plus ongoing HIV incidence. The number of women living with HIV infection from all exposure categories is also increasing in size and age (Fig. 3).
Average ages of new HIV diagnoses peaked in 2006, and since then, newly diagnosed MSM have become younger on average (Fig. 2A). This is consistent with the increasing numbers of younger MSM not enrolled on ART and the role they play in new infections.19
How Much Increased ART is Required?
For Australian MSM, the best correlate in terms of duplicating numbers and average ages of new HIV diagnoses was the group of MSM with diagnosed HIV infection but who were not taking ART.19 The mean number per year (and standard deviation) of new HIV diagnoses per HIV+ MSM not on ART for the years 1998–2007 for each age group (15–29, 30–39, 40–49, 50+ years) was given by: 0.198 (0.021), 0.176 (0.015), 0.155 (0.019), and 0.162 (0.028). A ratio of 0.198 for the 15- to 29-year age group implies that 1 new HIV diagnosis will arise annually for every 5 individuals in this age group with diagnosed untreated HIV infection.
Taking these ratios of estimates of new infections per diagnosed but untreated MSM, incorporating numbers for each age group, and projecting into the future while incorporating ageing between groups and expected AIDS and non-AIDS deaths (see Methods), allows us to estimate the impact of different levels of ART. This approximation omits explicit contributions from treated individuals with unsuppressed virus and from undiagnosed individuals, but implicitly incorporates their contributions through these ratios. Based on 2007 levels of ART usage for each age group (Fig. 2B), numbers of MSM living with HIV infection is expected to increase by 34% during the next 10 years (Figs. 4A, D), whereas annual new diagnoses will increase by 36%. The majority of this increase is because of a growth in new HIV diagnoses in the younger than 30 years bracket, so that under these ART levels, the average age of MSM living with HIV peaks at approximately 47 years in 2022 and begins to decrease after this time implying a significant expansion of the epidemic.
Scenarios assuming the higher ART usage observed in 1997 produce lower incidence and prevalence, whereas with a uniform 80% of MSM enrolled on ART from 2013, a level that has consistently been achieved by older diagnosed MSM (Fig. 2B), numbers of MSM living with HIV would peak in 2023 before decreasing. Each of these first 3 scenarios sees a sizable expansion of older MSM living with diagnosed HIV infection by 2025, as continuing infection ages through to this group (Figs. 4D–F). Simulations with 90% ART usage in each age group is estimated by our projections to reduce numbers of individuals living with HIV almost immediately (Fig. 4G). This loss of numbers with high levels of ART is because of natural mortality of those living with HIV infection, here taken to be community death rates rather than any high loss from AIDS deaths, plus 70% fewer new HIV infections as a result of expanded treatment.
Although higher ART enrollment increases person-years and cost of ART early in these scenarios, by 2020, all scenarios are estimated to result in virtually equivalent levels of annual person-years of ART (Fig. 4C). By the year 2028 and beyond, the 90% ART scenario requires the lowest cumulative ART person-years and becomes extremely cost effective on this basis alone.
By definition, undiagnosed levels are hard to accurately quantify. Approximately 25% of individuals living with HIV infection are thought to be unaware of their status in the United States.20 Testing rates among MSM in Australia are among the highest in the world,21 so it would be expected that the undiagnosed percentage of MSM and other groups would be lower than elsewhere. The testing rates, markers of PHI, and CD4+ T-cell counts at HIV diagnosis determined from the National HIV/AIDS Registry data suggest that there is also a reasonable proportion of MSM in Australia who are undiagnosed. Although men and women in older age groups at HIV diagnosis have lower CD4+ T-cell counts consistent with findings from other countries,22,23 this is not entirely representative of poorer surveillance of these individuals because their PHI CD4+ T-cell counts also decrease with age. CD4+ T-cell counts for all MSM diagnoses differed by approximately 100 cells per cubic millimeters or more compared with PHI counts for 30- to 59-year olds indicating that surveillance over all ages can improve.
Women newly diagnosed were more likely to present with a lower CD4+ T-cell count. Because CD4+ T cell counts tend to be higher in women than men of the same age without HIV infection,24 women in Australia may have been undiagnosed for longer, although a contributing aspect may be the cohort that have emigrated from high prevalence countries.17,25
Among gay socially engaged men, it is the younger age group those are most likely to have never been tested for HIV (22% for the 30 years and younger age group) with much lower percentages for other age groups.21 This was in contrast to our findings, where the 50 years and older age group was less likely to have been tested. The approximate 60% of diagnoses with no reported prior HIV test also differs significantly from these community-based surveys. Although the exact proportions of prior HIV testing may be underreported in these databases, it is unlikely to be greatly in error considering that individuals with no reported prior HIV test also presented with lower CD4 counts (362 vs. 519 CD4+ T cells per cubic millimeters), and older MSM were less likely to be diagnosed in PHI. Our results highlight lower testing in older MSM that can be improved, especially since the population living with HIV infection is ageing. Certainly, testing among women in Australia can be improved as rates of prior testing were considerably lower than among MSM.
The delay in ART commencement for younger individuals is possibly a consequence of CD4-guided recommendations and where younger individuals are more likely to present with higher CD4+ T-cell counts. TasP will need to offer incentives for these younger individuals, in particular, to commence ART. ART is now recommended for all adults in the United States regardless of CD4 count and with increasing strength of that recommendation with lower CD4 counts.26 Our calculations add support to these recommendations that increased ART will not only be beneficial to the individual on ART, who will be subject to less immune destruction and risk of opportunistic infections, but also to the community at large.
The richer the available data, the fewer free parameters required in a mathematical model to describe those data. This is the case here where the detailed information on 30,486 HIV diagnoses and 6819 deaths after an AIDS diagnosis allowed estimation of how numbers and ages of those living with HIV infection have changed in Australia between 1980 and 2010. Settings where the data are less descriptive require models with more uncertain parameters and with additional assumptions on the underlying dynamics that naturally lead to a greater uncertainty in their predictions.3 Our model provides the simplest and most extensive description of the HIV epidemic in Australia to date. This same model with inclusion of how new diagnoses relate to ART levels,19 also enables an estimate of HIV diagnoses into the future, while maintaining the age, and gender groupings contained within the original data. A related model was used to estimate burdens of neurocognitive impairment and dementia in the future,17 a concern in many developed countries with a sizable older age cohort living with HIV infection. A limitation of our procedure is that we have not explicitly included HIV transmission from individuals on ART nor from an undiagnosed group. However, the ratios correlating all the annual new diagnoses to numbers of individuals not on ART implicitly incorporates contributions from both these sectors because it incorporates data of all diagnoses. A further limitation is that our calculations have used estimates of new HIV diagnoses as a surrogate for new infections. Given there is some delay between infections proceeding to diagnosis, any effect on prevalence of increased ART coverage will also be delayed in comparison to our calculations.
Our analysis indicates that treating at 80% levels, a value that has been consistently achieved by older MSM in Australia, can result in a peaking of HIV prevalence in 10 years' time, without any requirement for expanded testing. Treating at 90% over all age groups will result in an almost immediate decrease in HIV prevalence, and would be cost neutral in terms of ART by 2028, while providing substantial benefits in terms of infections avoided. It should be noted that these treatment levels refer to those diagnosed at current testing levels, and any expansion in testing programs with concurrent enrollment on ART will only improve these outcomes. Expansion of ART usage among injection drug users may be more difficult given they are less likely to access health care and exhibit poorer HIV treatment outcomes,27 so that additional support would be required in countries where injection drug users comprise a substantial component of those living with HIV infection.
In summary, younger individuals are more likely to be diagnosed with higher CD4+ T-cell counts and choose to delay ART, thus providing a sector for increased ART enrollment for TasP. On the other hand, older individuals were significantly less likely to have been tested and be diagnosed early in infection, providing a more resistant sector for these programs but who would correspondingly benefit from TandT. Expanding ART enrollment for all age groups, in particular for younger individuals, is required if rising HIV incidence is to be curtailed. A level of 90% ART usage will significantly lower incidence and prevalence and becomes cost effective on a simple pill count basis within 15 years. Treatment as Prevention to ART levels that can substantially impact both HIV incidence and prevalence is feasible and beneficial in a developed world setting.
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Keywords:© 2013 by Lippincott Williams & Wilkins
Treatment as Prevention; Test and Treat; Australia; mathematical model; CD4; age