Determinants of survival of people living with HIV/AIDS on antiretroviral therapy in Brazil 2006-2015.

BACKGROUND: We compared AIDS-related mortality rates in people living with HIV (PLHIV) starting antiretroviral therapy (ART) in Brazil during 2006-2015 and examined associated risk factors . METHODS: Data on ART use in PLHIV and AIDS mortality in Brazil was analysed with piecewise constant exponential models. Mortality rates and hazard ratios were estimated for 0-6, 6-12, 13-24, 25-36 and > 36 months of ART use and adjusted for region, age, sex, baseline CD4 cell count and calendar year of ART initiation. An additional analysis restricted to those with data on risk group was also performed. RESULTS: 269,076 individuals were included in the analysis, 165,643 (62%) males and 103,433 (38%) females, with 1,783,305 person-years of follow-up time. 21,749 AIDS deaths were reported and 8898 deaths occurred in the first year of ART. The risk of death in the first six months decreased with early ART initiation; those starting treatment early with CD4 > 500 cells per µL had a hazard ratio of 0.06 (95% CI 0.05-0.07) compared with CD4 < 200 cells per µL. Older age, male sex, intravenous drug use and starting treatment in earlier calendar years were associated with higher mortality rates. People living in the North, Northeast and South of Brazil experienced significantly higher AIDS mortality rates than those in the Southeast (HR 1.44, [95% CI 1.35-1.54], 1.10 [1.05-1.16] and 1.22 [1.17-1.28] respectively). CONCLUSIONS: Early treatment is likely to have contributed to the improved survival in PLHIV on ART, with the greatest benefits observed in women, younger age-groups and those living in the North.

Estimating HIV incidence from surveillance data indicates a second wave of infections in Brazil.

Emerging evidence suggests that HIV incidence rates in Brazil, particularly among men, may be rising. Here we use Brazil's integrated health systems data to develop a mathematical model, reproducing the complex surveillance systems and providing estimates of HIV incidence, number of people living with HIV (PLHIV), reporting rates and ART initiation rates. An age-structured deterministic model with a flexible spline was used to describe the natural history of HIV along with reporting and treatment rates. Individual-level surveillance data for 1,077,295 cases (HIV/AIDS diagnoses, ART dispensations, CD4 counts and HIV/AIDS-related deaths) were used to calibrate the model using Bayesian inference. The results showed a second wave of infections occurring after 2001 and 56,000 (95% Credible Interval 43,000-71,000) new infections in 2015, 37,000 (95% CrI 28,000-54,000) infections in men and 16,000 (95% CrI 10,000-23,000) in women. The estimated number of PLHIV by end-2015 was 838,000 (95% CrI 675,000-1,083,000), with 80% (95% CrI 62-98%) of those individuals reported to the Ministry of Health. Women were more likely to be diagnosed and reported than men; 86.8% of infected women had been reported compared with 75.7% of men. Likewise, ART initiation rates for women were higher than those for men. The second wave contradicts previous estimates of HIV incidence trends in Brazil and there were persistent differences in the rates of accessing care between men and women. Nevertheless, the Brazilian HIV program has achieved high rates of detection and treatment, making considerable progress over the past ten years.

The impact and cost-effectiveness of combined HIV prevention scenarios among transgender women sex-workers in Lima, Peru: a mathematical modelling study.

BACKGROUND: HIV incidence remains high among transgender women in Lima, Peru, most of whom report sex work. On the basis of a stakeholder analysis and health system capacity assessment, we designed a mathematical model to guide HIV programmatic planning among transgender women sex workers (TWSW) in Lima. METHODS: Using a deterministic compartmental model, we modelled HIV transmission among TWSW, their stable partners, and their clients to estimate the impact and cost-effectiveness of combinations of interventions compared with the standard of care on reducing HIV incidence over a 10-year period. We simulated HIV transmission accounting for differences in sexual positioning in anal intercourse and condom use by partner type and fitted the model to HIV surveillance data using Latin hypercube sampling. The interventions we considered were 15% relative increase in condom use with clients and 10% relative increase with stable partners; increase in antiretroviral treatment (ART) coverage at CD4 count lower than 500 cells per mm3 and greater than or equal to 500 cells per mm3; and 15% pre-exposure prophylaxis (PrEP) coverage using generic and branded formulations. We considered a basic scenario accounting for current limitations in the Peruvian HIV services and an enhanced scenario assuming achievement of the UNAIDS 90-90-90 targets and general improvements in HIV services. The 50 best fits according to log-likelihood were used to give the minimum and maximum values of intervention effect for each combination. We used disability-adjusted life-years (DALYs) to measure the negative health outcomes associated with HIV infection that could be averted through the interventions investigated and calculated incremental cost-effectiveness ratios to compare their cost-effectiveness. FINDINGS: Under the basic scenario, combining the four interventions of increasing condom use with clients and stable partners, extending ART to people with CD4 count greater than or equal to 500 cells per mm3, and 15% PrEP coverage with generic drugs would avert 47% (range 27-51) of new infections in TWSW, their clients, and their stable partners over 10 years, with an incremental cost-effectiveness ratio of US$509 per DALY averted. Under the enhanced scenario, this strategy would avert 61% (44-64) of new infections among this population with an incremental cost-effectiveness ratio of $1003 per DALY averted. Under both scenarios, implementation of this strategy approaches or surpasses the 50% incidence reduction goal and would represent a cost-effective use of country resources if generic PrEP drugs are used. The total cost of implementing this strategy under the enhanced scenario would be approximately $1·2 million per year over 10 years, corresponding to 10% of the current Global Fund's yearly contribution in Peru. INTERPRETATION: Investments in HIV services among TWSW in Lima would be cost-effective, even under stringent cost-effectiveness criteria when accounting for setting-specific resource constraints. Notable improvements in HIV testing rates, innovative interventions to increase condom use, and reduced PrEP costs will be key to achieving the 50% incidence reduction goal. Modelling studies incorporating stakeholders' perspectives and health system assessments can bring added value to HIV policy making. FUNDING: National Institutes of Health.

Estimating HIV incidence from case-report data: method and an application in Colombia.

OBJECTIVE: Quantifying HIV incidence is essential for tracking epidemics but doing this in concentrated epidemic can be a particular challenge because of limited consistent high-quality data about the size, behaviour and prevalence of HIV among key populations. Here, we examine a method for estimating HIV incidence from routinely collected case-reporting data. METHODS: A flexible model of HIV infection, diagnosis and survival is constructed and fit to time-series data on the number of reported cases in a Bayesian framework. The time trend in the hazard of infection is specified by a penalized B-spline. We examine the performance of the model by applying it to synthetic data and determining whether the method is capable of recovering the input incidence trend. We then apply the method to real data from Colombia and compare our estimates of incidence with those that have been derived using alternative methods. RESULTS: The method can feasibly be applied and it successfully recovered a range of incidence trajectories in synthetic data experiments. However, estimates for incidence in the recent past are highly uncertain. When applied to data from Colombia, a credible trajectory of incidence is generated which indicates a much lower historic level of HIV incidence than has previously been estimated using other methods. CONCLUSION: It is feasible, though not satisfactory, to estimate incidence using case-report data in settings with good data availability. Future work should examine the impact on missing or biased data, the utility of alternative formulations of flexible functions specifying incidence trends, and the benefit of also including data on deaths and programme indicators such as the numbers receiving antiretroviral therapy.

Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk.

BACKGROUND: Some, but not all, observational studies have suggested an increase in the risk of HIV acquisition for women using injectable hormonal contraception (IHC). METHODS: We used country-level data to explore the effects of reducing IHC use on the number of HIV infections, the number of live births and the resulting net consequences on AIDS deaths and maternal mortality for each country. RESULTS: High IHC use coincides with high HIV incidence primarily in southern and eastern Africa. If IHC increases the risk of HIV acquisition, this could generate 27 000-130 000 infections per year globally, 87-88% of which occur in this region. Reducing IHC use could result in fewer HIV infections but also a substantial increase in live births and maternal mortality in countries with high IHC use, high birth rates and high maternal mortality: mainly southern and eastern Africa, South-East Asia, and Central and South America. For most countries, the net impact of reducing IHC use on maternal and AIDS-related deaths is dependent on the magnitude of the assumed IHC-HIV interaction. CONCLUSIONS: If IHC use increases HIV acquisition risk, reducing IHC could reduce new HIV infections; however, this must be balanced against other important consequences, including unintended pregnancy, which impacts maternal and infant mortality. Unless the true effect size approaches a relative risk of 2.19, it is unlikely that reductions in IHC could result in public health benefit, with the possible exception of those countries in southern Africa with the largest HIV epidemics.

The potential impact of pre-exposure prophylaxis for HIV prevention among men who have sex with men and transwomen in Lima, Peru: a mathematical modelling study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. METHODS AND FINDINGS: We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. CONCLUSIONS: A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.

Condom use by female sex workers and their clients in Mexico: who decides and does it matter?

OBJECTIVES: To explore the effect of different patterns of condom use by clients and female sex workers (FSW) on HIV transmission in Mexico. METHODS: Data from 2401 face-to-face interviews among FSW from Morelos and Michoacán in Mexico were used to build and parameterise a deterministic model of HIV transmission between FSW, their stable partners and clients. RESULTS: For the observed patterns of condom use among FSW, a range of patterns of use among clients would be consistent. Two extreme patterns were explored: either clients conformed to FSW decision, or they had a strict preference for bought sex with or without condoms. HIV prevalence in the model is greater in the first of these scenarios. CONCLUSIONS: Patterns of condom use between sex workers and clients are an important, but hidden, determinant of epidemic spread. More detailed information on condom use negotiation and behavioural patterns of clients is needed to understand the potential for transmission in these populations and in order to direct intervention efforts more effectively.

Estimates of HIV incidence from household-based prevalence surveys.

OBJECTIVE: To estimate HIV incidence in the general population in countries where there have been two recent household-based HIV prevalence surveys (the Dominican Republic, Mali, Niger, Tanzania, and Zambia). METHODS: We applied a validated method to estimate HIV incidence using HIV prevalence measurement in two surveys. RESULTS: We estimate incidence among men and women aged 15-44 years to be: 0.5/1000 person-years at risk in the Dominican Republic 2002-2007, 1.1/1000 in Mali 2001-2006, 0.6/1000 in Niger 2002-2006, 3.4/1000 in Tanzania 2004-2008, and 11.2/1000 in Zambia 2002-2007. The groups most at risk in these epidemics are typically 15-24-year-old women and 25-39-year-old men. Incidence appears to have declined in recent years in all countries, but only significantly among men in the Dominican Republic and Tanzania and women in Zambia. CONCLUSION: Using prevalence measurements to estimate incidence reveals the current level and age distribution of new infections and the trajectory of the HIV epidemic. This information is more useful than prevalence data alone and should be used to help determine priorities for interventions.