Variability in life expectancy among people with HIV in Brazil by gender and sexual orientation.

INTRODUCTION: In Brazil, though Antiretroviral Therapy (ART) is available to all, the benefits may not be experienced uniformly. We projected Life Expectancy (LE) for People Living with HIV (PLHIV) in care as currently observed and estimated the impact of guideline-concordant care. METHODS: Using a microsimulation model, we projected LE for a cohort of PLHIV and for four population groups: cisgender Men who have Sex with Men (MSM), cisgender Men who have Sex with Women (MSW), Cisgender Women (CGW), and Transgender Women (TGW). Cohort data from Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation (INI/Fiocruz) informed model parameters. We modeled five scenarios: 1) Current care: ART initiation, adherence, and retention in care as currently observed, 2) Guideline-concordant care: immediate ART initiation, full adherence to treatment, and consistent retention in care, 3) Immediate ART initiation with observed adherence to treatment and retention in care, 4) Full adherence to treatment with observed timing of ART initiation and retention in care, and 5) Consistent retention in care with observed timing of ART initiation and adherence. RESULTS: With current care, LE from age 15 would be 45.9, 44.4, 54.2, and 42.3 years, for MSM, MSW, CGW, and TGW. With guideline-concordant care, LE would be 54.2, 54.4, 63.1, and 53.2 years, for MSM, MSW, CGW and TGW, with TGW experiencing the greatest potential increase in LE (10.9 years). When investigating the components of care separately, MSW and CGW would gain most LE with immediate ART initiation, whereas for MSM and TGW consistent retention in care would be most impactful. CONCLUSIONS: In settings like INI/Fiocruz, MSW and CGW would benefit most from interventions focused on earlier diagnosis and linkage to care, whereas TGW and MSM would benefit from interventions to sustain engagement in care. Assessment of the HIV care continuum for specific populations should inform care priorities.

Variability in life expectancy among people with HIV in Brazil by gender and sexual orientation

Abstract Introduction In Brazil, though Antiretroviral Therapy (ART) is available to all, the benefits may not be experienced uniformly. We projected Life Expectancy (LE) for People Living with HIV (PLHIV) in care as currently observed and estimated the impact of guideline-concordant care. Methods Using a microsimulation model, we projected LE for a cohort of PLHIV and for four population groups: cisgender Men who have Sex with Men (MSM), cisgender Men who have Sex with Women (MSW), Cisgender Women (CGW), and Transgender Women (TGW). Cohort data from Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation (INI/Fiocruz) informed model parameters. We modeled five scenarios: 1) Current care: ART initiation, adherence, and retention in care as currently observed, 2) Guideline-concordant care: immediate ART initiation, full adherence to treatment, and consistent retention in care, 3) Immediate ART initiation with observed adherence to treatment and retention in care, 4) Full adherence to treatment with observed timing of ART initiation and retention in care, and 5) Consistent retention in care with observed timing of ART initiation and adherence. Results With current care, LE from age 15 would be 45.9, 44.4, 54.2, and 42.3 years, for MSM, MSW, CGW, and TGW. With guideline-concordant care, LE would be 54.2, 54.4, 63.1, and 53.2 years, for MSM, MSW, CGW and TGW, with TGW experiencing the greatest potential increase in LE (10.9 years). When investigating the components of care separately, MSW and CGW would gain most LE with immediate ART initiation, whereas for MSM and TGW consistent retention in care would be most impactful. Conclusions In settings like INI/Fiocruz, MSW and CGW would benefit most from interventions focused on earlier diagnosis and linkage to care, whereas TGW and MSM would benefit from interventions to sustain engagement in care. Assessment of the HIV care continuum for specific populations should inform care priorities.

Impact of pre-exposure prophylaxis uptake among gay, bisexual, and other men who have sex with men in urban centers in Brazil: a modeling study.

BACKGROUND: Men who have sex with men (MSM) in Brazil remain disproportionately affected by HIV. We estimated the potential incidence reduction by five years with increased uptake of publicly-funded, daily, oral tenofovir/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) among MSM using the Cost Effectiveness of Preventing AIDS Complications microsimulation model. We used national data, local studies, and literature to inform model parameters for three cities: Rio de Janeiro, Salvador, and Manaus. RESULTS: In Rio de Janero, a PrEP intervention achieving 10% uptake within 60 months would decrease incidence by 2.3% whereas achieving 60% uptake within 24 months would decrease incidence by 29.7%; results were similar for Salvador and Manaus. In sensitivity analyses, decreasing mean age at PrEP initiation from 33 to 21 years increased incidence reduction by 34%; a discontinuation rate of 25% per year decreased it by 12%. CONCLUSION: Targeting PrEP to young MSM and minimizing discontinuation could substantially increase PrEP's impact.

The cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men and transgender women at high risk of HIV infection in Brazil.

INTRODUCTION: Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre-exposure prophylaxis (PrEP) programme in these populations. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50. Mean age (31 years, SD 8.4 years), age-stratified annual HIV incidence (age ≤ 40 years: 4.3/100 PY; age > 40 years: 1.0/100 PY), PrEP effectiveness (43% HIV incidence reduction) and PrEP drug costs ($23/month) were from Brazil-based sources. The analysis focused on direct medical costs of HIV care. We measured the comparative value of PrEP in 2015 United States dollars (USD) per year of life saved (YLS). Willingness-to-pay threshold was based on Brazil's annual per capita gross domestic product (GDP; 2015: $8540 USD). RESULTS: Lifetime HIV infection risk among high-risk MSM and TGW was 50.5% with No PrEP and decreased to 40.1% with PrEP. PrEP increased per-person undiscounted (discounted) life expectancy from 36.8 (20.7) years to 41.0 (22.4) years and lifetime discounted HIV-related medical costs from $4100 to $8420, which led to an incremental cost-effectiveness ratio (ICER) of $2530/YLS. PrEP remained cost-effective (<1x GDP) under plausible variation in key parameters, including PrEP effectiveness and cost, initial cohort age and HIV testing frequency on/off PrEP. CONCLUSION: Daily tenofovir/emtracitabine PrEP among MSM and TGW at high risk of HIV infection in Brazil would increase life expectancy and be highly cost-effective.

Survival benefits of antiretroviral therapy in Brazil: a model-based analysis.

OBJECTIVE: In Brazil, universal provision of antiretroviral therapy (ART) has been guaranteed free of charge to eligible HIV-positive patients since December 1996. We sought to quantify the survival benefits of ART attributable to this programme. METHODS: We used a previously published microsimulation model of HIV disease and treatment (CEPAC-International) and data from Brazil to estimate life expectancy increase for HIV-positive patients initiating ART in Brazil. We divided the period of 1997 to 2014 into six eras reflecting increased drug regimen efficacy, regimen availability and era-specific mean CD4 count at ART initiation. Patients were simulated first without ART and then with ART. The 2014-censored and lifetime survival benefits attributable to ART in each era were calculated as the product of the number of patients initiating ART in a given era and the increase in life expectancy attributable to ART in that era. RESULTS: In total, we estimated that 598,741 individuals initiated ART. Projected life expectancy increased from 2.7, 3.3, 4.1, 4.9, 5.5 and 7.1 years without ART to 11.0, 17.5, 20.7, 23.0, 25.3, and 27.0 years with ART in Eras 1 through 6, respectively. Of the total projected lifetime survival benefit of 9.3 million life-years, 16% (or 1.5 million life-years) has been realized as of December 2014. CONCLUSIONS: Provision of ART through a national programme has led to dramatic survival benefits in Brazil, the majority of which are still to be realized. Improvements in initial and subsequent ART regimens and higher CD4 counts at ART initiation have contributed to these increasing benefits.

Prenatal Transmission of Syphilis and Human Immunodeficiency Virus in Brazil: Achieving Regional Targets for Elimination.

Background. The Pan-American Health Organization has called for reducing (1) human immunodeficiency virus (HIV) mother-to-child transmission (MTCT) to ≤0.30 infections/1000 live births (LB), (2) HIV MTCT risk to ≤2.0%, and (3) congenital syphilis (CS) incidence to ≤0.50/1000 LB in the Americas by 2015. Methods. Using published Brazilian data in a mathematical model, we simulated a cohort of pregnant women from antenatal care (ANC) through birth. We investigated 2 scenarios: "current access" (89.1% receive one ANC syphilis test and 41.1% receive 2; 81.7% receive one ANC HIV test and 18.9% receive birth testing; if diagnosed, 81.0% are treated for syphilis and 87.5% are treated for HIV) and "ideal access" (95% of women undergo 2 HIV and syphilis screenings; 95% receive appropriate treatment). We conducted univariate and multivariate sensitivity analyses on key inputs. Results. With current access, we projected 2.95 CS cases/1000 LB, 0.29 HIV infections/1000 LB, 7.1% HIV MTCT risk, and 11.11 intrauterine fetal demises (IUFD)/1000 pregnancies, with significant regional variation. With ideal access, we projected improved outcomes: 1.00 CS cases/1000 LB, 0.10 HIV infections/1000 LB, HIV MTCT risk of 2.4%, and 10.65 IUFD/1000 pregnancies. Increased testing drove the greatest improvements. Even with ideal access, only HIV infections/1000 LB met elimination goals. Achieving all targets required testing and treatment >95% and reductions in prevalence and incidence of HIV and syphilis. Conclusions. Increasing access to care and HIV and syphilis antenatal testing will substantially reduce HIV and syphilis MTCT in Brazil. In addition, regionally tailored interventions reducing syphilis incidence and prevalence and supporting HIV treatment adherence are necessary to completely meet elimination goals.

Cost-effectiveness of genotype testing for primary resistance in Brazil.

OBJECTIVE: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. DESIGN: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). METHODS: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as "cost-effective" compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12,300. RESULTS: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45,000 to $44,770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges. CONCLUSIONS: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil.

Effectiveness of first-line antiretroviral therapy in the IPEC cohort, Rio de Janeiro, Brazil.

BACKGROUND: While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression. METHODS: Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ≤400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression. RESULTS: From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression. CONCLUSIONS: Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression.

A randomized trial of ready-to-use supplementary food versus corn-soy blend plus as food rations for HIV-infected adults on antiretroviral therapy in rural Haiti.

BACKGROUND: The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities. METHODS: We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth. RESULTS: A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/µL (interquartile range [IQR], 197-475 cells/µL) for the CSB+ group, and 341 cells/µL (IQR, 213-464/µL) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant. CONCLUSIONS: In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti.

Food assistance is associated with improved body mass index, food security and attendance at clinic in an HIV program in central Haiti: a prospective observational cohort study.

BACKGROUND: Few data are available to guide programmatic solutions to the overlapping problems of undernutrition and HIV infection. We evaluated the impact of food assistance on patient outcomes in a comprehensive HIV program in central Haiti in a prospective observational cohort study. METHODS: Adults with HIV infection were eligible for monthly food rations if they had any one of: tuberculosis, body mass index (BMI) <18.5kg/m2, CD4 cell count <350/mm3 (in the prior 3 months) or severe socio-economic conditions. A total of 600 individuals (300 eligible and 300 ineligible for food assistance) were interviewed before rations were distributed, at 6 months and at 12 months. Data collected included demographics, BMI and food insecurity score (range 0 - 20). RESULTS: At 6- and 12-month time-points, 488 and 340 subjects were eligible for analysis. Multivariable analysis demonstrated that at 6 months, food security significantly improved in those who received food assistance versus who did not (-3.55 vs -0.16; P < 0.0001); BMI decreased significantly less in the food assistance group than in the non-food group (-0.20 vs -0.66; P = 0.020). At 12 months, food assistance was associated with improved food security (-3.49 vs -1.89, P = 0.011) and BMI (0.22 vs -0.67, P = 0.036). Food assistance was associated with improved adherence to monthly clinic visits at both 6 (P < 0.001) and 12 months (P = 0.033). CONCLUSIONS: Food assistance was associated with improved food security, increased BMI, and improved adherence to clinic visits at 6 and 12 months among people living with HIV in Haiti and should be part of routine care where HIV and food insecurity overlap.

HIV morbidity and mortality in Jamaica: analysis of national surveillance data, 1993--2005.

OBJECTIVES: Pre-antiretroviral therapy (ART) HIV-related survival and timing of HIV identification have not been reported from the Caribbean. Using Jamaican national surveillance data, we estimated overall, AIDS-free, and AIDS survival, identified factors influencing HIV-related mortality, and examined factors associated with late HIV/AIDS identification. METHODS: The Jamaican HIV/AIDS tracking system (HATS) national surveillance data included timing of first positive HIV test, stage at identification, date of AIDS diagnosis, and death. We estimated overall and AIDS-free survival by initial stage, using a proportional hazard model to identify factors associated with worse survival, and logistic regression to examine factors related to later case identification. RESULTS: Of 10674 reported HIV cases, 48% were asymptomatic, 14% symptomatic, and 38% first reported with AIDS. Five-year AIDS-free survival was 77% for asymptomatic persons and 63% for symptomatic. Median survival after AIDS diagnosis was 1.02 years. Age, number of opportunistic diseases, and initial stage were strongly associated with mortality. Older age, drug use, and sex with a commercial sex worker were associated with later identification. CONCLUSIONS: In the pre-ART era, over one-third of HIV-infected persons in Jamaica were first identified with advanced disease. This highlights the need for earlier diagnosis as ART programs roll out in the Caribbean.

Provider-initiated HIV testing in rural Haiti: low rate of missed opportunities for diagnosis of HIV in a primary care clinic.

As HIV treatment is scaled-up in resource-poor settings, the timely identification of persons with HIV infection remains an important challenge. Most people with HIV are unaware of their status, and those who are often present late in the course of their illness. Free-standing voluntary counseling and testing sites often have poor uptake of testing. We aimed to evaluate a 'provider-initiated' HIV testing strategy in a primary care clinic in rural resource-poor Haiti by reviewing the number of visits made to clinic before an HIV test was performed in those who were ultimately found to have HIV infection. In collaboration with the Haitian Ministry of Health, a non-governmental organization (Partners In Health) scaled up HIV care in central Haiti by reinforcing primary care clinics, instituting provider-initiated HIV testing and by providing HIV treatment in the context of primary medical care, free of charge to patients. Among a cohort of people with HIV infection, we assessed retrospectively for delays in or 'missed opportunities' for diagnosis of HIV by the providers in one clinic. Of the first 117 patients diagnosed with HIV in one clinic, 100 (85%) were diagnosed at the first medical encounter. Median delay in diagnosis for the remaining 17 was only 62 days (IQR 19 - 122; range 1 - 272). There was no statistical difference in CD4 cell count between those with and without a delay. 3787 HIV tests were performed in the period reviewed. Provider-initiated testing was associated with high volume uptake of HIV testing and minimal delay between first medical encounter and diagnosis of HIV infection. In scale up of HIV care, provider-initiated HIV testing at primary care clinics can be a successful strategy to identify patients with HIV infection.