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.     

Antiretroviral therapy and Kaposi’s sarcoma trends and outcomes among adults with HIV in Latin America

IntroductionKaposi’s sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART).MethodsCohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression.ResultsOf 25 981 PWH, 481 had incident KS, including 200 ART‐naïve and 281 ART‐treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person‐years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male‐to‐male sex, KS risk after ART was associated with age and history of other AIDS‐defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation.ConclusionsKS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.     

Long-term usage patterns and clinical outcomes in a community-based differentiated antiretroviral therapy delivery programme in South Africa

Introduction

There is little data on long-term implementation and outcomes for people living with HIV (PLHIV) in differentiated antiretroviral therapy (ART) delivery programmes. We aimed to analyse usage patterns of and associated treatment outcomes in a community ART programme, within the Centralized Chronic Medicines Dispensing and Distribution programme, in South Africa over 3.5 years.

Methods

We performed a retrospective cohort study among PLHIV on first-line ART who were eligible for community ART delivery between October 2016 and March 2019, from 56 urban clinics in KwaZulu-Natal, South Africa. Follow-up ended in March 2020. We measured referral rates and, among those referred, we characterized patterns of community ART usage using group-based trajectory modelling following referral. We used survival analysis to measure the association between community ART usage and loss-to-care (no visit for ≥365 days) and logistic regression to measure the association between community ART usage and viraemia (≥50 copies/ml).

Results

Among the 80,801 patients eligible for community ART, the median age was 36 years, 69.8% were female and the median (interquartile range [IQR]) follow-up time was 22 (13–31) months. In total, 49,961 (61.8%) were referred after a median of 6 (IQR 2–13) months from first eligibility. After referral, time spent in community ART varied; 42% remained consistently in community ART, 15% returned to consistent clinic-based care and the remaining 43% oscillated between community ART and clinic-based care. Following referral, the incidence of loss-to-care was 3.93 (95% confidence interval [CI]: 3.71–4.15) per 100 person-years during periods of community ART usage compared to 5.75 (95% CI: 5.28–6.25) during clinic-based care. In multivariable models, community ART usage was associated with a 36% reduction in the hazards of loss-to-care (adjusted hazard ratio: 0.64 [95% CI: 0.57–0.72]). The proportion of patients who became viraemic after first community ART referral was 5.2% and a 10% increase in time in community ART was associated with a 3% reduction in odds of viraemia (adjusted odds ratio: 0.97 [95% CI: 0.95–0.99]).

Conclusions

Community ART usage patterns vary considerably, while clinical outcomes were good. Promoting consistent community ART usage may reduce clinic burden and the likelihood of patients being lost to care, while sustaining viral suppression.     

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape,South Africa

Introduction

There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.

Methods

The Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.

Results

Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.

Conclusions

We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

     

Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected patient on antiretroviral therapy

Abstract

Antiretroviral medications, specifically tenofovir, have been linked to acute tubular necrosis in humans with a suggested mechanism of direct tubular injury. Rhabdomyolysis has rarely been described in patients on highly active antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two different triple antiretroviral regimens has not been reported. We present a HIV-positive patient who first developed heme pigment-induced oliguric AKI due to non-traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral therapy. Renal function normalized 2 months after discontinuation of antiretroviral therapy. Two weeks after reinitiating a different HAART regimen, our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI. Both rhabdomyolysis and AKI resolved after discontinuation of the second antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity followed by a literature review on rhabdomyolysis in HIV-infected patients.     

Twelve‐year mortality in adults initiating antiretroviral therapy in South Africa

Introduction : South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV‐positive South Africans. To ensure that further expansion of services does not compromise quality of care, long‐term outcomes must be monitored. Few studies have reported long‐term mortality in resource‐constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long‐term mortality and viral suppression among adults starting ART in South Africa. Methods : The study was a cohort analysis of routine data on adults with IDs starting ART 2004–2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan‐Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV‐negative. Viral suppression in patients with viral loads (VLs) in their last year of follow‐up was the secondary outcome. Results : Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02–3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007–2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIV‐negative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV‐negative population, and SMRs were similar for all baseline CD4 strata. Three‐quarters of patients had VLs in their last year, and 86% of these were virally suppressed. Conclusions : The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale‐up, testing and initiating men on ART must be a national priority.     

Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

Introduction

Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.

Methods

Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm³ or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.

Results

A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm³. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm³ in 2008 to a peak of 302 cells/mm³ after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035).

Conclusions

Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.     

Uptake of community‐ versus clinic‐based antiretroviral therapy dispensing in the Central Chronic Medication Dispensing and Distribution program in South Africa

IntroductionSouth Africa''s government‐led Central Chronic Medication Dispensing and Distribution (CCMDD) program offers people living with HIV the option to collect antiretroviral therapy at their choice of community‐ or clinic‐based pick‐up points intended to increase convenience and decongest clinics. To understand CCMDD pick‐up point use among people living with HIV, we evaluated factors associated with uptake of a community‐ versus clinic‐based pick‐up point at CCMDD enrolment.MethodsWe collected baseline data from October 2018 to March 2020 on adults (≥18 years) who met CCMDD clinical eligibility criteria (non‐pregnant, on antiretroviral therapy for ≥1 year and virologically suppressed) as part of an observational cohort in seven public clinics in KwaZulu‐Natal. We identified factors associated with community‐based pick‐up point uptake and fit a multivariable logistic regression model, including age, gender, employment status, self‐perceived barriers to care, self‐efficacy, HIV‐related discrimination, and perceived benefits and challenges of CCMDD.Results and DiscussionAmong 1521 participants, 67% were females, with median age 36 years (IQR 30–44). Uptake of a community‐based pick‐up point was associated with younger age (aOR 1.18 per 10‐year decrease, 95% CI 1.05–1.33), being employed ≥40 hours per week (aOR 1.42, 95% CI 1.10–1.83) versus being unemployed, no self‐perceived barriers to care (aOR 1.42, 95% CI 1.09–1.86) and scoring between 36 and 39 (aOR 1.44, 95% CI 1.03–2.01) or 40 (aOR 1.91, 95% CI 1.39–2.63) versus 10–35 on the self‐efficacy scale, where higher scores indicate greater self‐efficacy. Additional factors included more convenient pick‐up point location (aOR 2.32, 95% CI 1.77–3.04) or hours (aOR 5.09, 95% CI 3.71–6.98) as perceived benefits of CCMDD, and lack of in‐clinic follow‐up after a missed collection date as a perceived challenge of CCMDD (aOR 4.37, 95% CI 2.30–8.31).ConclusionsUptake of community‐based pick‐up was associated with younger age, full‐time employment, and systemic and structural factors of living with HIV (no self‐perceived barriers to care and high self‐efficacy), as well as perceptions of CCMDD (convenient pick‐up point location and hours, lack of in‐clinic follow‐up). Strategies to facilitate community‐based pick‐up point uptake should be tailored to patients’ age, employment, self‐perceived barriers to care and self‐efficacy to maximize the impact of CCMDD in decongesting clinics.     

Breast cancer and HIV in the era of highly active antiretroviral therapy: two case reports and review of the literature

Abstract: The incidence of human immunodeficiency virus (HIV) infection is rising in US women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and use of highly active antiretroviral therapy (HAART) on the natural history of breast cancer we present two cases of breast cancer in HIV‐infected women and also review the literature. A literature search was done on Medline using the key words HIV/AIDS, breast cancer, and HAART therapy, restricted to English language. There were mostly case reports and one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response, and toxicity associated with treatment were reviewed. The literature review shows that the breast cancer incidence is either same or less in HIV‐infected patients compared to the general population. However, the patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. The impact of HAART on breast cancer incidence in HIV‐infected patients is still unclear.     

平均红细胞体积在HIV感染者高效抗反转录病毒治疗疗效评价中的应用

高效抗反转录病毒治疗（HAART）能最大限度地抑制HIV的复制,保存和恢复机体免疫功能,有效升高CD。^＋T淋巴细胞的数量和比例,降低病死率和HIV相关疾病的发病率,是治疗和预防艾滋病的有效手段。由于HIV耐药、治疗时机、治疗方案、经济条件及严重的药物不良反应等原因,HAART在部分患者中疗效不佳。