A Novel Approach to Accounting for Loss to Follow-Up when Estimating the Relationship between CD4 Count at ART Initiation and Mortality

Background

While CD4 strongly predicts mortality on antiretroviral therapy (ART), estimates from programmatic data suffer from incomplete patient outcomes.

Methods

We conducted a pooled analysis of one-year mortality data on ART accounting for lost patients. We identified articles reporting one-year mortality by ART initiation CD4 count. We estimated the average mortality among those lost as the value that maximizes the fit of a regression of the natural log of mortality on the natural log of the imputed mean CD4 count in each band.

Results

We found 20 studies representing 64,426 subjects and 51 CD4 observations. Without correcting for losses, one-year mortality was >4.8% for all CD4 counts <200 cells/mm³. When searching over different values for mortality among those lost, the best fitting model occurs at 60% mortality. In this model, those with a CD4≤200 had a one-year mortality above 8.7, while those with a CD4>500 had a one-year mortality <6.8%. Comparing those starting ART at 500 vs. 50, one-year mortality risk was reduced by 54% (6.8 vs. 12.5%). Regardless of CD4 count, mortality was substantially higher than when assuming no mortality among those lost, ranging from a 23–94% increase.

Conclusions

Our best fitting regression estimates that every 10% increase in CD4 count at initiation is associated with a 2.8% decline in one-year mortality, including those lost. Our study supports the health benefits of higher thresholds for CD4 count initiation and suggests that reports of programmatic ART outcomes can and should adjust results for mortality among those lost.     

Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study

Background

Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.

Methods and Findings

Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.

Conclusions

HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors'' Summary.     

When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa

Background

There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm³ or CD4 percentage (CD4%) <25%.

Methods and Findings

ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping.The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm³ (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm³ or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data.

Conclusions

The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm³ or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors'' Summary     

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha,South Africa: Impact on Mortality and Treatment Success

Setting

Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.

Objective

To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.

Design

A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.

Results

Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm³. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).

Conclusions

Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.     

Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

Background

Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART.

Methods

We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment.

Results

Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm³) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm³) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment.

Conclusions

HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS.     

The Effect of a Maturing Antiretroviral Program on Early Mortality for Patients with Advanced Immune-Suppression in Soweto,South Africa

Objective

We hypothesize that time to initiate care and maturity of a treatment program impact on outcome of severely immuno-compromised patients with higher risk of mortality.

Design

We conducted a retrospective cohort analysis at the Perinatal HIV Research Unit Adult ART clinic, Soweto, South Africa.

Methods

Eligibility criteria for this analysis were: attendance for minimum one visit between August 2004 and August 2010, age >18 years, CD4 count < 50 cells/mm³ and ART-naïve at screening. We followed participants up to one year after ART initiation. We defined years 2004-2007 and 2008-2010 as the early and late eras respectively. Chi-square test and survival analysis methods were used for mortality comparisons between eras.

Results

Of 2357 patients eligible for antiretroviral treatment, 395 (17%) had CD4 counts < 50 cells/mm³ and ART-naïve at screening. Overall 261 (66%) were women. Patients had similar median age (35 vs. 33.5 years, p=0.08), time to HAART initiation (7 days, p=0.18) and baseline CD4 count (20 vs. 23 cells/mm³, p=0.5) between eras. Overall 63 (16%) patients died in their first year of treatment (2 per 100 person-months) and the main cause of death was tuberculosis (n=23, 37%). The proportion of deaths (52/262 vs. 11/133, p=0.003) and time to death from enrolment (logrank p=0.04) were significantly different between eras.

Conclusion

Mortality decreased as the ART program matured in Soweto while time to initiation of treatment remained similar in both eras. Because ART guidelines were consistent during both eras, it is possible that with time, management of patients improved as expertise was gained.     

Clinical,Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe

Objective

To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.

Methods

A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10–19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.

Results

Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.

Conclusions

During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.     

HIV status disclosure and retention in care in HIV-infected adolescents on antiretroviral therapy (ART) in West Africa

Objective

We assessed the effect of HIV status disclosure on retention in care from initiation of antiretroviral therapy (ART) among HIV-infected children aged 10 years or more in Cote d''Ivoire, Mali and Sénégal.

Methods

Multi-centre cohort study within five paediatric clinics participating in the IeDEA West Africa collaboration. HIV-infected patients were included in this study if they met the following inclusion criteria: aged 10–21 years while on ART; having initiated ART≥200 days before the closure date of the clinic database; followed ≥15 days from ART initiation in clinics with ≥10 adolescents enrolled. Routine follow-up data were merged with those collected through a standardized ad hoc questionnaire on awareness of HIV status. Probability of retention (no death or loss-to-follow-up) was estimated with Kaplan-Meier method. Cox proportional hazard model with date of ART initiation as origin and a delayed entry at date of 10th birthday was used to identify factors associated with death or loss-to-follow-up.

Results

650 adolescents were available for this analysis. Characteristics at ART initiation were: median age of 10.4 years; median CD4 count of 224 cells/mm³ (47% with severe immunosuppression), 48% CDC stage C/WHO stage 3/4. The median follow-up on ART after the age of 10 was 23.3 months; 187 adolescents (28.8%) knew their HIV status. The overall probability of retention at 36 months after ART initiation was 74.6% (95% confidence interval [CI]: 70.5–79.0) and was higher for those disclosed compared to those not: adjusted hazard ratio for the risk of being death or loss-to-follow-up = 0.23 (95% CI: 0.13–0.39).

Conclusion

About 2/3 of HIV-infected adolescents on ART were not aware of their HIV status in these ART clinics in West Africa but disclosed HIV status improved retention in care. The disclosure process should be thus systematically encouraged and organized in adolescent populations.     

Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

Background

Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs.

Methods

We analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART.

Results

31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation.

Conclusions

Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.     

Morbidity and Mortality According to Latest CD4+ Cell Count among HIV Positive Individuals in South Africa Who Enrolled in Project Phidisa

Background

Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents.

Methods and Findings

A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50–99, 100–199, 200–349, 350–499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm³. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200–349 (2.2/100py), death rates were significantly lower (p<0.001), as expected, for those with 350–499 (0.9/100py) and with 500+ cells (0.8/100py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350–499 and 7.9 for 500+ cells) and lower than those with counts 200–349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events.

Conclusion

Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350–499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.     

Association of pre-treatment nutritional status with change in CD4 count after antiretroviral therapy at 6, 12, and 24 months in Rwandan women

Background

Body mass index (BMI) independently predicts mortality in studies of HIV infected patients initiating antiretroviral therapy (ART). We hypothesized that poorer nutritional status would be associated with smaller gains in CD4 count in Rwandan women initiating ART.

Methods and Findings

The Rwandan Women''s Interassociation Study and Assessment, enrolled 710 ART-naïve HIV-positive and 226 HIV-negative women in 2005 with follow-up every 6 months. The outcome assessed in this study was change in CD4 count at 6, 12, and 24 months after ART initiation. Nutritional status measures taken prior to ART initiation were BMI; height adjusted fat free mass (FFMI); height adjusted fat mass (FMI), and sum of skinfold measurements. 475 women initiated ART. Mean (within 6 months) pre-ART CD4 count was 216 cells/µL. Prior to ART initiation, the mean (±SD) BMI was 21.6 (±3.78) kg/m² (18.3% malnourished with BMI<18.5); and among women for whom the following were measured, mean FFMI was 17.10 (±1.76) kg/m²; FMI 4.7 (±3.5) kg/m² and sum of skinfold measurements 4.9 (±2.7) cm. FFMI was significantly associated with a smaller change in CD4 count at 6 months in univariate analysis (−6.7 cells/uL per kg/m², p  = 0.03) only. In multivariate analysis after adjustment for covariates, no nutritional variable was associated with change in CD4 count at any follow up visit.

Conclusion

In this cohort of African women initiating ART, no measure of malnutrition prior to ART was consistently associated with change in CD4 count at 6, 12, and 24 months of follow up, suggesting that poorer pre-treatment nutritional status does not prevent an excellent response to ART.     

Laboratory and Clinical Predictors of Disease Progression following Initiation of Combination Therapy in HIV-Infected Adults in Thailand

BACKGROUND: Data on determinants of long-term disease progression in HIV-infected patients on antiretroviral therapy (ART) are limited in low and middle-income settings. METHODS: Effects of current CD4 count, viral load and haemoglobin and diagnosis of AIDS-defining events (ADEs) after start of combination ART (cART) on death and new ADEs were assessed using Poisson regression, in patient aged ≥18 years within a multi-centre cohort in Thailand. RESULTS: Among 1,572 patients, median follow-up from cART initiation was 4.4 (IQR 3.6-6.3) years. The analysis of death was based on 60 events during 6,573 person-years; 30/50 (60%) deaths with underlying cause ascertained were attributable to infections. Analysis of new ADE included 192 events during 5,865 person-years; TB and Pneumocystis jiroveci pneumonia were the most commonly presented first new ADE (35% and 20% of cases, respectively). In multivariable analyses, low current CD4 count after starting cART was the strongest predictor of death and of new ADE. Even at CD4 above 200 cells/mm(3), survival improved steadily with CD4, with mortality rare at ≥500 cells/mm(3) (rate 1.1 per 1,000 person-years). Haemoglobin had a strong independent effect, while viral load was weakly predictive with poorer prognosis only observed at ≥100,000 copies/ml. Mortality risk increased following diagnosis of ADEs during cART. The decline in mortality rate with duration on cART (from 21.3 per 1,000 person-years within first 6 months to 4.7 per 1,000 person-years at ≥36 months) was accounted for by current CD4 count. CONCLUSIONS: Patients with low CD4 count or haemoglobin require more intensive diagnostic and treatment of underlying causes. Maintaining CD4≥500 cells/mm(3) minimizes mortality. However, patient monitoring could potentially be relaxed at high CD4 count if resources are limited. Optimal ART monitoring strategies in low-income settings remain a research priority. Better understanding of the aetiology of anaemia in patients on ART could guide prevention and treatment.     

Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention

BackgroundMultistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality.ConclusionsOur results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART.     

Attrition through Multiple Stages of Pre-Treatment and ART HIV Care in South Africa

Introduction

While momentum for increasing treatment thresholds is growing, if patients cannot be retained in HIV care from the time of testing positive through long-term adherence to antiretroviral therapy (ART), such strategies may fall short of expected gains. While estimates of retention on ART exist, few cohorts have data on retention from testing positive through long-term ART care.

Methods

We explored attrition (loss or death) at the Themba Lethu HIV clinic, Johannesburg, South Africa in 3 distinct cohorts enrolled at HIV testing, pre-ART initiation, and ART initiation.

Results

Between March 2010 and August 2012 we enrolled 380 patients testing HIV+, 206 initiating pre-ART care, and 185 initiating ART. Of the 380 patients enrolled at testing HIV-positive, 38.7% (95%CI: 33.9–43.7%) returned for eligibility staging within ≤3 months of testing. Of the 206 enrolled at pre-ART care, 84.5% (95%CI: 79.0–88.9%) were ART eligible at their first CD4 count. Of those, 87.9% (95%CI: 82.4–92.2%) initiated ART within 6 months. Among patients not ART eligible at their first CD4 count, 50.0% (95%CI: 33.1–66.9%) repeated their CD4 count within one year of the first ineligible CD4. Among the 185 patients in the ART cohort, 22 transferred out and were excluded from further analysis. Of the remaining 163, 81.0% (95%CI: 74.4–86.5%) were retained in care through two years on treatment.

Conclusions

Our findings from a well-resourced clinic demonstrate continual loss from all stages of HIV care and strategies to reduce attrition from all stages of care are urgently needed.     

Predictors of Mortality among Patients Enrolled on Antiretroviral Therapy in Aksum Hospital,Northern Ethiopia: A Retrospective Cohort Study

Background

Since launching of antiretroviral (ART) treatment, the numbers of patients enrolled in to ART are increasing in many developing countries. But many studies done across Africa including Ethiopia on antiretroviral therapy programs have shown higher mortality at the first six months of treatment initiation. But the factors associated with this high mortality are poorly characterized. So this study aims to determine mortality and identify predictors of it among patients on ART.

Methods

Retrospective cohort study was employed among a total of 520 records of patients who were enrolled on antiretroviral therapy in Aksum hospital from September 2006 to August 2011. Baseline patient records were extracted from electronic and paper based medical records database and analysed using Kaplan Meier survival and Cox proportional hazard model to identify the independent predictors of mortality of patients on ART.

Results

A total of 46 (8.85%) deaths was observed giving an overall mortality rate of 3.2 per 100 person-years. The independent predictor of mortality identified for this cohort were haemoglobin level <11 mg/dl (Hazard Ratio (HR) = 1.9, 95%-CI = 1.01, 3.52), CD4 cell counts lower than 50 cells/µl (HR = 2.1, 95%- CI = 1.13,3.89), Male gender (HR = 1.9, 95%-CI = 1.01,3.52), Weight <40 kg (HR = 2.3,95% CI = 1.24,4.55), primary level of education and lower (HR = 2.6, 95%- CI = 1.29,5.55).

Conclusions

The over all mortality of adults patients on ART was low but higher in the early months of ART initiation. low levels of haemoglobin <11 gm/dl, lower CD4 cell count, male gender, weight <40 Kg and individuals who have primary level of education and lower were indentified as the independent predictors of mortality. For this reason, early initiation of ART despite the CD4 count and method of HIV diagnosis, nutritional support and close monitoring of patients in the early periods of ART treatment initiation is very crucial to improve patient survival.     

Retention in Care of HIV-Infected Children from HIV Test to Start of Antiretroviral Therapy: Systematic Review

Background

In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined.

Methods

We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate.

Results

Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years.

Conclusion

Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.     

Outcomes of Nigeria's HIV/AIDS Treatment Program for Patients Initiated on Antiretroviral Treatment between 2004-2012

BackgroundThe Nigerian Antiretroviral therapy (ART) program started in 2004 and now ranks among the largest in Africa. However, nationally representative data on outcomes have not been reported.MethodsWe evaluated retrospective cohort data from a nationally representative sample of adults aged ≥15 years who initiated ART during 2004 to 2012. Data were abstracted from 3,496 patient records at 35 sites selected using probability-proportional-to-size (PPS) sampling. Analyses were weighted and controlled for the complex survey design. The main outcome measures were mortality, loss to follow-up (LTFU), and retention (the proportion alive and on ART). Potential predictors of attrition were assessed using competing risk regression models.ResultsAt ART initiation, 66.4 percent (%) were females, median age was 33 years, median weight 56 kg, median CD4 count 161 cells/mm³, and 47.1% had stage III/IV disease. The percentage of patients retained at 12, 24, 36 and 48 months was 81.2%, 74.4%, 67.2%, and 61.7%, respectively. Over 10,088 person-years of ART, mortality, LTFU, and overall attrition (mortality, LTFU, and treatment stop) rates were 1.1 (95% confidence interval (CI): 0.7–1.8), 12.3 (95%CI: 8.9–17.0), and 13.9 (95% CI: 10.4–18.5) per 100 person-years (py) respectively. Highest attrition rates of 55.4/100py were witnessed in the first 3 months on ART. Predictors of LTFU included: lower-than-secondary level education (reference: Tertiary), care in North-East and South-South regions (reference: North-Central), presence of moderate/severe anemia, symptomatic functional status, and baseline weight <45kg. Predictor of mortality was WHO stage higher than stage I. Male sex, severe anemia, and care in a small clinic were associated with both mortality and LTFU.ConclusionModerate/Advanced HIV disease was predictive of attrition; earlier ART initiation could improve program outcomes. Retention interventions targeting men and those with lower levels of education are needed. Further research to understand geographic and clinic size variations with outcome is warranted.     

Treatment outcome and mortality at one and half year follow-up of HIV infected TB patients under TB control programme in a district of South India

BACKGROUND: There is paucity of data from India on the impact of HIV related immunosuppression in response to TB treatment and mortality among HIV infected TB patients. We assessed the TB treatment outcome and mortality in a cohort of HIV infected TB patients treated with intermittent short course chemotherapy under TB control programme in a high HIV prevalent district of south India. METHODOLOGY/ FINDINGS: Among 3798 TB patients registered for treatment in Mysore district from July 2007 to June 2008, 281 HIV infected patients formed the study group. The socio-demographic and treatment related data of these patients was obtained from TB and HIV programme records and patient interviews 19 months after TB treatment initiation by field investigators. Treatment success rate of 281 patients was 75% while in smear positive pulmonary tuberculosis cases it was 62%, attributable to defaults (16%) and deaths (19%). Only 2 patients had treatment failure. Overall, 83 (30%) patients were reported dead; 26 while on treatment and 57 after TB treatment. Association of treatment related factors with treatment outcome and survival status was studied through logistic regression analysis. Factors significantly associated with 'unfavourable outcome' were disease classification as Pulmonary [aOR-1.96, CI (1.02-3.77)], type of patient as retreatment [aOR-4.78, CI (2.12-10.76)], and non initiation of ART [aOR-4.90, CI (1.85-12.96)]. Factors associated with 'Death' were non initiation of ART [aOR-2.80, CI (1.15-6.81)] and CPT [aOR-3.46, CI (1.47-8.14)]. CONCLUSION: Despite the treatment success of 75% the high mortality (30%) in the study group is a matter of concern and needs immediate intervention. Non initiation of ART has emerged as a high risk factor for unfavourable treatment outcome and mortality. These findings underscore the importance of expanding and improving delivery of ART services as a priority and reconsideration of the programme guidelines for ART initiation in HIV infected TB patients.     

Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial

Background

Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.

Methods and Findings

We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log₁₀ copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.

Conclusions

We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00050089","term_id":"NCT00050089"}}NCT00050089     

43 例HIV/AIDS 患者抗病毒治疗情况分析

目的:研究来第四军医大学唐都医院传染科就诊的人类免疫缺陷病毒/艾滋病(Human immunodeficiency virus/Acquired immuno deficiency syndrome,HIV/AIDS)患者感染状况及抗病毒治疗效果。方法:采用前瞻性随访研究的方法,收集来我院就诊的HIV/AIDS患者的基本信息,并对其实验室检查结果、治疗方案及后续随访结果进行分析。结果:随访观察的43例HIV/AIDS患者治疗前平均基线CD4+T淋巴细胞计数为(330.74±176.35)cells/μL,CD8+T淋巴细胞计数为(1177.80±321.49)cells/μL,CD4+,CD8+T淋巴细胞比值为0.30±0.19;治疗一年后平均CD4+T淋巴细胞计数为(482.74±217.77)cells/μL,CD8+T淋巴细胞计数为(861.53±282.85)cells/μL,CD4+,CD8+T淋巴细胞比值为0.59±0.28。所有患者治疗一年后血浆HIV-RNA载量均达到检测限以下(500copies/m L)。结论:规范的抗病毒治疗对于改善HIV/AIDS患者预后至关重要;基线CD4+T淋巴细胞计数越低,抗病毒治疗效果越差。