Monita R. Patel

Temporal trends in presentation and survival for HIV-associated lymphoma in the antiretroviral therapy era

BACKGROUND Lymphoma is the leading cause of cancer-related death among HIV-infected patients in the antiretroviral therapy (ART) era. METHODS We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems from 1996 until 2010. We examined differences stratified by histology and diagnosis year. Mortality and predictors of death were analyzed using Kaplan-Meier curves and Cox proportional hazards. RESULTS Of 23 050 HIV-infected individuals, 476 (2.1%) developed lymphoma (79 [16.6%] Hodgkin lymphoma [HL]; 201 [42.2%] diffuse large B-cell lymphoma [DLBCL]; 56 [11.8%] Burkitt lymphoma [BL]; 54 [11.3%] primary central nervous system lymphoma [PCNSL]; and 86 [18.1%] other non-Hodgkin lymphoma [NHL]). At diagnosis, HL patients had higher CD4 counts and lower HIV RNA than NHL patients. PCNSL patients had the lowest and BL patients had the highest CD4 counts among NHL categories. During the study period, CD4 count at lymphoma diagnosis progressively increased and HIV RNA decreased. Five-year survival was 61.6% for HL, 50.0% for BL, 44.1% for DLBCL, 43.3% for other NHL, and 22.8% for PCNSL. Mortality was associated with age (adjusted hazard ratio [AHR] = 1.28 per decade increase, 95% confidence interval [CI] = 1.06 to 1.54), lymphoma occurrence on ART (AHR = 2.21, 95% CI = 1.53 to 3.20), CD4 count (AHR = 0.81 per 100 cell/µL increase, 95% CI = 0.72 to 0.90), HIV RNA (AHR = 1.13 per log10copies/mL, 95% CI = 1.00 to 1.27), and histology but not earlier diagnosis year. CONCLUSIONS HIV-associated lymphoma is heterogeneous and changing, with less immunosuppression and greater HIV control at diagnosis. Stable survival and increased mortality for lymphoma occurring on ART call for greater biologic insights to improve outcomes.

Association of early HIV viremia with mortality after HIV-associated lymphoma.

Objective:To examine the association between early HIV viremia and mortality after HIV-associated lymphoma. Design:Multicenter observational cohort study. Setting:Center for AIDS Research Network of Integrated Clinical Systems cohort. Participants:HIV-infected patients with lymphoma diagnosed between 1996 and 2011, who were alive 6 months after lymphoma diagnosis and with at least two HIV RNA values during the 6 months after lymphoma diagnosis. Exposure:Cumulative HIV viremia during the 6 months after lymphoma diagnosis, expressed as viremia copy-6-months. Main outcome measure:All-cause mortality between 6 months and 5 years after lymphoma diagnosis. Results:Of 224 included patients, 183 (82%) had non-Hodgkin lymphoma (NHL) and 41 (18%) had Hodgkin lymphoma. At lymphoma diagnosis, 105 (47%) patients were on antiretroviral therapy (ART), median CD4+ cell count was 148 cells/&mgr;l (interquartile range 54–322), and 33% had suppressed HIV RNA (<400 copies/ml). In adjusted analyses, mortality was associated with older age [adjusted hazard ratio (AHR) 1.37 per decade increase, 95% CI 1.03–1.83], lymphoma occurrence on ART (AHR 1.63, 95% CI 1.02–2.63), lower CD4+ cell count (AHR 0.75 per 100 cells/&mgr;l increase, 95% CI 0.64–0.89), and higher early cumulative viremia (AHR 1.35 per log10copies × 6-months/ml, 95% CI 1.11–1.65). The detrimental effect of early cumulative viremia was consistent across patient groups defined by ART status, CD4+ cell count, and histology. Conclusion:Exposure to each additional 1-unit log10 in HIV RNA throughout the 6 months after lymphoma diagnosis was associated with a 35% increase in subsequent mortality. These results suggest that early and effective ART during chemotherapy may improve survival.

Lymphoma immune reconstitution inflammatory syndrome in the center for AIDS research network of integrated clinical systems cohort.

BACKGROUND Lymphoma incidence is increased among human immunodeficiency virus (HIV)-infected individuals soon after antiretroviral therapy (ART), perhaps due to unmasking immune reconstitution inflammatory syndrome (IRIS). Clinical characteristics and survival for unmasking lymphoma IRIS have not been described. METHODS We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) from 1996 until 2011. Unmasking lymphoma IRIS was defined as lymphoma within 6 months after ART accompanied by a ≥ 0.5 log10 copies/mL HIV RNA reduction. Differences in presentation and survival were examined between IRIS and non-IRIS cases. RESULTS Of 482 lymphoma patients, 56 (12%) met criteria for unmasking lymphoma IRIS. Of these, 12 (21%) had Hodgkin lymphoma, 22 (39%) diffuse large B-cell lymphoma, 5 (9%) Burkitt lymphoma, 10 (18%) primary central nervous system lymphoma, and 7 (13%) other non-Hodgkin lymphoma. Median CD4 cell count at lymphoma diagnosis among IRIS cases was 173 cells/µL (interquartile range, 73-302), and 48% had suppressed HIV RNA <400 copies/mL. IRIS cases were similar overall to non-IRIS cases in histologic distribution and clinical characteristics, excepting more frequent hepatitis B and C (30% vs 19%, P = .05), and lower HIV RNA at lymphoma diagnosis resulting from the IRIS case definition. Overall survival at 5 years was similar between IRIS (49%; 95% confidence interval [CI], 37%-64%) and non-IRIS (44%; 95% CI, 39%-50%), although increased early mortality was suggested among IRIS cases. CONCLUSIONS In a large HIV-associated lymphoma cohort, 12% of patients met a uniformly applied unmasking lymphoma IRIS case definition. Detailed studies of lymphoma IRIS might identify immunologic mechanisms of lymphoma control.

Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

Background:A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Methods:Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100–350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). Results:ART uptake increased (17%–69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Conclusions:Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy: a systematic review.

Objective:To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4+ cell count response to cART. Methods:Systematic review and meta-analysis of studies reporting HIV RNA and CD4+ cell count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible. Results:Twenty-five eligible cohort studies reported data on 49 578 (range 42–15 646) adults, of whom 8826 (18%) were receiving TB treatment at cART initiation. Seventeen studies reported virologic response; 21 reported CD4+ cell count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86–1.29) at 1–4 months, 0.91 (0.83–1.00) at 6 months, 0.99 (0.94–1.05) at 11–12 months, and 0.99 (0.77–1.28) at 18–48 months. The overall RRRE at 1–48 months was 0.97 (95% confidence interval 0.92–1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4+ cell count gain between those receiving vs. not receiving TB treatment ranged from −10 to 60 cells/&mgr;l (median 27) by 6 months (seven estimates) and −10 to 29 (median 6) by 11–12 months (five estimates), although the heterogeneity of the response measures did not support meta-analysis. Conclusion:Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4+ cell count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.

Effect of smoking history on outcome of patients diagnosed with TB and HIV

Tobacco use, infection with HIV and active tuberculosis (TB) are important public health problems worldwide. Smoking affects susceptibility to TB, with an increased risk of infection, TB disease and TB death [1, 2]. An estimated 1.1 million of the 8.6 million people who developed TB in 2012 were HIV-positive [3]. It has been estimated that smoking could cause 18 million excess cases of TB and 40 million excess deaths between 2010 and 2050 [4], but little is known about the effect of smoking on the outcomes of people receiving care for both HIV and TB. Among TB–HIV patients on antiretrovirals those who smoke(d) are more likely to have adverse TB treatment outcomes http://ow.ly/DyPqW

The Impact of Implementation Fidelity on Mortality Under a CD4-Stratified Timing Strategy for Antiretroviral Therapy in Patients With Tuberculosis

Among patients with tuberculosis and human immunodeficiency virus type 1, CD4-stratified initiation of antiretroviral therapy (ART) is recommended, with earlier ART in those with low CD4 counts. However, the impact of implementation fidelity to this recommendation is unknown. We examined a prospective cohort study of 395 adult patients diagnosed with tuberculosis and human immunodeficiency virus between August 2007 and November 2009 in Kinshasa, Democratic Republic of the Congo. ART was to be initiated after 1 month of tuberculosis treatment at a CD4 count of <100 cells/mm(3) or World Health Organization stage 4 (other than extrapulmonary tuberculosis) and after 2 months of tuberculosis treatment at a CD4 count of 100-350 cells/mm(3). We used the parametric g-formula to estimate the impact of implementation fidelity on 6-month mortality. Observed implementation fidelity was low (46%); 54% of patients either experienced delays in ART initiation or did not initiate ART, which could be avoided under perfect implementation fidelity. The observed mortality risk was 12.0% (95% confidence interval (CI): 8.2, 15.7); under complete (counterfactual) implementation fidelity, the mortality risk was 7.8% (95% CI: 2.4, 12.3), corresponding to a risk reduction of 4.2% (95% CI: 0.3, 8.1) and a preventable fraction of 35.1% (95% CI: 2.9, 67.9). Strategies to achieve high implementation fidelity to CD4-stratified ART timing are needed to maximize survival benefit.

The Effect of Tuberculosis Treatment at Combination Antiretroviral Therapy Initiation on Subsequent Mortality: A Systematic Review and Meta-Analysis

Objective We aimed to perform a systematic review and meta-analysis examining the impact of TB treatment at the time of combination antiretroviral therapy (cART) initiation on subsequent mortality. Methods We searched PubMed, EMBASE, and selected conference proceedings for studies that report adult mortality on cART, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used to examine the influence of study and population characteristics. Results 22 eligible cohort studies reported data on 98,350 (range 74-15,225) adults, of whom 14,779 (15%) were receiving TB treatment at cART initiation. Studies of those receiving vs. not receiving TB treatment had an average mortality relative risk of 1.10 (95% confidence interval 0.87-1.40) at 1-3 months (based upon 8 estimates), 1.15 (0.94-1.41) at 6-12 months (11 estimates), and 1.33 (1.02-1.75) at 18-98 months (10 estimates) following cART initiation. However, there was a wide range of estimates and those at later time points were markedly heterogeneous. Meta-regression identified factors associated with elevated average risk estimates: lower median baseline CD4 counts and adjustment for baseline hemoglobin at 1-3 months; longer length of follow-up and women-only studies at 6-12 months; and not adjusting for BMI/weight at 18-98 months. Conclusions Patients receiving TB treatment at cART initiation did not have a statistically significant estimated increase in short-term risk of all-cause mortality as compared to those not receiving TB treatment. TB treatment was significantly associated with increased mortality after about a year of cART, suggesting that patients with concurrent TB treatment at cART initiation may benefit from continued support after TB treatment completion.

Prevalence of Gonorrhea and Chlamydia Testing by Anatomical Site Among Men Who Have Sex With Men in HIV Medical Care, United States, 2013–2014

Abstract Fewer than one-third of men who have sex with men were tested for Neisseria gonorrhoeae or Chlamydia trachomatis as part of HIV medical care in the United States in 2013 to 2014, and only 11.6% were tested for either sexually transmitted disease at an extragenital site.