Antiretroviral Therapy For HIV Infection Research Articles

Is weak CD4+ gain in the course of suppressive combination antiretroviral therapy for HIV infection a current clinical challenge? A case report and brief review of the literature

BackgroundIndividuals lacking immune recovery during suppressive cART will still represent a clinical issue in the years to come, given the high proportion of HIV-infected subjects introducing therapy late in the course of disease. Understanding the mechanisms underlying poor CD4+ T-cell gain is crucial for the correct clinical management of individuals in this context.Case presentationAn HIV-infected subject with poor CD4+ T-cell gain in the course of suppressive antiretroviral therapy was extensively investigated to identify the mechanisms behind inadequate CD4+ reconstitution. In particular, we studied the phenotype of circulating T-cells, interleukin-7 signaling in peripheral blood and bone marrow, gut function and microbial translocation markers as well as the composition of the faecal microbiota. Numerous therapeutic interventions ranging from antiretroviral therapy intensification to immunotherapy and anti-hepatitis C virus treatment were also employed in order to target the possible causes of poor immune-recovery.ConclusionsPoor CD4+ T-cell gain on suppressive antiretroviral therapy is multifactorial and thus represents a clinical challenge. Clinicians should investigate subjects’ immune profile as well as possible causes of chronic antigenic stimulation for the administration of the most appropriate therapeutic strategies in this setting.

Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection

Background:Obesity is common among patients with HIV. The objective of this study was to characterize response to antiretroviral therapy (ART) in a cohort of obese incarcerated adults compared to a nonobese cohort.Methods:A retrospective matched cohort study was conducted in an HIV telemedicine clinic. Patients with body mass index (BMI) >30 kg/m2 who received the same ART with >95% adherence for at least 6 months were matched to nonobese patients by age, gender, ART, CD4 count, and viral load at baseline.Results:Twenty pairs were included, with an average BMI of 24 kg/m2 in the nonobese cohort and 35 kg/m2 in the obese cohort. No difference was observed in the proportion of patients who achieved virologic suppression or the change in CD4 count from baseline to 6 to 12 months.Conclusion:This study revealed no differences in immunologic recovery or virologic suppression between obese and nonobese patients in an adult correctional population.

Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients.

Background & objectives:Nucleoside reverse transcriptase inhibitors (NRTIs) are known to cause mitochondrial toxicity. This study was done to estimate mitochondrial DNA (mtDNA) content of peripheral blood mononuclear cells (PBMCs) among human immunodeficiency virus (HIV) infected, NRTI treated and antiretroviral therapy (ART)-naïve patients and evaluate the utility of mtDNA content as a biomarker of mitochondrial toxicity.Methods:mtDNA content in PBMCs of 57 HIV-infected ART untreated and 30 ART treated with stavudine (d4T) or zidovudine (AZT) containing regimen were compared against 24 low-risk healthy controls (LoRHC).Results:There was a significant (P=0.01) reduction in mtDNA content among HIV-infected (104; 80-135) compared to LoRHC (127; 110-167), and it was the same in both the treated (104.8; 88-130) and untreated patients (104.7; 78-142). mtDNA significantly (P=0.014) declined in ART treated patients symptomatic for toxicity (97; 74-111) than the asymptomatic patients (128; 103- 153).Interpretation & conclusions:mtDNA depletion in PBMCs was evident among HIV-infected individuals on ART. Moreover, as mtDNA content was reduced among the patients symptomatic for toxicity than the asymptomatic in both the HIV-infected groups, the current study supports mtDNA content of PBMCs to serve as a biomarker of mitochondrial dysfunction induced by NRTI and HIV. Longitudinal studies with a large sample need to be done to confirm these findings.

Mortality under plausible interventions on antiretroviral treatment and depression in HIV-infected women: an application of the parametric g-formula

PurposeAmong HIV-infected persons, antiretroviral therapy (ART) and depression are strongly associated with mortality. We estimated reductions in 5-year mortality in Women's Interagency HIV Study participants under plausible hypothetical increases in ART initiation and reductions in depression (CES-D score≥16). MethodsWe followed 885 ART-naïve Women's Interagency HIV Study participants for 5 years from their first study visit after April 1998 to death or censoring. We used the parametric extended g-formula to estimate cumulative mortality under the natural course (NC) and alternative exposure distributions. ResultsBaseline prevalence of depression was 52% and 62% initiated ART by 5 years. Compared with mortality under NC (13.2%), immediate ART and elimination of 36% or 67% of depressive episodes were associated with risk differences (RDs) of −5.2% (95% CI: −7.7%, −2.6%) and −5.7 (95% CI: −8.7, −2.7). Compared with immediate ART and NC for depression, additionally eliminating 67% of the depressive episodes was associated with RD = −1.6 (95% CI: −3.9, 0.8). Compared with 5-year mortality under NC for ART and elimination of 67% of depression, also initiating ART immediately was associated with RD = -2.6 (95% CI: -5.0, -0.3). ConclusionsIncreasing ART initiation and reducing depression were associated with moderate reductions in 5-year mortality among HIV-infected women.

Nucleoside inhibitors of reverse transcriptase as a basis for the first line anti-retroviral therapy of HIV infection

Aim. Comparative assessment of safety and effectiveness of various medications used in the first line anti-retroviral therapy (ART) of HIV. Material and methods. Patients with stage IV HIV infection were treated using one of the ART modalities for 48 weeks. 38 patients of group 1 were given fosfazid (Farma K.B, Russia) at a dose of 0.4 twice daily and 41 patients of group 2received abacavir. Both drugs were used in combination with lamivudine and efavirinez at standard doses. The results were evaluated within 0-4-12-24-36 and 48 weeks after ART based on the absence of myelo- and hepatotoxic manifestations, immunological, virological and clinical effectiveness. Results. The safety of ART is evidenced by the absence of myelo- and hepatotoxic symptoms. Fosfazid caused a significant (p<0.05) increase of hemoglobinlevel starting from week 4 up to week 48. No such increase was documented after abacavir therapy. An increaseinthe number of CD4 lymphocyte by 100 cells/mcl suggested positive effect of the treatment on the immune status of all HIV-infected patients. ART inhibited HIV replication in 95% and 88% of the patients in groups 1 and 2 respectively which suggests its high efficiency.

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

NCT00867048. © 2017 American Society for Bone and Mineral Research.

INCIDENCE AND RISK FACTORS OF RENAL IMPAIRMENT IN HIV-1 INFECTED PATIENTS RECEIVING TENOFOVIR BASED ANTIRETROVIRAL THERAPY IN A SOUTH INDIAN HOSPITAL

Objective: To identify the incidence and risk factors of tenofovir (TDF) induced nephrotoxicity among People Living with HIV/AIDS (PLHA) receiving TDF-based anti-retroviral therapy (ART) in a South Indian Hospital.Methods: A retrospective cohort study was conducted among HIV-infected ART naïve patients taking TDF as part of either a first-line or second-line ART between July 2013 and June 2015 at Asha kirana Hospital Mysore, India.Results: A total of 380 patients have been initiated on TDF-based ART. Out of these, 335 patients were on tenofovir+lamivudine+efavirenz, 30 patients were on the tenofovir+lamivudine+nevirapine regimen and 25 patients were on tenofovir+lamivudine+atazanavir/ritonavir regimen. Renal impairment was documented for 35 patients with 9.21% incidence. 34% of renal impaired patients had a severe impairment with eGFR<30 ml/min. Elderly patients (>61 y) had higher chances of developing TDF toxicity compared to adult patients (P=0.0018). Other possible risk factors for TDF-induced renal impairment was CD4>200 (P=0.003). TDF was withdrawn and substituted with Nucleoside Reverse Transcriptase Inhibitor (NRTI) drug following the diagnosis of renal impairment.Conclusion: TDF-associated renal impairment was not uncommon in real-life practice and considered as a frequent complication during treatment with TDF. Risk factors for developing renal impairment include increasing age and CD4>200 cells.

Acute Care Management of the HIV-Infected Patient: A Report from the HIV Practice and Research Network of the American College of Clinical Pharmacy.

Patients infected with human immunodeficiency virus (HIV) admitted to the hospital have complex antiretroviral therapy (ART) regimens with an increased medication error rate upon admission. This report provides a resource for clinicians managing HIV-infected patients and ART in the inpatient setting. A survey of the authors was conducted to evaluate common issues that arise during an acute hospitalization for HIV-infected patients. After a group consensus, a review of the medical literature was performed to determine the supporting evidence for the following HIV-associated hospital queries: admission/discharge orders, antiretroviral hospital formularies, laboratory monitoring, altered hepatic/renal function, drug-drug interactions (DDIs), enteral administration, and therapeutic drug monitoring. With any hospital admission for an HIV-infected patient, a specific set of procedures should be followed including a thorough admission medication history and communication with the ambulatory HIV provider to avoid omissions or substitutions in the ART regimen. DDIs are common and should be reviewed at all transitions of care during the hospital admission. ART may be continued if enteral nutrition with a feeding tube is deemed necessary, but the entire regimen should be discontinued if no oral access is available for a prolonged period. Therapeutic drug monitoring is not generally recommended but, if available, should be considered in unique clinical scenarios where antiretroviral pharmacokinetics are difficult to predict. ART may need adjustment if hepatic or renal insufficiency ensues. Treatment of hospitalized patients with HIV is highly complex. HIV-infected patients are at high risk for medication errors during various transitions of care. Baseline knowledge of the principles of antiretroviral pharmacotherapy is necessary for clinicians managing acutely ill HIV-infected patients to avoid medication errors, identify DDIs, and correctly dose medications if organ dysfunction arises. Timely ambulatory follow-up is essential to prevent readmissions and facilitate improved transitions of care.

Performance of the SAMBA I and II HIV-1 Semi-Q Tests for viral load monitoring at the point-of-care

Although access to antiretroviral therapy for HIV infection is increasing in resource-poor countries, viral load testing for monitoring of treatment efficacy remains limited, expensive, and confined to centralized laboratories. The SAMBA HIV-1 Semi-Q Test is a nucleic acid–based amplification assay developed for viral load monitoring performed on either the semi-automated SAMBA I system for laboratory use or the fully automated SAMBA II system for point-of care use. We have assessed the performance characteristics of the SAMBA HIV-1 Semi-Q Test on SAMBA I and SAMBA II systems according to the Common Technical Specifications of the European Community's 98/79 In Vitro Diagnostic Medical Devices Directive. The sensitivity, specificity, reproducibility, and viral subtype coverage of the test were similar on the SAMBA I and SAMBA II platforms. The clinical performance on the SAMBA I system was compared with the Roche CAP/CTM assay and evaluated in-house with 130 patient specimens from London as well as in the field with 390 specimens in Kenya and Zimbabwe. The overall concordance between the SAMBA and CAP/CTM assays was 98.1%. The clinical performance of the test on the SAMBA II platform in comparison with the Abbott HIV-1 RealTime Assay was evaluated in-house with 150 specimens from Ukraine, yielding a concordance of 98.0%. The results thus show that the SAMBA HIV-1 Semi-Q Test performs equivalently on SAMBA I and SAMBA II, and they suggest that the test is suitable for implementation at the point-of-care in resource-poor regions where viral load testing is desperately needed but often unavailable.

The study of aids morbidity in HIV-infected population and antiretroviral therapy effect

Aim. To estimate AIDS morbidity dynamics in Ivano-Frankivsk region and the degree of its controllability by antiretroviral therapy existing incidence of HIV-infected people. Methods. We calculated the number of detected people living with HIV in Ivano-Frankivsk region = all identified HIV-infected people for the entire period of epidemiological observation – (dead HIV-positive people + people with removed diagnosis + people who left the region). We estimated HIV-infection annual transition in patients to AIDS stage (ATA = the number of new registered AIDS cases × 100 % / detected people who leaves with HIV), the incidence of HIV-people by antiretroviral therapy (IART), and Pearson correlation coefficient. The tendency of cerebral toxoplasmosis morbidity was determined automatically by least squares method using Excel program, and its prognosis was determined by extrapolation into the future. Results. It was found, that the identified 1661 HIV-positive people leaved in the region in 2015, but only 892 of them were under clinical observation (53.7%). ATA decreases from 9.1% in 2013 to 5.1% in 2015, but no reverse correlation between ATA and IART was found. IART was insufficient – 69.8% of people who was under the clinical observation, and 37.2% of all detected HIV-people. According to a growing tendency of cerebral toxoplasmosis morbidity, we expected 10 cases in 2016 and 11 in 2017. Conclusion. The incidence of HIV-people by antiretroviral therapy was insufficient, therefore, it did not have the preventive effect on AIDS and, particularly, on cerebral toxoplasmosis among HIV-people

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

BackgroundChildren (<15 years) are vulnerable to TB disease following infection, but no systematic review or meta-analysis has quantified the effects of HIV-related immunosuppression or antiretroviral therapy (ART) on their TB...

Inflammatory Function of CX3CR1+ CD8+ T Cells in Treated HIV Infection Is Modulated by Platelet Interactions.

Increases in inflammation, coagulation, and CD8+ T-cell numbers are associated with an elevated cardiovascular disease (CVD) risk in human immunodeficiency virus (HIV)-infected antiretroviral therapy (ART) recipients. Circulating memory CD8+ T cells that express the vascular endothelium-homing receptor CX3CR1 (fractalkine receptor) are enriched in HIV-infected ART recipients. Thrombin-activated receptor (PAR-1) expression is increased in HIV-infected ART recipients and is particularly elevated on CX3CR1+ CD8+ T cells, suggesting that these cells could interact with coagulation elements. Indeed, thrombin directly enhanced T-cell receptor-mediated interferon γ production by purified CD8+ T cells but was attenuated by thrombin-induced release of transforming growth factor β by platelets. We have therefore identified a population of circulating memory CD8+ T cells in HIV infection that may home to endothelium, can be activated by clot-forming elements, and are susceptible to platelet-mediated regulation. Complex interactions between inflammatory elements and coagulation at endothelial surfaces may play an important role in CVD risk in HIV-infected ART recipients.

Mortality and retention in hospital-based and CDC-based antiretroviral service delivery in people living with HIV in the Guangdong Province, China: a prospective cohort study

BackgroundEnormous efforts have been made to decentralise HIV service delivery in China, gradually developing a network of thousands of Centres For Disease Control And Prevention (CDCs) with or without local hospitals providing antiretroviral therapy (ART) to every village or equivalent. However, in the Guangdong Province, China, most infected patients from CDCs delivering HIV services have been switched to sentinel hospitals, providing an opportunity to examine this shift on linkage to care, retention, and mortality among people living with HIV. We examined long-term outcomes of people living with HIV who accessed services through sentinel hospitals and CDCs in the Guangdong Province. MethodsThis is a post-hoc analyses of an open cohort from an observational database of 22 qualified HIV/AIDS sentinel hospitals and two CDC-based drug delivery health facilities in Guangdong. We recruited all outpatients of health facilities receiving ART from Jan 1, 2005, to June 1, 2014. Patients were excluded if they did not start triple drug therapy based ART, had missing treatment regimen information, or used ART outside of national guidelines. We followed up the patients for 10 years. We defined and calculated linkage to initial ART, mortality, overall survival, and retention rate according to the WHO Guideline 2006 for ART in HIV infection in adult. The institutional review board of the Guangzhou Eighth People's Hospital approved this analysis. Written informed consent was obtained from all patients. FindingsOf the 18 921 people living with HIV, 14 885 (79%) were initiated ART with follow-up, and thus were available for analysis. Among these participants, 12 966 (87%) individuals received ART from hospitals and 1919 (13%) received ART from a CDC, the linkage to care was 80·7% in hospitals and 79·9% in CDC facilities (p=0·352). Excess mortality was 1·4 deaths per 100 person-years (95% CI 1·1–1·8) in CDC facilities compared with 0·4 deaths per 100 person-years (0·3–0·5) in hospitals (p=0·001). A Cox-regression analysis showed that mortality was much higher in patients receiving ART from the CDC-based health facilities than in those receiving ART from the sentinel hospitals, with an adjusted hazard ratio (HR) of 3·3 (95% CI 2·3–4·6). Kaplan–Meier analysis showed a mean overall survival time of 105·3 months (95% CI 104·6–106·1) in the hospital group compared with 78·7 months (76·2–81·2) in the CDC group (p<0·0001). Retention rate was 94·1% in sentinel hospital and 84·0% in CDC facilities (p<0·0001). A crude HR of treatment termination in CDC health facilities was 7·5 (95% CI 6·3–9·0) compared with hospital geographical distributions. InterpretationSentinel hospital HIV service delivery had better retention, and substantially lower mortality than did CDC-based service delivery. This study has implications for the expansion HIV service delivery, and should be made to adopt a sentinel hospital-based system of integrated HIV care and treatment. FundingThis study was supported by Twelve Fifth Key Research grant from the Ministry of Science and Technology, People's Republic of China (2012ZX10001003–003), Science and Technology Program of Guangzhou (201300000092), and the US National Institutes of Health Fogarty International Center Global Infectious Diseases Training Grant (1D43TW009532–01). These fundings had no role in study design and data analyses.

The Benefits of Early Antiretroviral Therapy for HIV Infection: How Early is Early Enough?

The case of the “Berlin Patient” is well-known. In 2007, an HIV-infected adult with leukemia underwent allogeneic hematopoietic stem cell transplant and was cured of his cancer (Hutter et al., 2009). As the donor was homozygous for the CCR5Δ32 deletion (which makes CD4+ T cells difficult to infect with HIV), the repopulated immune system lacked any detectable HIV and the patient has been apparently been cured. Two subsequent allogeneic transplants performed under potent ART (which protected the donor cells from de novo infection) resulted in a dramatic reduction in the frequency of cells harboring replication-competent HIV (generally referred to as the HIV “reservoir”) (Henrich et al., 2014). This was not enough to cure these two patients, however, as both individuals experienced a delayed but robust rebound in viremia after stopping therapy. A true cure will likely require complete eradication of the entire reservoir of HIV. This is a formidable challenge.

Profiles of HIV-infected anti-retroviral therapy naïve children from Mumbai, India

This study aimed to investigate the demographic profiles of human immunodifficiency virus (HIV) infected anti-retroviral therapy (ART) naïve children in our hospital and their relations to the clinical, immunological and nutritional status. A cross-sectional study was conducted in an Integrated Counselling and Testing Center (ICTC) at a tertiary care hospital in Mumbai. ART naïve HIV positive children were enrolled in the study. The demographic profiles, clinical features, immunological (CD4%/CD4 count) and nutritional status of these children were recorded. The agreement between clinical, immunological and nutritional staging was determined using Cohen's kappa test. In 192 HIV-infected ART naive children enrolled with a median age of 9 years (range 3 months-14 years), 97.4% acquired infection through vertical transmission. The most common clinical presentation was fever (39.6 %), followed by generalized lymphadenopathy (32.3%), cough (22.4%) and diarrhoea (9.9%). Tuberculosis was seen in 22.9% of the children. The agreement was fair between clinical and immunological staging, and slight between nutritional, immunological and clinical staging. Perinatal transmission is the most common mode of acquiring HIV infection in children. The Prevention of Parent to Child Transmission (PPTCT) program should be strengthened for lowering the transmission rate by providing extended ART to mothers during pregnancy and breast-feeding. Tuberculosis remains a major concern in HIV-infected children. The poor correlation between WHO clinical and immunological staging emphasizes the importance of making CD4 facilities available in HIV prevalent areas. Malnutrition cannot be used as a surrogate marker for predicting stage or severity as it is common at all stages of HIV disease.

Wide Variations in Compliance with Tuberculosis Screening Guidelines and Tuberculosis Incidence between Antiretroviral Therapy Facilities - Côte d'Ivoire.

BackgroundIn Côte d’Ivoire, tuberculosis (TB) is a common cause of death among HIV-infected antiretroviral therapy (ART) enrollees. Ivorian guidelines recommend screening for TB and initiation of TB treatment before ART initiation. Compliance with these guidelines can help reduce TB-related mortality during ART and possibly nosocomial TB transmission.Methods and FindingsIn a retrospective cohort study among 3,682 randomly selected adults (≥15 years old) starting ART during 2004–2007 at 34 randomly selected facilities, documentation of TB screening completion, prevalence of active TB at ART initiation, and incidence of TB during ART were evaluated. At ART initiation, median age was 36 years, 67% were female, and median CD4 count was 135 cells/μL. Among all 3,682 enrollees, 73 (2%) were on TB treatment at the time of referral to the ART facility. Among the 3,609 not on TB treatment, 1,263 (36%) were documented to receive some TB screening before ART initiation; 21% were screened for cough, 21% for weight loss, 18% for fever, 18% for TB contacts, and 12% for night sweats. Among the 1,263 screened, 111 (11%) were diagnosed with TB and started TB treatment before ART. No associations between patient characteristics and probability of being screened were noted. However, documentation of TB screening completion before ART varied widely by ART facility from 0–100%. TB incidence during ART was 3.0 per 100 person-years but varied widely by ART facility from 0/100 person-year to 13.1/100 person-years.ConclusionsScreening for TB before ART initiation was poorly documented. Facility-level variations in TB screening documentation suggest facility-level factors, such as investment in training programs, might determine documentation practices. Targeting under-performing ART facilities with improvement activities is needed. Variations among facilities in TB incidence warrant further research. These incidence variations could reflect differences between facilities in TB screening, diagnostic tests, documentation practices, or TB risk possibly related to infection control practices or local community TB incidence.

Case Report: Right flank pain as the only symptom for acute pancreatitis in a patient on treatment for HIV infection

Acute pancreatitis often presents with severe epigastric pain and referred pain to the back. In practice, epigastric pain of pancreatitis may also occasionally present with associated left sided flank pain. Here, we present a case of a 38 year old man on antiretroviral therapy for HIV infection, who came with severe right sided lumbar pain to the emergency department. The initial abdominal ultrasonogram was normal and the patient was misdiagnosed as possible renal associated pain. The CECT scan done the following day showed acute pancreatitis with peripancreatic fat stranding, fluid upto the right perinephric space and thickening of pararenal fascia. Urinalysis and renal function tests were within normal limits. On literature search, we could not find any reported cases of acute pancreatitis with right lumbar pain as the only presenting symptom. Patients taking anti-retroviral therapy develop pancreatitis most commonly due to hypertriglyceridemia. However, this patient had a normal lipid profile. On ruling out other causes, we conclude that his pancreatitis was caused by Azatanavir, which has only post marketing reports of pancreatitis and we could find no specific study linking the drug to the disease.KEY WORDS: Pancreatitis; HIV infection; ART; Azatanavir

Elevation and persistence of CD8 T-cells in HIV infection: the Achilles heel in the ART era.

IntroductionHIV infection leads to a disturbed T-cell homeostasis, featured by a depletion of CD4 T-cells and a persistent elevation of CD8 T-cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T-cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.MethodsA comprehensive literature review of publications in English language was conducted using major electronic databases. Our search was focused on factors contributing to CD8 T-cell dynamics in HIV infection and following antiretroviral therapy (ART).DiscussionNormalization of CD8 counts is seldom observed even with optimal CD4 recovery following long-term treatment. Initiation of ART in primary HIV infection leads to enhanced normalization of CD8 count compared with long-term ART initiated in chronic infection. Importantly, such CD8 elevation in treated HIV infection is associated with an increased risk of inflammatory non-AIDS-related clinical events independent of CD4 T-cell recovery. The mechanisms underlying CD8 persistence remain largely unknown, which may include bystander activation, exhaustion and immunosenescence of CD8 T-cells. The information provided herein will lead to a better understanding of factors associated with CD8 persistence and contribute to the development of strategies aiming at CD8 normalization.ConclusionsPersistence of CD8 T-cell elevation in treated HIV-infected patients is associated with an increased risk of non-AIDS-related events. Now that advances in ART have led to decreased AIDS-related opportunistic diseases, more attention has been focused on reducing non-AIDS events and normalizing persistent CD8 T-cell elevation.

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa.

BackgroundIn sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up.MethodsIn a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05.ResultsData from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4 % had CD4+ T-cell counts <100 cells/μL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9 % (established cumulative mortality = 2.3 %, loss to follow-up = 24.6 %), 5.6 % were transferred to other service providers, and 67.5 % were retained in care. A diagnosis of Kaposi’s sarcoma (hazard ratio (HR) = 3.3, 95 % CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95 % CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95 % CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95 % CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10 %; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status.ConclusionsAmong HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

High MIP-1β Levels in Plasma Predict Long-Term Immunological Nonresponse to Suppressive Antiretroviral Therapy in HIV Infection.

HIV-infected patients who fail to reconstitute their CD4 T-cell counts during suppressive antiretroviral therapy (ART) have increased risk of both AIDS-related and non-AIDS-related morbidity and mortality. Improved understanding of immunological nonresponse (INR) is necessary to enable earlier clinical intervention. In a cohort of 112 HIV-infected patients starting ART, we performed a serial analysis of 32 plasma-soluble markers, assessed by multiplex cytokine and enzyme immunoassay. Samples were drawn pre-ART and during the first 3 years of treatment, with a final observation time of 8.4 years (interquartile range, 7.0-10.7 years) on ART. Long-term INR (LT-INR) was defined as failure to reach a CD4 T-cell count >350 cells per microliter. Marker stability was evaluated by parallel analysis of samples from ART-naïve and HIV-seronegative controls. Baseline CD4 T-cell counts predicted subsequent LT-INR (n = 15) [odds ratio, 1.10 (95% confidence interval: 1.01 to 1.19) pr. 10 cells/μL reduction in CD4 count, P = 0.030] in the cohort as a whole, but not in patients with baseline CD4 counts <200 cells per microliter (n = 78). LT-INR was best characterized by elevated plasma levels of the CC chemokine macrophage inflammatory protein 1β (MIP-1β), both at baseline (pre-ART) and during ART. In patients with baseline CD4 counts <200 cells per microliter, baseline MIP-1β predicted LT-INR [odds ratio 1.23 (95% confidence interval: 1.02 to 1.47) per 10 pg/mL increase in MIP-1β, P = 0.029]. Elevated pre-ART levels of MIP-1β identified LT-INR patients who started ART at CD4 counts <200. INR was characterized by persistently high MIP-1β during suppressive ART. Thus, MIP-1β may be of use for early identification of LT-INR.