HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy

Introduction

We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART.

Methods

365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm.

Results

PDR to any ARV drug was 11.5% (95% CI 8.4–15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p<0.0001). No significant trends in time were observed when comparing 2013 and 2014, when using a moving average approach along the study period or when comparing individuals with >500 vs. <350 CD4+ T cells/μL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%). The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the ≥48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343). M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01), but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naïve individuals and between ART-naïve individuals.

Conclusions

The global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.     

Glucose Metabolism Disorders,HIV and Antiretroviral Therapy among Tanzanian Adults

Introduction

Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.

Methods

In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.

Results

HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.

Conclusions

HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.     

Antiretroviral Therapy,Especially Efavirenz,Is Associated with Low Bone Mineral Density in HIV-Infected South Africans

Purpose

We determined the prevalence and correlates of low bone mineral density (BMD) in HIV-infected South Africans as there is a paucity of such data from Africa.

Methods

BMD and serum 25-hydroxyvitamin D were measured in HIV-positive participants on antiretroviral therapy (ART) and in those not yet on ART (ART-naïve).

Results

We enrolled 444 participants [median age 35(IQR: 30, 40) years; 77% women]. BMD was low (z score <-2SD) in 17% and 5% of participants at the lumbar spine and total hip, respectively. Total hip [0.909 (SD 0.123) vs 0.956 (SD 0.124) g/cm², p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm², p = 0.0001] were lower in the ART, compared to the ART-naïve group. Vitamin D deficiency was present in 15% of participants and was associated with efavirenz use [adjusted OR 2.04 (95% CI 1.01 to 4.13)]. In a multivariate linear regression, exposure to efavirenz or lopinavir-based ART was associated with lower total hip BMD, whereas higher weight, being male and higher vitamin D concentration were associated with higher total hip BMD (adjusted R² = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R² = 0.13).

Conclusions

Vitamin D status, use of efavirenz or lopinavir/ritonavir, weight, age and sex are significantly associated with lower BMD in this young cohort of HIV-infected South Africans.     

Cardiac Effects of Antiretroviral-Na?ve versus Antiretroviral-Exposed HIV Infection in Children

Background

Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown.

Methods

This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values.

Results

Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children.

Conclusions

ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter and higher mass, but less functional impairment.     

Comparison of Cryptococcal Antigenemia between Antiretroviral Na?ve and Antiretroviral Experienced HIV Positive Patients at Two Hospitals in Ethiopia

Background

Cryptococcal meningitis is a major cause of HIV/AIDS-related deaths in Africa. Cryptococcosis is a neglected killer. However, meningitis can be prevented by early cryptococcal antigen (CrAg) screening and preemptive antifungal treatment during a prolonged period of detectable, subclinical infection. We determined the prevalence of cryptococcal antigenemia in comparison to CD4 count and clinical symptoms.

Methods

We surveyed 254 consenting HIV-infected participants to obtain demographic information and clinical history. Serum CrAg was measured by latex agglutination at two sites in the Oromia region of Ethiopia among all persons receiving a CD4 count.

Results

Of the 254 participants, 127(50.0%) were ART-naïve, 121(47.6%) were ART-experienced, and 6(2.4%) were ART-defaulters. The prevalence of cryptococcal antigenemia was 10.2% overall being 14.2% among ART-naive, 4.1% among ART-experienced, and 50% (3/6) among ART-defaulters, irrespective of CD4 count. Cryptococcal antigenemia was more frequently detected from ART-naïve patients (p = 0.012) and ART-defaulters (p = 0.001) compared with ART-experienced. Serum CrAg positivity was 20.9% in persons with CD4≤150 cells/µL, 12.2% in 151–200 cells/µL, 5.8% among 201–350 CD4/µL, and none above 350 cells/µL. Potential meningitis symptoms were common in the outpatient cohort irrespective of CrAg-status, with only fever and altered mental status statistically more common in CrAg-positive compared to CrAg-negative persons (P<0.05), yet no symptom had a positive predictive value >33%.

Conclusion

We report a 20.9% cryptococcal antigenemia prevalence among those with CD4+ T cells count ≤150 cells/µL, irrespective of ART status, with even higher CrAg prevalence in ART-naïves and ART-defaulters. These groups are target populations for CrAg screening at entry into HIV care.     

Increasing Transfers-Out from an Antiretroviral Treatment Service in South Africa: Patient Characteristics and Rates of Virological Non-Suppression

Objectives

To determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township.

Methods

This retrospective cohort study included all patients aged ≥15 years who enrolled between September 2002 and December 2009. Follow-up data were censored in December 2010. Kaplan-Meier survival analysis was used to describe time to transfer-out and cox proportional hazard analysis was used to determine associated risk factors.

Results

4511 patients (4003 ART-naïve and 508 non-naïve at baseline) received ART during the study period. Overall, 597 (13.2%) transferred out. The probability of transferring out by one year of ART steadily increased from 1.4% in 2002/2004 cohort to 8.9% for the 2009 cohort. Independent risk factors for transfer-out were more recent calendar year of enrolment, younger age (≤25 years) and being ART non-naïve at baseline (i.e., having previously transferred into this clinic from another facility). The proportions of patients transferred out who had a CD4 cell count <200 cells/µL and/or a viral load ≥1000 copies/mL were 19% and 20%, respectively.

Conclusions

With scale-up of ART over time, an increasing proportion of patients are transferring between ART services and information systems are needed to track patients. Approximately one-fifth of these have viral loads >1000 copies/mL around the time of transfer, suggesting the need for careful adherence counseling and assessment of medication supplies among those planning transfer.     

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.     

Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambaréné, Gabon

Background

Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections.

Methodology and Principal Findings

This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence.

Conclusions/Significance

CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established.     

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

Objective

We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin.

Design

Cohort study of adult patients on ART.

Setting

GHESKIO Clinic in Port-au-Prince, Haiti.

Participants

4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008.

Main Outcome Measure

Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin.

Results

In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used.

Conclusions

If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted.     

Decreased Chronic Morbidity but Elevated HIV Associated Cytokine Levels in HIV-Infected Older Adults Receiving HIV Treatment: Benefit of Enhanced Access to Care?

Background

The association of HIV with chronic morbidity and inflammatory markers (cytokines) in older adults (50+years) is potentially relevant for clinical care, but data from African populations is scarce.

Objective

To examine levels of chronic morbidity by HIV and ART status in older adults (50+years) and subsequent associations with selected pro-inflammatory cytokines and body mass index.

Methods

Ordinary, ordered and generalized ordered logistic regression techniques were employed to compare chronic morbidity (heart disease (angina), arthritis, stroke, hypertension, asthma and diabetes) and cytokines (Interleukins-1 and -6, C-Reactive Protein and Tumor Necrosis Factor-alpha) by HIV and ART status on a cross-sectional random sample of 422 older adults nested within a defined rural South African population based demographic surveillance.

Results

Using a composite measure of all morbidities, controlling for age, gender, BMI, smoking and wealth quintile, HIV-infected individuals on ART had 51% decreased odds (95% CI:0.26-0.92) of current morbidity compared to HIV-uninfected. In adjusted regression, compared to HIV-uninfected, the proportional odds (aPOR) of having elevated inflammation markers of IL6 (>1.56pg/mL) was nearly doubled in HIV-infected individuals on (aPOR 1.84; 95%CI: 1.05-3.21) and not on (aPOR 1.94; 95%CI: 1.11-3.41) ART. Compared to HIV-uninfected, HIV-infected individuals on ART had >twice partial proportional odds (apPOR=2.30;p=0.004) of having non-clinically significant raised hsCRP levels(>1ug/mL); ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9ug/mL;p=0.008).

Conclusions

Although HIV status was associated with increased inflammatory markers, our results highlight reduced morbidity in those receiving ART and underscore the need of pro-actively extending these services to HIV-uninfected older adults, beyond mere provision at fixed clinics. Providing health services through regular community chronic disease screening would ensure health care reaches all older adults in need.     

Helicobacter pylori Infection Is Associated with Higher CD4 T Cell Counts and Lower HIV-1 Viral Loads in ART-Na?ve HIV-Positive Patients in Ghana

Background

Worldwide, there is a high co-endemicity of HIV and H. pylori infection and there is growing evidence that H. pylori co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of H. pylori infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country.

Methods

HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana. H. pylori status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to H. pylori status.

Results

The prevalence of H. pylori infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p<0.0001). In HIV patients, H. pylori prevalence decreased in parallel with CD4+ T cell counts. In ART-naïve HIV-infected individuals, but not in those taking ART, H. pylori infection was associated with higher CD4 cell counts (312 vs. 189 cells/μL, p<0.0001) and lower HIV-1 viral loads (4.92 vs. 5.21 log10 copies/mL, p = 0.006). The findings could not be explained by socio-demographic confounders or reported use of antibiotics. Having no access to tap water and higher CD4+ T cell counts were identified as risk factors for H. pylori infection.

Conclusions

H. pylori prevalence was inversely correlated with the degree of immunosuppression. In ART-naïve individuals, H. pylori infection is associated with favorable immunological and virological parameters. The underlying mechanisms for this association are unclear and warrant investigation.     

Restoration of CMV-Specific-CD4 T Cells with ART Occurs Early and Is Greater in Those with More Advanced Immunodeficiency

Objectives

Restoration of Cytomegalovirus-specific-CD4 T cell (CMV-Sp-CD4) responses partly accounts for the reduction of CMV-disease with antiretroviral-therapy (ART), but CMV-Sp-CD4 may also drive immune activation and immunosenescence. This study characterized the dynamics of CMV-Sp-CD4 after ART initiation and explored associations with CD4 T cell recovery as well as frequency of naïve CD4 T cells at week 96.

Methods

Fifty HIV-infected, ART-naïve Thai adults with CD4 T cell count ≤350cells/µL and starting ART were evaluated over 96 weeks (ClinicalTrials.gov identifier NCT01296373). CMV-Sp-CD4 was detected by co-expression of CD25/CD134 by flow cytometry after CMV-antigen stimulation.

Results

All subjects were CMV sero-positive, 4 had quantifiable CMV-DNA (range 2.3-3.9 log₁₀ copies/mL) at baseline but none had clinically apparent CMV-disease. Baseline CMV-Sp-CD4 response was positive in 40 subjects. Those with CD4 T cell count <100cells/µL were less likely to have positive baseline CMV-Sp-CD4 response (P=0.003). Positive baseline CMV-Sp-CD4 response was associated with reduced odds of quantifiable CMV-DNA (P=0.022). Mean CD4 T cell increase at week 96 was 213 cells/µL. This was associated positively with baseline HIV-VL (P=0.001) and negatively with age (P=0.003). The frequency of CMV-Sp-CD4 increased at week 4 (P=0.008), then declined. Those with lower baseline CMV-Sp-CD4 (P=0.009) or CDC category C (P<0.001) had greater increases in CMV-Sp-CD4 at week 4. At week 96, CD4 T cell count was positively (P<0.001) and the frequency of CMV-Sp-CD4 was negatively (P=0.001) associated with the percentage of naïve CD4 T cells.

Conclusions

Increases in CMV-Sp-CD4 with ART occurred early and were greater in those with more advanced immunodeficiency. The frequency of CMV-Sp-CD4 was associated with reduced naïve CD4 T cells, a marker associated with immunosenescence.     

Lipid Peroxidation and Total Cholesterol in HAART-Na?ve Patients Infected with Circulating Recombinant Forms of Human Immunodeficiency Virus Type-1 in Cameroon

Background

HIV infection has commonly been found to affect lipid profile and antioxidant defense.

Objectives

To determine the effects of Human Immunodeficiency Virus (HIV) infection and viral subtype on patient’s cholesterol and oxidative stress markers, and determine whether in the absence of Highly Active Antiretroviral Therapy (HAART), these biochemical parameters could be useful in patient’s management and monitoring disease progression in Cameroon. For this purpose, we measured total cholesterol (TC), LDL cholesterol (LDLC), HDL cholesterol (HDLC), total antioxidant ability (TAA), lipid peroxidation indices (LPI), and malondialdehyde (MDA) in HIV negative persons and HIV positive HAART-naïve patients infected with HIV-1 group M subtypes.

Methods

We measured serum TC, LDLC, HDLC, plasma MDA, and TAA concentrations, and calculated LPI indices in 151 HIV-positive HAART-naïve patients and 134 seronegative controls. We also performed gene sequence analysis on samples from 30 patients to determine the effect of viral genotypes on these biochemical parameters. We also determined the correlation between CD4 cell count and the above biochemical parameters.

Results

We obtained the following controls/patients values for TC (1.96±0.54/1. 12±0. 48 g/l), LDLC (0. 67±0. 46/0. 43±0. 36 g/l), HDLC (105. 51±28. 10/46. 54±23. 36 mg/dl) TAA (0. 63±0. 17/0. 16±0. 16 mM), MDA (0. 20±0. 07/0. 41±0. 10 µM) and LPI (0. 34±0. 14/26. 02±74. 40). In each case, the difference between the controls and patients was statistically significant (p<0.05). There was a positive and statistically significant Pearson correlation between CD4 cell count and HDLC (r = +0.272; p<0.01), TAA (r = +0.199; p<0.05) and a negative and statistically significant Pearson correlation between CD4 cell count and LPI (r = −0.166; p<0.05). Pearson correlation between CD4 cell count and TC, CD4cell count and LDLC was positive but not statistically significant while it was negative but not statistically significant with MDA. The different subtypes obtained after sequencing were CRF02_AG (43.3%), CRF01_AE (20%), A1 (23.3%), H (6.7%), and G (6.7%). None of the HIV-1 subtypes significantly influenced the levels of the biochemical parameters, but by grouping them as pure subtypes and circulating recombinant forms (CRFs), the CRF significantly influenced TC levels. TC was significantly lower in patients infected with CRF (0.87±0.27 g/l) compared to patients infected with pure HIV-1 subtypes (1.32±0.68 g/l) (p<0.017). MDA levels were also significantly higher in patients infected with HIV-1CRF01_AE (0.50±0.10 µM), compared to patients infected with CRF02_AG (0. 38±0. 08 µM) (p<0.018).

Conclusion

These results show that HIV infection in Cameroon is associated with significant decrease in TAA, LDLC, HDLC and TC, and increased MDA concentration and LPI indices which seem to be linked to the severity of HIV infection as assessed by CD4 cell count. The data suggests increased oxidative stress and lipid peroxidation in HIV-infected patients in Cameroon, and an influence of CRFs on TC and MDA levels.     

An Evaluation of HIV Elite Controller Definitions within a Large Seroconverter Cohort Collaboration

Background

Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype.

Methods

We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve).

Results

Most definitions classify ∼1% as ECs with median HIV-RNA 43–903 copies/ml and median CD4>500 cells/mm³. Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up≥ six months, or with 90% of measurements <400 copies/ml over ≥10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5–19.0 for non-ECs compared to ECs).

Conclusions

ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥10 years be used to define this phenotype.     

Plasma HIV-2 RNA According to CD4 Count Strata among HIV-2-Infected Adults in the IeDEA West Africa Collaboration

Background

Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve.

Method

A cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL).

Results

A total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (<10 cps/mL), it was detectable between 10-100 cps/mL in 35.8%, between 100-1000 cps/mL in 11.7% and >1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm³ and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm³ (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm³ with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm³, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL.

Conclusion

This study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment.     

Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

Background

There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.

Methodology/Principal Findings

To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females.

Conclusions/Significance

Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.