ART-naive Patients Research Articles

No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen. In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list). Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40). This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

Ready for HIV Dual Therapy? - New Data from International HIV/AIDS Society 2017

The introduction of combination antiretroviral therapy (ART) in the 1990s has fundamentally transformed the landscape of HIV medicine, greatly improved disease morbidity and mortality, and reduced transmission rates across all demographic groups. Central to this success was the idea that to achieve best disease outcomes and minimize the development of drug resistance, at least three antiretroviral agents should be used for HIV treatment. This therapeutic strategy is a core tenet of HIV medicine, backed by incontrovertible scientific evidence, and made easy to deploy by the high compliance levels with once-daily coformulations, which have generally been well tolerated. However, there has been increasing support for a paradigm shift toward dual therapy in recent years, particularly during the maintenance therapy phase of treatment. This concept advocates that once virologic suppression has been achieved with at least three antiretroviral drugs during the treatment initiation phase, a switch to a two-drug regimen should be possible. The results of Phase III of the SWORD trials (Llibre et al., Abstract 44LB) and LAMIDOL trial (Joly et al., Abstract 458) presented at the 2017. Conference on Retroviruses and Opportunistic Infections earlier this year seemed to lend support this hypothesis. More new evidence was recently presented at the 2107 International HIV/AIDS Society (IAS) meeting in Paris that adds to the growing body of evidence in favor of a two-drug regimen approach in maintenance therapy. The LATTE-2 study (Eron et al., Abstract 5628) was of major interest because of the exciting new therapeutic options that long-acting injectable antiretroviral agents may bring in the near future. However, more than that, the findings of comparable response between a traditional three-drug oral regimen and a novel injectable two-drug regimen at 96 weeks were quite noteworthy. In this Phase II, multicenter open-label study of 286 HIV-infected ARTnaïve patients, once-daily oral cabotegravir/abacavir/lamivudine achieved virologic suppression in 84% of study participants. In comparison, 87% in the injectable cabotegravir/rilpivirine once every 4-weekly group and 94% in injectable cabotegravir/rilpivirine once every 8-weekly group remained suppressed at 96 weeks. Crucially, no drug resistance mutations were seen in study participants who remained on their regimen. While the idea of a two-drug regimen has been entertained for maintenance therapy, there may be little willingness to push this further into the area of antiretroviral treatment initiation, for the justifiable concerns that exist around the emergence of drug resistance. Despite this, new data presented at the IAS 2017 showed that the idea is not without merit. In a proof of concept, the ACTG A5353 single-arm pilot study of 120 treatment naïve HIV-infected participants with high viral load (VL ≥1000 and >500,000 copies/mL), showed that once-daily dolutegravir/lamivudine had virologic efficacy of 90% at 24 weeks, with 96% of the as-treated study population achieving VL >50 copies/mL (Taiwo et al., Abstract MOAB0107LB). The regimen was well tolerated, with no reported drug resistance mutations while on treatment. There are many real-world advantages to a two-drug regimen approach, among them lower costs (crucial in resource-limited settings where affordability may be a limiting factor), fewer adverse effects or drug toxicities, and possibly improved compliance. These are all important considerations, given that improved mortality now means patients are going to stay on ART treatment for much longer than previously seen. But how the two-drug regimen approach will hold up against firmly held norms and tradition is far from clear, and it is almost certain that the understandable nervousness that surrounds this idea will continue to last. Until the case for the two-drug regimen approach is made more convincingly in ongoing and future trials, the "three or more" rule will reign, not only as the orthodoxy but also as the cornerstone of good clinical practice.

Moderate Levels of Pretreatment HIV Drug Resistance — Zimbabwe, April–July 2015

BackgroundThe World Health Organization (WHO) HIV Drug Resistance (HIVDR) report 2012 demonstrated that the levels of HIVDR to first-line antiretroviral therapy (ART) are increasing. This finding threatens to reverse a decade of gains in HIV/AIDS epidemic control. The WHO Global Action Plan for HIVDR emphasizes strengthening surveillance of drug resistance through the implementation of national cross-sectional surveys. We conducted such survey to determine the prevalence of HIVDR among ART-naive patients in Zimbabwe and to describe the profile of the surveillance drug resistance mutations (SDRM) encountered in the country.MethodsA prospective, nationally representative, cross-sectional survey was conducted in 35 clinical sites selected using two stage probability proportional to size sampling. Patients were enrolled during April–July 2015. Specimens were sent for genotyping to CDC Atlanta. SDRM were interpreted using Stanford HIV Drug Resistance Database classification.ResultsA total of 361 subjects were surveyed. Most participants were female (60.3%) and the median age was 35.8 years. Thirty-four out of 361subjects presented with ≥1 SDRM (9.4%, 95% confidence interval: 6.8–12.8%) prior to initiation antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected mutation (n = 30). Only two patients presented with a nucleoside reverse transcriptase inhibitor mutation and one patient presented with a protease inhibitor mutation. In two patients, ≥3 SDRMs were detected, which may suggest they were not truly ART-naïve.ConclusionThis study provides national estimates of HIVDR in a high burden country with broad access to ART and provides valuable inisight on the state of HIVDR in such setting. Zimbabwe has reached moderate levels of HIVDR in ART-naive patients, as specified by the WHO classification. These levels may impact the ability to achieve viral suppression in a significant number of patients initiating standard ART regimens in Zimbabwe, where NNRTI-based regimens are used as the first line. The use of drugs with high resistance barrier, such as dolutegravir, may improve the care of patients in the developing world, where individualized pretreatment genotype is not feasible.Disclosures All authors: No reported disclosures.

Risk factors for delayed antiretroviral therapy initiation among HIV-seropositive patients.

Prompt initiation of combination antiretroviral therapy (ART) is important to reduce comorbidity and mortality among people living with HIV, especially for those with a low CD4 cell count. However there is evidence that not everyone receives prompt initiation of ART after enrolling into HIV care. The current study investigated factors associated with failure to initiate ART within two years of entering into care among those with a CD4 count at or below 350 cells/mm3. The sample included 4,907 ART-naive patients with a CD4 count at or below 350 cells/mm3 enrolled between January 1, 2003 and December 31, 2012 at any of eight clinical sites in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). The two-year risk of delayed ART initiation was estimated using a log-binomial regression model with stabilized inverse probability of censoring weights for those lost to follow-up. Adjusting for other factors, an earlier enrollment date was the sole demographic characteristic associated with an increased risk of delayed ART initiation. Higher CD4 count, lower viral load, and a prevalent AIDS diagnosis were clinical characteristics associated with delayed ART initiation. Gender, age, race/ethnicity and HIV risk factors such as reported male-to-male sexual contact and injection drug use were not associated with delayed ART initiation. This study identified characteristics of patients for whom treatment was strongly to moderately recommended but who did not initiate ART within two years of entering care. Despite the known benefits of early antiretroviral therapy initiation, a lower viral load measurement may continue to be an important clinical characteristic in the more recent era with current ART initiation guidelines. These findings provide a target for closer monitoring and intervention to reduce disparities in HIV care.

Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients.

The global intensification of antiretroviral therapy (ART) can lead to increased rates of HIV drug resistance (HIVDR) mutations in treated and also in ART-naive patients. ART-naive HIV-1-infected patients from Cameroon were subjected to a multimethod HIVDR analysis using amplification-refractory mutation system (ARMS)-PCR, Sanger sequencing, and longitudinal next-generation sequencing (NGS) to determine their profiles for the mutations K103N, Y181C, K65R, M184V, and T215F/Y. We processed 66 ART-naive HIV-1-positive patients with highly diverse subtypes that underlined the predominance of CRF02_AG and the increasing rate of F2 and other recombinant forms in Cameroon. We compared three resistance testing methods for 5 major mutation sites. Using Sanger sequencing, the overall prevalence of HIVDR mutations was 7.6% (5/66) and included all studied mutations except K65R. Comparing ARMS-PCR with Sanger sequencing as a reference, we obtained a sensitivity of 100% (5/5) and a specificity of 95% (58/61), caused by three false-positive calls with ARMS-PCR. For 32/66 samples, we obtained NGS data and we observed two additional mismatches made up of minority variants (7% and 18%) that might not be clinically relevant. Longitudinal NGS analyses revealed changes in HIVDR mutations in all five positive subjects that could not be attributed to treatment. In one of these cases, superinfection led to the temporary masking of a resistant virus. HIVDR mutations can be sensitively detected by ARMS-PCR and sequencing methods with comparable performances. Longitudinal changes in HIVDR mutations have to be considered even in the absence of treatment.

Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia

BackgroundHighly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The aim of this study was to evaluate the durability of first line antiretroviral therapy and to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART.MethodsA Hospital based retrospective study was conducted from January 2007 to August 2013 at Jimma University Hospital, Southwest Ethiopia. Data on the prescribed ARV along with start date, switching date, and reason for change was collected. The primary outcome was defined as the time-to-treatment change. We adopted a multi-state survival modeling approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another.ResultA total of 1284 ART naive patients were included in the study. Almost half of the patients (41.2%) changed their treatment during follow up for various reasons; 442 (34.4%) changed once and 86 (6.69%) changed more than once. Toxicity was the most common reason for treatment changes accounting for 48.94% of the changes, followed by comorbidity (New TB) 14.31%. The HAART combinations that were robust to treatment changes were tenofovir (TDF) + lamivudine (3TC)+ efavirenz (EFV), tenofovir + lamivudine (3TC) + nevirapine (NVP) and zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) with 3.6%, 4.5% and 11% treatment changes, respectively.ConclusionMoving away from drugs with poor safety profiles, such as stavudine(d4T), could reduce modification rates and this would improve regimen tolerability, while preserving future treatment options.

Association of Metabolic Syndrome and Oxidative DNA Damage in HIV/AIDS Patients.

HIV-infected adults may be likely to have metabolic syndrome (MS) at younger ages and in the absence of obesity compared with general population. In the present study, we determined prevalence of MS and its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1 infected patients with different ART status. We used plasma level of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as a biomarker of oxidative DNA damage. To measure plasma 8-OHdG we used 8-OHdG enzyme-linked, immunosorbent assay. The biomarkers of MS were insulin resistance, Cholesterol/HDL ratio, Waist circumference and Hypertension. MS and oxidative DNA damage were significantly higher in HIV-positive patients with second line ART and first line ART than ART-naive patients. In a logistic regression analysis, increased MS was positively associated with the increased DNA damage (OR: 29.68, 95%:13.47, CI: 65.40) P=0.0001. ART plays a significant role in the development of MS and oxidative DNA damage in HIV-positive patients taking antiretroviral therapy. Awareness and knowledge of MS and DNA damage in HIV/AIDS patients may prove helpful to clinicians to manage non-AIDS diseases such as cardiovascular disease and cancer. To determine exact role of ART in induction of MS and DNA damage larger studies are warranted.

Selecting patients who can be re-challenged with Nevirapine in case of skin rash with Efavirenz – A Study

Introduction and Objectives: A common adverse effect of Efavirenz (EFV) – a first line drug used in treatment of patients with HIV infections is skin rash. In case of EFV-induced skin rash, the usual practice is to switch to a Protease Inhibitor (PI), as another non-nucleoside reverse transcriptase inhibitor (NNRTI) might have cross-­reactivity with a higher incidence of skin rash which is often severe. The aim of the study was therefore to determine whether with careful evaluation and stratification, using pre­defined criteria of patients who developed rash with EFV, it might be possible to find a subset of patients among whom Nevirapine (NVP) may be safely used, sparing PIs for second-­line treatment. Methods: Of 7000 ART naive patients initiated on EFV in an 18 month period from November 2014 to April 2016, 97(1.9%) developed a rash. Patients developing rash with EFV were carefully selected using pre­defined criteria: grade of rash (only Grade I/II rash were selected), hepatic function, age, gender and CD4 levels (males > 400 cells/cmm and females >250 cells/cmm were excluded if hepatic function was deranged), co­-infection status (Hepatitis B/C were excluded), opportunistic infections, concomitant use of other drugs. Based on these stratification criteria, 23 of the 97 patients were selected for challenge with NVP. Results: Of the 23 selected patients, only 3 (13%) patients developed recurrence of rash, all being mild in nature. Conclusions: In carefully selected patients, challenge with NVP can be done in case of rash with EFV as the theory of cross­-reactivity does not always hold true. This might help spare PIs in the initial phase, which could then be used as second line therapy - a particularly helpful strategy in developing countries, where newer drugs are still not available under public health programmes.

Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A cross-sectional study.

HIV/AIDS causes high morbidity and mortality through both immunosuppression and complications not directly related to immunosuppression. Haematological abnormalities, including various cytopenias, occur commonly in HIV through immune and non-immune pathways. Though these complications could potentially cause serious clinical implications, published literature on the magnitude of this problem and its associated factors in Tanzania is scarce. This study aimed at determining the prevalence and risk factors of HIV-associated cytopenias among ART-naive patients enrolling for care and treatment services at Bugando Care and Treatment Centre (CTC) in Mwanza, Tanzania. This was a cross-sectional clinic-based study done between March 2015 and February 2016, involving all antiretroviral therapy (ART)-naive adult HIV-positive patients enrolling for care and treatment services at Bugando CTC. Patients younger than 18 years and those with missing data were excluded. Data were analysed using Stata version 11 to determine the prevalence and risk factors of cytopenias. A total of 1205 ART-naive patients were included. Median age was 41 years (interquartile range [IQR] 32 to 48). Most participants were female (n = 789; 65.6%), with a female-to-male ratio of 2:1. The median baseline CD4 count was 200 cells/µL (IQR 113 to 439). About half (49%) of the study participants had baseline CD4 counts less than 200 cells/µL. Anaemia, leucopenia, and thrombocytopenia were found in 704 (58.4%), 285 (23.6%), and 174 (14.4%) participants, respectively, and these were strongly associated with advanced HIV infection. The magnitude of cytopenias is high among ART-naive HIV-positive adults, and cytopenias are more marked with advanced HIV infection. Early diagnosis of HIV and timely initiation of ART could potentially reduce the number of people living with advanced HIV disease and its associated complications, including the cytopenias investigated in this study. Patients with cytopenias should undergo thorough screening for tuberculosis, which is an important and treatable correlate of cytopenia, in addition to close follow-up for any potential negative outcomes.

Production of IgG antibodies to pneumococcal polysaccharides is associated with expansion of ICOS+ circulating memory T follicular-helper cells which is impaired by HIV infection.

Dysfunction of T follicular-helper (TFH) cells is a possible cause of impaired germinal centre (GC) and IgG antibody responses in individuals with human immunodeficiency virus-1 (HIV-1) infection and might contribute to decreased magnitude and isotype diversification of IgG antibodies to pneumococcal polysaccharides (PcPs). We examined the production of IgG1 and IgG2 antibodies to PcPs 4, 6B, 9V and 14 by enumerating antibody secreting cells (ASCs) at day (D) 7 and determining fold-increase in serum antibody levels at D28 after vaccination with unconjugated PcPs in HIV seronegative subjects (n = 20) and in HIV patients who were receiving antiretroviral therapy (ART) (n = 28) or who were ART-naive (n = 11) and determined their association with ICOS+ and ICOS- circulating memory TFH (cmTFH) cells (CD4+CD45RA-CD27+CXCR5+PD-1+) and short lived plasmablasts (SPBs) at D7, and with PcP-specific and total IgM+ and IgG+ memory B cells at D0. In HIV seronegative subjects, production of IgG1+ and IgG2+ ASCs was consistently associated with the frequency of ICOS+ cmTFH cells but not ICOS- cmTFH cells or memory B cells. In contrast, post-vaccination ASCs in HIV patients, regardless of ART status, were lower than in HIV seronegative subjects and not associated with ICOS+ cmTFH cells, the expansion of which was absent (ART-naive patients) or much lower than in HIV seronegative subjects (ART-treated patients). Production of SPBs was also lower in ART-naive patients. Fold-increase in IgG2 antibodies at D28 also correlated with ICOS+ cmTFH cells at D7 in HIV seronegative subjects but not in HIV patients. These novel findings provide evidence that ICOS+ cmTFH cells contribute to the regulation of PcP-specific IgG antibody responses, including isotype diversification, and that TFH cell dysfunction may be a cause of impaired PcP-specific IgG antibody responses and increased susceptibility to pneumococcal disease in HIV patients.

The Epidemiology of IRIS in Southern India: An Observational Cohort Study.

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon but dynamic phenomenon seen among patients initiating antiretroviral therapy (ART). We aimed to describe incidence, risk factors, clinical spectrum, and outcomes among ART-naive patients experiencing IRIS in southern India. Among 599 eligible patients monitored prospectively between 2012 and 2014, there were 59.3% males, with mean age 36.6 ± 7.8 years. Immune reconstitution inflammatory syndrome incidence rate was 51.3 per 100 person-years (95% confidence interval: 44.5-59.2). One-third (31.4%) experienced at least 1 IRIS event, at a median of 27 days since ART initiation. Mucocutaneous infections and candidiasis were common IRIS events, followed by tuberculosis. Significant risk factors included age >40 years, body mass index <18.5 kg/m2, CD4 count <100 cells/mm3, viral load >10 000 copies/mL, hemoglobin <11 g/dL, and erythrocyte sedimentation rate >50 mm/h. Immune reconstitution inflammatory syndrome-related morality was 1.3% (8 of 599); 3 patients died of complicated diarrhea. These findings highlight the current spectrum of IRIS in South India and underscore the importance of heightened vigilance for anemia and treatment of diarrhea and candidiasis during ART initiation.

Low incidence of the immune reconstitution inflammatory syndrome among HIV-infected patients starting antiretroviral therapy in Gabon: a prospective cohort study

There is a paucity of data on the immune reconstitution inflammatory syndrome (IRIS) in the Central African region. We followed ART-naive HIV-infected patients initiating antiretroviral therapy in an HIV clinic in Gabon, for 6 months. Among 101 patients, IRIS was diagnosed in five. All IRIS cases were mucocutaneous manifestations. There were no cases of tuberculosis (TB) IRIS, but active TB (n = 20) was associated with developing other forms of IRIS (p = 0.02). Six patients died. The incidence of IRIS is low in Gabon, with mild, mucocutaneous manifestations.

Impact of long term homeopathic treatment on disease progression in ART naive HIV patients – a case series

Impact of long term homeopathic treatment on disease progression in ART naive HIV patients – a case series

PREVALENCE OF ADVERSE DRUG REACTIONS AMONG HIV/AIDS PATIENTS ON HAART IN UNIVERSITY OF MAIDUGURI TEACHING HOSPITAL (UMTH), NIGERIA: A FOUR-YEAR RETROSPECTIVE STUDY

BackgroundCurrent evidence on highly active antiretroviral therapy (HAART) indicates that each person will have to take the drugs for life [1]. Since 2000, the prevalence of HIV in Nigeria has...

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

SummaryBackgroundThe effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.MethodsThe START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048.FindingsPatients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26–0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71–0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50–1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately.InterpretationImmediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count.FundingNational Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

Antitubercular therapy induced liver function tests abnormalities in human immunodeficiency virus infected individuals

BackgroundBoth antitubercular therapy (ATT) and antiretroviral therapy (ART) can cause drug induced liver injury (DILI) in tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection. The aim of this research was to study ATT-induced liver function test (LFT) abnormalities in HIV-infected patients. MethodsHIV-infected patients diagnosed with TB were evaluated with baseline LFT and CD4 counts. ATT regimen was modified if baseline LFT was significantly abnormal. Patients on protease inhibitors were given rifabutin instead of rifampicin. In patients on nevirapine-based ART, efavirenz was substituted for nevirapine. In ART-naive patients, the timing of introduction of ART was according to CD4 cell counts. LFT were repeated fortnightly or as clinically indicated for 10 weeks. ResultsWe studied 100 patients with HIV ([M – 67, F – 23], mean age: 40.05±10.75 years, mean CD4 cell count: 239.157±228.49cells/dL). Sixty-one patients were on ART prior to diagnosis of TB. Baseline LFT abnormalities (n=40) were similar in ART and non-ART group (28/61 vs 12/39, p=0.13). After starting ATT, derangement of LFT was observed in majority of patients (99/100). However, liver sparing ATT was required only in 15 patients. Bilirubin >2.5mg/dL was seen only in 9 patients. Significant rise in transaminases was commoner in patients on concurrent ART and ATT (p=0.044) and with baseline LFT abnormalities (p=0.00016). There was no case of acute liver failure or mortality. ConclusionMild LFT abnormalities are common in HIV-infected individuals on ATT. Concomitant use of ATT and ART and baseline LFT abnormalities increase the risk of significant DILI. However, with closer follow-up, serious liver injury can be prevented.

Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

Background and Objectives:Insulin resistance (IR) is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy (ART). Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1-infected patients with different ART status.Materials and Methods:In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment.Results:All subjects were randomly selected and grouped as HIV-negative (control group) (n = 300), HIV-positive without ART (n = 100), HIV-positive with ART first line (n = 100), and HIV-positive with ART second line (n = 100). IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509) P < 0.001.Interpretation and Conclusions:In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

Factors associated with the quality of life among ART naive adult patients in Rwanda

Factors associated with the quality of life among ART naive adult patients in Rwanda

Neurocognitive Decline in People Living with HIV in India and Correlation with 3T Magnetic Resonance Spectroscopy

Background Neurocognitive decline in asymptomatic HIV patients and its correlation with metabolic changes in brain has not been studied in developing countries like India. In the present study we aim to examine the correlation between cognitive decline and changes in brain metabolites using MRS.Methods ART naïve HIV-positive patients, in the age group 2050 years attending ART center of the hospital from July to December 2016 were included in the study. All patients underwent evaluation using MRS of left frontal white matter (FWM) and left basal ganglia (BG). Levels of Nacetyl aspartate (tNAA), choline (tCho), creatine (tCr), lipids and macromolecules at 0.9ppm (Lip09+MM09) were measured. Cognition was tested using a battery validated for Indian population. Locally normalized zscores were used to calculate brain dysfunction score. Spearman correlation coefficient was used to assess the correlation between two continuous variables. There were 28 (29% female and 71% male) cases and 30 (37% female and 63% male) controls.ResultsThe mean age was comparable in the 2 groups (33 and 34 years). There was a significant difference (P < 0.05) in the concentration (mmol/kg) of tNAA (9.29 ± 311 vs. 7.45 ± 0.64), tCho (2.08 ± 0.70 vs. 1.74 ± 0.25), tCr (6.95 ± 2.56 vs. 5.43 ± 0.61), in the FWM and Lip09 + MM09 (5.87 ± 1.05 vs. 4.80 ± 0.35) in BG, with higher levels in controls. There was no significant correlation between CD4 count and metabolites or overall dysfunction score and metabolites except Cr in FWM with more dysfunction associated with lower concentration (see Table 1)Table 1:MR spectrum acquired from FWM of a patient.Graph 1:MR spectrum acquired from FWM of a patient.Conclusion The results show that HIV-associated changes are present in asymptomatic people which may be contributing to the early neurocognitive decline. Knowledge of metabolic changes within studied brain regions can help understand the pathology and design interventions to cater to this unmet need in people living with HIV.Disclosures All authors: No reported disclosures.

Once a Daily Dose of Nevirapine (400 mg) Versus Twice-Daily Dose (200 mg) of Nevirapine-Based Highly Active Antiretroviral Therapy Regimens in Antiretroviral Naïve Patients with HIV and Tuberculosis Infection in India

Nevirapine-based antiretroviral therapy against human immunodeficiency virus (HIV) among Tuberculosis (TB) co-infected individual is complicated as administration of rifampicin along with Nevirapine reduces the plasma concentration of Nevirapine. The objective of the present study is to compare efficacy and safety of Nevirapine 400 mg once daily (OD) based antiretroviral therapy (ART) with efavirenz based ART and twice daily dose (200 mg) of Nevirapine-based ART regimens in HIV-TB co-infected individuals. ART-naive HIV-TB patients were randomly assigned to receive either Nevirapine 400 mg OD with zidovudine and lamivudine (Group 1; n=30), Nevirapine 200 mg BD (Group 2; n=30), efavirenz 600 mg (Group 3, n=31); Nevirapine 400 mg OD with tenofovir (Group 4; n=30) and Nevirapine 400 mg OD without concomitant antitubercular therapy (ATT) (Group 5; n=30). The end points were virological (viral load), immunological (CD4 count) and clinical responses and progression of HIV disease marked by the failure of ART. Our results suggest that Nevirapine 400 mg OD based therapy is as effective as efavirenz-based ART in terms of clinical, immunological and virological response. Our data suggests that Nevirapine 400 mg OD group had favorable treatment outcome as compared to Nevirapine 200 mg 1 BD group. We conclude that Nevirapine 400 mg OD based ART combined with tenofovir and lamivudine could be an effective alternative to improve compliance in the resource-limited settings in patients with HIV-TB co-infection. Further large multicentric study with bigger sample size will be required to confirm these findings.