Mycobacterium intracellulare as an unmasked IRIS after initiating treatment for HIV.Immune reconstitution syndrome (IRIS) is an uncommon complication seen in patients living with human immunodeficiency virus (HIV) characterized by the decline in a pre-existing condition or a new diagnosis of a masked disease. It is associated with a significant inflammatory component that occurs after starting antiretrovirals, being most frequent in those with severe immunosuppression. Thereby, different types of opportunistic diseases such as non-tuberculous mycobacteria are more frequent in this group of patients, especially those with low lymphocyte counts of below 50 cells/µL. Here, we present the case of an HIV-positive patient who developed lymphadenitis caused by  It is well known that highly active antiretroviral therapy (HAART) leads to immunovirological control in the treatment of human immunodeficiency virus (HIV) infection, decreasing the frequency of opportunistic diseases and improving survival. However, it is associated with different complications such as the immune reconstitution syndrome (IRIS). IRIS was first described as being related to an increase in localized non-tuberculous mycobacteria after the introduction of treatment with zidovudine in the early 1990s [Mycobacterium intracellulare as an unmasked IRIS after initiating treatment for HIV.Here, we present the case of an HIV-positive patient who developed lymphadenitis caused by A 22-year-old heterosexual male with a history of daily tetrahydrocannabinol use was diagnosed with HIV in 2019. He was lost to follow-up after the first medical visit but returned in May 2020 when he decided to start HAART with tenofovir disoproxil 300 mg + efavirenz 600 mg + emtricitabine 200 mg; suspending it three days later because of marked intolerance with no reintroduction after this episode. Later, he was hospitalized in June 2020 with a new diagnosis of meningeal cryptococcosis treated with amphotericin B and fluconazole. In the July 2020 follow-up, he initiated abacavir 600 mg + lamivudine 300 mg + dolutegravir 50 mg with good adherence and tolerance, achieving undetectable viral load  of the neck revealed a left lymphadenopathy conglomerate with central hypodensity and loss of the cleavage plane with the adjacent muscular structures Figure . Chest pMycobacterium intracellulare with an absence of rrl and rrn gene mutations (macrolide and aminoglycoside sensibility). With these new findings, the treatment was switched to rifampicin 600 mg qd + ethambutol 1,200 mg qd + azithromycin 500 mg qd, and no further use of steroids was necessary. Rapid response was seen within a month during the follow-up visit.A fine-needle aspiration biopsy was performed. The results showed negative Gram staining and bacterial culture. The acid-fast bacilli smear was positive (++), but the polymerase chain reaction assay GeneXpert MTB/RIF was negative. The patient started antituberculous treatment , prednisone 40 mg qd for two weeks, and an adjustment of dolutegravir dosage (50 mg bid) due to the possible interactions with rifampicin. During the next few months, there was no clinical response, despite the fact that the patient was adherent to his treatment, and drug interactions were ruled out, triggering the possibility of non-tuberculous mycobacteria. This was confirmed by the definitive culture results and a new molecular test (GenoType) isolating Multiple infectious agents and pathological processes are related to IRIS Table , hinderiIn a meta-analysis involving a total of 13,103 patients from 54 studies, Muller et al. found IRIS incidence at an average of 16.1% with a mortality of 4.5%. They also identified a difference in the etiologies: 37.7% cytomegalovirus retinitis, 19.5% meningeal cryptococcosis, 16.7% progressive multifocal leukoencephalopathy, 15.7% tuberculosis, and 6.4% Kaposi sarcoma [Despite the heterogeneity of this syndrome, some risk factors have been described that help the identification of these patients: a rapid decline in the viral load (in the first three months), an initial CD4 count lower than 50 cells/µL, early initiation of HAART in patients with the concomitant opportunistic disease, and no previous HAART exposure . IRIS haMycobacterium intracellulare, a slow-growing and ubiquitous microorganism in the environment belonging to the Mycobacterium avium complex (MAC), which typically affects individuals with HIV in advanced stages of the disease, especially with CD4 lymphocyte counts less than 50 cells/µL [Different infectious etiologies related to IRIS has been described such as cells/µL .Mycobacterium tuberculosis infection, non-tuberculous mycobacterial (NTM) infections are not mandatory to report, hindering the understanding of epidemiological behavior. Henkle et al. identified 334 patients with extrapulmonary NTM infection from 2007 to 2012. In their study, 8.4% of the patients had lymph node involvement. The authors reported an annual incidence of 0.7 cases of Mycobacterium avium/intracellulare complex (MAC) for 100,000 habitants [Unlike The onset of symptoms is usually slow, with patients initially presenting with constitutional symptoms , which may be absent or can be associated with anemia, hepatosplenomegaly, and lymphadenopathy. Regarding lymphadenitis, the growth of the lymph nodes begins painlessly, evolving with the production of pus . ImagingMycobacterium tuberculosis must be ruled out [Lymphadenitis diagnosis is based on cultures (positivity range from 50% to 80%), molecular test, or histopathological findings, typically caseating granulomas. The presence of acid-alcohol-resistant bacilli is variable, and infection by uled out .Treatment is based on a macrolide plus ethambutol and/or rifampicin with a duration ranging between six to twelve months, depending on clinical evolution and sometimes requiring surgical management. MAC-related IRIS in HIV patients is based on surgical and antimicrobial management, the continuation of antiretroviral therapy, and the use of systemic corticosteroids, generally when it presents with painful lymphadenopathy .IRIS is a condition that must be considered at the time of antiretroviral therapy initiation, especially in patients with marked immunosuppression. Despite not being a frequent disease, non-tuberculous mycobacterial infections should not be forgotten, especially when molecular identification tests for tuberculosis are negative.


Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV‐1 infection (PHI). Four‐drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four‐drug regimens used in the Research in Viral Eradication of HIV‐1 Reservoirs (RIVER) study.At enrolment, ART‐naïve adult participants or those newly commenced on ART were initiated or intensified to four‐drug regimens within 4 weeks of PHI. Rapid start was defined as pre‐confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient‐reported adherence measured by 7‐day recall and regimen switches between enrolment and randomization, respectively.Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV‐1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV‐1. Twenty (37%) started a four‐drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable , respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post‐randomization.Overall, four‐drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three‐drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment. Following the findings of the START and TEMPRANO trials in 2015 , 4. TherCurrent guidelines for rapidly starting ART in PHI recommend triple ART regimens comprising a tenofovir‐based, dual nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone combined with integrase strand transfer inhibitors (INSTIs), or a boosted protease inhibitor (PI) such as darunavir/ritonavir (DRV/r) . Some phDespite the recommendations for rapid start of ART in PHI, there is a paucity of data on the tolerability and adherence in this setting, a time when patients are dealing with the burden of a new diagnosis of HIV‐1, potentially compounded by symptoms of seroconversion. As such, our aim was to review the tolerability of four‐drug regimens in the Research in Viral Eradication of HIV‐1 Reservoirs (RIVER) trial (NCT02336074) .The RIVER trial methodology is described in the primary manuscript . RIVER wParticipants were recommended a four‐drug ART regimen as per the RIVER protocol. This included daily DRV/r 800/100 mg, as per the guidance for ART initiation prior to genotype availability at the time of recruitment , raltegrOur primary outcome was patient‐reported adherence measured by 7‐day recall at weeks 0, 4, 12, 22 and 24 (randomization). The 7‐day recall tool is widely used in trials conducted by the AIDS Clinical Trials Group and the International Network for Strategic Initiatives in Global HIV Trials . Our secn = 54) had a median age of 32 years [interquartile range (IQR): 29–40], 72.2% were of white ethnicity (n = 39), and in 92.6% (n = 50) sex with men was the likely mode of HIV‐1 acquisition. Median (IQR) HIV‐1 viral load was 48 295 (19 408–1 073 031) copies/mL; 42.6% (n = 23) had a viral load ≥ 100 000 copies/mL. The majority  were enrolled in the study based on a recent infection test algorithm [n = 15/54) started ART ≤ 7 days after a confirmed diagnosis (rapid start).This male cohort , 22.2% (n = 12), 16.7% (n = 9) and 33.3% (n = 18), respectively. Seven (13.0%) started ART before HIV‐1 diagnosis confirmation; 85.2% (n = 46) remained on the same four‐drug regimen from enrolment to randomization which occurred at week 24 (range 22–54). By weeks 4, 12, and 24 post‐enrolment, 37.0%, 69.0%, and 94.0% had a viral load < 50 copies/mL respectively.Of the 34 (63.0%) on ART pre‐enrolment, 21 received a PI‐based three‐drug regimen, three received a raltegravir‐based three‐drug regimen, and nine received a four‐drug regimen with raltegravir, boosted darunavir, tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). One participant received TDF/FTC pre‐exposure prophylaxis. The 20 (37.0%) ART‐naïve individuals at enrolment all started a four‐drug regimen (Table n = 48/54), 87.0% (n = 47/54), 82.4% (n = 42/51) and 94.1% (n = 48/51) of participants, respectively. Three individuals withdrew or were lost to follow‐up before randomization. Five changed to a three‐drug regimen [at weeks 7 (n = 2), 24, 26 and 40) and three changed components of, but remained on, a four‐drug regimen , recreational drug interaction (n = 1) and patient choice (n = 1). Only two participants changed their four‐drug regimen post‐randomization – one for declining renal function and one due to nausea and vomiting.Adherence at weeks 4, 12, 22, and 24 (randomization) indicated 100% adherence to ART in 88.9%  had a truly ‘rapid’ ART start, everyone had commenced ART within four weeks of confirmed PHI diagnosis. Importantly, the design of the trial allowed the inclusion of those who had already started ART, and thus any delays should not have been attributed to screening/enrolment procedures for the trial. The RIVER trial patient population was small, male and highly motivated, limiting the generalizability to other cohorts, although despite this, our data demonstrate that four‐drug regimens are feasible in the PHI setting, including for rapid ART initiation.While three‐drug regimens using a dolutegravir, bictegravir or darunavir/r third agent are recommended in PHI, barriers to four‐drug regimens (e.g. pill burden) are diminished with modern fixed‐dose combinations. Similarly, while the prevalence of transmitted INSTI resistance in the UK is currently low, this may rise with greater use . HoweverViable four‐drug regimens offer flexibility by expanding treatment options for people newly diagnosed with HIV, particularly in PHI, wishing to start treatment promptly. In these scenarios, clinical teams may also be reassured that a robust regimen is being utilized pending initial investigations; the regimen can then easily be rationalized when results are available or when viral suppression has been achieved.JEB and SLP drafted the initial manuscript. SLP developed the concept. WS performed the statistical analysis. All other authors contributed to the review and finalisation of the manuscript


Point-of-care CD4 testing could address this gap and assure differentiated care to these vulnerable patients with low CD4 counts.South Africa, with the highest burden of HIV infection globally, has made huge strides in its HIV/ART programme, but AIDS deaths have not decreased proportionally to ART uptake. Advanced HIV disease  or standard-of-care central laboratory CD4 testing (n = 298 patients) to assess the proportion initiating ART at 3 months. Cox regression, with robust standard errors adjusting for clustering by week, were used to assess the relationship between treatment initiation and arm.P = 0.112). The time-to-treat analysis was not significantly different in patients with CD4 counts of 201-500 cells/mm3 which could have been due to appointment scheduling to cope with the large burden of cases. However, in patients with advanced HIV disease (CD4 < 200cells/mm3) 65% more patients started ART earlier in the point-of-care group  = 0.99-2.75; P = 0.052) compared to the standard-of-care group.Among the 578 (299 point-of-care and 279 standard-of-care) patients eligible for analysis, there was no significant difference in the number of eligible patients initiating ART within 3 months in the point-of-care (73%) and the standard-of-care (68%) groups (Point-of-care testing decreased time-to-treatment in those with advanced HIV disease. With universal test and treat for HIV, rollout of simple point-of-care CD4 testing would ensure early diagnosis of advanced HIV disease and facilitate differentiated care for these vulnerable patients as per the World Health Organisation 2020 target product profile for point-of-care CD4 testing.ISRCTN14220457. South Africa bears more than double the HIV burden and antiretroviral treatment (ART) numbers of any other country , as well3) from both late initial presentation which remains relatively unchanged over the last decade [There is growing evidence of continued persistent advanced HIV disease , CD4 count thresholds were removed in December 2015 by the World Health Organization (WHO) , with unPoint of care (POC) CD4 testing has been shown to be accurate ,27  clinic in Durban, South Africa, to evaluate if POC CD4 testing improved ART initiation, time to treatment initiation and linkage to care.TM PIMA POC CD4 (now Abbot PIMATM CD4) testing at the clinic. SOC weeks were 2; 4; 6-7; 11-14; 17; 20; 22; 24; 25 (13 weeks) and POC weeks were 1; 3; 5; 8-10; 15-16; 18-19; 21; 23; 26 (13 weeks). Participants were referred by clinic staff for testing and no participants refused participation. Voluntary written informed consent was obtained from all participants.A time-randomized effectiveness-implementation study was conducted at Lancers Road PHC clinic, adjacent to a busy taxi rank in the Durban city-center from April to October 2015. The clinic initiated over 2500 patients on ART in 2015. HIV positive adults, ART naïve and not pregnant, requiring CD4 testing were enrolled. Weeks were randomized to either: standard-of-care (SOC) central laboratory CD4 testing sent from the clinic via the Addington Hospital Laboratory to the Prince Mshiyeni Hospital for flow-cytometry CD4 testing; or Alere 3 PIMA analyzers were available for testing during PIMA randomized weeks and packed away on SOC weeks. Control beads were run each morning on the analyzers and all results were sent to Datapoint daily via the modem supplied by Alere. Study staff received Alere PIMA end user training with certificates. Study questionnaires were completed during the 20-minute PIMA specimen processing time during POC weeks. Participants were given the choice of fingerstick or venous blood draw (EDTA tube) for the POC testing with 148/299 (50%) choosing fingerstick. Participants known to be ART eligible were advised to have a venous draw to include required baseline bloods tests. All required phlebotomy was performed by the study staff. PIMA results were printed out (on supplied heat printers) and retained for study records. SOC participants were given a return date for 3-7 days to collect their results. Participants were integrated back into the clinic system and given a follow-up study visit appointment after 3 months if eligible for ART and 6 months if not yet eligible. These follow-ups were in-person or by telephone call if they did not attend a visit. Text message reminders were sent for follow-up visits if they did not attend. Study questionnaires collecting demographic and background information were administered at baseline and follow-up visits  would achieve 80% power to detect a 15% improvement . Block randomization with block sizes of 4 were used to randomize the POC/SOC across clusters. Generalised estimating equations models, with logit link were used to assess the relationship between study arm and starting ART within 90 days, while adjusting for correlation within cluster (randomization week). The probability of initiating treatment was presented graphically using Kaplan-Meier failure curves. Cox regression, with robust standard errors adjusting for clustering by week, were used to assess the relationship between treatment initiation and arm. Interaction effects between arm and CD4 count category were included in the models to conduct subgroup analyses. The Shapiro-Wilk test as well as quantile-quantile (Q-Q) plots and normal probability plots were used to assess normality assumptions of the continuous variables. Normally distributed variables were thus expressed as means with standard deviations, while continuous variables that violated normality assumptions were expressed as medians with interquartile ranges (IQRs). All analysis was conducted using Stata 15 .Ethics approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (BF 480/14) and the eThekwini Research Ethics Committee. Clinical Trial Number: ISRCTN14220457.A flow diagram (There were no notable significant differences between the POC and SOC groups at baseline. 3), 40% tested HIV positive for the first time. The majority of those previously diagnosed were in the preceding year (41%), with almost a quarter knowing their status for more than 5 years. Over a third (36%) had never had a CD4 test despite knowing their HIV status and of those who had a previous CD4 count, 55% had been at a different health care facility.3) while 131/578 (23%) had advanced HIV disease (CD4 ≤ 200 cells/mm3). There was no significant difference between the SOC and POC groups. Males had a lower median CD4 count of 256 cells/mm3 (IQR = 157-467) compared to females’ median CD4 383 cells/mm3 (IQR = 234-548). The overall proportion of males was 26% but increased in the ≤350 cells/mm3 category to 32% and in the ≤200 cells/mm3 category, with advanced HIV disease, males constituted 39%.The CD4 results and distribution is seen in In the SOC group there were 7 laboratory errors, 2 of which were repeated, 2 were LTFU and 3 had PIMA (as returned in a PIMA week) and were therefore excluded. PIMA testing had an error rate of 7.3% with all giving a result on repeat testing.P = 0.41) , 73% in the POC PIMA and 68% in the SOC Central laboratory group, initiated ART within 3 months/90 days, although this difference did not reach statistical significance. The time to treatment analysis excluded those eligible for ART who were LTFU after enrolment (n = 39) and revealed no significant difference across all patients eligible for ART at 3 months / 90days  = 0.85-1.48; 3 category ; effectively 65% more patients in the POC group started ART within 90 days. This however denotes only borderline significance due to the small sample number in this group. The supplementary material shows the other CD4 category’s Kaplan-Meier curves  were lost to follow up (LTFU) directly after their enrolment visit. Another 45/578 (8%) were found to have linked to care at other clinics upon follow up call: 24/45 (53%) within eThekweni, 8/45 (17%) in KwaZulu-Natal province, 7/45 (15%) in other provinces and 6/45 (13%) at unknown clinics and GPs. Of the patients who started ART at Lancers Road PHC, 17/410 (4%) never returned after their first ART initiation visit – and so it is unknown if they truly started treatment.This cohort tells the all too familiar story of HIV in Sub-Saharan Africa – of patients in and out of care, vulnerable patients, few men in care, poverty, and a heavily burdened clinic service . DespitePrevious CD4 testing had been at a different facility in 55% of patients presenting for care, 8% of the cohort linked to care at a different facility after testing, and 11% had transferred out from ART care by 5 years, highlighting the well documented mobility of patients accessing care ,40,41.3 becoming eligible and placing further strain on the health system.The introduction of UTT in 2016 caused the ART initiation numbers to increase by a further 30%, with the patients with CD4 > 500 cells/mmUNAIDS proposed the 90-90-90 targets: 90% of PLWH know their status, 90% of those diagnosed with HIV receive ART and 90% of those on ART are virally suppressed. While the study was not designed to detect the 5% difference in time to treat, this difference is clinically meaningful as every patient on ART adds towards reaching the second ‘90’ target, which is currently at 72% ,42 while3 were also given appointments to return for ART initiation 4-6 weeks after eligibility due to high patient numbers, which interfered with the time to treat analysis for the groups – a real-world challenge in implementation studies [The study design allowed a robust, time-randomized implementation method where all study participants were part of the same process, with half randomized to the POC intervention. This ensured that they all received the same time with a health care worker, counselling and information, which has been shown to be an important factor in ART initiation and linkage to care ,47. As p studies .Despite this cohort being prior to UTT rollout, it demonstrates that POC CD4 testing benefits those with advanced HIV disease significantly by identifying them and differentiating care for this vulnerable population. This benefit is even more applicable since UTT, where CD4 testing is being neglected and advanced HIV disease and mortality persists , and theThe five-year follow-up data for the cohort at Lancers Road clinic shows 47% of patients still in care at the clinic, with 11% having formally transferred to other clinics, and increasing LTFU with time. The deaths are likely underestimated and self-transfers are not able to be tracked beyond the follow-up calls. This is similar to other reports of retention in care at similar time periods ,51. This3, half of patients may have asymptomatic disease [CD4 count is the primary method of assessment of advanced HIV disease, as even with a CD4 < 100cells/mm disease . Advance disease ,55. CD4 a baseline assessment for all at ART initiation,continued monitoring for those with advanced HIV disease on prophylaxis regimens,those presenting for ART after disengagement/ treatment interruption,those with unsuppressed viral loads (due to poor adherence or treatment failure),ad hoc CD4 testing for those presenting with symptomatic disease.Point-of-care CD4 testing will allow health care workers to identify rapidly those requiring differentiated care for advanced disease, therefore providing the correct care, counselling, and education for this population at highest risk of morbidity, mortality, and ongoing transmission. Other valuable POC tests at this time point are creatinine and haemoglobin, the TBLAM urine test, Cryptococcal Ag test, Hepatitis B Ag test and a POC TB sputum test which would assist with a comprehensive diagnostic picture and ensure the comprehensive package of care is delivered, together with the adapted adherence support and follow-up as per WHO guidelines .POC CD4 testing has been found to be acceptable to staff and patients  and requA limitation of this study was that the POC testing was performed by study staff and not by the clinic staff, however other studies have shown feasibility and effectiveness of nurses, or even task shifting to lay health care workers, to perform PIMA testing . The pos3 had prior ART exposure [In the era of ‘test-and-treat’ the CD4 result is only reviewed after ART has started. This means that the vulnerable, low CD4 patients may be put at risk if they have TB or cryptococcal infection that may preferentially require treatment initiation before starting ART. POC testing for Cryptococcal Ag, TB (TBLAM and Xpert®MTB/RIF), Haemoglobin, Creatinine, Hepatitis B and HIV viral load are all commercially available. Cotrimoexposure . They maexposure . Immunodexposure .TMCD4 devices are robust, tried and tested in the field, having WHO prequalification since 2012 and used widely in lower- and middle-income settings. With CD4 being linked to advanced HIV disease and thus mortality, it is important to monitor CD4s across maturing ART programmes to monitor these vulnerable patients. Next generation POC devices will perform multiple assays and combinations of assays within 10 minutes, which would further assist the clinical team in making on the spot decisions across the broad spectrum of communicable and non-communicable diseases for best patient care. Connectivity allows disease surveillance, quality monitoring and supply chain monitoring. South Africa has not implemented POC CD4 testing due to sufficient central laboratory capacity, but this deserves a clinical review.In 2020, the WHO released guidance on the use of POC CD4 tests for advanced HIV disease with their product profile preferring a device-free test . The ben3), Cryptococcal Ag testing (CD4 < 100 cells/mm3), and the differentiated care package required for these patients to improve care and decrease morbidity and mortality which will reduce the cost and health care burden of hospitalization. It is time to contend for those with low CD4 counts who are most likely to die of AIDS.Where POC CD4 testing was previously found to improve assessment of ART eligibility and hasten ART start, it should now be used to improve rapid assessment of advanced HIV disease in those initiating ART, returning from interrupted ART and failing ART. This should include POC TBLAM testing (CD4 < 100-200 cells/mm


Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) demonstrated potent efficacy and favorable safety in older PLWH; however, real-world data would be useful to validate these results.Retrospective cohort study.We evaluated records from PLWH aged ≥50 years at the Orlando Immunology Center who were switched to B/F/TAF between February 2018 and August 2019. Eligible patients had baseline HIV-1 RNA <50 copies/mL and 48 weeks of follow-up data. The primary endpoint was maintenance of HIV-1 RNA <50 copies/mL at Week 48. The impact of switching to B/F/TAF on drug–drug interactions (DDIs) and safety parameters were also assessed.Three-hundred and fifty patients met inclusion criteria, median age was 57 years, 20% were women, and 43% were non-White. Fifty-five percent of patients switched from integrase inhibitor-based regimens; the most common reason for switch was simplification. At Week 48, 330 (94%) patients maintained an HIV-1 RNA <50 copies/mL and 20 (6%) had an HIV-1 RNA between 50 and 400 copies/mL. One-hundred and forty potential DDIs were identified in 121 (35%) patients taking a boosting agent or rilpivirine at baseline that were resolved after switching to B/F/TAF. Treatment-related adverse events occurred in 51 (15%) patients  and led to 8 discontinuations.In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. These characteristics make B/F/TAF attractive for lifelong ART treatment, especially in older adults who are more prone to polypharmacy and metabolic complications. In 2018, surveillance data revealed that over half of people living with HIV (PLWH) in the United States are aged ≥50 years and 17% of new HIV diagnoses occurred among this group. Older PLWH are at increased risk of cardiovascular disease, impaired cognition, and accelerated kidney disease and osteoporosis, and some of this excess risk maybe related to long-term ART exposure. Therefore, it is important that we continue to generate long-term data on the safety and efficacy of ARVs in this population.Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is approved for the treatment of HIV-1 infection in treatment-naïve and -experienced adults who are stable on their current antiretrovirals (ARVs).,6 Among 511 virologically suppressed, treatment-experienced adults aged ≥50 years, B/F/TAF was non-inferior to 3-drug boosted PI- and DTG-containing regimens though 48 weeks, and virologic suppression was maintained in 99% to 100% of participants continuing B/F/TAF through 144 weeks.,8 In a secondary analysis of patient-reported outcomes, B/F/TAF was associated with fewer bothersome symptoms compared with participants on dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Treatment-naïve participants receiving B/F/TAF reported less fatigue, nausea/vomiting, dizziness/light-headedness, and insomnia, whereas virologically suppressed participants receiving B/F/TAF reported less nausea/vomiting, sadness/depression, nervousness/anxiety, and insomnia compared with those on DTG/ABC/3TC. These symptoms are prevalent in older populations, and the use of ARVs that are associated with fewer bothersome symptoms in the elderly would be highly beneficial.In clinical studies, B/F/TAF was non-inferior to 3-drug dolutegravir (DTG)-containing regimens among 196 treatment-naïve adults aged ≥50 years through 144 weeks. At Week 72, no participant had an HIV-1 RNA ≥50 copies/mL, and there were no cases of treatment-emergent resistance. B/F/TAF was well tolerated in this population with only 2% discontinuing due to drug-related adverse events (AEs); there were no discontinuations related to renal, bone, or hepatic AEs through Week 72. A Week 48 subgroup analysis demonstrated significant reductions in total cholesterol and triglycerides among those switched to B/F/TAF, with no significant changes in low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, or total cholesterol to HDL ratio.Clinical trials of B/F/TAF in adults aged ≥65 years demonstrate high efficacy and a favorable safety and tolerability profile in this population. Data from GS-US-380–4449 demonstrated that 94% of virologically suppressed adults aged ≥65 years who switched to B/F/TAF, the majority of whom were on elvitegravir/cobicistat/F/TAF at baseline, maintained virologic suppression at Week 72 despite a high proportion with baseline comorbidities requiring multiple concomitant medications. No participant developed virologic failure, and there was no treatment-emergent resistance observed. Only one participant discontinued B/F/TAF due to a drug-related AE, and there were no serious drug-related AEs. Modest improvements in fasting lipid parameters were observed, and only 4% initiated lipid-lowering therapy throughout the study.A pooled analysis of 4 international trials that included data from GS-US-380–4449 revealed that among 140 virologically suppressed adults aged ≥65 years who switched to B/F/TAF, 92% maintained virologic suppression through Week 48. Overall, 89% of treatment-experienced patients persisted on B/F/TAF at Month 12, and only 7.7% of discontinuations among this group were due to AEs. There were no discontinuations due to drug-related renal, hepatic, or bone events. An analysis of patient-reported outcomes data from this cohort revealed statistically higher treatment satisfaction scores among 209 treatment-experienced patients switched to B/F/TAF, 49% of whom were ≥50 years of age.Real-world data from older PLWH who are switched to B/F/TAF are currently lacking. Results from the BICSTaR cohort which included a subset of participants from Germany, Canada, France, and the Netherlands demonstrated that 93% of 182 treatment-experienced patients aged ≥50 years who switched to B/F/TAF, the majority of whom were virologically suppressed at baseline, achieved an HIV-1 RNA <50 copies/mL at Month 12.These clinical trial and real-world data suggest that B/F/TAF has a favorable efficacy and safety profile in older PLWH; however, these studies were largely composed of White patients with few women, and only one study included data from patients in the United States (US). Real-world data from larger, more diverse cohorts of older PLWH in the US would be useful to validate these results.2This was a retrospective observational cohort study to describe the effectiveness, safety, and tolerability of switching to B/F/TAF in adults aged ≥50 years old through 48 weeks seen at the Orlando Immunology Center (OIC). The OIC is a private infectious disease practice located in downtown Orlando, Florida that provides HIV and primary care services to approximately 5700 PLWH. The center serves a diverse population of PLWH; 25% are women, 30% report Hispanic and or Latino ethnicity and 20% identify as black or African American. The OIC is staffed by 3 infectious disease physicians, 1 primary care physician, and 3 advanced practice registered nurses (APRNs) who have completed residencies in infectious disease. ARV management decisions are made by 1 of the 3 infectious disease physicians who supervise all patient visits where ARVs are initiated or switched.Eligible patients included all PLWH who were switched to daily B/F/TAF as a complete ARV regimen between February 2018 and August 2019 and were aged ≥50 years old at the time of switch. Other inclusion criteria included the availability of 2 consecutive baseline HIV-1 RNA values <50 copies/mL (at least 3 months apart) in the year prior to switch, attendance at a minimum of 2 clinic visits in the year prior to switch, and attendance at ≥2 clinic visits during the study period with a minimum of 2 HIV-1 RNA measurements following switch to allow for an efficacy estimate. Key exclusion criteria included a prior history of virologic failure on an integrase strand transfer inhibitor (INSTI)-containing regimen, documented primary INSTI resistance and a documented HIV-1 RNA ≥50 copies/mL in the year prior to switch. Informed consent was waived due to the retrospective observational nature of the study, which utilized data collected as a part of routine clinical care.Subjective, Objective, Assessment and Plan (SOAP) note that is used by all OIC providers to document decisions and considerations surrounding ARV switch. The primary endpoint of the study was the proportion of patients with plasma HIV-1 RNA <50 copies/mL at Week 48. Secondary endpoints included the change in number of DDIs following switch to B/F/TAF, change in CD4+ cell count from baseline to Week 48, change in lipid parameters  from baseline to Week 48, and safety and tolerability of treatment with B/F/TAF. The change in DDIs pre- and post-switch was assessed by performing 2 DDI analyses for each patient using the University of Liverpool HIV DDI database. The first analysis assessed DDIs associated with the patient's preswitch ARV regimen and concomitant medications. The second analysis assessed DDIs associated with B/F/TAF and the same concomitant medications. All laboratory abnormalities and documented AEs were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events.Demographics, lab values, and clinical parameters were extracted from the charts of all eligible patients through Week 48 of treatment with B/F/TAF. Reasons for switching to B/F/TAF were obtained from a templated “ARV switch” + count or lipid parameters from baseline to Week 48. The Sterling Institutional Review Board (IRB) determined that the study met IRB exemption criteria based on the observational nature of the study which utilized retrospective data collected as a part of routine clinical care (Sterling IRB ID 7532). Informed consent was not utilized for this retrospective, observational cohort and was determined to not be required by the Sterling IRB.Descriptive statistics  were calculated for participant baseline demographic and clinical characteristics, virologic outcomes, change in weight, DDIs pre- and post-switch, AEs, and discontinuations throughout the study. Descriptions of adherence were summarized based on clinician documentation in the medical record. For AEs, drug-relatedness was assigned based on whether the clinician documented a possible relationship between the AE and B/F/TAF. The Wilcoxon paired rank test was used to determine whether there were significant changes in CD43During the study period, 727 PLWH aged ≥50 years switched to B/F/TAF as a complete ARV regimen. Two-hundred and ninety-eight did not have at least 2 HIV-1 RNA measurements following switch, 53 were lost-to-follow-up immediately after switch and 245 had recently switched to B/F/TAF; of these 198 only had a single HIV-1 RNA measurement following switch and 46 did not yet have any HIV-1 RNA measurements following switch at the time of data cut-off. Seventy-nine patients had baseline HIV-1 RNA ≥50 copies/mL prior to switch hence only 350 met criteria for inclusion. The median age (range) was 57  years, 69 (20%) were women, and 136 (40%) were non-White (Table The most common regimen prior to switch consisted of an INSTI plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 193 (55%); 80 (23%) were switched from regimens containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus 2 NRTIs; 45 (13%) were switched from a PI plus 2 NRTIs, and 32 (9%) were switched from non-traditional ARV regimens consisting of either a PI plus an INSTI, an NNRTI plus an INSTI, or an ARV regimen consisting of ≥3 ARV classes  patients, of whom 35 (34%) had NRTI resistance, 33 (32%) had NNRTI resistance, 37 (36%) had PI resistance, and 2 (2%) had INSTI resistance (both with minor INSTI resistance associated mutations [RAMs] not associated with resistance to bictegravir). Twenty-six (25%) patients had an M184 V/I mutation present on historical resistance testing: 6 (5%) had an M184 V/I plus 1 additional NRTI RAM and 10 (10%) had an M184 V/I plus at least 2 additional NRTI RAMs  patients maintained virologic suppression, while 20/350 (6%) had an HIV-1 RNA ≥50 copies/mL .Subgroup analyses revealed no difference in virologic response at Week 48 based on the presence of historical NRTI resistance; 88% of those with an M184 V/I maintained an HIV-1 RNA <50 copies/mL versus 91% of those without an M184 V/I. Eighty-nine percent of patients with at least 1 NRTI RAM maintained virologic suppression at Week 48 versus 91% with no NRTI RAMs  patients taking a boosting agent or rilpivirine at baseline , median HDL cholesterol decreased by 1 mg/dL , median LDL cholesterol decreased by 8 mg/dL , and median triglycerides decreased by 18 mg/dL   throughout the study period; the most common were fatigue in 14 (4%), weight gain in 11 3%), and arthralgia in 11 (3%) ; this corresponded to a median percent change from baseline in weight of +1.2% . Throughout the study period, 123 (37%) patients experienced weight loss, 13 (4%) experienced no change in weight, and 196 (59%) experienced weight gain. Sixty-three (19%) experienced ≥5% weight gain and 15 (5%) experienced ≥10% weight gain, whereas 23 (7%) experienced ≥5% weight loss and 6 (2%) experienced ≥10% weight loss.4–13 Study 380–4449 reported durable virologic efficacy with 94% of PLWH aged ≥65 years maintaining an HIV-1 RNA <50 copies/mL after switching to B/F/TAF at Week 72. Many in these prior studies were switched to B/F/TAF from regimens consisting of 2 NRTIs plus a third agent. Our study also included a small proportion switched from non-traditional regimens not evaluated in prior studies, including 2-drug INSTI-based regimens and regimens containing ≥3 ARV classes, and revealed similarly high suppression rates among this subgroup  was also observed after switching to B/F/TAF in patients receiving concomitant medications for a variety of comorbidities including cardiovascular disease, neurological/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions, and conditions requiring hormonal therapy. Many have warned about the complications associated with DDIs in older PLWH as comorbidities accumulate and have found that polypharmacy and DDIs are a source of increased morbidity and higher healthcare costs in this population.–26 A recent analysis of AEs due to inappropriate prescribing in older PLWH demonstrated that 30% of PLWH aged ≥65 years experienced ≥1 AE due to inappropriate prescribing, and the risk of having an AE increased as the total number of non-HIV medications increased . Such studies underscore the importance of identifying ARVs with favorable DDI profiles for use in older PLWH. Our data support B/F/TAF as a preferred option to minimize DDIs in this population.In our study switching to B/F/TAF was associated with mitigation of DDIs in 35% of patients, all of whom were on a boosting agent or rilpivirine at baseline Table . Other s and small numerical declines in total cholesterol, LDL cholesterol, triglycerides, and total cholesterol to HDL ratio among those continuing B/F/TAF through Week 96. In comparison, switching from DTG/ABC/3TC was not associated with any significant changes in lipid parameters through Week 48, and small numeric increases in LDL cholesterol were observed among those continuing B/F/TAF through Week 96. In studies focused on older PLWH, switching to B/F/TAF in virologically suppressed adults aged ≥65 years was associated with significant declines in total cholesterol and triglycerides; however, 93% of patients in this study were switched from regimens containing cobicistat. These data are consistent with our results, which additionally demonstrated a significant decline in LDL cholesterol following switch to B/F/TAF. However, only 54% of patients in our cohort were switched from regimens containing cobicistat or ritonavir, and 25% were switched from regimens containing TDF. These results are somewhat unusual given the known lipid-lowering effects of TDF compared with TAF–31 and suggest that B/F/TAF may be more “lipid-neutral” compared with other ARV regimens. Given the increased risk of vascular disease and metabolic complications among older PLWH, these data are critical and highlight B/F/TAF as a potentially “lipid-friendly” ARV option for this population.Switching to B/F/TAF resulted in significant reductions in total cholesterol, LDL cholesterol, and triglycerides in our cohort Fig. . In othe,12Safety data from our cohort demonstrated that B/F/TAF was well-tolerated with Grade 2–5 drug-related AEs and discontinuations due to AEs occurring in only 5% and 2% of older PLWH, respectively Table . There wLimitations of our study include the retrospective nature of the analysis, the inability to control for confounding factors and the fact that data are from a single center in the Southeastern United States, which limits generalizability to other populations. We also acknowledge that a significant proportion of PLWH aged ≥50 years switched to B/F/TAF in our cohort were not eligible for study inclusion due to lost to follow-up immediately following switch (53/727) and not accruing enough follow-up time to have at least 2 HIV-1 RNA measurements following switch (245/727). The lack of inclusion of these populations may represent a source of selection bias as the strategy of only including those switched to B/F/TAF with at least 48 weeks of follow-up data may favor the switch regimen. However, this is the first real-world study evaluating the efficacy and safety of switching to B/F/TAF in a racially diverse cohort of older PLWH from the United States and provides important insight on the potential benefits of this treatment option in our rapidly growing ageing population.In conclusion, switching to B/F/TAF was associated with high virologic suppression, improvement in lipid parameters, and avoidance of DDIs in a large proportion from this real-world cohort of older PLWH. These data support B/F/TAF as a potential switch option in PLWH aged ≥50 years with no history of virologic failure on an INSTI-based regimen and highlight some important benefits of use to consider in this population.All authors listed have contributed sufficiently to the project to be included as authors, and all those who are qualified to be authors are listed in the author byline. Each author's specific contribution is noted below.Charlotte-Paige Rolle – Gathered, analyzed, and interpreted the data necessary for the writing of this article, drafted and heavily revised the paper, provided the final review for the approval of submission, and has agreed to be fully accountable of the work ensuring its accuracy and integrity.Vu Nguyen – Responsible for the conception and design of the study, assisted in revision of the article, provided the final review for the approval of submission, and has agreed to be fully accountable of the work ensuring its accuracy and integrity.Kiran Patel – Responsible for the conception and design of the study, assisted in revision of the article, provided the final review for the approval of submission, and has agreed to be fully accountable of the work ensuring its accuracy and integrity.Dan Cruz – Responsible for the conception and design of the study, assisted in revision of the article, provided the final review for the approval of submission, and has agreed to be fully accountable of the work ensuring its accuracy and integrity.Edwin DeJesus – Responsible for the conception and design of the study, assisted in revision of the article, provided the final review for the approval of submission, and has agreed to be fully accountable of the work ensuring its accuracy and integrity.Federico Hinestrosa – Responsible for the conception and design of the study, assisted in revision of the article, provided the final review for the approval of submission, and has agreed to be fully accountable of the work ensuring its accuracy and integrity.Conceptualization: Charlotte-Paige Rolle, Kiran Patel, Edwin DeJesus.Data curation: Charlotte-Paige Rolle, Dan Cruz, Edwin DeJesus, Federico Hinestrosa.Formal analysis: Charlotte-Paige Rolle, Vu Nguyen.Funding acquisition: Charlotte-Paige Rolle, Kiran Patel.Investigation: Charlotte-Paige Rolle, Kiran Patel.Methodology: Charlotte-Paige Rolle.Project administration: Charlotte-Paige Rolle.Resources: Charlotte-Paige Rolle.Supervision: Charlotte-Paige Rolle, Edwin DeJesus.Validation: Charlotte-Paige Rolle.Visualization: Charlotte-Paige Rolle.Writing – original draft: Charlotte-Paige Rolle.Writing – review & editing: Charlotte-Paige Rolle, Kiran Patel, Dan Cruz, Edwin DeJesus, Federico Hinestrosa.


Type 2 diabetes (T2D) is a common comorbidity in people living with HIV (PLWH). Anti-hyperglycemic treatment in PLWH is still a challenge, and no randomized controlled studies using new glucose-lowering agents are currently available.A 55-year-old-women was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. The medical history included HIV infection and insulin-treated diabetes. On clinical examination, the lady appeared dehydrated with dry buccal mucosa, tachycardia, altered mental status, genital infection, and fever. On admission, plasma glucose was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L with no detectable serum ketones. The patient was treated with i.v. fluid and insulin, and antibiotic therapy commenced. Upon HHS and sepsis resolution, a basal-bolus insulin therapy was implemented that was followed by significant improvement of daily glucose profiles and progressive reduction of insulin requirement until complete discontinuation. A low dose of metformin plus linagliptin was started. Since a severe atherosclerotic disease was diagnosed, a GLP-1 receptor agonist, dulaglutide, was added to metformin upon linagliptin withdrawal with maintenance of good glycemic control, treatment adherence and amelioration of quality of life and no side effects.This case suggests that GLP-1 receptor agonist therapy may be effective and safe for treatment of T2D with high cardiovascular risk in PLWH, supporting the need of clinical trials directly assessing the safety and the efficacy of GLP-1 receptor agonist in these individuals. In the last few years, introduction of antiretroviral therapy (ART) has much improved treatment of people living with HIV (PLWH) . AtherosWe herein report the successful use of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in a patient with T2D, HIV, and high atherosclerotic risk.2). The Malnutrition Universal Screening Tool (MUST) excluded malnutrition, undernutrition, or weight loss ≥5% in past 3-6 months. No drug addiction was apparent. Systolic blood pressure was 155 mmHg and diastolic blood pressure 90 mmHg. On admission, plasma glucose level was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L, and there were no detectable serum ketones  and creatinine value (from 129.9 to 96.4 μmol/L) improved as well and the HIV viral load was markedly reduced (29 copies/ml). In April 2021, a 55-year-old woman was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. Prior medical history included HIV infection, insulin-treated diabetes mellitus (both diagnosed at age 42), hypercholesterolemia, non-proliferative diabetic retinopathy, and chronic kidney disease. Home therapy included a three-drug combination ART , arbitrarily stopped due to intolerance, atorvastatin 10 mg) and insulin therapy with poor adherence to treatment due to fear of hypoglycemia. On clinical examination, patient appeared dehydrated with dry buccal mucosa, tachycardia (120 beats per minute), altered mental status, fever (38.3°C), and ulcerated vulvar lichen sclerosus with signs of genital infection and purulent secretions. Her body weight was 48.5 kg . Plasma C-peptide was measured by a radioimmunoassay . Anti-GAD and anti-IA2 autoantibodies were analyzed by a radioimmunoassay using a commercial kit . All other parameters were determined according to standard methods. Clinical laboratory data are reported in Standard International units. Reference values for healthy adults in our Laboratory are reported in via “glycemic” and “extra- glycemic” actions including a beneficial effect on blood pressure, lipid profile, body fat, insulin resistance, and inflammation among the many ones  in people living with HIV and T2D is sparse. Only one prospective (24 weeks) observational study reported the experience with the SGLT2i canagliflozin in 8 HIV-infected diabetic subjects , and onlany ones .On the other hand, to the best of our knowledge, cardiovascular outcome trials (CVOTs) investigating the safety and efficacy of GLP-1RAs did not specifically report HIV infection as an inclusion or exclusion criterion and no analyses or sub-analyses on this specific subgroup of patients have been reported out of these CVOTs –25. The In conclusion, our experience, although limited to a single case report, suggests that GLP-1 RA therapy may be a valid therapeutic opportunity in people living with HIV. Our observation calls for proper clinical studies exploring the potential use of GLP-1 RA in patients with special forms of diabetes or diabetes associated with special clinical condition such as HIV and its anti-viral treatment. To this extent, two randomized clinical trials are currently investigating the potential of GLP-1 RAs in these individuals. The first study will assess the efficacy of semaglutide as an adjunct to diet and exercise in achieving greater weight loss as compared to diet and exercise alone in HIV-1 infected patients ≥ 18 years with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and hypertension, dyslipidemia or type 2 diabetes . The second trial will evaluate the efficacy of semaglutide vs placebo in treating lipohypertrophy among non-diabetic people living with HIV .The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval were not required for a case report study in accordance with the local legislation and institutional requirements. The patient provided the written informed consent to partecipate in this study.AD conceived the case report description and wrote the first draft. AD and MA were involved in the clinical management of the patient. AD, GD, and RM made a critical literature review. SDP made a critical interpretation of the intellectual content of the article. AD is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Ethiopia launched free access for antiretroviral therapy in 2005. The number of patients on second line antiretroviral treatment has increased with each passing year. The objectives of this study were to describe the clinical, immunological and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals, Yekatit 12 and Zewditu Memorial Hospitals, in Addis Ababa, Ethiopia.This was a hospital based retrospective cohort study conducted among children and adolescents aged 18 years and less and receiving a second line antiretroviral drugs. Data was collected using structured questionnaires. Means and percentages were used for nominal variables. Statistical analysis was made using statistical software–SPSS 23.0. Kaplan Meier analysis, long rank test and multivariate Cox proportion model were used to identify factors affecting survival.A total of 75 children and adolescents were studied with a mean age of 13.28 years (SD: 4) with a mean treatment period on second line regimens of 35.2 months (SD: 21.8 months). Forty-eight participants were experiencing successful measures  for their second line anti-retroviral treatment. Ten had virologic treatment failure while seven had died. Both treatment failure and death rates were higher within the first two years of treatment. Poor treatment adherence ) and advanced World Health Organization clinical stage at start of the second line antiretrovirals ) correlated significantly with survival of children and adolescents receiving treatment.The study describes clinical, immunological and virologic outcomes of second line antiretroviral treatment in a pediatric cohort under care in two hospitals in Addis Ababa, Ethiopia. Poor adherence and pre-treatment advanced clinical stages were predictors of survival. Human immunodeficiency virus (HIV) continues to challenge health care in sub-Saharan Africa . A 2019 Antiretroviral treatment (ART) has prevented millions of deaths and contributed to better life expectancy and global economy. But 41% of people living with HIV were not receiving ART globally in 2017 . Only a Options for second line ART  are limited in low resource settings . PediatrIdentifying the success of second line ART regimens and addressing short-comings using intensive counseling, adherence support and improving facilities for virologic testing prevents premature switches to difficult-to-access third line regimens .Little is known about the success of second line ART regimens initiated for children in Ethiopia. A study reporting from a pediatric cohort at Tikur Anbessa hospital of Addis Ababa, Ethiopia (mean age: 16 years) showed high rates of virologic failure 18%) and marked delays in identifying a failed first line regimen 71 months) and initiating second line ART (close to 5 months) [1 months % and marst March to 30th June 2019.This was a hospital based retrospective cohort study conducted among children and adolescents aged 18 years and less and receiving second line antiretroviral drugs. The study was conducted from 1The two study sites are both government hospitals. The pediatric HIV clinic of Yekatit 12 Hospital and Medical College gives care to 430 children and adolescents with 78 receiving second line ART regimens. The pediatric HIV clinic at the Zewditu Memorial Hospital gives care to 50 children and adolescents on second ART regimens and is one of the foremost HIV treatment and care centers in Ethiopia.All children and adolescents receiving second line ART formulations at the two study sites and aged 18 years or less were invited for participation.Data was collected from patients’ charts’ using structured paper forms consisting of sociodemographic, pre- and post-treatment clinical, virologic, immunologic and therapeutic variables. Participants had follow-up periods in their respective clinics which ranged from January 2009 to June 2019. Data was collected by pre-trained intern physicians  and nurses serving in the two study sites. Data quality was ensured by three hour training sessions prior to data extraction for data collectors and periodic follow-ups by the principal investigator.Treatment adherence was determined as good (at least 95% of pills taken since last visit), fair (85–95%) and poor (less than 85%) based on national treatment guidelines . Clinica3 or CD4% < 10%;Ages < 5 years: Persistent CD4 levels < 200/mm3 andAges 5–10 years: Persistent CD4 levels < 100/mm3 after clinical failure or persistent CD4 < 100/mm3Ages 10–18 years: CD4 < 250/mmVirologic failure was taken as plasma viral loads of above 1000 copies/ml on two consecutive viral load measurements three months apart with enhanced adherence support after the first record of viral load above 1000 copies/ml, and after taking at least six months of second line ART .After data was collected and recorded using paper forms, it was transferred to the Statistical Package for Social Sciences (SPSS) version 23.0 software for analysis. Kaplan-Meier analysis, log rank test and multivariate Cox proportion model were utilized to predict survival curves.Statistical results are expressed using medians and inter-quartile ranges while regression analyses reported using adjusted hazard ratios, confidence intervals and p-value whose significance was taken as less than 0.05. We selected variables for testing based on findings from similar previous studies –20, 24. The study protocol was reviewed and cleared by the Research and publications’ ethics committee of the Department of Pediatrics and child health, College of health sciences, Addis Ababa University. All data were fully anonymized before investigators accessed them.A total of 75 participants took part in the study. Of these, 34 were on follow-up at Yekatit 12 Hospital and Medical College and 41 at Zewditu memorial hospital. The mean age of participants was 13.28 years . Forty-one were males and 34 females. The differing clinical backgrounds of participants and their caregivers/parents is presented in The mean duration on first line ART prior to shifting to a second line antiretroviral drugs (ARVs) was 78.7 months (SD: 29.01). There was a mean delay of 12.56 months (SD: 8.23) between confirmation of failure of first line ART and initiation of second line ARVs. From 67 children and adolescents with complete follow-up records, 25 had intermittent losses to follow-up while on first line treatment while 26 had never missed a follow-up appointment. Data on quality of follow-up visit frequency was unknown for the remaining 16. The component antiretroviral drugs of the first line regimens taken by participants is as depicted in Majority of participants (59/75) had experienced virologic failure for their first line regimens: 22 had both clinical and immunologic failures, 19 had both clinical and virologic failures, with 31 having both immunologic and virologic failures. Eleven patients had fulfilled criteria for clinical, immunologic and virologic failure by the time they were switched to second line ART regimens.3  and mean viral load was 124,473 copies/ml .Upon initiating second line treatment, 30 patients were in WHO clinical stage I, 16 in stage II, 18 in stage III and 11 patients in stage IV. Further on, mean CD4 counts at baseline was 257/mmAdherence to second line ART regimens was good in 48, poor in 4 and fair in 23  and the median absence period from follow-up while on second line regimens was 6 months (IQR: 4.50–16.75). Most study participants (54/75) were at disclosure stage III (DS3), while 17 and 3 were at stages DS2 and DS1 respectively.At the time of conduct of the study, 61 participants were alive, 7 had died after a mean and median duration on treatment of 25.7 and 18 months respectively (4 with a failed second line ARV regimen) and 5 had been lost to follow-up while 2 had transferred out. Ten children and adolescents were experiencing virologic treatment failure . Among 7 patients, criteria to declare treatment failure were not met because they only had a single viral load measurement above 1000 copies/ml and were awaiting enhanced counseling and repeat testing. Of the remaining participants, 48 had suppressed viral loads with 10 having no virologic measures. Fifty-three participants had successful treatments based on immunological measures (CD4 counts) .None of the patients who had a failed second line treatment had been started on third line ARVs. Resistance testing for anti-retrovirals was unavailable in both study sites.Testing for CD4 counts and viral loads were sup-optimal. Of the 75 participants, only 48 patients had records of follow-up CD4 testing and 38 had follow-up viral load determinations upon clinical evaluations done after a minimum of 6 months of second line ART .The mean survival time using Kaplan Meir analysis is 53.3 months (95% CI: 49.5–57.1). Among those who had developed treatment failure, six out of ten did so in the first 6 to 12 months. Survival was notably good after 30 months of treatment .Follow up analysis using log rank test showed significant difference in survival time only for two variables: baseline WHO clinical stage upon initiating second line ART and adherence to second line ART drugs.When survival time based on baseline WHO clinical stage was analyzed using multivariate cox proportion model, those with WHO clinical stages I and II fared better than those with advanced stages (III and IV)  .Those who have good adherence had a mean survival of 54.9 months (95% CI: 50.7–59.1) versus those who had poor adherence   .The study showed that second line ART regimens were preceded by delayed initiation, high baseline viral and CD4 counts. There was an approximate gap of one year between conformation of a failed first line ART regimen and initiation of a second one. This fared worse than pediatric cohorts receiving second line ART in South Africa 171 days) and two other studies from Ethiopia (89 days and 144 days) 1 days an, 11. PosAdherence for initial and second rounds of ARVs was sub-optimal. Recording of adherence is based on parents or caretakers’ report and is at risk for bias in interpretation. Therefore, attempting correlations between adherence and virologic failure among children has proved discrepant , 15.The mean viral load upon initiation of second line ARVs was high. Similar elevated viral set-points were seen among children and adolescents upon being started on second line ARVs in Ethiopia and Nigeria , 16. ThiTen out of seventy-five (13.3%) children and adolescents were experiencing virologic treatment failure (10.6 per 100 person years). These findings were comparable to reports from other low-resource settings in sub-Saharan Africa and south Asia –20. The Out of the ten children with failed treatments, six developed their treatment failure within 6–12 months of initiating the second ART. This was shorter than the 17.6 months it took till failure seen in another pediatric cohort in an Ethiopian referral hospital [Testing for CD4 counts and viral loads were sup-optimal. Strategies to monitor treatment failure differ with the income level of the country. Very few (3%) of pediatric cohorts across sub-Saharan countries barring South Africa receive regular CD4 and viral load monitoring while receiving second line ART . Lack ofAt the time of data collection, close to 10% 7/75) children had died after a mean duration on treatment of 25.7 months. Four had virologic failure. The mean survival using Kaplan Meir analysis is 53.3 months. Poor prognosis regarding survival correlated with poor adherence and advanced WHO clinical stages upon starting second line ART. Across low- and middle-income countries, adolescent ages, being underweight, a longer period of taking first line ARVs and undetectable drug levels correlated with virologic failure . While a/75 childThe study also showed that 5 out of 75 participants (6.7%) had been lost to follow-up. This mimicked the cumulative incidence of loss to follow-up (LTFU) at the end of 2 years of follow-up among similar cohorts in sub-Saharan Africa (7.1%) versus less than 5% globally, reported by the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration .This study’s analysis of performance of second line ART among the study population showed delayed initiation of treatment, high viral set-points and poor treatment adherence. There was poor implementation of regular viral load and immunologic tests during follow-up. Within this restricted clinical environment, the described virologic failure was in agreement with other pediatric cohorts in low-resource countries. Virologic failure occurred early on into treatment. Poor treatment adherence and advanced pre-treatment WHO clinical stages correlated with survival. Limitations include a small study population, incomplete follow-up testing to further determine performance of treatment and incomplete records of study participants.The performance of second line antiretroviral treatments for children and adolescents under care at pediatric HIV clinics in two referral hospitals in Addis Ababa, Ethiopia is described. Improving the depth of knowledge of health workers targeted towards frequent monitoring and early initiation of treatment, improving laboratories’ capacity including their ability to conduct pre-treatment anti-retroviral drug resistance testing and adherence counseling should be priority areas for improvement of HIV care in children and adolescents. We recommend further larger-scale studies to outline the extent of the problem nationwide.S1 File(SAV)Click here for additional data file.


Despite the decreasing morbidity associated with the human immunodeficiency virus (HIV), a large percentage of persons with HIV have at least 1 drug resistance mutation. Ibalizumab, a recently approved drug, targets multidrug-resistant HIV. We present a case of reactivation of hepatitis B after initiation of ibalizumab therapy. One of these drugs is ibalizumab, a recombinant humanized IgG4 monoclonal antibody to CD4 which was approved by the Food and Drug Administration in 2018.2 Although the drug has generally been deemed safe, we present the case of reactivation of hepatitis B after its initiation.With the advent of antiretroviral therapy (ART), both the morbidity and mortality associated with the human immunodeficiency virus (HIV) have declined. However, there remains a large percentage of persons with HIV who have at least 1 drug resistance mutation.A 53-year-old man with multidrug-resistant HIV (diagnosed in 1985), latent tuberculosis, and previous exposure to hepatitis B presented from the clinic with jaundice and elevated liver enzymes. The patient had been on several ART regimens. After years of suboptimal adherence, he acquired resistance to all nucleoside reverse transcriptase inhibitors, most non-nucleoside reverse transcriptase inhibitors, all protease inhibitors, several integrase strand transfer inhibitors, entry inhibitors, and to dual/mixed tropic virus  immunity . HBV serologies were not repeated since that time, given normal liver function tests and no new exposures. Liver tests drawn 6 weeks before presentation were notable for slightly elevated aspartate aminotransferase (AST) of 60 and alanine aminotransferase (ALT) of 97, but were otherwise normal.On presentation, scleral icterus and jaundice were noted on physical examination. Laboratory workup revealed AST 1,052 U/L, ALT 1,589 U/L, alkaline phosphatase 182 U/L, INR 1.4, bilirubin of 6.7 mg/dL, a CD4 188 cells/μL, and an HIV viral load of 76 copies/mL. An abdominal ultrasound demonstrated an unremarkable sonographic appearance of the liver. The patient reported no history of significant alcohol use, new or over-the-counter medications, or sexual exposures. Autoimmune markers, hepatitis C viral load, and hepatitis D antibody were negative. HBV serologies were drawn and were notable for sAg and core antibody (IgM) positivity with surface antibody negativity. An HBV viral load resulted at 6,963,119 IU/mL, consistent with reactivation of hepatitis B. He was started on entecavir, and all ARTs were stopped. His liver enzymes peaked with an AST 2,014 U/L, an ALT 1,557 U/L, and a bilirubin 6.9 mg/dL.One month after presentation, the patient was switched from entecavir to combination emtricitabine/tenofovir alafenamide to better treat both his HBV and HIV. Ibalizumab along with his other ARTs were recently readded as this was the only combination that had been successful at suppressing his HIV. Presently, his HBV viral load is 181 IU/mL, and his liver function has normalized.3 Ibalizumab is believed to inhibit the conformational changes in the CD4/gp120 complex that allows binding to CXCR4, thus inhibiting HIV fusion entry.4 Notably, the CD4 T-cell receptor that is the target of ibalizumab is believed to be distant from the binding site of major histocompatibility complex class II molecules, thereby supposedly preventing an major histocompatibility complex II–mediated immune response after binding. This would imply that it should not be immunosuppressive.6 In addition, ibalizumab is not believed to deplete CD4+ T cells secondary to its low affinity for C1q and for a cellular cytotoxic-dependent response.7 These properties make it a very desirable drug.We describe the case of reactivation of HBV after initiation of ibalizumab, a drug with a unique mechanism of action for use in patients with multidrug-resistant HIV. HIV typically enters the host's cell membrane in a multistep process. The virus contains glycoprotein 120 (gp120) which binds to CD4+ T-cell receptors on the host cell and leads to a conformational change that then allows gp120 to interact with host CCR5/CXCR4 coreceptors. This interaction then leads to HIV fusion entry.7 Immune reconstitution inflammatory syndrome normally occurs around the time of initiation of a drug, when a patient's CD4+ T-cell count rises quickly, but it can also occur up to 2 years after an offending medication is discontinued.8 Our patient's immune system had already reconstituted by the time of hepatitis flare, but the possibility of immune reconstitution inflammatory syndrome is still present. Second, patients with resolved HBV infection could have occult infection with persistent viremia despite the absence of circulating HBsAg.9 Third, although very rare, HBV superinfection with different HBV genotypes can cause acute exacerbations in hepatitis B carriers.10In our patient, however, we believe that the introduction of ibalizumab led to the reactivation of HBV, despite the fact that it should not suppress immunity. This could have happened by several mechanisms. One is by immune reconstitution inflammatory syndrome, which has been previously described with ART, including ibalizumab, when a patient presented with progressive multifocal leukoencephalopathy.11 For these reasons, patients who are HBsAg-negative and anti-HBc-positive should be monitored for HBV reactivation during and after completion of treatment with ibalizumab. Reactivation of hepatitis B or any serious hepatic adverse event in the setting of ibalizumab has not been previously reported. In drug trials with ibalizumab, liver enzyme elevations occurred in up to 25% of patients, but these were usually mild or self-limited.12 Caution should be exercised in prescribing ibalizumab in a patient with previous hepatitis exposure without appropriate prophylaxis.Finally, although seroconversion to positive HBsAg has not been previously described with ibalizumab, there are other monoclonal antibody class of drugs, including rituximab, obinutuzumab, ocrelizumab, and brentuximab where there is a well-documented risk of reactivation of hepatitis B.Author contributions: A. Kaplan wrote the manuscript and revised the manuscript for intellectual content. E. DeHaan and C. Maltz revised the manuscript for intellectual content. C. Maltz is the article guarantor.Financial disclosure: None to report.Informed consent was obtained for this case report.


BRAAVE 2020 demonstrated the efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) among African American adults with suppressed HIV through Week (W) 48 . We present resistance, viral blips, adherence, and virologic outcomes through W72.Figure 1. BRAAVE 2020 study design  and virologic suppression at weeks 24 and 48*Allowed 3rd agents: any FDA-approved protease inhibitor, nonnucleoside reverse transcriptase inhibitor (except etravirine), integrase strand transfer inhibitor (except bictegravir), or maraviroc.Enrollment criteria permitted NNRTI resistance (-R), PI-R, and certain NRTI-R  and excluded known primary INSTI-R. Preexisting drug resistance was assessed with historical genotypes and retrospective baseline proviral DNA genotyping. Adherence was calculated by pill count. Viral blips (transient HIV-1 RNA ≥50 copies/mL) and outcomes based on last available on-treatment HIV-1 RNA were assessed.489 participants received B/F/TAF and had ≥1 post-switch HIV-1 RNA measurement. Baseline genotypic data from cumulative historical and/or proviral genotypes were available for 96% (468/489) in protease/reverse transcriptase and 93% (453/489) in integrase. Preexisting NRTI-R, M184V/I, ≥1 TAMs, NNRTI-R, and PI-R were observed in 15% (68/468), 11% (50/468), 8% (36/468), 22% (101/468), and 13% (61/468), respectively. Primary INSTI-R was detected post-randomization in 2% (11/453); all remained in the study and were included in efficacy analyses. Through W72, 99% (486/489) of participants had HIV-1 RNA < 50 copies/mL at their last study visit, including all with baseline NRTI-R or INSTI-R . Mean frequency of viral blips was 1% per timepoint, and blips were not associated with virologic failure. 112 participants (23%) had < 95% adherence by pill count, 98% (110/112) of whom had HIV-1 RNA < 50 copies/mL at last visit, including 14 of 14 (100%) with < 80% adherence. No participant discontinued due to lack of efficacy or had treatment emergent resistance to study drugs.Figure 2. Virologic suppression by preexisting resistance, viral blips, and adherenceVirologic suppression was maintained through W72 of B/F/TAF treatment, including those with preexisting resistance, viral blips, and suboptimal adherence. Continued HIV suppression and absence of treatment-emergent resistance demonstrate the efficacy of B/F/TAF in African Americans regardless of adherence or preexisting resistance to NNRTIs, PIs, or non-tenofovir NRTIs.Kristen Andreatta, MSc, Gilead Sciences, Inc  Michelle L. D'Antoni, PhD, Gilead Sciences Gilead Sciences, Inc  Silvia Chang, Masters, Gilead Sciences, Inc  Aiyappa Parvangada, MS Computational Biology, Gilead Sciences, Inc  Ross Martin, PhD, Gilead Sciences, Inc  Christiana Blair, MS, Gilead Sciences, Inc  Sean E. Collins, MD, MS, Gilead Sciences, Inc  Kirsten L. White, PhD, Gilead Sciences, Inc


In people living with HIV/AIDS (PLWHA), initiation of antiretroviral therapy (ART) leads to sustained effective suppression of viral replication and increasing CD4 + T cell count. However, a fraction of ART-treated patients still fail to reach adequate CD4 + T cell number despite a suppressed viral load (VL), and this phenomenon is defined as immunovirological discordance (IVD). In Africa, several studies have reported immunovirological outcomes of antiretroviral therapy, but little is known about IVD occurrence in Female sex workers (FSW). This study aimed to assess the prevalence of IVD and associated factors among a cohort of HIV infected FSW in Burkina Faso.We conducted a cohort study from December 2003 to October 2016. Immunovirological discordance was defined as CD4 + T cell gain < 100 cells/µL despite a suppressed VL (VL < 1000 copies/mL) 12 months after ART initiation. The CD4 + T cells were counted using BD FACSCount™ System and point of care Pima™ CD4 + Analyzer. HIV-1 RNA was quantified by real-time polymerase-chain-reaction assay with the use of the ABI 7000 system. We conducted a logistic regression to identify factors associated with discordant responses.Among the 123 HIV-1 infected FSW having at least 12 months follow-up on ART, 105 (85.4%) achieved HIV-1 RNA suppression. Among the latter 25 gained less than 100 CD4 + T cells within 12 months follow-up. The IVD rate was 23.8% (95%CI 16.04%–33.11%). After adjustment for age, WHO clinical stage and ART regimen including nucleoside/nucleotide reverse transcriptase inhibitors, only baseline CD4 + T cell count between 200 to 350 cells/µL  and 350 to 500 cells/µL  remain significantly associated with IVD occurrence.Immunovirological discordance response was common in FSW with proportions close to those observed in the general population. A diagnosis and personalized follow-up of patients who do not achieve full immune reconstitution would make it possible to avoid complications in terms of morbidity and mortality. In people living with HIV/AIDS (PLWHA), initiation of the antiretroviral therapy (ART) lead to sustained effective suppression of viral replication, increasing CD4 + T cell count, reversal of most immunological disturbances, and reduction in risk of morbidity and mortality . HoweverIn resource constrained countries including Africa, Latin America, and Asia, the antiretroviral therapy collaboration network reported an IVD prevalence of 19.07% after six months on ART . Recent Multiple factors have been associated with IVD occurrence but none of these factors provides a full explanation for the lack of immune reconstitution –15. SociIn Africa, several studies have reported immunovirological outcomes of ART but few of them have been focused on IVD assessment in Female Sex Workers (FSW). Whereas, FSW are exposed to multiple factors that could favor IVD occurrence namely, substance use, ART non-adherence, coinfections due to the high frequency of viral and bacterial sexually transmitted infections (STI) , 25, 26,Knowing that the immune reconstitution that occurs during ART is essential for successful treatment of PLWHA and the lack of data on IVD occurrence among FSW, we sought to assess the prevalence of IVD and its associated factors at 12 months follow up in FSW living with HIV in Burkina Faso.We analyzed data from an open cohort of high-risk women followed up from December 2003 to October 2016 , as described previously –29. ThisCohort of HIV infected and uninfected FSW were recruited through a network of peer educators, then enrolled after informed consent. The recruitment and inclusion have been described elsewhere –29. BrieCollected variables included socio-demographic characteristics, clinical and biological data at ART initiation, and 12 months follow-up on ART. Study participants who started ART were followed at closer intervals: weekly during the first two weeks, and monthly during the whole follow-up for clinical examination, detection of drug adverse effects, and counseling on adherence . AdherenART was initiated and monitored according to national guidelines adapted from the WHO recommendation for each period . The firBlood samples were collected in EDTA-containing tubes. The CD4 + T cells were counted using BD FACSCount™ System  and point of care Pima™ CD4 + Analyzer .BD FACSCount™ CD4 reagents are complete kits used to enumerate the absolute counts and the percentage of CD4 + T lymphocytes. Briefly, 50 µL of adequately mixed EDTA whole blood was added into the reagent tube. The tube was vortexed for 6 s and incubated for 30 min at room temperature in the workstation protected from light. Then, 50 µL of the fixative solution was added and vortexed upright for 6 s before being analyzed with the BD FACSCount instrument.The Pima CD4 test comprises a disposable Pima CD4 test cartridge and the Pima Analyser. It is an automated, image-based immune hematology test intended for the absolute CD3 + /CD4 + T lymphocyte counts in whole blood. Succinctly, 25 µL of adequately mixed EDTA whole blood was added into the sample collector of the Pima CD4 test cartridge. Then, Insert the Pima CD4 test cartridge into the Pima Analyser to run a test.For viral load measurement, briefly, RNA was extracted manually from plasma using the QIAamp viral RNA mini kit . HIV-1 RNA was quantified by real-time polymerase-chain-reaction assay with the use of the ABI 7000 system (Applied Biosystems) as described previously . The lowal. [There is no consensus in the literature on how best to define immunologic response or immunological failure during ART and it is not clear which criteria are optimal. Aldrete et al.  explorinGood adherence to ART was defined as adherence rate > 95% and poor adherence as < 95% .Statistical analyses were performed with Epi Info™ 7. Categorical variables were expressed as frequency and/or percentage (%) whereas quantitative variables as median with interquartile range (IQR). Logistic regression by stepwise model selection was used to analyze predictors of IVD in univariate and multivariate analyses. The independent variables were included in the multivariate model if they had a p-value ≤ 0.20 on bivariate analysis. The variable age and WHO clinical stage were forced in the final model irrespective of p values. P values < 0.05 were considered statistically significant.Of 243 cohort participants who started ART during the study period, 123 met inclusion criteria for this analysis  and 76.4% were single or widowed or divorced. At ART initiation, 52.0% were at WHO clinical stages 3 or 4, and the median CD4 + T cell count was 147 (IQR 79–200) cells/µL. Regarding ART molecules, most patients 83 (67.5%) started the Efavirenz-based regimen, and 73 (59.3%) a Zidovudine-based regimen  had attained VL suppression (VL < 1000 copies/mL) . Irrespective of VL suppression, 86 patients (69.9%) achieved a CD4 + T cells gain greater than 100 cells after 12 months of treatment (Table 86. IrresWhen we assessed immunologic recovery as a function of VL suppression status (VL < 1000 copies/mL), the IVD rate was 23.8% (95%CI 16.04%–33.11%).At 12 months follow-up, 78 (63.4%) patients achieved good adherence with a median ART adherence rate of 98.6% (IQR 97.0–100). The adherence rate was 97.0% (IQR 93.5–99.6) for those with suppressed VL and 96.4% (IQR 95.3–100) for those who presented an IVD. Table We next evaluated factors associated with IVD in 105 patients who obtained VL suppression. In bivariate analysis, patients with baseline CD4 + T cell count between 200 and 350 cells  and between 350 and 500 cells  were more likely to present IVD at 12 months on ART compared to those with CD4 + T cell count below 200 cells/µL . Other factors like age, body mass index, and WHO clinical stage were not associated with IVD occurrence at 12 months on ART : 4.15; 95%CI 1.13–15.22) and between 350 and 500 cells/µl  remain significantly associated with IVD occurrence (Table The frequency of IVD in our population of FSW was 23.81% after 12 months of follow-up on ART. This finding was similar to previous reports in the general population which noticed that 10–30% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication , 16, 35.In this study, a discordant response was associated with a higher CD4 + T cell count above 200 cells/µl at ART initiation. Other studies have reported similar findings to ours, with higher pre-therapy CD4 + T cell count being associated with smaller gains in CD4 + T cell count at 12 months , 16, 23.Contrariwise, some studies reported that a low baseline CD4 + T cell count was predictive of immunological discordant treatment responses , 36, 37 Another contributing factor that could particularly expose FSW to IVD and not assessed in our study is coinfection with other pathogens which is prevalent in Africa , 40. NumIn contrast to most of the studies, age was not associated with IVD in our study. In the evaluation of immune recovery, younger age was described to predict greater early CD4 + T cell gain and supporting the importance of thymic function , 44, 45.Unexpectedly, patients that initiated therapy with a tenofovir containing regimen were more likely to develop IVD than patients on a Zidovudine or stavudine containing regimen. This could probably be explained by the fact that tenofovir was introduced when the threshold for CD4 count to initiate ARV treatment was 350 cells. In addition, the relatively small number of patients on tenofovir compared to other molecules could also explain these results. However, evidence on nucleoside/nucleotide reverse transcriptase inhibitors effect on CD4 + T cells recovery was controversial , 47. MosContrary to Abrogoua et al.  who notiTo date, no antiretroviral or immune system-based strategy has yet demonstrated a clinically meaningful outcome in the treatment of IVD. Some data support less frequent CD4 + T cell monitoring in clinically stable virally suppressed patients and suggest that routine CD4 + T cell monitoring for this population may be unnecessary , 51. ForOur study has some limitations. Some findings could be explained by the relatively small size of the sample, which does not ensure sufficient power to be able to extrapolate the statistical analysis results to the overall population. We did not have baseline HIV-1 RNA measurements for more than half of the patients. These results would have made it possible to better assess the evolution of viral load under ART. The CD4 + T cell count was not performed with the same counting device for all patients. A study showed a 2% difference between the results of the CD4 + T cell count performed with the BD FACSCount device and the Pima analyzer from a threshold of 350 cells/µL . As a reDespite the difficult context linked to the lack of a consensual definition of IVD and the period over which it must be evaluated, our results show a frequency of IVD in FSW comparable to those observed in the general population. Despite several pejorative considerations, the monitoring set up in the Yerelon cohort makes it possible to obtain the same rates of IVD in FSW as in the general population. A better understanding of IVD occurrence and associated factors may lead to better therapies to improve the level of immune reconstitution and ultimately the possible development of adjuvants that reverse the immunologic perturbations caused by HIV infection and that persist despite ART induced viral suppression.


However, the therapy is not without its side effects. This study was aimed at assessing the self- reported orofacial manifestations due to long term use of HAART, as well as the pattern of oral lesions on examination.this was a cross-sectional study conducted among HIV seropositive adult patients in Ibadan, who had been on HAART for at least two years. Data were collected using an interviewer-administered questionnaire. Clinical diagnosis of HIV-related oral lesions was made according to the EC-Clearinghouse criteria. Data analysis was done using SPSS version 25.3, with a median count of 341 cells/mm3. About half (45%) of the participants noted one or more orofacial changes since they commenced HAART. These oral changes included dryness of mouth, burning sensation, abnormal taste, melanotic hyperpigmentation, oral thrush, ulcers, and parotid swelling. Most of those who reported oral changes had been on HAART over 10 years (p=0.03), and the changes were more reported among those on the first-line regimen.the study participants comprised of 227 HIV seropositive patients who were HAART experienced, with 54 (24%) males and 173 (76%) females. Their mean age (±SD) was 44.7 (±9.4) years. The participants CD4 count ranged from 13-1338cells/mmmelanotic hyperpigmentation was the most common oral lesion found and burning mouth syndrome was the most commonly reported complain among HIV-seropositive adults who are on long-term HAART. Highly active antiretroviral therapy (HAART) has become a standard treatment for HIV infection globally and has been found to induce marked reduction in viral load and an increase in the CD4+ cell count . The intNucleotide reverse transcriptase inhibitors (NRTIs) such as Zidovudine can cause bone marrow suppression, which may predispose to oral ulcers, oral lichenoid reaction, and mucositis . Non-nucThe Federal Government of Nigeria introduced the national antiretroviral therapy (ART) program in 2002 with free drug provision to adults and children . CurrentThe study was a descriptive cross-sectional design conducted among HIV-seropositive patients attending the outpatient adult HIV clinic of the Infectious Diseases Institute, College of Medicine, University of Ibadan, Nigeria. Ethical approval was obtained from the University of Ibadan and University College Hospital, Ibadan Joint Ethical Review Committee. The study was conducted over a period of four months, from August to November 2018. The inclusion criteria were adults who had been on HAART for at least two years . All conData collection was done using an interviewer-administered questionnaire. Information obtained were socio-demographics, social habits , co-morbidity, CD4 count, mode of HIV infection, duration, and type of antiretroviral therapy. Oral examination was carried out by two dental surgeons using facemasks, disposable wooden spatulas, and latex gloves under natural light. Clinical diagnosis of HIV-related oral lesions was made according to the criteria proposed by the EC-Clearinghouse . The parData analysis was done using SPSS version 25. Quantitative variables such as age and duration on HAART were summarized using means and standard deviation. Categorical variables such as gender, marital status, and oral lesion types were expressed as proportions. Pearson´s Chi-square test was used to assess the association between the independent variables and the outcome variables, and the level of significance was set at 5% (p<0.05).The study participants comprised of 227 HIV-seropositive patients on HAART, consisting of 54 (24%) males and 173 (76%) females. Their ages ranged from 18- 80 years with a mean age of 44.7 (±9.4) years. The majority were married (63%), while more participants reported Christianity (64.3%) as their religion . Only 15Forty-five percent of the participants reported one or more oral changes since they commenced HAART. Some of the self-reported oral related changes were dryness of mouth, burning sensation, abnormal taste, dark spots, oral thrush, ulcers, and parotid swelling . More pa3 and 341 cells/mm3 (IQR 13-1838) respectively. Almost half (48%) of the participants had CD4 count ranging from 200 cells/mm3 to 500 cells/mm3. The majority (77.8%) of respondent with CD4 count <500 cells/mm3 had oral lesions on examination (p=0.01)  was the most common lesion. Others included candidiasis (13%), periodontal diseases (7%), oral ulcers (1%), and fibroma (1%). The mean (±SD) and median (inter-quartile range) CD4 count of the participants were 387.2 (±277.6) cells/mm(p=0.01) .The oral findings in the present study align with those in earlier documented works that have assessed HIV-infected patients who were HAART experienced , 14, 15.et al. [et al. [et al. [Also, about half of the study participants reported having witnessed some changes in their oral cavity since the time they commenced HAART. The most-reported oral symptom in long term use of HAART from this study was burning mouth syndrome . This was found mostly among those who had been on HAART for more than 10 years. This finding is consistent with studies from India as reported by Nittayananta  [et al.  among HI [et al. .3; almost half of these were severely immunosuppressed (CD4 <200 cells/mm3). This was significantly related to the presence of some HIV-related oral lesions, as documented. The level of immunosuppression found among our participants could be due to their inadequate adherence to HAART as well as poor nutrition due to low socioeconomic status. We suggest more extensive multi-center studies in Nigeria to investigate the relationship between CD4 count and orofacial lesions.Despite the use of HAART for at least two years, among the respondents in this study, a high degree of immunosuppression was observed among them. Most of our respondents had CD4 count < 500 cell/mmThe study has its limitations; since the participants´ responses were self-reported, they are prone to misreporting bias. There is also the risk of recall bias, considering that some of them had been on HAART for several years. The study employed a cross-sectional design, therefore, causality and temporality could not be established; the identified orofacial lesions could be due to other causes apart from HAART.Burning mouth syndrome was the most recurring oral symptom associated with long-term use of HAART among HIV patients in Ibadan, Nigeria. As well, melanotic hyperpigmentation was the most commonly found orofacial lesion among them. A significant association was found between the presence of oral lesions and immunosuppression among the study participants.Highly active antiretroviral therapy (HAART) helps to reduce HIV-associated lesions;HAART, like many other pharmacological agents, has its attendant side effects.Identification of burning mouth syndrome as the most reported oral complaints among people living with HIV/AIDS (PLWHA) on long term HAART in Ibadan, Nigeria;Identification of melanotic hyperpigmentation as the most common orofacial lesion found among HAART-experienced PLWHA in Ibadan, Nigeria;3 are more likely than those with >500 cells/mm3 to have orofacial lesion.Among PLWHA who are on long-term HAART in Ibadan, Nigeria, those with a CD4 count of <500 cells/mm